Oxygen Therapy Second Edition Jaypee PDF

Oxygen Therapy
Oxygen Therapy
Second Edition
Edited by
S K Jindal
Professor and Head
Department of Pulmonary Medicine
Postgraduate Institute of Medical Education and Research
Chandigarh
Ritesh Agarwal
Assistant Professor
Chandigarh
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Oxygen Therapy
© 2008, Jaypee Brothers Medical Publishers
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system,
or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or
otherwise, without the prior written permission of the editors and the publisher.
This book has been published in good faith that the material provided by contributors is original.
Every effort is made to ensure accuracy of material, but the publisher, printer and editors will
not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters are
to be settled under Delhi jurisdiction only.
First Edition: 1998 (North India Chapter, American College of Chest Physicians, Chandigarh)
Second Edition: 2008
ISBN 81-8448-197-7
Typeset at JPBMP typesetting unit
Printed at Paras Press
Contributors
A N Aggarwal
Associate Professor
Chandigarh
Ajay Handa
Ex-Senior Resident
Chandigarh
Anil Narang
Professor and Head
Department of Pediatrics
Chandigarh
Chandana Reddy
Ex-Senior Resident
Chandigarh
D Gupta
Additional Professor
Chandigarh
Meenu Singh
Additional Professor
Chandigarh
vi Oxygen Therapy
Navneet Singh
Research Officer
Chandigarh
Puneet Malhotra
Ex-Senior Resident
Chandigarh
R Agarwal
Assistant Professor
Chandigarh
S K Jindal
Professor and Head
Chandigarh
S Venkatseshan
Chandigarh
Surg Cdr (Dr) PS Tampi

Classified Specialist and Pulmonologist
Bombay Hospital and Medical Research Center
II Floor, New Wing, 12, New Marine Lines
Mumbai
V K Jindal
Professor
Advanced Centre for Physics
Panjab University, Sector 14
Chandigarh
Preface to the Second Edition
The first edition of the book on Oxygen Therapy was received with
a welcome note by the medical community especially the students
pursuing their postgraduate courses in Medicine and Chest
Diseases. It is now nearing a decade since the first edition of this
book was published. Numerous advances have taken place during
this period. The reliance on oxygen therapy has enhanced and
indications expanded. Some of the broad areas in which the
progress has been specially noticeable include the long-term use
of domiciliary oxygen, the hyperbaric oxygen therapy and the
alternate oxygen carriers. There are also several advancements in
oxygen delivery devices and the related equipments. The
understanding of the side effects and the toxicity of oxygen has
also increased. Oxygen being an environmental gas, is significantly
influenced by natural changes in the environment. One can foresee
the widening arena of oxygen use in the light of developments in
medicine and physiology which have taken place during
exploration and exploitation of different environments, example
at high altitude and in the space on one hand and in the depth of
the seas on the other. Obviously therefore, there was a great need
of a revision.
In the revised edition, we have taken care to include some of
the new scientific developments as well as update the information
on other subjects. We have also included the contributions from
several other authors and experts to whom we express our sincere
gratitude. This book provides short but concise information on
different aspects of oxygen meant as a therapeutic agent. It lays
the scientific foundations on oxygen therapy, primarily for the
clinicians. It also lays stress on a rational and well regulated use
of oxygen as a core drug than a mere add on tonic. We sincerely
hope that the readers will enjoy the reading and find the book
useful in their day-to-day practice of medicine.
SK Jindal
Ritesh Agarwal
Preface to the First Edition
Oxygen as a gas, has fascinated me since my early childhood which

was spent in the neighborhood of a vendor who used to supply
gas cylinders for welding and other miscellaneous, nonmedical
uses in a small town. Later, I was overwhelmed by the immense
faith and confidence which oxygen enjoyed as a last ritual of a
patient on the death-bed. The span of life in Hindu philosophy
has been linked with the number of breaths, and oxygen alluded
to as a “Prana-Vayu” (the life-air). People, therefore, expect
miracles from oxygen.
Oxygen therapy plays a pivotal role in the management of
respiratory, cardiac and other serious illnesses. Indications for
Oxygen Therapy continue to expand. Numerous advances have
been made in the understanding of both the physiological and
clinical aspects of oxygen. Yet it remains one of the most ill-
practised subject in clinical medicine. Its administration is
erroneously identified with placement of a nasal catheter (or a
face mask) attached with a tube to an oxygen cylinder. There is
much more to know about oxygen.
There is a great lack of information on oxygen and its uses.
There are plenty of reviews and comprehensive books on different
aspects of Respiratory Failure and Oxygen Therapy. But a third-
world perspective is often lacking. The present monograph is an
attempt to collate this information and intermix with our own
experience at this Institute, in a single volume which covers the
physiological and pharmacological basis of Oxygen Therapy as
well as the practical aspects related to its administration.
The monograph is intended for use of not only the graduate
and postgraduate students, but also the practicing physicians and
other specialists. It should particularly interest internists and
physicians who practice general and/or pulmonary medicine,
critical care, pediatrics, cardiology and other specialities wherever
oxygen is required. To make it more relevant for clinicians of all
hues, it includes chapters on different aspects such as hyperbaric
x Oxygen Therapy
therapy, oxygen use for non-pulmonary diseases, during air travel

and at high altitude, and special considerations for the neonates.
It is hoped that the readers shall enjoy the book and benefit from
its reading.
SK Jindal
Contents
Part A: General Introduction

1. Historical Aspects ..................................................................... 3
SK Jindal
2. Applied Physics of Gases ...................................................... 14
SK Jindal, VK Jindal
Part B: Physiological Considerations

3. Respiratory Physiology .......................................................... 33
D Gupta, R Agarwal
4. Oxygen and Carbon Dioxide Transport ............................. 55
Navneet Singh
5. Tissue Oxygenation ................................................................ 71
Puneet Malhotra
Part C: Clinical Considerations

6. Blood Gases and Acid-Base Balance ................................... 89
SK Jindal, N Singh and R Agarwal
7. Blood Gas Monitoring ......................................................... 126
Chandana Reddy, R Agarwal
8. Hypoxemia and Goals of Oxygen Therapy ..................... 143
SK Jindal
9. Clinical Prescription of Oxygen ........................................ 152
SK Jindal
10. Oxygen Therapy for Pulmonary Disorders ..................... 157
SK Jindal
11. Oxygen Therapy for Non-Pulmonary Disorders ............ 183
SK Jindal, R Agarwal
xii Oxygen Therapy
12. Long-Term Oxygen Therapy .............................................. 193

R Agarwal, SK Jindal
13. Oxygen Therapy in the Intensive Care Unit ................... 211
AN Aggarwal
14. Air Travel and Oxygen Therapy ........................................ 221
Ajay Handa
15. High Altitude Problems ...................................................... 227
16. Oxygen Use in Diving Medicine ....................................... 231
PS Tampi
17. Hyperbaric Oxygen Therapy .............................................. 240
PS Tampi, SK Jindal
18. Complications of Oxygen Therapy ................................... 254
D Gupta, SK Jindal
Part D: Special Issues

19. Alternate Oxygen Carriers .................................................. 269
20. Oxygen Delivery Devices .................................................... 280
R Agarwal
21. Oxygen Therapy: Special Considerations for
Neonates ................................................................................. 300
Anil Narang, S Venkatseshan
22. Oxygen Therapy in Children ............................................. 323
Meenu Singh
23. Oxygen Storage and Supply in Hospitals ....................... 358
SK Jindal
Index ......................................................................................... 371
Part A
General Introduction
1
Historical Aspects
SK Jindal
INTRODUCTION
Oxygen is a wonderful gas. It catches the imagination of the lay
and the scientists alike. Its story is both interesting and perplexing-
it reflects the story of life. Its evolution had preceded the appearance
of life on earth. Subsequently, it has supported survival of all living
beings including man, animals and plants. Sadly, the story is also
laced with tragic happenings. Lavoisier, the man who first used
the term oxygen was guillotined during the French Revolution
without any recognition at that time of his immense contributions.
EVOLUTION OF ATMOSPHERIC OXYGEN

The history of evolution of atmospheric oxygen is long and tardy.
It has remained a matter of intense investigations. It is believed
that the earth was practically devoid of oxygen, only about one
thousandth of the present level, when it was formed some 4.6 billion
years ago. Water itself had appeared much later after the earth
had cooled down. Oxygen was produced by photo-dissociation of
water by the ultraviolet light from the sun. There was plenty of
water on earth and the ultraviolet light from the sun. Why was
then the concentration of oxygen negligible?
It is easy to understand the answer to this question. One single
oxygen atom (or radical) is unstable and does not exist in the natural
form. The oxygen molecule (O2) which we need and breathe, is
formed of two oxygen radicals. Whenever there was an excess of
4 Oxygen Therapy
oxygen radicals, they formed ozone (O3) which in turn cut out the
ultraviolet light from the sun. This would decrease further photo-
dissociation and production of oxygen.
There are two very puzzling facts about relationship of origin
of life and oxygen: one, life could initially develop only in an oxygen
free atmosphere; and two, it was the presence of living organisms
which resulted in an increase in oxygen in the atmosphere.
The explanation for the development of life in an oxygen-free
atmosphere is attributed to the formation of organic compounds
from which the living organisms subsequently developed. They
are the essential components in the structure of all living things—
plants and animals. The compounds could form from water, carbon
dioxide and ammonia only in oxygen-free surroundings. Oxygen
would have oxidized and destroyed the compounds. In the absence
of oxygen, the organic compounds could accumulate and result in
the formation of life. The presence of primitive cellular life
encouraged an increase in oxygen concentration by permitting an
increase in photo-dissociation of water.
Almost half the duration of existence of earth had passed when
primitive life had surfaced in the form of a single-celled organism.
It is interesting to know that the living organisms themselves were
responsible for increase in the concentration of oxygen in the
atmosphere. They started consuming oxygen for respiration and
thereby encouraging further photo-dissociation and production of
oxygen.
Algae, the most primitive form of life, appeared about a billion
years after the formation of organic compounds. It is photosynthetic
in its function, i.e. it synthesizes energy in the presence of sunlight.
At this stage, there was a marked increase in oxygen—about ten
times the previous concentration. This concentration remained
fairly constant for the next 2 billion years by a process of stabili-
zation known as the Pasteur effect. An increase in oxygen encoura-
ged respiration, which in turn reduced the available oxygen. This
caused a reversal to fermentation and dissociation to produce more
oxygen. This cycle went on for the next 2 billion years when there
was a dramatic increase in oxygen concentration and development
of multicellular organisms. This was perhaps a major milestone in
the evolution of life.
Even though the atmospheric oxygen got established at same
levels as of now some 100 million years ago, it was less than
Historical Aspects 5
2 million years when primitive man appeared. It has been explicitly

illustrated with a simple example of time clock. If the total time
period of earth’s formation is reduced to 24 hours, man had
surfaced on the earth in the last half minute.
Talking of oxygen, it is only about 100 million years since when
we have concentrations similar to those of today. This is attributed
to the formation of ozone layer above the earth’s atmosphere. The
ozone layer formed from excess of oxygen, could screen the
dangerous ultraviolet light from sun and other stars of the universe.
It acts like a canopy (or a tent) under which life could evolve without
the danger of death from extra terrestrial rays.
It is difficult to know as to when the importance of oxygen in
sustenance of life was realized. Although the true scientific
references to its role were not available until the medieval period,
the ancient cultures did allude to the need of respiration and the
requirement of air.
ANCIENT HINDU CONCEPT OF OXYGEN

The presence of lungs had been recognized in ancient Hindu
medicine. Both Charaka and Susrata the two famous physicians/
surgeons of the Vedic period (500 BC), recognized a ‘prana vayu’,
i.e. life-air. Charaka mentions the head, the chest, the ears, the
tongue, the mouth and the nose as the seat of the ‘pran vayu’.
Susrata (1000 BC) spoke of ‘prana vayu’ as flowing in the mouth.
What else than oxygen can this ‘prana vayu’ be identified with?
It was Sarangadhara, a 13th century physician who explicitly
described the concept of respiration:
In summary, it implied that the ‘vayu’ located in the ‘hrdya’

(Chest) goes out and after drinking the ‘Ambarapiyush’ (nectar) it
goes back very quickly. It touches the interior of ‘hydaya’, promotes
the ‘Jatharanatha’ (life) and nourishes the entire body.
Sarangadhara had described the sequences leading to the
inhalation of ambrosia, the food of gods, or a nectar like substance
6 Oxygen Therapy
vital to life, from the outside air, its circulation through the heart
to the brain and all other parts of the body. This ‘nectar like
substance’ is likely to be what we now know as oxygen.
ANCIENT GREEK CONCEPTS

More than 2500 years ago, the Greek philosophers had believed
that air or some essential component of air distributed a very vital
need to the body. In the 4th century BC, Aristotle identified few
essential elements—earth, air, fire and water. The need for ‘air’
remained well recognized, although its role was not identifiable.
It was perhaps in the 3rd century BC that Erasistatus, a medical
teacher at Alexandria in Egypt recognized the interplay between
air and blood as an essential function for life. It took four more
centuries to postulate a theoretical concept of life based on
knowledge from multiple sources. Galen in the 1st-2nd century
AD made several conclusions, one of whom related to air exchange.
He laid down a schema which involved a two-way traffic of
inspired air and effluent waste vapors.
Most of the beliefs on essential role of air were based on
philosophical ideas than physiological evidence. The ideas were
somewhat similar to those of other cultures. But oxygen as an
independent component of air was neither known nor firmly
conceived.
MODERN HISTORY OF OXYGEN

Paracelsus, a Swiss alchemist had suggested in 1541 that air
contained a life sustaining substance. But the clearer basis of
physiology was laid by William Harvey who discovered the
circulation of blood although nothing much was talked of
breathing. The credit of the work on role of breathing goes to the
four famous Oxford physiologists of 17th century. It was clearly
shown in the laboratory that air was necessary for life and could
keep an animal alive even when breathing movements were
arrested. It was also shown that the dark venous blood became
bright red when it passed through the lungs. This change in color
was attributed to the uptake of “nitro-aerial particles” from the air
insufflated into the lungs. In the 17th century, John Mayow had
suggested that only a portion of air was necessary for life, but his
work was not acknowledged during his lifetime. This was to be
labeled as oxygen more than a century later when the gas was
discovered and produced in the laboratory.
The medieval Europe from 14th century onwards had gone
through a period of renaissance which saw changes in innumerable
scientific concepts. The mid eighteenth century was the period of
discovery of gases such as hydrogen, nitrogen and carbon dioxide.
Oxygen was isolated by Joseph Priestley in 1772 and prepared in a
pure form by heating mercuric oxide. He had also demonstrated
that the gas supported life of a mouse better than the air. He
commented: “It might be salutary to the lungs in certain cases when
the common air would not be sufficient to carry off the phlogistic
putrid effluvium fast enough”. Priestley, a clergyman, teacher and
librarian was the son of a weaver and a married farmer’s daughter.
Priestley also discovered that the gas obtained on fermenting grain
(now known as CO2) produced the drink known as seltzer when
dissolved in water. He fell seriously ill from tuberculosis but got
well to die at the age of seventy one in 1801. Interestingly, oxygen
was independently discovered a year before Priestley by Scheele
who had named oxygen as ‘fire-air’. Most of the gases were being
actively investigated for their role in burning which had remained
a major concern for survival of man since the very inception of
life. Different materials on burning (i.e. oxidation) were supposed
to loose a substance called phlogiston as per the Stahl’s belief;
Priestley therefore called oxygen as the dephlogisticated air.
It was later when the dephlogisticated air was labeled as
“oxygen” (means “acid begetting” in Greek) by Antoine Laurent
Lavoisier. He compared respiration with the process of combustion
and demonstrated that animal respiration involved absorption of
oxygen by the lungs from the inhaled air and elimination of carbon
dioxide and water. He also demonstrated the indispensable nature
of oxygen for human life and that the oxygen consumption
increased with increased body activity. Lavoisier was executed
during the French Revolution in 1789 since he was an aristocrat by
birth.
One important development which significantly advanced our
knowledge on clinical applications of oxygen related to the
assessment of oxygen and carbon dioxide in the blood. Blood was
first described to be slightly alkaline by Des Plantes in 1776. Oxygen
and carbon dioxide were detected by Davy in 1799. Robert Boyle
extracted “air” from blood. Magnus in 1837 used the vacuum
8 Oxygen Therapy
extraction technique to measure the content of these gases in the

whole blood. Several other methods were employed in the first
half of this century by Van Slyke, Scholander and others. Those
methods used the manometric or volumetric methods which were
slow, elaborate and required careful precision. Further refinements
led to the development of highly accurate and fast response
analysers.
Tissue respiration was described in 1870 by Pfluger and others
who identified the locus of respiration in the cells. In fact there
had been a lot of debate between Ludwig, Pfluger and others about
the gas exchange, in the 19th century. This had further encouraged
the discovery of methods for precise blood gas assessment.
Several other discoveries ran almost parallel such as the role of
hemoglobin in transport of oxygen by the blood by Hoppe-Seyler
during 1860s. Dalton came up with his atomic theory of respiratory
gases and Paul Bert with the oxygen dissociation curve in early
1870s. It was depicted as ‘hyperbolic’ which got changed to the
sigmoid shape later by Bohr. The ‘Bohr’ effect and the ‘Haldane
effect’ were reported later in the early 20th century.
Oxygen deficiency was perhaps first established as “anoxemia
of high altitude” in 1878 by Bert who attributed the altitude sickness
and death to lack of oxygen. Even earlier, Joseph Ch Hamel, a
Russian physician had believed that the lack of oxygen was
responsible for muscular weakness at altitude. On an ascent to Mont
Blanc in 1820, he had planned to study the oxygen content of air
and blood at the summit and the effects of oxygen administration.
Unfortunately, the expedition was stopped by an avalanche which
killed three of his guides shortly before the summit. It was almost
half a century later that the term”anoxia” was used by Barcroft
and Van Slyke. Uptake of oxygen was another issue which
remained controversial between Bohr and his former assistant
August Krogh and wife Marie Krogh. While Bohr supported the
theory of secretion of oxygen, the Krogh team showed diffusion of
gases in the lungs to explain oxygen uptake. It was Joseph Barcroft
who finally demonstrated that diffusion alone was the mechanism
for gas exchange.
OXYGEN THERAPY
Thomas Beddoes used oxygen for the first time in early 1800s for
treatment of medical disorders. He built a pneumatic piston with
help from James Watt—the inventor of steam-engine for storing

and delivering oxygen. Soon after, oxygen became a therapeutic
panacea for many illnesses. It was used for diseases such as cholera,
infertility, hysteria and glycosuria. It was considered a ‘cure-all’
medicine until early 20th century. Cunningham, a famous US
physician treated his patients of arthritis, anemia, syphilis,
glaucoma, diabetes and cancers with high pressures of oxygen.
He reported recovery of his patients but did not find any scientific
support from others. As expected, no consistent benefit could be
found for most patients and soon its use became unpopular and
achieved a kind of notoriety. This got compounded by reports on
toxic effects of excessive oxygen use. William Osler, who recogni-
zed “imperfectly oxidized” blood in pneumonia was also more
fearful of its toxicity than benefits. Use of oxygen for treatment of
pneumonia was reported first in 1885 by George Holtzapple to
benefit ‘‘average country practitioners’’.
Meanwhile, there were other developments in respiratory
physiology which helped in re-establishing the role of oxygen
therapy. In 1920s, it was established that oxygen deficiency resulted
in serious physiological disturbances which could be corrected with
supplemental oxygen. These observations were supported by firm
clinical and experimental evidence. Oxygen therapy now achieved
a prime role in treatments of cardiac and respiratory diseases. It
was commercially produced for the first time in 1895 by Carl Von
Linde using fractional distillation of liquid air.
John Haldane used oxygen to treat chlorine poisoning during
First world war. He had stated that ‘hypoxia not only stops the
machine but wrecks the machinery’. He had also advocated the
use of oxygen for treatment of other respiratory illnesses. During
this period in 1921, Meakins used oxygen therapy in the manage-
ment of lobar pneumonia and reported that oxygen therapy was
perhaps the most important factor in the treatment apart from the
specific cure of infection. This was perhaps the major landmark in
oxygen therapy in modern medicine after its initial use and
subsequent disrepute. Its use became widespread in the following
years.
Parallel to the discovery of oxygen use were the developments
concerning its toxicity. Its toxic effects were suspected by von
Liebig, Pasteur and Bent. Terms such as ‘oxygen toxicity lung’ and
‘respirator lung’ were used to describe respiratory failure caused
10 Oxygen Therapy
by excessive oxygen use or ‘oxygen free radicals’. Devison

compared the oxygen molecule to a grenade which could cause
tremendous damage once the safety pin was pulled out.
The history of respiratory failure is relatively more recent. The
terms ‘anoxia’ and subsequently ‘hypoxia’ were used in the 3rd
and 4th decades of the twentieth century. The concept of
‘pulmonary insufficiency’ was introduced in 1940 by Cournand
and Richard. More precise and meaningful terms have been used
thereafter. The definition continues to be debated and refined. But
the facts that the respiratory failure was directly linked to oxygen
deficiency and it treatment with oxygen administration, were
clearly established.
The methods and devices used for oxygen administration have
also undergone a sea change. Many different kinds of pipes had
been used in the past. Gas pipes were popular treatment devices
in the late nineteenth and early twentieth centuries. Different types
of masks, oxygen tents and cannulae were developed during the
world wars. Closed circuit oxygen equipment was commonly
employed in the 1930s and 1950s, for example during mountainee-
ring. Tom Bourdillon and Charles Evans who had climbed to within
90 m of Mt Everest in 1953, two days before the summit was finally
conquered had to abandon their effort because of the circuit’s
malfunction.
HYPERBARIC OXYGEN
Development of hyperbaric oxygen therapy is another long story
which saw quite a few upheavals. Some of these developments
have been discussed in the chapter on hyperbaric oxygen.
Hyperbaric air chambers to treat different ailments have been used
since 1662 in one or the other form with varying degrees of
enthusiasm and antagonism. It was in early 20th century, when
hyperbaric oxygen was first used to treat decompression sickness.
Later, the scope of therapy extended to cover several other clinical
indications.
DOMICILIARY OXYGEN
Alvan Barach used oxygen for reversal of hypoxemia in 1920s. He
also recognized the need of continuous use of oxygen in patients
with chronic obstructive lung disease. The ambulatory use of
oxygen to improve exercise tolerance was tried by Cotes in 1956 in

UK and Barach in North America in 1959. Rapid progress was made
in the next few years. Chamberlain showed the reversal of
polycythemia by oxygen administration. The first two studies on
domiciliary use made by Levine, et al (1967) and Abraham, et al
(1969) also showed improvements in polycythemia and pulmonary
hypertension in patients of chronic obstructive lung disease.
Once the domiciliary use was shown to be effective, refinements
were introduced into the design and modes of administration. Low
flow oxygen delivery with the help of nasal cannulae was shown
to be effective and safe. The previously held belief that intermittent
oxygen could cause greater CO2 retention and aggravate hypoxe-
mia was dispelled. A significant improvement in overall survival
was shown by Neff and Petty in 1970.
Studies by the Medical Research Council (MRC) and the
National Institute of Health (NIH) in 1980-81 are considered as
landmark studies in the use of domiciliary oxygen. Further
improvements in oxygen therapy continue to occur thereafter. But
the role of oxygen as a maintenance drug was settled.
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Ancient Greek Concept

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12 Oxygen Therapy
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Modern History of Oxygen

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12. Perkins JF Jr. Historical development of respiratory physiology, in Fenn WO,
Rahn H (Editors), Handbook of Physiology. Section 3: Respiration, vol. 1,
Bethesda, MD, American Physiological Society, 1964, pp.1-62.
13. Priestley J. Experiments and observations on different kinds of air (1775).
Alembic Club Reprints, Part 1, No. 7, Chicago, University of Chicago Press,
1906.
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Biol 2001; 2:545-9.
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Med 2005; 28:221-4.
16. Warren CP. The introduction of oxygen for pneumonia as seen through the
writings of two McGill University professors, William Osler and Gonatham
Meakins. Can Respir J 2005; 12:81-5.
Oxygen Therapy
17. Astrup P, Severinghaus JW. The history of blood gases. Acids and Bases.
Copenhagen, Munksgaard International Publishers, 1986.
18. Campbell EJM. Oxygen and hypoxia. Seminar Respir Med 1981;3:59.
19. Cotes JE, Gilson JC. Effect of oxygen on exercise ability in chronic respiratory
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Scadding G (editors), Scientific Foundations of Respiratory Medicine, London:
Heineman Medical 1981, pp.221-37.
21. Meakins J. Observations on the gases in human arterial blood in certain
pathological pulmonary conditions and their treatment with oxygen. J Pathol
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Domiciliary Oxygen
26. Flenley DC. Long- term home oxygen therapy. Chest 1985; 87:99-103.
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2
Applied Physics of Gases
SK Jindal, VK Jindal
INTRODUCTION
The air we normally breathe is a mixture of gases of which oxygen
and nitrogen constitute the main bulk. Breathing of additional or
supplemental gases is required in abnormal situations. While the
role of anesthetic gases required for brief periods, has greatly
diminished, helium is another gas which has found an expanded
role in emergency clinical practice. The physical properties of these
gases influence the mechanics of normal breathing as well as the
therapeutic strategies. It is therefore, important to know the
physical principles governing the gases.
STATE OF MATTER
Matter can exist in three classically different forms in nature—solid,
liquid or gas although plasma, a fourth state of matter has also
been identified under extremes of temperature and pressure. Matter
is either an element made from similar atoms, e.g. iron or
compound made from two or more types of atoms, e.g. water (H2O).
An element is a basic unit of matter which retains the same
properties on subdivisions by chemical or mechanical means.
Oxygen and other gases such as hydrogen, helium, chlorine and
nitrogen are elements in nature.
Atom and Element

An atom, is the smallest part of an element which acts like its
‘building block’. On further subdivision of an atom, the elemental
Applied Physics of Gases 15
properties are lost and therefore, sub-atomic constituents of all

atoms are identical. Atoms of certain elements (e.g. hydrogen,
helium) can exist in free stage (H, He) and there is no difference
between the atoms and molecules of these elements. Atoms of many
other elements (such as oxygen) do not exist free but combine with
other atoms of the same element to form molecules (e.g. O2, i.e.
O′+O′). Atoms of different elements may form molecules or
compounds. Hydrogen can exist in atomic or molecular form,
whereas nitrogen and oxygen occurs in molecular form (N 2
and O2).
Molecule and Compound

All substances consist of exceedingly small particles called
molecules. There are about 1019 molecules in 1 mL of air under
normal conditions of temperature (T) and pressure (P). A molecule
possesses the distinctive properties of the parent element or
compound. A molecule is found to consist of two or more atoms of
same kind or of different kinds.
The number of molecules comprising a macroscopic quantity
of a gas is enormous typically around 1023 molecules. The number
of molecules and their velocity determine many properties of gases.
A compound is composed of two or more elements united
chemically to form a substance different from the individual
elements forming that compound. For example, carbon dioxide is
a compound of carbon and oxygen. On subdivisions, the compound
loses its properties and may resume those of the constituent
elements. Both elements and compounds exist as molecules as
smallest component.
Molecular Movement
All the molecules of matter are in a state of incessant motion. This
is known as Brownian movement and forms the basis of kinetic
theory of matter. This motion results from temperature—the higher
the temperature, the larger the velocity of the molecules. At absolute
zero temperature, the velocity of a classical molecule goes to zero.
Molecules of a gas have great mobility and travel longer distances
before colliding with other molecules. It is because of this mobility
that a gas has no fixed shape and mixes readily with other gases.
16 Oxygen Therapy
Atomic and Molecular Weights

The mass of an atom is concentrated at its nucleus, which contains
a definite number of neutrons and protons of identical masses.
The neutrons or protons are also called nucleons. The mass of a
nucleon is H ≈ 1.6 × 10–24 gms (sometimes also called atomic mass
unit, amu). Therefore, total number of nucleons of an atom
determine the mass of an atom and is usually called atomic weight.
This H′ atom has atomic weight equaling 1, whereas O′ atom has
atomic weight equaling 16. Though their actual masses are around
1 × 1.6 × 10–24 gms and 16 × 1.6 × 10–24 gms, respectively. Similarly,
molecular weight is determined by summing up atomic weights
of the constituent atoms forming that molecule. As an example,
H2 molecule has a molecular weight = 2, and H2O molecule has a
molecular weight = 2 + 16 = 18. For obtaining their actual weights,
we multiply those weights by amu (= 1.6 × 10–24 gm) to get the
mass in gms.
If M is the molecular weight of given substance, then 1 molecule
of that substance weighs M × 1.6 × 10–24 gm. This gives us that M
gm of the substance will have 1/1.6 × 10–24 molecules, which is
called Avogadro number (No ≈ 6.02 × 1023). It is thus clear that M
gms (also called 1 mole) of any substance will have N0 molecules.
Gaseous substance (which behave like an ideal gas) follow an
equation PV = nRT.
One can easily calculate the volume at NTP (normal
temperature 0oC, and Pressure ≡ 760 mm Hg) from η = 1 mole. It
comes out to be 22.4 liters for any gas. Therefore, a quantity of any
substance equaling molecular weight as gms has 6.02 × 1023
molecules and as a gas, occupies 22.4 liters at NTP.
PHYSICAL PROPERTIES OF GASES

Volume
Volume is the space occupied by a gas. The volume of a cuboid
shape vessel is determined by the multiplication of internal length,
width and height of the vessel. It is expressed in cubic centimeters
(cc), cubic feet or litres (L), etc. (1 L = 1000 cc or mL).
Volume = Length × Width × Height
A 10 cm cube has the volume equaling 1 L. Volume of a
container of uniform cross-sectional area A and height is given by
V = A h.
The gas shall occupy the available volume irrespective of the

amount (mass) of gas. For example, if a small vessel containing
oxygen is emptied in a larger vessel, the entire volume of the larger
vessel will be occupied by the same amount of gas (Fig. 2.1).
Fig. 2.1: Mass of a gas such as O2 (i.e. number of molecules) in vessels A and B is
unchanged, but the volumes are different therefore, the density of the gas in vessel
A is greater than that in vessel B
Mass and Weight

Mass is the bulk or the total mass of number of molecules of the
gas. In the above mentioned example, the mass of the gas in two
cylinders shall remain the same, although the volume has changed.
The number of molecules per unit of volume in the two vessels
has changed, i.e. lesser number of molecules per unit volume in
the larger vessel (Fig. 2.1).
Weight is often used synonymously with mass. Weight is
determined by the pull of gravity on mass (i.e. m × g). Since the
force of gravity on the earth is nearly constant, mass is equivalent
to weight on the surface of the earth. In fact, weight is scaled to
indicate mass and therefore both represent the same thing.
W ≡ force = m × g
Density
Density is expressed as the weight in grams of one liter of a gas.
Since the weight of 22.4 liters of a gas is that of a gram molecule of
18 Oxygen Therapy
that gas, one liter of the gas shall weigh molecular weight/22.4
grams. When expressed this way, the density will be measured in
gm/liter. It is also measured in gm/cc which will equal 1/1000 in
value to that in gm/liter.
Molecular weight of oxygen = 32
Density = 32/22.4
= 1.43 gm/liter
The density of a gas is also expressed as relative to the density
of air. Density of air shall vary depending upon its composition.
For all practical purposes, it comprises of 1 volume of oxygen (about
20%) and 4 volumes of nitrogen (about 80%). At NTP, the density
of air is (32 × 1/5 + 28 × 4/5)/22.4 = 1.3 gm/L. Therefore, the
density of oxygen relative to that of air is 1.1. When expressed this
way, as relative density it becomes unimportant if the density of
individual gases was calculated in gm/liter or gm/cc.
Pressure
The gas molecules are always in a state of motion and constantly
bombard the walls of the container. The force applied to (or acting
upon) a unit area of the wall is called the gas pressure. The closer
the molecules, the greater the number which strike each unit area
and therefore the greater the pressure applied. Also, larger the
velocity (or temperature), larger is the impact on the walls, leading
to greater pressure.
Gas pressure is generally considered as that of a stationary gas
when the pressure exerted is the same at any point in a gas
container. The pressure is usually expressed in millimeters of
mercury (mm Hg) or centimeters of water (cm H2O) or pounds
per square inch (psi). One mm of Hg means force on a unit area
(1 cm2) on which 1 mm of height of Hg is placed. The volume of
height h cm on unit area is A × h = h cm3 and in mass is hd where d
is the density of the liquid. The force on unit area due to this is hdg
which is also the pressure p. Thus p due to a height h of a liquid of
density d, p = hdg. The pressure due to 1 mm of Hg can be calculated
by putting h = 0.1 cm, d = 13.6 gm/cc and g = 980 cm/s2.
1 mm Hg≡ 1334 CGS units or dynes/cm2
= 133.4 Pa (Pascal is another unit of pressure)
Atmospheric Pressure
Atmospheric air is pulled to the earth by gravity and generates a
force upon the surface of the earth, resulting in atmospheric
pressure. Atmospheric pressure is the sum of pressures of all gases
(e.g. N2, O2 and CO2) present in air. It is measured with the help of
a glass tube filled with either mercury or water (manometer). The
height of the column of mercury (or water) multiplied by its density
is a measure of the atmospheric pressure. Standard pressure is
measured at sea level and expressed in mm Hg (torr) or cm H2O.
One atmospheric pressure = 760 mm Hg or
14.7 psi or
1030 cm H2O
It is important to convert atmospheric pressure (a ≡ 76 cm of
Hg) in CGS units. This is approximately 106 CGS units.
1 atm a ≡ 76 cm of Hg ~ 106 CGS ~ 1 bar
It is relevant here to mention that the lungs are subject to
atmospheric pressure all the time. Since the alveoli are in direct
communication with the atmosphere through the tracheobronchial
tree, the alveolar pressure is the same as the atmospheric pressure.
The changes in alveolar pressure during inspiratory and expiratory
phases of respiration are relative to the atmospheric pressure.
During inspiration when the alveolar pressure is –10 cm H2O, it
implies the presence of atmospheric pressure minus 10 cm H2O
(i.e. 1030 – 10 cm H2O). Similarly, when positive pressure is admin-
istered to a patient through a ventilator, the ventilator gauge
pressure of 10 or 20 cm H2O refers to a total pressure of 1040 or
1050 cm H2O (i.e. atmospheric pressure + gauge pressure).
Partial Pressure
In a mixture of gases in a container, each gas exerts the same
pressure which it would if it alone occupied the container. There is
no interference from the presence of other gas/es. The pressure
exerted by each individual gas is called the partial pressure. The
total pressure exerted by the mixture of gases is equal to the sum
of the partial pressures of all the gases contained in the mixture
(Dalton’s Law). The partial pressure is determined by the fraction
of the concentration of the gas in the mixture.
The atmospheric air has a total pressure of 760 mm Hg (when
dry) at sea level. The partial pressures of N2 (79%) and O2 (21%)
20 Oxygen Therapy
therefore, are as follows:

PN2 = 79% of Patm = 600.4 mm Hg
PO2 = 21% of Patm = 159.6 mm Hg
Temperature
Temperature is the thermal state of a substance which determines
whether the substance will give or receive heat from another
substance in contact. It is an indication of the level of molecular
activity. Heat is the thermal energy of a substance which can be
given to or abstracted from it. Temperature is the measurement of
heat.
Calorie (cal) is the unit of heat. It is defined as the quantity of
heat required to raise the temperature of 1 gm of water by 1oC.
To raise the temperature to a given range, similar weights of
different substances require different quantities of heat. The
number of calories required to raise the temperature of 1 gm of
that substance by 1oC is the specific heat of that substance. Similarly,
specific heat from 1cc of a substance is expressed in cal/cc.
The specific heat depends on the state of the matter- solid, liquid
or gas. Specific heat of water is 1 (It follows from the definition of
1 calorie).
For gases such as O2 and air, it is 0.0603 cals per cc, this number
is quite high when expressed per gm.
We can calculate the total quantity of heat required to raise the
temperature of a given volume by multiplying the volume with
specific heat and temperature rise, i.e. volume (cc) × specific heat
(cals per cc) × temperature rise (oC).
THE GAS LAWS

There is a definite relationship between the gas properties described
above. These relationships are described in different laws to
understand the behavior of gases. These laws are valid for ideal
gases only, where the assumption that the gas particles are very
small and do not interact with each other is valid.
Boyle’s Law
Pressure (P) of a gas is inversely proportional to its volume (V)
provided the absolute temperature (T) of the mass of gas is kept
constant. In other words the product of pressure and volume

remains constant. It follows immediately from the ideal gas
equation,
I
P∝ or P × V = constant, if T is constant.
V
Or
P1 V1 = P2 V2
The application of this law in respiratory physiology is best
exemplified in the use of body plethysmography to measure total
lung capacity. It is also employed in many mechanical ventilators
whereby the gas is driven into patient’s lungs or into the cylinder
of the ventilator by the up-stroke and down-stroke movements of
the piston.
Charles’ Law
When pressure and mass of a gas are kept constant, the volume of
the gas will vary directly with its absolute temperature. Again from
gas equation,
V
= Constant (K), if P is constant
T
It is because of this reason that volumes measured with the
help of lung function equipments (at room temperature) are a little
lower than those at body temperature (37oC) and need to be
corrected for the same. If the temperature of a container of a gas is
lowered, the volume shrinks. Therefore, more gas can be stored in
the same cylinder at a lower temperature.
Gay-Lussac Law
Temperature and pressure of a gas are directly proportional when
the volume and mass are kept constant.
P
P ∝ T or = K at constant V
T
It implies an increase in pressure if the temperature is increased.
For this reason safety valves are provided with devices using high
pressure gases to vent high pressures in case there is an accidental
heating.
22 Oxygen Therapy
The General Gas Law

Assume N ideal non-interacting molecules of a gas each of mass m
are contained in a cube of volume V. They are in motion if the
temperature is above 0oK (0oK = –273oC). If the temperature is T in
Kelvin, the kinetic energy from each molecule is of the order of kT,
where k is called Boltzmann constant (k = 1.38 × 10–16 CGS units).
Because of this kinetic motion, the molecules of the gas keep
bombarding the walls of the cube and exert pressure. The pressure
increase results in extra energy (obtainable from force × distance
or p × volume relation). In this way it is quite evident that one can
equate the energy because of pressure (PV) as resulting from kinetic
energy of N molecules, PV = NkT
If N is expressed in No (Avogadro No.),
PV = ηNokT,
where η = N/No
This is the famous gas equation valid for all ideal gases. η is the
number of moles of the gas, Nok is also called gas constant R.
R ~ 6 × 1023 × 1.38 × 10–16 erg/deg K
~ 2 cal/deg K
The gas equation can be used to determine how the given initial
state (P1, V1, T1) relates to (P2, V2, T2), some final state by using
(P1V1/T1 = P2V2/T2).
P1 V1 PV
= 2 2
T1 n 1 T2 n 2
It may be stated here that under conditions of lower temperature
and high pressure the gas changes its state to a liquid. This is
because the gas molecules get attracted to each other (Van der
Waal’s force) rather than being repelled. The higher pressure
condenses the molecules and the lower temperature reduces their
activity.
The temperature at which the gas turns into liquid is the
“Critical temperature” of that gas. For oxygen, it is –116oC. A
pressure of 50 atmospheres is required to liquefy oxygen at –116oC.
To keep the oxygen in a liquid form at 1 atmosphere in a flask
open to the atmosphere, the temperature is lowered to below
–183oC. This principle forms the basis of availability of oxygen in
the liquid form for storage and ambulatory use.
Henry’s Law
The amount of gas that enters into physical solution in a liquid is
directly proportional to the partial pressure of the gas. For example,
the greater the partial pressure of oxygen in the alveoli, the greater
the solubility in plasma.
Graham’s Law
The rate of diffusion (D) of a gas is inversely proportional to the
square root of its density (d).
D1 d 2
=
D 2 d1
Therefore a light gas (such as helium) will diffuse at a faster rate
than a heavier gas (such as oxygen).
Bernoulli’s Principle
Flow of a gas through a partially obstructed tube can be described
by Bernoulli’s principle, i.e. the pressure required to produce flow
is the difference in velocity at two points and the density of the gas
(Fig. 2.2).
Fig. 2.2: Velocity of a fluid increases with decrease in cross-section

area. It is maximum at the narrow part
GAS SOLUTION AND TENSION

The amount of gas dissolved in a liquid is directly proportional to
the pressure of the gas (Henry’s Law). It also varies with the
temperature—lesser amount is dissolved at the same pressure if
24 Oxygen Therapy
temperature is increased. A state of equilibrium is reached when

no further gas dissolves in the liquid. This is a state of full saturation
with the gas at a given temperature and pressure. The gas in
solution is said to exert the same “tension” as the partial pressure
of the gas over the liquid in equilibrium with it. For example, when
the partial pressure of oxygen in alveoli is 100 mm Hg, the tension
of O2 in alveolar capillaries is 100 mm Hg. At this pressure, 0.3 cc
of oxygen at NTP dissolves in 100 cc of water. The weight of oxygen
1.3
dissolved in 100 cc water is 0.3 × = 0.0004 gm (1.3 gm/L is
1000
the density of oxygen).
The amount of oxygen dissolved in plasma or water is the same
(0.004 gm/100 mL). This is quite sufficient to supply all the oxygen
necessary for the metabolism of the body.
VAPORS
Vapor is defined as the gaseous state of a substance which at room
temperature and pressure is a liquid. On the other hand a gas at
room temperature exists only in the gaseous state. Like any other
gas, the molecules of a vapor are continuously in violent motion
and bombard the walls of the container. The force exerted on each
unit area is called the pressure of the vapour (vapor pressure). A
vapor in a mixture of gases obeys the same laws as the gases. The
partial pressure of the vapor in a mixture bears the same proportion
to the total pressure as the volume, i.e. it depends on the percent
(or fractional) concentration in the mixture. For example, the
concentration of about 16 percent of water vapors in air at NTP
which is sufficient to saturate air with water vapors exerts a
pressure of 16 percent of 760 mm Hg (47 mm Hg).
The presence of water vapors in air or oxygen is referred to as
humidity. It is largely through the process of evaporation that the
molecules of water (or any other liquid) evaporate into the
overlying air (or any other gas in a container).
The molecules leave the liquid substance when their kinetic
energy exceeds the surface tension of the liquid. If a liquid is kept
in a closed container for long, a state of equilibrium is reached
when the number of molecules returning to the liquid (conden-
sation) is exactly equal to the number leaving it (evaporation). This
is called the saturation-point. This is further dependent upon
temperature; if the temperature increases, the number of molecules
leaving the liquid also increase and the saturation point is raised,
i.e. there is a greater amount of vapors in the same amount of gas.
The reverse happens with a fall in temperature.
The air we breathe is normally humid due to the presence of
water vapor. The actual amount of water vapor present in air is
expressed as “relative humidity” which is defined as the ratio of
the amount of water vapor present in a given volume with the
amount of water vapor which the air (or the gas) is capable of
holding at the given temperature, in the same volume.
The humidity of air varies with the atmospheric conditions.
Once inhaled in the lungs, air gets fully saturated. The amount of
water vapor required to saturate the alveolar air at body
temperature and pressure is the body humidity.
The presence of water vapor in the inhaled air exerts its own
partial pressure, and lowers the pressures of constituent gases of
air – oxygen and nitrogen. Therefore, PN2 or PO2 is calculated as a
proportion of the atmospheric pressure minus water vapor
pressure, i.e. Patm – PH 2 O .
When fully saturated, PH2 O of atmospheric air is equal to
47 mm Hg.
Therefore, PO2 = (Patm – PH 2 O ) × 21%
= (760 – 47) × 0.21 = 150 mm Hg.
The rest, i.e. 760 – (150 + 47) would be approximately the PN2.
EXPRESSION OF GAS VOLUMES AND PRESSURES

In view of the effects of temperature, pressure and humidity on all
gases, these are expressed with reference to those conditions. Some
of the common expressions are:
1. Standard (or normal) temperature and pressure (STP) or NTP
Temperature 0oC; Pressure 760 mm Hg.
2. STPD: D indicates ‘dry’ = complete absence of water vapor.
3. Ambient temperature and pressure – dry or saturated (ATPD
or ATPS): Ambient implies the room conditions.
4. Body temperature and pressure saturated (BTPS): Body
temperature (usually 37oC), ambient pressure and water vapor
pressure (47 mm Hg).
Normally, gas volume measurements are made in the ambient
conditions. Conversion is required to express the volume at BTPS
26 Oxygen Therapy
or STPD. STPD is used for uniformity of expression. This is done

by multiplying with conversion factors. Tables of conversion factors
from ATPS to STPD, STPD to BTPS or BTPS to ATPS are available
in most laboratories. Such corrections are also required to express
volume of a gas (such as O2) produced in the laboratory. The
volume is expressed at STPD which is different than that produced
at ATPS.
Flow of Gases
Flow is the movement of particles of a liquid or a gas from higher
to lower pressure. It is expressed in terms of volume per unit time,
e.g. litres per minute or per second (L/min or L/sec). The
movement of air into the lungs during inspiration and out into the
atmosphere during expiration is accomplished by the flow of air
through tracheo-bronchial tree. Similarly, oxygen flows from a
container cylinder to the lungs or a ventilator through connecting
tubes as long as there is a pressure difference.
The flow is described as laminar if it is smooth and gas particles
move along lines parallel to the walls of the tube (Fig. 2.3A). But it
is turbulent if the lines of flow are irregular, broken up and
disorderly (Fig. 2.3B). Whether the flow is laminar or turbulent, it
has to meet a certain resistance while moving from one to the other
end of the tube. The laminar flow is described by the Hagen-
Figs 2.3A and B: A. Patterns of flow: The particles of gas move linearly along
parallel lines; B. The flow of gas particles is irregular and disorderly
Poiseuille equation, i.e. V = π γ4ΔP)/(8ηl). The resistance is

dependent on the tube length (l) and diameter. It is also directly
proportional to the velocity of flow ( V• ) or rate in case of laminar
flow. The flow is also viscosity (η) dependent and density-
independent. When the flow is turbulent, the resistance rises for
steeply.
In this way the laminar flow through a straight tube of uniform
size is inversely proportional to the length (l) of the tube and directly
to the fourth power of radius (r).
When the flow exceeds a “Critical flow rate”, the laminar flow
is replaced by the turbulent flow throughout the length of the tube.
Turbulent flow is less efficient since the Δ P varies directly with V2.
Turbulent flow is density dependent and viscosity-independent.
The critical flow varies directly with the internal diameter of the
tube–the larger the diameter, the greater the flow. At a flow below
the critical rate, local turbulence may occur as a result of
irregularities in the pathways of the gas. During oxygen
administration this may occur due to constriction or kinking of the
tubes.
Turbulence in a flowing system can also be predicted by
Reynold’s number. It is the ratio between inertial (density
dependent, viscosity independent) and viscous (viscosity
dependent, density independent) forces – a dimensionless number.
In case of pipes,
Density × Velocity × Diameter
Reynold’s Number =
Viscosity
Flow is laminar when the number is less than 2000 and turbulent
when it is more than 3000. Turbulent flow is dominated by inertial
forces producing random eddies and flow fluctuations. Between
2000-3000, the flow is transitional, i.e. neither fully laminar nor
fully turbulent.
While administering oxygen, it is important that resistance is
kept at a minimum so that the effort of breathing is reduced.
Therefore, the breathing tube should be as wide and as short as
possible and have smooth walls. There should be no kinks and
constrictions and bends should be gradual.
Flow Through Orifices

An orifice is a narrow opening of a tube. Unlike a tube, the diameter
of the fluid pathway of the orifice exceeds the length. The greater
28 Oxygen Therapy
the diameter compared to the length, the more does the opening
approach the ‘ideal’ orifice. The flow through an orifice depends
on the diameter (or the cross-section area) of the orifice and the
difference in pressures on either side of the orifice.
The intrinsic property of a liquid which influences its flow
which we earlier termed as resistance is called viscosity. It is
attributed to the internal friction between different layers which
move at different speeds. While the laminar flow largely depends
on viscosity, it is the density which determines the flow when
turbulent. The coefficient of viscosity is equal to the force per unit
area necessary to maintain unit difference of velocity between two
parallel planes.
The flow through an orifice is at least partially turbulent. The
lower the density, i.e. the lighter the gas, the greater is its volume
flow for any given pressure difference on either side of the orifice.
Wave Speed
Wave speed (c) is the speed at which a small disturbance (wave)
travels in a compliant tube filled with a gas. In the airways, it
depends upon the cross-sectional area of the airway (A). The
density of the gas (p) and the slope of the pressure area curve of
A/p
the airway (dP/dA) : c2 =
dP/dA

Maximum flow ( V max) of a gas in an airway is the product of
the gas velocity at wave speed and the airway area (cA). It increases
as the density of the gas decreases.
Thermal Conductivity
It is a measure of a substance’s capacity to conduct heat. The high
thermal conductivity is likely to result in a higher skin heat loss.
But respiratory heat loss depends on heat capacity not conductance.
Heliox
Heliox is a mixture of oxygen with helium (He) in varying
concentrations, commonly as 20 percent oxygen and 80 percent
helium. It has a lower density than that of air, i.e. oxygen (21%)
with nitrogen (79%). Resistance offered to flow of heliox is lower
than that of air and of oxygen and depends on the fractional

concentrations. It diffuses 1.8 times faster than oxygen. This fact is
exploited in clinical practice for treatment of acute respiratory
distress of obstructive airway diseases such as asthma when the
flow is highly turbulent. Heliox diffuses fastly than oxygen through
partially obstructed airways. In view of the lower resistance offered
to heliox, the breathing effort is considerably reduced and the crisis
tide over.
BIBLIOGRAPHY
1. Brooks SM. Integrated Basic Science, St Louis CV Mosby Company, 1966.
2. Dawson SV, Elliott EA. Wave speed limitation on expiratory flow: A unifying
concept. J Appl Physiol 1977; 43:498-515.
3. Egan DF. Fundamentals of respiratory therapy, St. Louis: CV Mosby
Company, 1966.
4. Emsley J. Nature’s building blocks: An A-Z guide to the elements. New York:
Oxford University Press; 2001.
5. Hess DR, Fink JB, Venkataraman ST, Kim IK, Myers TR, Tano BD. The history
and physics of heliox. Respir Care 2006; 51:608-12.
6. Macintosh RR, Mushin WW, Epstein HG. Physics for the anesthetist,
Philadelphia: FA Davis Company, 1970.
7. Riggs JH. Respiratory Facts, FA Davis Company, 1989.
8. Varma YS. Applied physics for the anesthetist, Rajan, Chandigarh, 1988.
9. West JB. Ventilation/blood flow and gas exchange, Philadelphia: FA Davis
Company, 1970.
10. Young JA, Crocker D. Principles and practice of respiratory therapy, Chicago
Year Book Medical Publishers Inc.
Part B
Physiological
Considerations
3
Respiratory Physiology
D Gupta, R Agarwal
INTRODUCTION
Oxygen is essential for continuation of life. It is required by each
human cell for its survival. It is abundantly present in the
atmosphere and maintains a remarkably constant concentration
of 20.9 percent in ambient air. Oxygen is taken up by the lungs
through the act of inspiration and transported to the cells via blood.
At the cellular level, oxygen is utilized for production of energy.
In this process, carbon dioxide is released and transported back
via the blood to the lungs from where it is expired out into the
atmosphere. The act of exchange of oxygen and carbon dioxide is
called respiration. For effective respiration, air must be drawn
through the airways and distributed among approximately
400,000,000 alveolar compartments within the lung parenchyma.
Although respiration is normally described as the uptake of oxygen
and release of carbon dioxide by the lungs, it is essentially
happening at the level of lungs (‘external’ respiration) as well as
the tissues (‘internal’ respiration).
The respiratory system is made up of a gas-exchanging organ
(the lungs) and a pump that ventilates the lungs. The pump consists
of the chest wall and the respiratory muscles, which increase and
decrease the size of the thoracic cavity; the areas in the brain that
control the muscles; and the tracts and nerves that connect the brain
to the muscles. At rest, a normal human breathes 12-15 times a
minute. About 500 mL of air per breath, or 6-8 L/min, is inspired
and expired. This air mixes with the gas in the alveoli, and, by
simple diffusion, O2 enters the blood in the pulmonary capillaries
34 Oxygen Therapy
Fig. 3.1: Schematic diagram to represent different

process involved in respiration
while CO2 enters the alveoli. In this manner, 250 mL of O2 enters

the body per minute and 200 mL of CO2 is excreted.
Gas exchange by the human lungs is achieved with the help of
four processes (Fig. 3.1), which are also variably interdependent:
1. Ventilation: To and fro movement between the atmosphere and
the gas exchanging units of the lung.
2. Circulation: Supply and distribution of blood through the
pulmonary capillaries.
3. Diffusion: The movement of O2 and carbon dioxide across the
air-blood barrier between the alveoli and the pulmonary
capillaries.
4. Ventilation-perfusion relationships.
VENTILATION
Ventilation is the process of bulk movement of air from atmosphere,
through the conducting airways to the terminal respiratory gas
exchange units. This movement of air is made possible by the force
which is generated by the effort of respiratory muscles (or a
mechanical ventilator if the patient is being ventilated). Obviously,
it is also dependent on the mechanical properties of the conducting
airways and the lung parenchyma (i.e. the breathing units). The
mechanical properties are referred to as ‘static’ at zero (or no air
flow) flow and constant volume, and ‘dynamic’ if there is air flow.
Respiratory Physiology 35
The amount of air that moves in and out of the lungs with each
inspiration and expiration respectively is called the tidal volume.
The air inspired over and above the tidal volume with a maximal
inspiratory effort is the inspiratory reserve volume, and the volume
exhaled actively after passive expiration is the expiratory reserve
volume; the air left in the lungs after a maximal expiratory effort is
the residual volume. The respiratory dead space is the space in the
conducting zone of the airways occupied by gas that is not involved
in gas exchange. The vital capacity, the largest amount of air that
can be exhaled after a maximal inspiratory effort, is a frequently
measured index of pulmonary function. The fraction of the vital
capacity exhaled during the first second of a forced expiration is
the FEV1. The maximal voluntary ventilation is the largest volume
of gas that can be moved into and out of the lungs in one minute
by voluntary effort. There are several factors on which the
aforementioned lung volume and the air flow depend: compliance
(a volume term), which is a measure of the elastic properties of
lung, is an important determinant. Other elements include
resistance (a flow term) and inertance (an acceleration term).
Inertance
Since the respired gases, the lungs and the chest wall all have
appreciable mass and therefore inertia, they offer an impedance to
change in direction of gas flow. This component called inertance is
extremely difficult to measure, but offers impedance that increases
with frequency. Hence, inertial pressure is essentially negligible
for most clinical purposes and the gas flow depends primarily on
the compliance and resistance characteristics of the lung
parenchyma except in situations of increased respiratory
frequencies like high frequency ventilation.
Compliance
Pulmonary compliance (or distensibility) is defined as the change
in volume of the lung per unit change in the distending pressure
which in case of lung is the transpulmonary pressure (which is
defined as the pressure gradient between the alveolar [PA] and the
pleural pressures [Ppl]). Elastance is the reciprocal of compliance.
Compliance is equal to the exhaled tidal volume (or a change in
lung volume) divided by the alveolar pressure minus the pleural
pressure (or a change in the transpulmonary pressure).
36 Oxygen Therapy
C = Δ VL/ Δ (PA – Ppl), where

C = lung compliance
Δ VL = change in lung volume
Δ (PA – Ppl) = change in transpulmonary pressure
The interaction between the recoil of the lungs and recoil of the
chestwall can be demonstrated using body plethysmography. The
nostrils are clipped shut, and the subject breathes through a
spirometer that has a shutter just beyond the mouthpiece. The
mouthpiece contains a pressure-measuring device. The pleural
pressure is measured by insertion of an esophageal pressure
balloon. The subject performs a forced expiration following a full
inspiration (i.e. total lung capacity [TLC]). The respiratory muscles
are then relaxed while the pressure in the airway is recorded. The
procedure is repeated after inhaling or actively exhaling various
volumes. The alveolar air pressure is measured by interrupting
the flow at the mouth momentarily and measuring mouth pressure
(Pm [pressure at mouth] = PA [alveolar pressure] during zero flow
conditions), whereas the esophageal balloon gives the estimate of
pleural pressure. The curve of airway pressure obtained in this
way, plotted against volume, is the compliance of the total
respiratory system. One can also partition the chest wall and lung
compliance by subtracting total lung compliance from chest wall
compliance by using the esophageal balloon. The pressure is zero
at a lung volume that corresponds to the volume of gas in the lungs
at the end of quiet expiration (relaxation volume, which equals
the functional residual capacity [FRC]). It is positive at greater
volumes and negative at smaller volumes. The compliance is
normally measured in the pressure range where the relaxation
pressure curve is steepest. However, compliance depends on lung
volume with highest compliance at residual lung volume and low
compliance at high lung volumes.
The pressure volume relationship thus obtained is a curvilinear
graph. The elastic recoil pressure of lung always tends to collapse
the lung even at the residual volume. Theoretically therefore, if
removed from the thoracic cage, the lungs collapse to almost an
airless state. The pressure-volume curve is also slightly greater
when measured during deflation than when measured during
inflation, a property called hysteresis (Fig. 3.2). Hysteresis is
affected by the elasticity of lung parenchyma (in fact, hysteresis is
a universal property of all elastic materials) and the surface tension
of alveolar spaces.
Fig. 3.2: Diagramatic representation of pressure and volume changes during

quiet inspiration (line AXB) and expiration (line BZA). Line AYB is the compliance
line
Recruitment
This is a unique phenomenon observed in lung due to the closure
of some small airways at lower lung volumes. As the transpul-
monary pressure rises, the closed airways open sequentially. Thus
recruitment of additional lung units in the initial phase of
inspiration starting from lower lung volumes also contributes to
hysteresis. Two other important factors affecting lung compliance
are the surface tension and the physical nature of lung tissues.
Surface tension exerted by the air fluid interface is reduced by
surfactant - a surface active compound of phospholipids produced
by type II alveolar cells. Surface tension is further lowered at lower
lung volumes thereby increasing the compliance and decreasing
the force required during the next inflation. Also by the Laplace
law (Pressure = 2 × surface tension/radius), as the diameter of the
alveoli is decreased, the pressure would increase and this would
create an unstable system; this is also prevented by the surfactant
which decreases surface tension with decreasing radii of the alveoli,
and allows gas to flow from the larger to the smaller alveolus and
stability is maintained. This phenomenon is also mandatory for
the maintenance of stability of alveoli at lower lung volumes.
38 Oxygen Therapy
Physical elastic properties of lung tissue per se, are due to the
presence of elastic fibers in the pulmonary interstitium. Expansion
in lungs is probably more due to unfolding and geometric
rearrangement of elastic fibers rather than the actual lengthening.
Ageing alters the elastin and collagen fibers in lungs and thus
increases the compliance. Compliance is also increased in
emphysema due to the loss of elastic fibers of alveolar walls. It is
reduced wherever there is stiffness and thickening of alveolar
septae by processes such as fibrosis.
Elastic Properties of Chest Wall and

Lung-chest Wall Interactions
The resting volume of the thoracic cage is approximately equal to
70 percent of TLC. It implies that if the thoracic cage is opened and
support of lung withdrawn, it expands from FRC (the resting
position of the respiratory system at which the inward elastic recoil
of the lungs is exactly balanced by the outward recoil of the thoracic
cage) to a volume of about 70 percent of TLC. At volumes less than
70 percent (including FRC) the thoracic cage has a tendency to
expand and elastic recoil pressure is opposite to that of lungs, and
is directed outwards.
The total compliance of the respiratory system is analogous to
the electrical capacitance with the compliances of the lung and the
thoracic wall arranged in series. Thus the total compliance is the
reciprocal of the individual compliances, i.e.
1/total compliance = 1/lung compliance + 1/chest wall
compliance
Instead of compliance, we may consider its reciprocal, elastance
and the relationship is much simpler:
Total respiratory system elastance = lung elastance + chest wall
elastance
The total respiratory system compliance in an awake patient
can be measured using the body plethysmography as detailed
earlier whereas it is much easily measured in the mechanically
ventilated patient using the same principle.
Resistance
Resistance is the opposition to motion and in the respiratory system
opposition to the flow of gas. In the lung, resistance to air flow is of
two types: tissue and airway. The former, also known as elastic
resistance (resistance from tissues or tissue resistance), occurs when
no gas is flowing, and is due to elastic resistance of lung tissue and
chest wall and the resistance imparted from surface forces at the
alveolar gas/liquid interface. Approximately 80 percent of the
pulmonary resistance is due to airway resistance or non-elastic
resistance.
Resistance to airflow is computed by the simultaneous measure-
ments of airflow, and the driving pressure that is required to
achieve the flow, i.e.
Resistance = Driving pressure/Flow = P/ V
Most non-elastic resistance is provided by frictional resistance
to airflow and thoracic tissue deformation with small contributions
from the inertia of gas and tissue and compression of intrathoracic
gas.
Airway Morphology
Airways are the tubular structures designed to carry air to the
alveolocapillary membrane for gas exchange. The tracheobronchial
tree consists of several branches which arise by dichotomous
divisions of the parent bronchus. The airway divisions from trachea
to the alveoli are not uniform and may vary between 10-25 in
different areas - divisions being less near the hilar regions and more
at the bases. The diameter, angulation and course of the bronchial
divisions are also different in different lung zones. For example,
the air passages to alveoli at the lung bases are straighter and have
large cross-sectional areas. This asymmetric pattern of branching
is referred to as irregular dichotomy. It has a bearing on the
distribution of ventilation and deposition of inhaled material.
Airways are classified into two types—conducting and
respiratory airways. The conducting or central airways do not take
part in gas exchange. They are larger than 2 mm in diameter, have
cartilaginous support, are lined by ciliated columnar epithelium
and are supplied by systemic bronchial circulation. They are also
able to change their diameter in response to several neurohormonal
and chemical stimuli due to the presence of smooth muscles in
their walls and vagal innervation. The respiratory bronchioles or
terminal airways are situated beyond the conducting airways. They
are less than 2 mm in diameter, lack cartilaginous support, are lined
40 Oxygen Therapy
by cuboidal epithelium and are supplied by pulmonary circulation.

Due to their structural properties, they are susceptible to
compression and closure in response t changes in the intrapul-
monary pressures.
The geometric features of airway divisions have a direct
relationship with the partitioning of resistance and hence
distribution of ventilation. There is a progressive narrowing and
shortening of airways as the division progresses from trachea to
the peripheral airways. Despite the reduction in diameter of
daughter airways, the total cross-sectional area increases
tremendously as we go peripherally. This is because the total
number of airways increases geometrically with each division and
the diameter of each daughter airway is more than half of the parent
airway. This results in almost 2000 fold increase in total cross-
sectional area from trachea to peripheral airways.
Physical Principles of Gas Flow and Resistance

The geometric features described above are important in the
distribution of resistance within the lung. Since flow is inversely
proportional to the diameter of the tube, it decreases progressively
as air moves down the bronchial tree to the peripheral zones. In
the terminal bronchioles, flow is reduced to almost zero. It is the
Brownian motion of molecules which facilitates diffusion across
the alveolo-capillary membrane. As the flow velocity decreases,
the driving pressure and resistance also fall. It has been calculated
that 80 percent of total measurable resistance at mouth is
contributed by the central or conducting airways.
The precise relationship between pressure difference and flow
rate depends on the nature of the flow, which may be laminar,
turbulent or a mixture of the two. With laminar flow, gas flows
along a straight unbranched tube as a series of concentric cylinders
that slide over one another, with the peripheral cylinder stationary
and the central cylinder moving fastest, the advancing cone forming
a parabola. The advancing cone front means that some gas will
reach the end of the tube despite the volume of gas entering the
tube being less than the volume of the tube. This has relevance in
patients being ventilated using the high frequency ventilation
where there is significant alveolar ventilation despite the tidal
volume being less than or equal to the anatomical dead space.
In a straight unbranched tube, the Hagen-Poiseuille equation allows

gas flow to be quantified:
Flow rate = ΔP × π × (radius)4/8 × length × viscosity, where ΔP
is the pressure gradient and equals the product of flow rate and
resistance.
Thus, resistance = 8 × length × viscosity/π × (radius)4
In this equation the fourth power of the radius explains the
critical importance of narrowing of air passages. With constant tube
dimensions, viscosity is the only property of gas that is relevant
under conditions of laminar flow. Helium has a lower density but
a viscosity close to that of air, and thus will not improve gas flow if
the flow is laminar.
On the other hand, turbulent flow occurs when gas flows at
high rates through unbranched or irregular tubes, resulting in
formation of eddy currents. In contrast to laminar flow it has a
square front and the volume of gas entering the tube is equal to
the volume of the tube, the so called bulk flow. The relationship is
different from the laminar flow in that the driving pressure is
proportional to the square of the gas flow rate and the density of
gas but independent of its viscosity and the required driving
pressure is inversely proportional to the fifth power of the radius
of the tubing (Fanning’s equation).
The change in flow from laminar to turbulent characteristics is
determined by a dimensionless number, the Reynolds’ number (NR)
which is NR = density × velocity × diameter/viscosity. The property
of gas that affects NR is the ratio of density to viscosity. Flow is
laminar with NR less than 2000, and changes from laminar to
turbulent when the NR exceeds 4000. Between NR of 2000 and 4000,
both types of flow coexist; there is also a critical length of tubing
before the parabolic pattern of laminar flow is established and thus
for gases with low NR not only will resistance be less during
turbulent flow but also laminar flow will become established more
quickly after narrowed airways. In principle, turbulence occurs
only in the larger airways and not in the smaller airways because
of the large cross-sectional area, the small diameter and the slow
velocity of the small airways. Heliox has a density/viscosity ratio
of 0.31 compared to one for oxygen and thus has a lower NR and
higher potential for laminar flow thus explaining its usefulness in
patients with large airway diseases.
42 Oxygen Therapy
Total and Alveolar Ventilation

The total amount of air inhaled with each inspiration gets
distributed in the lungs depending upon the regional resistance
and compliance of the different lung units. Ventilatory require-
ments for adequate supply of oxygen and removal of carbon
dioxide depend on the metabolic demands of the body. The resting
ventilatory requirements are small and are met with minimal
expenditure of energy. A normal individual can maintain gas
exchange with a ventilation of about 80 mL/kg/minute which is
about one-tenth of the maximum ventilatory capacity. Therefore,
there is a vast reserve in ventilatory capacity and problems of gas
exchange would not occur should all the inspired volume be
available to the gas exchange units. However due to cyclical nature
of ventilation, a significant proportion of the inspired gas never
reaches the alveoli—a volume known as the dead space volume.
So, the total ventilation is contributed by the dead space ventilation
(VD) and alveolar ventilation (VA), i.e. the air that reaches the alveoli
to take part in gas exchange. The dead space ventilation is roughly
around the individual’s body weight in pounds.
The volume of conducting airways which constitute the
anatomical dead space is relatively fixed, i.e. about one-third of
the tidal resting ventilation. Its relative proportion to the total
ventilation decreases as the total ventilation increases, for example
on exercise. On the other hand, a decrease in tidal volume and
increase in respiratory rate (e.g. rapid shallow breathing) markedly
increases the proportion of dead space ventilation thereby affecting
the gas exchange.
Dead space is also increased when there is presence of lung
units which are adequately perfused but not ventilated, the so called
physiological dead space. It is important to distinguish between the
anatomic dead space (respiratory system volume exclusive of
alveoli) and the physiologic dead space (volume of gas in the alveoli
not equilibrating with blood, i.e. wasted ventilation). As will be
discussed subsequently in this chapter, ventilation has to be
matched by the perfusion of blood in the alveolar capillaries for
adequate gas exchange to occur. Ventilation and perfusion are not
homogenously distributed throughout the lung and areas which
receive more ventilation relative to perfusion result in wasted
ventilation and thus add to “dead space” ventilation. The sum of
the dead space ventilation by these two mechanisms constitutes

“total dead space” and is given by the formula:
VD/VE = 1 – PECO2/PACO2, where
VD = total dead space
VE = minute ventilation
PECO2 = partial pressure of carbon dioxide in the
expired air
PACO2 = partial pressure of carbon dioxide in the alveolar
air (which in practice is measured by the arterial
PCO2)
The relationship of total and alveolar ventilation was first
described by Christian Bohr and is also known as ‘Bohr dead space’.
Distribution of Ventilation
The alveolar ventilation is distributed throughout the lungs. With
each inspiration around 500 mL of air is distributed to around 400
million alveoli such that each alveolus receives an appropriate share
of the inspired gas. This fine distribution of air is essentially a
function of the “time constants” of the regional lung units. Time
constant is the product of regional compliance and resistance and
thus is also called the RC time constant. The relative distribution
of ventilation between two neighboring lung units can be
understood better with the two compartment lung model. In health,
the resistance and compliance of two adjacent units of lung are
essentially equal and thus their RC time constant is normal with
normal distribution of ventilation. However in a diseased lung,
different portions of the lung may have abnormal time constants
as a result of either the diseased airway lumen (increased resistance)
or because of stiffness of alveolar walls (increased compliance) or
both. Thus in a lung unit with abnormal RC time constant,
ventilation will be maldistributed with more ventilation to areas
with relatively normal time constant than other areas. A lung unit
with a large time constant (i.e. greater resistance and compliance)
does not completely fill by the end of inspiration and empties slowly
during expiration. In contrast, a lung unit with a small time constant
(i.e. smaller resistance and compliance) fills and empties rapidly.
When a lung unit with a large time constant is located adjacent to
a lung unit with a small time constant, the unit with the long time
constant may withdraw gas from the adjacent lung unit with a
44 Oxygen Therapy
short time constant rather than fresh inspired gas. This “to and
fro” behavior is known as pendelluft, and it can occur in abnormal
lungs. In addition, a lung unit with a small time constant may
receive a higher proportion of dead space gas, which reduces its
alveolar ventilation. This effect is prominent in chronic obstructive
lung disease, in which compliant lung units with extremely large
time constants behave essentially as dead space. The higher the
respiratory rate, the greater is the discrepancy in filling and
emptying between these two kinds of units, and thus greater the
inhomogeneity of ventilation.
Another reason for uneven ventilation of small lung units is a
gradient of gas concentration along the small airways, a condition
called stratified inhomogeneity. Inspired gas reaches near the
region of the terminal or respiratory bronchioles by convective flow,
but gas flow over the rest of the distance to the alveoli is
accomplished primarily by molecular diffusion within the airways.
When airway calibers are altered, as in emphysema, the process of
gas diffusion may be incomplete for each breath. Thus, alveoli more
distal to the conducting airways are less well ventilated than
proximal alveoli.
Several mechanisms tend to preserve the uniform distribution
of ventilation in the lung. One of these mechanisms is the pendelluft
phenomenon described above. Another mechanism is gas exchange
through collateral air channels between adjacent lung units.
Collateral ventilation can occur between alveolo-alveolar pores of
Kohn, bronchiolo-alveolar canals of Lambert, and bronchiolo-
bronchiolar foramina of Martin. Another factor that tends to
improve uniformity of ventilation is the interdependence of
peripheral lung units which stems from the observation that
contiguous lung units are attached integrally to each other by the
connective tissue framework of the lung parenchyma. The behavior
of one unit must therefore influence the behavior of its neighbors.
This framework serves to offset the tendency for regional
differences in compliance to make lung units larger or smaller than
they should be for optimal performance.
Role of Gravity
Gravity also plays some role in distribution of ventilation. In the
upright position, ventilation per unit lung volume is greater at the
base of the lung than at the apex. The reason is that at the start of
inspiration, intrapleural pressure is less negative at the base than

at the apex, and since the intrapulmonary-intrapleural pressure
difference is less than at the apex, the lung is less expanded.
Conversely, at the apex, the lung is more expanded, i.e, the
percentage of maximum lung volume is greater. Because of the
stiffness of the lung, the increase in lung volume per unit increase
in pressure is smaller when the lung is initially more expanded,
and ventilation is consequently greater at the base. The ventilation
differences tend to disappear in the supine position, and the weight
of the lung makes the intrapleural pressure lower at the base in
the upright position. However, the inequalities of ventilation and
blood flow in humans are found to persist to a remarkable degree
in the weightlessness of space. Therefore, other as yet unknown
factors apparently also play a role in producing the inequalities. It
should also be noted that at very low lung volumes such as those
after forced expiration, intrapleural pressure at the lung bases can
actually exceed the atmospheric pressure in the airways, and the
small airways such as respiratory bronchioles collapse (airway
closure). In older people and in those with chronic lung disease,
some of the elastic recoil is lost, with a resulting decrease in
intrapleural pressure. Consequently, airway closure may occur at
the bases of the lungs in the upright position without forced
expiration, at volumes as high as the functional residual capacity.
PULMONARY CIRCULATION
The circulation of the entire cardiac output through the lungs is
ideally suited for rapid gas exchange. The pulmonary vascular bed
resembles the systemic circulation, except that the walls of the
pulmonary artery and its large branches are about 30 percent as
thick as the wall of the aorta, and the small arterioles, unlike the
systemic arterioles, have relatively little muscle in their walls. There
is also some smooth muscle in the walls of the postcapillary venules.
Also, the pulmonary capillaries are large with multiple anasto-
moses, so that each alveolus sits in a capillary basket. The blood
from the right side of the heart flows through an intricate network
of pulmonary capillaries around the alveoli. After getting
oxygenated, blood drains back into the left atrium through four
pulmonary veins. The pulmonary bed is characteristically a low
pressure circuit. There is a dense network of capillaries around
46 Oxygen Therapy
each alveolus. Rough estimates put the total number of capillaries

at about six billion or two thousand capillaries per alveolus. Not
all the capillaries are perfused under resting conditions. An
increased blood flow due to an increased cardiac output (as much
as 25 liters per minute during exercise in contrast to 5-6 liters during
resting conditions) can be accommodated easily in the pulmonary
circulation without an increase in the pulmonary arterial pressure.
These are made possible as a result of two major mechanisms, and
include recruitment, which is the opening of previously unperfused
pulmonary capillaries in the upper lung zones, and distension in
the entire pulmonary vasculature due to increased transmural
pressure gradient. The best example of the ability of pulmonary
vasculature to adapt to increased blood flow is following pneumo-
nectomy, when the remaining lung will normally take the entire
resting pulmonary blood flow without an increase in pulmonary
arterial pressure.
Distribution of Perfusion
The distribution of pulmonary blood flow is non-uniform from
apex to base. In the upright position, the upper portions of the
lungs are well above the level of the heart, and the bases are at or
below it. Consequently, there is a relatively marked pressure
gradient in the pulmonary arteries from the top to the bottom of
the lungs, because of the effect of gravity, and a resulting linear
increase in pulmonary blood flow from the apices to the bases of
the lungs. The following three concepts about pressure in the
pulmonary vessels are important to understand the behavior of
the pulmonary circulation.
Intravascular Pressure
This is the blood pressure inside the lumen of the vessel relative to
the atmospheric pressure. The pulmonary arterial pressure (Pa) and
pulmonary venous pressure (Pv), can be measured directly by
placing catheters into the bloodstream at specific points, and in
clinical practice, capillary pressure can be estimated by wedging a
catheter into a lobar branch of pulmonary artery. The “wedge”
pressure measured under conditions of “no flow” reflects pressure
downstream of the next freely communicating channels, that is,
pulmonary capillaries or small pulmonary venules.
Transmural Pressure
This is the difference between the pressure inside a vessel and the
pressure in the tissue around it. For example, the pressure around
the pulmonary arteries and veins is approximately equal to the
intrapleural pressure. The pressure around the capillaries is
approximately the intra-alveolar pressure (PA). It is this difference
in transmural pressure that leads to the different behavior of
alveolar and extra-alveolar vessels under conditions such as lung
inflation. At the capillary level, the transmural pressure is also an
important determinant of the rate of transudation of fluid across
the capillary bed.
Pulmonary Driving Pressure

This is the difference in intravascular pressure between one point
in the circulation and another point downstream, and is the
pressure involved in overcoming the frictional resistance that
impedes blood flow between two points. The driving pressure for
the pulmonary circulation is the difference between the
intravascular pressure in the main pulmonary artery and that
immediately after the pulmonary circulation in the left atrium.
The intravascular pressures of the pulmonary circulation are
influenced by the hydrostatic pressure created by gravity and the
alveolar pressures significantly affect the intra-alveolar capillaries.
As alveolar pressure is relatively independent of gravity, the
relationships among pulmonary arterial, pulmonary venous and
alveolar pressures must also influence the distribution of
pulmonary blood flow. West subdivided the lung into four zones
with differing patterns of blood flow (Fig. 3.3). In zone 1, near the
apex of the lung, wherein the alveolar pressure exceeds both the
pulmonary arterial and venous pressures (PA > Pa > Pv), and thus
the alveolar vessels are collapsed and there is no pulmonary blood
flow. In zone 2, the pulmonary arterial pressure exceeds the alveolar
pressure, but alveolar pressure exceeds venous pressure (Pa > PA >
P v). Under these conditions, the resistance to blood flow is
determined by the difference between pulmonary arterial and
alveolar pressures, rather than by the expected arterial-venous
pressure difference. This behavior has been referred to variously
as the waterfall or sluice effect. Also in zone 2, blood flow increases
progressively down the lung because of the increasing hydrostatic
48 Oxygen Therapy
Fig. 3.3: West zones of perfusion
effect on pulmonary arterial pressure, which increases the driving

pressure in this region (pulmonary arterial pressure minus alveolar
pressure). In zone 3, the pulmonary venous pressure exceeds
alveolar pressure (Pa > Pv > PA), and blood flow is dependent on
the pressure difference between Pa and Pv, and is maximal. There
is also a progressive increase in the perfusion because of the
progressive ‘distension’ of vessels due to increase in Pa and Pv,
while PA remains constant. In zone 4, the relationships between
intravascular and alveolar pressures are the same as in zone 3, but
the blood flow decreases slightly. Zone 4 occurs in the lowermost
region of the upright human lung and diminishes as lung volume
increases. Conversely, as lung volume decreases, this region of
reduced blood flow extends farther and farther up the lung, so
that at FRC blood flow decreases progressively down the bottom
half of the lung. At residual volume, zone 4 extends nearly all the
way up the lung, so that blood flow at the apex exceeds that at the
base. This condition obviously cannot be explained by the
interactions among the pulmonary arterial, venous, and alveolar
pressures. Instead, the reduced blood flow in zone 4 is probably
due to narrowing of extra-alveolar vessels at the lung base that
result from lower lung inflation due to airways closing down at
the ‘closing volume’. The increased contribution of extra-alveolar
vessels to pulmonary vascular resistance results in the presence of
a zone of reduced blood flow in that region. Zone 4 would be

expected to increase in the presence of interstitial pulmonary
edema, because the edematous fluid increases interstitial pressure
in the vascular sheath and thereby narrows the extra-alveolar
vessels. This is a plausible mechanism for the inverted distribution
of blood flow (cephalization of pulmonary vasculature on chest
X-ray) in pulmonary edema.
However, not all the inhomogeneity of blood flow in the lung
can be explained by gravitational effects. Indirect measurements
of inhomogeneity (monitoring the magnitude of cardiogenic
oscillations on the expired carbon dioxide tracing) of pulmonary
blood flow have been made in astronauts in space shuttles, and a
striking reduction in inhomogeneity of blood flow was detected
during weightlessness compared with that observed in the upright
posture before or after the flight. Interestingly, substantial
inhomogeneity of blood flow still remained, indicating that some
gravity-independent mechanism was also present. Another
situation where the gravitational model fails is the situation of prone
position ventilation, where the perfusion is probably more
homogeneous and not dependent on gravity.
DIFFUSION
Diffusion is the rate at which oxygen from the alveolus is
transferred across the alveolo-capillary barrier to combine with
hemoglobin in the red blood cells of pulmonary capillaries.
(Fig. 3.4). The situation in lungs can be visualized as a two chamber
model with different partial pressures of oxygen and a liquid barrier
separating the two (Fig. 3.5). The transfer of gases from the alveoli
to the capillary blood during the pulmonary transit time of 0.75
seconds depends on their reaction of the molecules with
hemoglobin in the blood. For example, nitrous oxide (N2O) does
not react, and reaches equilibrium in about 0.1 seconds. In this
situation, the amount of N2O taken up is not limited by diffusion
but by the amount of blood flowing through the pulmonary
capillaries, i.e. it is flow-limited. On the other hand, carbon
monoxide (CO) is taken up by the hemoglobin in the red blood
cells at such a high rate that the partial pressure of CO in the
capillaries stays very low and equilibrium is not reached in the
0.75 seconds the blood is in the pulmonary capillaries. Therefore,
50 Oxygen Therapy
Fig. 3.4: Schematic diagram representing diffusion across the alveolo-capillary

membrane into the red blood cell. 1 and 2 represent the inner and outer layer of the
alveolar epithelium, 3 and 4 represent the inner and outer layer of the capillary
endothelium, 5 represents the red blood cell membrane
Fig. 3.5: Mismatching of ventilation and perfusion: Model A

(diminished ventilation) and B (decreased perfusion)
the transfer of CO is not limited by perfusion at rest and instead is

diffusion-limited. Oxygen is intermediate between N2O and CO;
it is taken up by hemoglobin, but much less avidly than CO, and it
reaches equilibrium with capillary blood in about 0.3 seconds. Thus,
its uptake is also perfusion-limited. The diffusing capacity of the
lung for a given gas is directly proportionate to the surface area of
the alveolo-capillary membrane and inversely proportionate to its
thickness. The factors that influence the movement of gas from
area of higher partial pressure (alveolus) to the area of low partial
pressure (capillaries) are governed by the Fick’s law:
 = Ad/T (P1 – P2), where
V
 = volume of gas diffusing per unit time
V
(mL/minute)
A = area available for diffusion (cm2)
P1 – P2 = pressure difference of gas on two sides
(mm Hg)
d = diffusion coefficient of the barrier (cm 2/
minute/mm Hg)
This diffusion coefficient d is further related to the solubility of
the gas within the liquid barrier and the square root of the molecular
weight of the gas. Other factors being constant, the driving pressure
is the most important factor determining the flow of oxygen across
the alveolo-capillary membrane. When this pressure falls, such as
travel at high altitudes, the oxygen delivery to the tissues becomes
diffusion limited. Similarly, diffusion is inversely proportional to
the thickness of the membrane.
Although diffusion is reduced in the presence of thickened
alveolo-capillary membrane (e.g. interstitial lung disease) or the
loss of gas exchange areas (e.g. chronic obstructive airway disease);
it is rarely the sole factor responsible for hypoxemia encountered
in these conditions. The reason is that the transfer of oxygen and
carbon dioxide is perfusion limited. The normal capillary transit
time across the alveolar walls is usually 0.75 seconds but in healthy
individuals only 0.25 seconds is required for gas exchange to be
completed. Thus there is an adequate time for gas exchange to occur
even in the presence of a diffusion defect. The gas exchange
however becomes diffusion dependent during conditions which
increase cardiac output such as exercise, anxiety, etc. when the
capillary transit time is significantly reduced.
52 Oxygen Therapy
  ) RELATIONSHIPS
VENTILATION-PERFUSION ( V/Q
The ratio of pulmonary ventilation to pulmonary blood flow for
the whole lung at rest is about 0.8 to 1 (4-6 liters/minute ventilation
divided by 5-6 L/minute blood flow), and this matching of
distribution of ventilation and perfusion is the most important
determinant of gas exchange. The ventilation-perfusion mismatch
is the final common pathway to cause hypoxemia in most
pulmonary diseases (Fig. 3.3). An area of lung that is well perfused
but under ventilated acts as a right to left shunt (physiological
shunt) whereas an area that is well ventilated but under perfused
acts like a dead space (physiological dead space). The spectrum of
V Q ratios in a healthy lung could vary between zero (perfused
but not ventilated) to infinity (ventilated but not perfused).
The ideal V Q ratio of one indicates perfectly matched
ventilation and perfusion. Although V Q mismatch includes both
physiologic shunt and physiologic dead space but in clinical
parlance, the term generally denotes physiologic shunt as
physiologic dead space, is rarely, if ever the cause of hypoxemia.
In an alveolar-capillary unit with a V Q ratio of 0 (physiologic
shunt), the blood leaving the unit has the composition of mixed
venous blood entering the pulmonary capillaries, i.e. PO2 of 40
mm Hg and PCO2 of 46 mm Hg whereas in an alveolar-capillary
unit with a high V Q ratio (physiologic dead space) the small
amount of blood leaving the unit has partial pressures of O2 and
CO2 are 150 mm Hg and 0 mm Hg approaching the composition
of inspired gas.
Because of the sigmoid shape of the oxyhemoglobin dissociation
curve, it is important to differentiate between the partial pressure
and the content of oxygen in the blood. Hemoglobin is almost fully
(> 90%) saturated at a PO2 of 60 mm Hg, and little additional O2 is
carried by hemoglobin even with a substantial elevation of PO2
above 60 mm Hg. On the other hand, significant O2 desaturation
of hemoglobin occurs once PO2 falls below 60 mm Hg and onto
the steep descending limb of the curve. As a result, blood coming
from regions of the lung with a high V Q ratio and a high PO2 has
only a small elevation in O2 content and cannot compensate for
blood coming from regions with a low V Q ratio and a low PO2,
which has a significantly decreased O2 content. Although V Q
mismatching can influence PCO2, this effect is less marked and is

often overcome by an increase in overall minute ventilation.
The alveolar PO2 appears to be the most important factor
involved in regulating the distribution of ventilation-perfusion
within the lung. In this respect, hypoxic pulmonary vasocons-
triction can be considered as part of a negative feedback loop. For
example, in lung units with low V Q ratios, there is a fall in the
local alveolar PO2, and constriction of the associated micro-
circulation reduces the local pulmonary blood flow. This tends to
restore the local V Q ratio toward its normal value. This effect can
be appreciated in residents of high altitudes, who are exposed
constantly to lower ambient O2 concentrations. Residents of high
altitudes have better V Q matching than sea level residents, as
reflected by a smaller alveolar-arterial PO2 difference. The intensity
of hypoxic pulmonary vasoconstriction varies among different lung
regions, and probably depends on the smooth muscle tone in
different vessels. More recently, a role for nitric oxide in regulating
local ventilation-perfusion matching has been suggested as nitric
oxide is a selective pulmonary vasodilator (no systemic effects),
and inhibits hypoxic pulmonary vasoconstriction. Theoretically,
the inhalation of nitric oxide can cause selective pulmonary vaso-
dilation in adequately ventilated areas and improve gas exchange.
The nitric oxide-mediated mechanism may also be important in
patients with inflammatory lung diseases, in whom production of
nitric oxide is increased. The loss of local hypoxic vasoconstriction
would worsen ventilation-perfusion mismatch.
BIBLIOGRAPHY
1. Cotes JE. Lung Function: Assessment and application in medicine. Oxford,
Blackwell Publications. 1993
2. Cotes JE. Lung Function. Oxford, Blackwell Scientific. 1975
3. Crystal RG, West JB (editors). The Lung: Scientific Foundations, New York,
Raven Press 1991.
4. Fishman AP. Pulmonary circulation. In: Fishman AP, Fisher AB, Geiger SR
(editors). Handbook of Physiology, Section 3. The respiratory system. Bethesda
MD: American Physiological Society, 1987.
5. Freedman S. Mechanics of ventilation. In: Brewers RAL, Corrin B, Gedded
DM, Gibson GJ (editors). Respiratory Medicine. London. WB Saunders 1995.
6. Lumb AB. In: Nunn’s Applied Respiratory Physiology. 5th edition.,
Edinburgh, Butterworth-Heinemann, 2000.
54 Oxygen Therapy
7. McCool FD, Hoppin FG. Respiratory mechanics. In Baum’s Textbook of

Pulmonary Diseases 7th edition. Baum GL, Glassroth JL, King TE Jr, Crapo
JD, Karlinsky J (editors), Lippincott Williams and Wilkins, New York. 2003.
8. Milic-Emili J, Robatto FM, Bates JHT. Respiratory mechanics in anesthesia.
Br J Anesth 1990; 65:4-12.
9. Weinberger SE, Drazen JM. Disturbances of respiratory function. In:
Harrison’s Principles of Internal Medicine. Kasper DL, Braunwald E, Fauci
AS, Hauser SL, Jameson JL, Longo DL (editors), McGraw Hill publications,
16th edition, New Delhi. 2005; 1498-1505.
10. West JB. Ventilation-perfusion inequality and overall gas exchange in
computer models of the lung. Respir Physiol 1969;7:88-110.
4
Oxygen and Carbon
Dioxide Transport
Navneet Singh
OXYGEN TRANSPORT
Introduction to Physiology of Oxygen Transport
Aerobic metabolism and cell integrity is dependent upon
availability of oxygen (the substrate utilized by cells in the greatest
quantity). Unfortunately, most tissues do not have any mechanism
to store oxygen and in fact are dependent upon the circulatory
system to receive the same continuously. Normally supply meets
demand but tissue hypoxemia can result if anaerobic metabolism
(and hence lactic acid production) starts occurring due to lack of
oxygen from any cause. A series of steps characterize the process
of oxygen transport from environmental air to the mitochondria
of individual cells. These oxygen transport processes are either
convective or diffusive in nature. Convective oxygen transport is
an active process that occurs in the tracheobronchial tree and
circulation. Diffusive transport is a passive process (determined
by differences in oxygen concentration in various tissues) and
occurs in the alveolar-capillary membrane as well as between tissue
capillaries, interstitium and individual cells. The presence of
hemoglobin (Hb) in the RBCs allows the blood to transport 30-100
fold as much oxygen as could be transported simply in the form of
dissolved oxygen in the “water” of blood. Similar mechanisms
increase the carbon dioxide carrying capacity of the blood 15-20
fold. The main steps in oxygen cascade thus include
1. Uptake from atmosphere into the lungs
2. Diffusion in the lungs from the alveoli into the blood
56 Oxygen Therapy
3. Combination with hemoglobin and transport in the circulation

4. Diffusion from capillary blood into the interstitium
5. Diffusion from interstitium to individual cells
6. Cell utilization for aerobic metabolism.
Uptake of Oxygen from Atmosphere into Lungs

The main factors affecting this are:
• Concentration of inspired oxygen
• Barometric pressure of oxygen which in turn is dependent upon
the atmospheric pressure
• Alveolar ventilation
• Ventilation-perfusion relationship.
Diffusion of Oxygen from the Alveoli into the Blood

The partial pressure of oxygen in the alveoli (PAO2) is the main
determinant of partial pressure of oxygen in arterial blood (PaO2)
and thus the key factor responsible for its diffusion into the
pulmonary capillaries. The (PAO2) – (PaO2) (A-a) gradient is a
reflection of the overall efficiency of oxygen uptake from alveoli
into the blood. Inadequate oxygenation rarely results from
inadequate pulmonary capillary transit time because of the
presence of a 200 percent reserve (normally the blood in pulmonary
capillaries is fully oxygenated before it has traveled 1/3rd of the
distance of the alveolar-capillary interface). Impaired diffusion of
oxygen from alveoli into blood in pulmonary capillaries is also
less common a cause for arterial hypoxemia than ventilation-
perfusion ( V Q ) mismatching.
Combination of Oxygen with Hemoglobin and

Transport in Circulation
Most oxygen is carried in the blood attached to hemoglobin (97-
98%) with only a small amount (2-3% if (PaO2) < 100 mm Hg)
dissolved in the plasma.
Oxygen Combined with Hemoglobin

Hemoglobin is the main component of human red blood cells. There
are about 280 million molecules of Hb in a single RBC. Each Hb
Oxygen and Carbon Dioxide Transport 57
molecule contains 4 atoms of iron which are important for oxygen

transport.
Normal mammalian Hb contains two pairs of heme containing
globin chains. Each chain is composed of a fixed number of amino
acids arranged sequentially. HbA, the major adult Hb contains two
alpha (α) and two beta (β) chains while HbA2 (the minor adult
Hb) contains two alpha and two delta (δ) chains. The Hb F contains
two alpha (α) and two gamma chains (ϒ). The heme iron Fe atoms
bound in the centre of each of the four prophyrin groups of Hb
bind O2 in a reversible fashion. The reversible binding increases
the effective solubility of O2 in blood than in other body fluids.
Hemoglobin, when combined with oxygen is called
oxyhemoglobin (HbO2) while oxygen free Hb is called “reduced”
Hb. The Hb-oxygen relationship is influenced by the following
important factors:
Heme-heme Interaction
There exists a physicochemical relationship between the four iron
binding sites in Hb molecule and O2 depending upon the size and
oxygenation status of the Hb moieties. This interaction within the
Hb molecule forms the major basis for the sigmoid shape of Hb
dissociation curve (Fig. 4.1). Had there been no Hb in blood, the
percent O2 saturation and oxygen content of plasma would be
directly and linearly proportional to the partial pressure.
Other Factors
Red blood cell enzyme systems such as 2,3 diphosphoglycerate
(2,3 DPG), hydrogen ion, CO2 concentration and RBC temperature,
are all important in the release and binding of O2 from Hb.
Hemoglobin Variants
Affinity of different hemoglobins is different for oxygen. For
example, the affinity for O2 of fetal Hb (normally found in neonates)
is increased. Similarly the affinity of the remaining heme sites not
bound to carbon monoxide in presence of carboxyhemoglobin, and
not oxidized to the ferric form in presence of methemoglobin, for
oxygen is increased.
58 Oxygen Therapy
The Oxygen-Hemoglobin Dissociation Curve

Figure 4.1 reflects the relationship of PO2 with O2 saturation of
hemoglobin. This is a sigmoid curve with the average values of
PO2 and SaO2 in arterial (and venous) blood being 95 mm Hg and
97 percent (40 mm Hg and 75%) respectively (Fig. 4.1). The
relationship of oxygen saturation of hemoglobin with PaO2 is not
linear and is influenced by various factors. On the other hand, the
O2 content dissolved in plasma bears a linear relationship with
PaO2 (Fig. 4.2). P50 is defined as the oxygen concentration at which
50 percent of the hemoglobin is saturated and is normally around
26 mm Hg. A shift of the oxygen-hemoglobin dissociation curve to
the right enhances release of oxygen to tissues and thus increased
availability to the cells (Fig. 4.3). The loss of oxygen uptake in the
lungs that occurs as a result of this shift is small and usually
insignificant. The factors that cause displacement of O2-hemoglobin
curve to right/left include:
1. pH
2. PCO2
3. Temperature
4. 2,3 - DPG
5. Percentage of fetal hemoglobin
1. pH - Fall in pH from 7.4 to 7.2 causes shift of the dissociation
curve by 15 percent to right. A similar shift to the left occurs
with an increase in pH of the same magnitude.
2. PCO2 - Shift of the oxygen-hemoglobin dissociation curve to
the right by increase in PCO2 is known as the Bohr effect and
plays an important role in enhancing oxygenation of blood in
lungs and release of O2 in the tissues. In the lungs, CO2 diffuses
out of the blood and simultaneously H+ concentration also
decreases because of a fall in H2CO3 concentration. This leads
to shift of oxygen-hemoglobin dissociation curve to the left
leading to stronger binding of O2 to hemoglobin and hence
increase in the quantity of O2 that can be transported to the
tissues. When the blood reaches the tissue capillaries, the
opposite occurs (fall in CO2 and rise in H+) and thus greater
release of oxygen.
3. Temperature-Rise in temperature leads to reduction in affinity
of oxygen for hemoglobin and hence shift of curve to right
Fig. 4.1: Hemoglobin dissociation curve for oxygen: Shows relationship

between PaO2 and percent saturation of O2
Fig. 4.2: Relationship between PaO2 and O2 dissolved in plasma

60 Oxygen Therapy
leading to enhanced release of oxygen at a given PO2. Opposite

changes occur with fall in temperature.
4. 2, 3- diphosphoglycerate-Increase in its levels lead to shift in
the curve to right and vice-versa with fall in its levels. One of
the very important clinical implications of this is that hypo-
phosphatemia if uncorrected leads to fall in concentration of
2, 3 - DPG inside RBCs and this may result in tissue hypoxia
because of impaired release of oxygen from hemoglobin.
5. Fetal hemoglobin-It causes shift of curve to left and thus
increases delivery of oxygen to fetus. If present in abnormally
high quantities in adults, tissue hypoxia can result.
Oxygen Content
It is the total amount of oxygen present in 100 mL of blood as
attached to Hb and dissolved in plasma. It is therefore, determined
by Hb level, PaO2 and oxygen saturation (SO2). It is calculated as
follows:
a. Oxygen attached to Hb = Hb (gms%) × 1.34 × SO2
(1 gm of Hb when fully saturated carries 1.34 mL oxygen)
b. Oxygen dissolved in plasma = PO2 × 0.003 (vol%)
(for each 100 mL of blood at BTPS, 0.003 mL of oxygen is
dissolved for each 1 mm Hg of oxygen tension) – i.e. the Bunsen
solubility coefficient for oxygen in blood.
Example: Normal oxygen content (Hb 15 gm%, PO2 100 mm
Hg, SO2 100%)
= Attached to Hb (15 × 1.34 × 100); plus
O2 dissolved in plasma (100 × 0.003) = 20.4 vol%.
Oxygen content is decreased in the following conditions:

a. Hypoxemia (low PO2)
b. Anemia (low Hb)
c. Hypercarbia, acidemia, hyperthermia (low SaO2)
Hb Oxygen Affinity
The strong Hb affinity for oxygen makes its release difficult at the
tissue level. Therefore the factors that affect Hb affinity also changes
the position of Hb dissociation curve. An increased affinity
(i.e. shift of the O2 dissociation curve to the left) causes decreased
Fig. 4.3: Shift in hemoglobin dissociation curve for oxygen
O2 dissociation and availability for the tissues, while decreased

affinity (shift of the curve to the right) produces increased
dissociation (Fig. 4.3). But these relationships are not useful in
disease states where sudden severe shift to the right is detrimental
and reduces the oxygen availability.
Decreased affinity
Hb affinity for O2 is said to decrease (i.e. the rightward shift of the
oxygen dissociation curve) when there is a decrease in the percent
O2 saturation of Hb for a given oxygen tension. In other words the
oxygen carrying capacity of blood is decreased. Such a shift aids
oxygen delivery to the tissues. But an extreme shift shall result in
decreased oxygen content and tissue hypoxia. A shift to the right
is the result of acidemia, hypercarbia, hyperthermia and increased
2,3-DPG.
Increased oxygen affinity
The oxygen affinity is increased (shift of the dissociation curve to
the left) when there is increased O2 percent saturation of Hb for a
given oxygen tension. This causes reduced oxygen delivery to the
tissues. This may occur as a result of alkalemia, hypothermia,
hypocarbia and decreased 2,3-DPG.
62 Oxygen Therapy
Oxygen affinity is measured by P50 , i.e. oxygen tension at which

50 percent of Hb is saturated (at laboratory conditions of 37oC,
PCO2 40 mm Hg and pH 7.40). The normal adult P50 is about 27
mm Hg. A reduced P50 indicates increased affinity and an increased
P50 indicates decreased affinity. The P50 measurement depends
upon the laboratory conditions of temperature and PCO2. Changes
in these parameters in the patient will affect the Hb affinity for O2
but not the P50 measurements. A fall in P50 is also observed when
the levels of enzyme system 2,3 DPG are decreased, for example in
blood stored for purposes of transfusion. In the presence of
increased Hb affinity, the ability of Hb to release O2 to the tissues
is decreased.
Diffusion of Oxygen from Capillary Blood into Interstitium

Oxygen diffuses rapidly from blood into interstitium because of
the large pressure gradient (95 mm Hg vs. 40 mm Hg). The
interstitial PO2 is affected by several factors including rate of blood
flow, rate of tissue metabolism and concentration of hemoglobin.
Increase in blood flow to four times normal increases PO2 from 40
to 66 mm Hg but the maximum that is reached with further increase
in flow is 95 mm Hg which is the PO2 in the arterial blood. The rate
of tissue metabolism has an inverse relationship with interstitial
fluid PO2 while hemoglobin concentration has an effect similar to
that of blood flow.
Diffusion of Oxygen from Interstitium into Cells

Intracellular PO2 is always lower than interstitial fluid PO2 because
the cells are constantly utilizing oxygen. Sometimes significant
distance exists between the capillaries and the cells. The amount
of oxygen that diffuses depends on the oxygen tension gradient
and the diffusion distance. The latter in turn is related to the tissue
capillary density. The greater the difference between capillary and
cellular oxygen concentrations and the shorter the distance, the
faster is the rate of diffusion. Normal intracellular PO2 varies from
5-40 mm Hg (average 23 mm Hg) against the normal intracellular
requirement of 3 mm Hg for optimal maintenance of metabolic
pathways. The fall in intracellular PO2 is more severe if delivery of
oxygen to tissues is reduced because of “hypoxic” hypoxia (a fall
in PaO2) rather than “stagnant” (a fall in flow) or “anemic” (reduced
hemoglobin) hypoxia.
Cellular Use of Oxygen

Overall oxygen consumption is determined by the intracellular
metabolic rate. Cellular use of oxygen can be inhibited by cellular
metabolic poisons that can be exogenous (e.g. cyanide) or
endogenous (e.g. endotoxins in septic shock).
Oxygen Delivery, Consumption and Extraction

The major function of the circulation is to transport oxygen to the
peripheral tissues at a rate that is sufficient to meet the rate of its
utilization (metabolic demands of tissues). Failure of this function
defines circulatory shock. Under normal resting conditions the total
or “global” oxygen delivery (DO2) is more than adequate to meet
the total or “global” oxygen consumption ( V O2) for aerobic meta-
bolism.
DO2 (mL/min) = Qt × CaO2, where cardiac output is denoted
by Qt and oxygen content of arterial blood
by CaO2.
CaO2 = hemoglobin × SaO 2 × K, where arterial
saturation is denoted by SaO 2 and the
coefficient for hemoglobin-oxygen binding
capacity by K (a constant).
Thus DO2 (mL/min) = Qt × hemoglobin × SaO2 × K and V  O2
(ml/min) = Qt × (CaO2 – C vO2) where oxygen content of venous
blood is denoted by C vO2. The amount of oxygen consumed (V O2)
as a fraction of oxygen delivery (DO2) defines the oxygen extraction
ratio ( V O2/DO2). In healthy resting adults, its value is around 25
percent but may increase to 70 to 80 percent during maximal
exercise in well trained athletes. The oxygen not extracted by the
tissues returns to the lungs and is represented by the mixed venous
saturation (S v O 2) measured in the pulmonary artery. It is
influenced by changes in both DO2 and V O2. Under normal resting
conditions the oxygen extraction is more than 65 percent.
As metabolic demand ( V O 2 ) increases or supply (DO 2 )
diminishes, the oxygen extraction ratio rises to maintain aerobic
64 Oxygen Therapy
metabolism. However, once the maximum extraction ratio is

reached (usually around 60-70 percent for most tissues) further
increases in demand or falls in supply lead to hypoxia.
Under normal circumstances, 5 mL of O2 is transported to
tissues by each 100 mL of blood since the amount of O2 in blood
reduces from 19.4 mL to 14.4 mL/100 mL of blood on passing
though the capillaries. This reflects a change in PO2 from 95 mm
Hg to 40 mm Hg (oxygen saturation of 97 percent and 75 percent
respectively).
Oxygen saturation in blood draining from different organs
varies widely (hepatic venous saturation is 30-40 percent and renal
venous saturation about 80 percent) and reflects both oxygen
delivery and metabolic demands of these tissues.
Oxygen Delivery During Exercise

During strenuous exercise, the oxygen requirement may be as high
as 20 times that of normal. The blood also remains in the capillary
bed for less than half the normal time because of increased cardiac
output. However oxygen saturation in the blood is not affected
because:
• Blood gets fully saturated in the first third of the normal time
available to pass through the pulmonary circulation.
• Diffusion capacity increases upto 3 fold since:
1. Additional capillaries open up and hence increased numbers
of capillaries participate in the process of diffusion.
2. Dilatation occurs of both alveoli and capillaries thereby reduc-
ing the thickness of the alveolar-capillary interface.
3. V Q ratio improves in upper part of lungs because blood flow
to upper part of lungs increases considerably.
Other changes that occur include
• Reduction in total content of oxygen in the blood at the tissue
capillary level to 4.4 mL/100 mL thereby increasing the total
amount of oxygen released to 15 mL/100 ml of blood (3 times
normal).
• O2-hemoglobin dissociation curve shifts to the right because of:
1. Increased release of CO2 from exercising muscles.
2. Increased concentration of H+ ions leading to a fall in pH
3. Increase in temperature.
4. Release of phosphates and hence increased levels of 2,3-
DPG.
Adaptation to hypoxia for example at high altitude, also requires

adjustments of blood oxygen affinity and oxygen transport. A
lowered affinity is advantageous to lower the circulatory load for
adequate oxygenation at an altitude of about 5000 m. At higher
altitude an increased affinity is more advantageous.
CARBON DIOXIDE TRANSPORT

Introduction to Physiology of Carbon Dioxide Transport
Carbon dioxide (CO2) is the end-product of aerobic metabolism.
Elimination of CO2 is an important function of the lungs. Diffusion
of CO 2 occurs from within the cells into the blood via the
interstitium (Fig. 4.4). After being transported in the blood to the
lungs, it again diffuses across the alveolo-capillary barrier into the
alveoli from where it is finally eliminated by the normal process of
ventilation. CO2 in the body is present in three different forms:
1. Dissolved in fluid/blood
2. Bound as bicarbonate
3. Bound as carbamate
The relative contribution of these different forms to overall CO2
transport changes markedly along its pathway for elimination,
because different forms have variable diffusion capabilities at
different places.
Fig. 4.4: Carbon dioxide transport in blood: Only 5 percent is dissolved in plasma,
95 percent is present in RBC’s either in combination with Hb (carbamino-CO2) or
converted to HCO3– with the help of carbonic anhydrase
66 Oxygen Therapy
Fig. 4.5: Carbon dioxide dissociation curve: The upper and lower curves
represent deoxygenated and oxygenated blood respectively
Carbon Dioxide Transport in Blood during

Rest and Exercise
Under normal resting conditions an average of 4 mL of CO2 is
transported from tissues to the lungs in each 100 mL of blood. CO2
diffuses out of the tissue cells in the gaseous form but it does not
leave the cells to any significant extent in the form of bicarbonate
since the cell membrane is almost impermeable to bicarbonate ions.
Most of the CO2 entering and leaving the blood is also in the gaseous
form though the amount carried in solution is very small. Within
the plasma there is little chemical combination of CO2 because there
is no carbonic anhydrase in plasma and hence carbonic acid is
formed very slowly (Fig. 4.5).
Dissolved CO2
CO2 as a gas has moderate solubility in water. According to Henry’s
law of solubility for gases, the PCO2 × α = [CO2], where a is the
Solubility Coefficient and [CO2] is the concentration of CO2 in
solution. Hence only a small portion, ~5 percent of total arterial
content, is present in the form of dissolved CO2. At rest, the
contribution of dissolved CO2 to the total arteriovenous CO2
concentration difference is only ~10 percent. In absolute terms only
0.3 mL of CO2/100 mL is transported in the dissolved form.

However, during heavy exercise, the contribution of dissolved CO2
can increase up to sevenfold and then it is responsible for almost
one-third of the total CO2 exchange.
CO2 Bound as Bicarbonate

The dissolved CO2 in the blood reacts with water to form carbonic
acid (CO2 + H2O H2CO3). Under physiological conditions, the
equilibrium of this equation is to the extreme left i.e. very negligible
amounts are dissolved as carbonic acid (<1%). Carbonic anhydrase
present inside RBCs, pulmonary capillary endothelium and other
tissues but not plasma, catalyzes this reaction - accelerating it 5000
fold both ways and markedly shortening the time required for
completion of this reaction. Carbonic acid dissociates into H+ and
bicarbonate ions (H2CO3 H+ HCO3–). Most of the H+ ions then
combine with hemoglobin since the latter is a powerful buffer while
bicarbonate ions diffuse out of the RBCs into the plasma in exchange
for chloride ions. This transfer is assisted by a carrier protein in the
RBC membrane, Band 3 HCO3–/Cl– that works on the basis of ping-
pong mechanism (one ion first moves out of the cell before the
other ion moves inwards) in contrast to most other ion pumps that
simultaneously exchange the two ions. Hence the chloride content
of venous RBCs is more than that of arterial cells, a phenomenon
called the Hamburger (chloride) shift. This mechanism is
responsible for transport of 70 percent of total CO2 from tissues to
lungs. Inhibition of carbonic anhydrase by acetazolamide can cause
the tissue PCO2 to increase from 45 mm Hg to as high as 80 mm
Hg. During heavy exercise, fall in pH of blood (and consequent
reduction in the dissociation of carbonic acid) leads to a reduction
in the relative contribution of bicarbonate to overall CO2 transport
although the total quantity of CO2 that is transported is higher
compared to that during rest.
CO2 Bound as Carbamate

CO2 reacts directly with hemoglobin to form the compound
carbaminohemoglobin. This is a reversible reaction that occurs with
a very loose bond so that the CO2 is easily released into the alveoli
68 Oxygen Therapy
where the PCO2 is lower than in the tissue capillaries. A small

amount of CO2 also reacts with plasma proteins but this is much
less significant because the quantity of these proteins is only 1/4th
that of hemoglobin. Around 15-25 percent of total CO2 transport is
through this mechanism. The amount of CO2 bound as carbamate
depends on:
• O2 saturation of hemoglobin and 2,3-diphosphoglycerate
(2,3-DPG) concentration (for binding to hemoglobin)
• H+ concentration (for binding to both hemoglobin and plasma
proteins).
During passage of blood through muscle and tissues, O2
saturation and H+ concentration change considerably, in particular
during exercise. However, the increase in hemoglobin desaturation
and the increase in H+ concentration experienced by red blood cells
in the capillary affect the amount of CO2 bound to hemoglobin in
opposite directions. Reduction of hemoglobin (reduced oxygena-
tion of heme) causes it to become more basic and hence increases
carriage of CO2 as bicarbonate since more H+ ions bind to reduced
hemoglobin in view of increased basicity and this promotes
dissociation of carbonic acid further. Deoxygenation of hemoglobin
thus increases the amount of CO2 bound to hemoglobin (Haldane
effect). Another implication of the Haldane effect is that binding
of O2 with hemoglobin tends to displace CO2 from the blood and
this is quantitatively more important in promoting CO2 transport
than is the Bohr effect in promoting O2 transport. Combination of
O2 with hemoglobin causes:
1. Hemoglobin to become a stronger acid and displace CO2
because acidic hemoglobin has less tendency to combine with
CO2 to form carbamino-hemoglobin.
2. Increased acidity of hemoglobin causes it to release an excess
of H+ ions and these in turn bind with bicarbonate to form
carbonic acid which then dissociates into CO2 and H2O.
The Haldane effect leads to increased uptake of CO2 in the
tissues (when O2 is released) and increased release of CO2 in the
lungs (when O2 gets bound to hemoglobin). The Haldane effect
approximately doubles the amount of CO2 released from the blood
in the lungs and that picked up in the tissues.
Spectrum of Pressure Gradients During Diffusion of CO2

At each point in gas transport chain, CO2 diffuses in the opposite
direction to O2 but twenty times faster. Therefore, the pressure
differences required for CO2 diffusion are smaller compared to

those required for O2 diffusion:
1. Intracellular PCO2 is about 46 mm Hg and interstitial PCO2
about 45 mm Hg thus leading to a pressure gradient of only
1 mm Hg.
2. PCO2 of arterial blood entering the tissues is about 40 mm Hg
and that of the venous blood leaving the tissues is about
45 mm Hg and hence the tissue capillary blood PCO2 comes
almost exactly to equilibrium with the interstitial PCO2.
3. PCO2 of venous blood entering the pulmonary capillaries is
around 45 mm Hg and PCO2 of alveolar air is around 40 mm
Hg thus causing only a 5 mm Hg pressure gradient which is
responsible for the diffusion of entire amount of CO2 out of the
pulmonary capillaries into the alveoli. The fall in its level in
capillary blood takes place before it has passed one-third of the
distance through the capillaries (similar to O2).
Effect of Tissue Metabolism and Blood Flow on

Interstitial PCO2
1. A decrease in blood flow from normal to one fourth normal
increases the tissue PCO2 from 45 mm Hg to 60 mm Hg while
increasing the blood flow to six times normal decreases the
PCO2 from 45 mm Hg to 41 mm Hg (which is almost equal to
arterial blood levels).
2. An increase in tissue metabolism by ten times normal increases
the PCO2 at all levels of blood flow while decreasing the
metabolism to one-fourth normal decreases the PCO2 from
45 mm Hg to 41 mm Hg (almost equal to arterial blood levels).
Transfer of CO2 Across Cell Membranes

Blood brain barrier and other cell membranes are impervious to
H+ and bicarbonate ions but permit rapid diffusion of CO2. CO2
can pass through these membranes and within the cells combine
with water to form carbonic acid that dissociates into H+ and
bicarbonate ions. Hence intracellular H+ ion concentrations are
relatively unaffected by changes in extracellular pH but changes
in PCO2 can cause significant alterations in their values. No other
substance normally present in the body is able to affect the
intracellular pH as strongly as CO2.
70 Oxygen Therapy
BIBLIOGRAPHY
1. Breen D, Bihari D. Clinical assessment and measurement of oxygen transport
in the critical care setting. Transfus Sci 1997; 18:437-45.
2. Geers C, Gros G. Carbon dioxide transport and carbonic anhydrase in blood
and muscle. Physiological Reviews 2000; 80:681-715.
3. Habler OP, Messmer KF. The physiology of oxygen transport. Transfus Sci
1997;18:425-35.
4. Huang YC. Monitoring oxygen delivery in the critically ill. Chest 2005;
128:554S-560S.
5. Levy MM. Pathophysiology of oxygen delivery in respiratory failure. Chest
2005; 128:547S-553S.
6. Lumb AB. In: Nunn’s Applied Respiratory Physiology. 5th edition,
Edinburgh, Butterworth- Heinemann, 2000.
7. Maizes JS, Murtuza M, Kvetan V. Oxygen transport and utilization. Respir
Care Clin N Am 2000; 6:473-500.
8. Peruzzi WT, Martin M. Oxygen transport. Respir Care Clin N Am 1995; 1:23-
34.
9. Pittman RN. Oxygen transport and exchange in the microcirculation.
Microcirculation 2005; 12:59-70.
10. Richardson RS. Oxygen transport and utilization: an integration of the muscle
systems. Adv Physiol Educ 2003; 27:183-91.
11. Samaja M, Crespi T, Guazzi M, Vandegriff KD. Oxygen transport in blood at
high altitude: role of the hemoglobin-oxygen affinity and impact of the
phenomena related to hemoglobin allosterism and red cell function. Eur J
Appl Physiol 2003; 90:351-9.
12. Scheufler KM. Tissue oxygenation and capacity to delivery O2 : Do the two
go together? Transfus Apher Sci 2004; 31:45-54.
13. Treacher DF, Leach RM. Oxygen transport – Basic Principles. BMJ 1998; 317:
1302-6.
14. Treacher DF, Leach RM. Oxygen Transport – Tissue Hypoxia. BMJ 1998; 317:
1370-3.
15. Tyuma I. The Bohr effect and the Haldane effect in human hemoglobin. Jpn
J Physiol. 1984; 34:205-16.
5
Tissue Oxygenation
Puneet Malhotra
INTRODUCTION
The final link in the transport of oxygen from the atmosphere to
the cells is known as internal respiration or tissue oxygenation
which involves the exchange of gases between capillaries and tissue
cells (Fig. 5.1).
More than 90 percent of the body’s oxygen consumption is
utilized by a single enzyme, cytochrome oxidase during the process
of oxidative phosphorylation, which generates adenosine
triphosphate (ATP). This is the most efficient means of producing
Fig. 5.1: The delivery of oxygen to tissues for cellular metabolism

is three-step process
ATP since a total of 38 molecules of ATP are generated per molecule

of glucose. Aerobic cellular respiration depends on the efficient
supply of oxygen to the mitochondria, which is a function of the
72 Oxygen Therapy
Fig. 5.2: Aerobic metabolism via oxidative phosphorylation in the mitochondria

produces 19 times more energy (ATP) than anaerobic glycolysis
coordinated interaction between the respiratory and circulatory

systems. When oxygen supply is inadequate, anaerobic metabolism
sets in and generates only 2 molecules of ATP per molecule of
glucose (Fig. 5.2). In addition, H+ ions are formed which can lead
to systemic metabolic acidosis. Tissue oxygenation is often impaired
in critically ill patients who have poor cardiopulmonary reserve
and optimizing oxygen delivery to meet oxygen demand has the
potential to improve outcomes in these patients.
The main determinant of tissue oxygenation is a balance
between oxygen delivery (DO2) and oxygen consumption ( V O2).
An imbalance between the two results in oxygen debt.
OXYGEN DELIVERY (DO2)

Calculation of DO2
Tissue oxygen delivery depends on two factors
1. arterial O2 content (CaO2), and
2. cardiac output ( Q) (Fig 5.3).
DO2 = Q × CaO2
The normal range for DO2 is 520 to 570 mL/min/m2 and under
normal physiological conditions DO2 is considerably in excess of
the oxygen consumption (110-160 mL/min/m2). This “spare
Tissue Oxygenation 73
Fig. 5.3: O2 delivery to the tissue: Determined by

O2 content of blood and cardiac output
capacity” enables the body to cope with a fall in oxygen delivery

without initially compromising aerobic respiration.
Factors Influencing DO2

Arterial O2 Content (CaO2)
It is the total amount of O2 present in blood, i.e. combined with
hemoglobin (Hb) and dissolved in plasma.
CaO2 = (1.34 × Hb × SaO2) + (0.0031 × PaO2)
The contribution of Hb is described by the first part of the
equation. This relationship states that each gram of Hb will bind
1.34 mL of O2 when it is fully saturated with oxygen. The SaO2 is
expressed as a fraction, not a percentage (i.e. 1.0 instead of 100%).
Therefore at a Hb level of 15 g/dL and an SaO2 of 98 percent the
oxygen carried by Hb will be:
1.34 × 15 × 0.98 = 19.7 mL/100 mL
74 Oxygen Therapy
From the second part of the equation one can infer that, at a
PaO2 of 100 mm Hg the expected concentration of dissolved O2 in
blood is
0.0031 × 100 = 0.3 mL/100 mL
The total concentration of O2 in arterial blood therefore is 19.7
+ 0.3 = 20 mL/100 mL. Thus it is clear that CaO2 primarily depends
on Hb and SaO2 and to a lesser extent on PaO2.
Cardiac Output
In critically ill patients, cardiac output can be measured by invasive
as well as non-invasive methods:
1. Invasive Methods: Direct and indirect Fick methods which require
pulmonary artery catheterization and intubation respectively.
2. Non-invasive Methods: Electrical impedance cardiography (EIC)
and transesophageal echocardiography (TEE).
DO2 is directly related to changes in cardiac output which is
the product of heart rate and stroke volume. Any alteration in either
of these two parameters alters the cardiac output. Stroke volume,
the amount of blood ejected per beat is affected by the following
factors:
Preload
It is the load imposed on a muscle before the onset of contraction
and is synonymous with the initial length (or stretch) of cardiac
fibers. An increase in preload augments muscle length and leads
to a more forceful cardiac contraction (Frank-Starling pheno-
menon). In fact, in the normal heart, the diastolic volume/preload
is the principal force that governs the strength of ventricular
contraction. This emphasizes the value of avoiding hypovolemia
and correcting volume deficits promptly when they exist. The
relationship between preload and cardiac output is however not
linear and is also influnced by changes in ventricular compliance
and geometry. Since ventricular end-diastolic volume is not easily
measured at the bedside, end-diastolic pressure (EDP) and central
venous pressure (CVP) are more commonly used as reflections of
preload in clinical practice.
Afterload
It is the sum of all forces opposing ventricular ejection. It is
influenced by aortic and pulmonary arterial pressures, systemic
and pulmonary vascular resistance, and compliance of ventricular

muscle. As determination of these forces is complex, systolic left
ventricular pressure is usually used as a reasonable measure of
afterload. In addition, since afterload is a transmural force, it is
influenced by the pleural pressures at the surface of the heart.
Positive pleural pressures can promote ventricular emptying by
facilitating the inward displacement of the ventricular wall during
systole and this is one of the mechanisms by which non-invasive
positive pressure ventilation is beneficial in cardiogenic pulmonary
edema.
Contractility
Refers to the intrinsic contractile property of cardiac myocytes and
is influenced by catecholamine levels as well as extracellular
calcium concentration. Cardiac contractility is measured indirectly
by impedance cardiography and doppler echocardiography.
Steps Involved in DO2

The final link in delivery of O2 to cells involves two steps:
1. Cellular O2 supply and
2. Cellular O2 utilization
Cellular O2 Supply
Although all arteries in the body carry virtually identical
concentrations of O2, the distribution of O2 is not equal to all cells.
This is because of the following factors:
Differences in regional blood flow
The gatekeeper of blood supply to a capillary network is the local
arteriole. Arterioles may dilate or constrict in response to various
local and central regulatory factors. Local factors causing dilatation
include hypoxia, increased CO2, increased temperature and
decreased pH. The release of catecholamines is a central mechanism
that attempts to preferentially distribute blood to vital organs when
DO2 is compromised. When the body is confronted with a declining
DO2, both central and local mechanisms are stimulated. In the short
term, central effects predominate while if the O2 shortage persists,
local effects override and generalized vasodilatation occurs.
76 Oxygen Therapy
Differences in capillary architecture

Some cells are simply closer to capillaries than others. Because
movement of O2 depends on pressure gradients, the cells furthest
away from capillaries are most vulnerable to hypoxia. In addition
many capillaries are normally closed and open only when perfusion
to that particular region increases. For example, actively contracting
muscle may have 10 times more open capillaries than resting
muscle.
Cellular O2 Utilization
Metabolic utilization of O2 in cells occurs by oxidation of pyruvic
acid in the Krebs cycle (Fig. 5.2). This series of reactions takes place
in mitochondria and results in the production of 38 molecules of
ATP. The availability of O2 is crucial in the production of ATP from
adenosine diphosphate (ADP) in the Krebs cycle. The actual process
of ATP formation is called oxidative phoshphorylation as
phosphate is added to ADP by using the energy from oxidation. In
the absence of O2 metabolism is less efficient and only 2 molecules
of ATP are generated by the metabolism of glucose (anaerobic
glycolysis). Furthermore, anaerobic metabolism results in the
production of lactic acid, which may lead to systemic metabolic
acidosis.
OXYGEN CONSUMPTION ( V O2)
Calculation of V O2
Oxygen consumption refers to the rate of uptake of O2 by tissues

from the microcirculation. It is a product of the cardiac output and
the difference in oxygen content between arterial and venous blood.
V O2 = Q × (CaO2 – C v O2)
V O2 = Q × 1.34 × Hb × (SaO2 – S v O2)
The normal range for V O2 is 110-160 ml/min/m2 and it can be
measured in three ways:
1. Using Fick’s equation given above, which requires placement
of a pulmonary artery catheter.
2. By measurement of inspired and expired minute ventilation
(Vi and Ve) and of fractional concentrations of O2 (FiO2 and
FeO2) in the two samples. This is a non-invasive method but is

relatively unreliable in mechanically ventilated patients on high
FiO2.
V O2 = (Vi × FiO2) – (Ve × FeO2)
3. V O2 can also be measured directly with the help of a re-
breathing spirometer system filled with oxygen; the expired
CO2 is absorbed from the system and any change in the volume
of gas in the spirometer reflects the V O2.
O
Calculated Versus Measured V 2
The V O2 is usually derived from Fick’s equation and not directly

measured. The derivation is based on four measured variables:
cardiac output ( Q), hemoglobin concentration (Hb), arterial O2
saturation (SaO2), and mixed venous O2 saturation (SV O2). Each
of these measurements varies and their summed contribution can
lead to considerable variability in the final calculated V O 2.
Therefore to be considered a physiologically significant change,
the calculated V O2 should change by at least 15 percent.
O2 Extraction Ratio (O2ER)

It is the ratio of oxygen uptake to oxygen delivery ( V O2/DO2),
and reflects the fraction of O2 delivered to the microcirculation
that is taken up by the tissues. The O2ER varies between different
organs. For example the brain has an O2ER of 34 percent while
exercising muscle can remove all O2 from its microcirculation and
thus have an O2ER approaching 100 percent. Overall the normal
O2ER is 20-30 percent. Thus only a small fraction of the available
O2 delivered to the capillaries is taken up into the tissues. Oxygen
extraction is adjustable, and in conditions where O2 delivery is
impaired, the O2ER can increase upto 50-60 percent.
 O Curve
The DO2- V 2
The relationship between O2 delivery and O2 uptake is described

by the curve in Figure 5.4. As DO2 decreases below normal, the
78 Oxygen Therapy
Fig. 5.4: Graph describing the relationship between oxygen delivery (DO2) and O2
uptake ( V O 2). As DO 2 decreases below normal, O 2 extraction increases
proportionally to keep V O2 constant and therefore, “supply independent”. When
DO2 fall below a critical level V O2 becomes “supply dependent”
O2ER increases proportionally to keep V O2 constant. When O2ER

reaches its maximum level (50-60%), further decreases in DO2 result
in proportional decreases in V O2. Since under normal physiological
conditions DO 2 is considerably in excess of the V O2, tissue
oxygenation to a large extent is supply-independent. However
when DO2 falls below a certain critical level, V O2 becomes supply
dependent and this condition, in which cellular metabolism is
limited by the supply of O2 is called dysoxia. This critical O2 delivery
point (critical DO2) varies between 150 to 1000 mL/min/m2 in
critically ill patients, though on an average it is approximately 300
mL/min/m2. When DO2 falls below this level, tissue hypoxia
ensues, blood lactate increases and prognosis becomes poor. Thus,
maintenance of DO2 in excess of the critical delivery point is crucial
in the management of critically ill patients. This is particularly true
when PEEP is being used because PEEP may be associated with a
fall in DO2 despite improvements in PaO2 because of its effect on
cardiac output.
Factors Influencing V O2
Causes of Decreased V O2
1. Decreased blood supply to tissues: Shock (Cardiogenic/hypovole-
mic).
2. Cytotoxicity: An intrinsic defect in O2 utilization at the cellular
level is seen in carbon mono-oxide and cyanide poisoning as
well as in sepsis.
3. Increased O2 demand: This is seen in most critically ill patients
with increased metabolic rates. e.g. Acute pancreatitis, burns
and others.
It is noteworthy that tissue hypoxia in sepsis involves all the
three mechanisms mentioned above (i) decreased blood supply
as a result of redistribution of blood flow due to pathologic
capillary dilatation and arteriovenous shunting, as well as
microvascular occlusion due to platelet and fibrin micro-
thrombi, (ii) disruption of cellular metabolism by cytokines and
free radicals and iii) increased O2 demand.
Causes of Increased V O2
Whenever stress or tissue injury occurs, there is an increase in
metabolic rate and V O2. In normal subjects, exercise increases V O2
almost simultaneously with the onset of work. Most of this increase
is accounted for by increase in cardiac output. A relative
hemoconcentration and therefore increased O2 content may also
occur with high levels of exercise. The V O2 may increase 10 to 15
fold during exercise. In addition O2 extraction (see above) may
also increase to as much as 80 percent of V O2 in order to meet the
additional O2 requirement. This is made possible by capillary
dilatation and recruitment in exercising muscles.
Causes of increased V O 2 in sick patients include fever,
tachypnea, shivering and seizures. In a very ill patient, even
innocuous activities such as chest physiotherapy, getting up or
turning in bed and tracheal suctioning can increase V O2 and tilt
the already precarious O2 balance.
80 Oxygen Therapy
Oxygen Debt (V O2 Deficit)

Oxygen debt or V O2 deficit is the difference between the metabolic
demand for O2 and the actual V O2. As demand increases, V O2
must increase to preserve aerobic metabolism. This is met with by
increasing DO2 either by physiological compensation, e.g. an
increase in cardiac output or O2ER or by therapeutic interventions
such as intravenous fluids or ionotropes. If this increase in DO2 is
delayed, O2 debt continues to grow and a stage is reached from
where recovery is not possible. Studies of the O 2 debt after
resuscitation from hemorrhagic shock and in postoperative patients
show a direct relationship between the magnitude of O2 debt and
the risk of multiorgan failure and death. This indicates that early
correction of V O2 deficits is warranted to limit the severity of tissue
ischemia.
ASSESSMENT OF TISSUE OXYGENATION

Unlike hypoxemia, which denotes a low PaO2 and has standard
normal and abnormal values, there are no normal values for tissue
PO2 and it cannot be routinely measured at the bedside. Tissue
hypoxia is defined as abnormal O2 utilization by cells and should
be distinguished from other terms such as hypoxic, anemic,
histotoxic and stagnant hypoxia, which can lead to but are not
synonymous with tissue hypoxia. There are three ways to detect
tissue hypoxia.
Clinical Assessment
Clinical examination should be the first step in assessing tissue
oxygenation. A number of well-known signs (mental obtundation,
oligura, abnormal vital signs, delayed capillary refill) often indicate
specific organ dysfunction as a sequel of tissue hypoxia. However,
clinical signs are often insensitive as they occur late during the
course of tissue hypoxia. Direct or indirect measurements of local
tissue oxygenation of an organ suspected to suffer from hypoxia
will facilitate the assessment. Local tissue oxygen probes have been
used in critical care areas in some instances (e.g. brain). The normal
values of the tissue oxygenation parameters is shown in Table 5.1.
Table 5.1: Normal values and equations of tissue oxygenation parameters
Parameter Equation Normal range
Arterial O2 content CaO2 = (1.34 × Hb × SaO2) + 20 mL/dL

(CaO2) (0.0031 × PaO2)
)
Cardiac output ( Q  = hr × sv
Q 4-8L/min
Cardiac index (CI)  / BSA
CI = Q 2.4-4.0 L/min/m2
Oxygen delivery (DO2) 
Q × 1.34 × Hb × SaO 2 900-1000 mL/min
Oxygen delivery index DO2/ BSA 520-570 mL/min/m2
(DO2 index)
O )
Oxygen uptake ( V  × 1.34 × Hb × (SaO2-S v O2)
Q 180-280 mL/min/m2
2
Oxygen uptake index  O / BSA
V 110-160 mL/min/m2
2
 O index)
(V 2
Oxygen extraction ratio (SaO2 - S v O2/SaO2) x 100 20-30%
(O2ER)
BSA = body surface area, Hb = hemoglobin, hr = heart rate, PaO2 = partial

pressure of O2 in arterial blood, SaO2 = arterial O2 saturation, S v O2 = mixed
venous O2 saturation, sv = stroke volume.
Physiological Parameters
Mixed Venous O2 Saturation (S v O2)
Mixed venous blood represents blood returning from all the venous
beds of the body “mixed” together in the right ventricle. It is
obtained from the distal end of the pulmonary artery with the help
of a specialized pulmonary artery catheter, the tip of which emits
infrared light and records light reflected back from hemoglobin in
circulating erythrocytes. This technique is called reflectance
spectrophotometry (whereas pulse oximeters use transmission
spectrophotometry). S v O2 can also be measured intermittently by
withdrawing blood from the catheter. In the proximal part of the
pulmonary artery, blood from the two venae cavae and coronary
sinus is not fully blended and therefore does not represent total
body venous gas values. S v O2 is a marker of the balance between
whole body oxygen delivery and O2 demand, and is normally
between 65 to 75 percent, i.e. O2 demand is usually about 25-35
percent that of O2 delivery.
82 Oxygen Therapy
Causes of Decreased S v O2
a. Decrease in DO 2 : which may occur due to hypovolemia,
decreased cardiac output, low Hb, low PaO2 and SaO2.
b. Increase in O2 demand: critical illness, sepsis, thyrotoxicosis, etc.
Causes of increased S v O2
a. Increased DO2: Increased cardiac output (e.g. exercise, use of
ionotropes), increased Hb (hypertransfusion).
b. Decrease in O2 demand: Deep sedation and paralysis in ventilated
patients.
c. Decreased tissue O2 utilization: Cyanide and CO poisoning, sepsis
d. Left to right shunts: These can usually be diagnosed by an
abnormal “step-up” of S v O2 at the level of the defect as the
pulmonary artery catheter is passed into the right atrium or
ventricle.
A limitation of S v O 2 as a parameter for assessing tissue
oxygenation is that normal or increased values do not always mean
that tissue oxygenation is adequate. For example, in sepsis and
CO poisoning, impaired tissue O2 utilization results in a normal or
high S v O2. In addition, pathologic vasodilatation and increased
cardiac output in sepsis also tend to increase S v O2 even though
tissue hypoxia is ongoing.
Dual Oximetry
By simultaneously measuring SaO2 by pulse oximetry one can get
a continuous measurement of whole body O2 extraction, i.e. SaO2
– S v O2 . This method is known as dual oximetry and its normal
value is 20 to 30 percent.
DO2 / V O2 Measurements
The measurement of changes in V O2 in response to changes in

DO2 has been suggested as a sensitive method of determining
whether tissue hypoxia exists. However, it entails multiple
measurements at baseline and after various interventions carried
out to increase DO2 (such as the administration of fluids and
ionotropes) and is therefore impractical.
Biochemical Parameters
Blood Lactate Level
Blood lactate levels increase when tissue hypoperfusion results in
anaerobic metabolism. This is known as Type A lactic acidosis and
is different from Type B or non-hypoxic causes of lactic acidosis,
e.g. delayed clearance of lactate due to liver disease, thiamine
deficiency (blocks pyruvate metabolism) and metabolic alkalosis
(stimulates glycolysis). A blood lactate value higher than 4 mmol/
L is generally taken as abnormal. It is easy to measure and can be
followed sequentially to assess prognosis as well as response to
therapy. Recent studies indicate that blood lactate concentrations
are a better prognostic indicator than oxygen-derived physiological
variables.
Gastric Tonometry
Physiological variables of oxygen transport detailed above and
lactate are indices of global tissue oxygenation and cannot identify
oxygen deficits in individual organs. This lead to the development
of gastric tonometry to measure regional perfusion in the gut that
employs a balloon in the stomach to measure intramucosal pH
(pHi). Despite its complexity, tonometry is a reasonably good
prognostic indicator in critically ill patients.
Sublingual Capnography
Recently capnography in the sublingual area, a technique that is
less invasive and easier to use has been shown to yield tissue PCO2
measurements that correlate with those obtained by gastric
tonomtery.
Nuclear Magnetic Resonance Spectrometry

This laboratory technique, not applicable at the bedside, can
measure biochemical processes at the cellular level, e.g. levels of
ATP, NADH and cytochrome oxidase. Radionucleide imaging such
as Position Emission Tomography (PET) scanning has emerged as
an important tool to characterize tumor oxygenation to optimize
and individualize therapy for cancers.
84 Oxygen Therapy
Most of the different parameters of in vivo oxygen measure-

ments measure different things and differ in their sensitivity,
accuracy and repeatability. It has been proposed that a proper
model that relates the various measurements to each other can serve
as a powerful tool to assess tissue oxygenation. Unfortunately, such
a functional model is not available as yet.
RECENT DEVELOPMENTS
Hemodynamic monitoring which relies on physical signs such as
pulse rate, blood pressure, urine output and mentation is
inadequate for detecting tissue hypoxia. It has been recently been
shown that measurement of central venous oxygen saturation
(ScvO2), and its manipulation in patients with severe sepsis has
improved survival. In a trial examining ScvO2 in severe sepsis,
patients with ScvO2 levels higher than 70 percent had lower serum
lactate levels, higher pH and base deficit and improved mortality
(26% vs. 42%). Also ScvO2 has been shown to correlate well with
S v O2 measurements and both serum lactate and ScvO2 appear to
be independent predictors of poor outcome. The advantage of
ScvO2 lies in the fact that it can be easily measured by insertion of
a catheter in the internal jugular or subclavian vein whereas the
measurement of S v O2 requires the placement of a pulmonary
arterial catheter.
BIBLIOGRAPHY
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Philadelphia, WB Saunders Company, 1995.
3. Dickens JJ. Central venous oxygenation saturation monitoring: A role for
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2004; 32:1928-1948.
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6. Leach RM, Treacher DF. The pulmonary physician in critical care 2: Oxygen
delivery and consumption in the critically ill. Thorax 2002; 57:170-7.
7. Malley WJ. Oxygen transport and internal respiration. In: Malley WJ (editor).
Clinical blood gases 1st edition 1990. WB Saunders Company, pp 85-101.
8. Marino P. Tissue oxygenation. In: Marino P (editor). The ICU book, 2nd
edition. Williams & Wilkins. 1998; 187-203.
9. Nathan AT, Singer M. The oxygen trail: tissue oxygenation. Br Med Bull 1999;
55:96-108.
10. Ng I, Lee KK, Wong J. Brain tissue oxygenation monitoring in acute brain
injury. Acta Neurochir Suppl 2005; 95:447-51.
11. Pierce LNB. Mechanical ventilation and intensive respiratory care.
Philadelphia, WB Saunders Company, 1995.
12. Reinhart K, Kuhn HJ, Hartog C, Bredle DL. Continuous central venous and
pulmonary artery oxygen saturation monitoring in the critically ill. Intensive
Care Med 2004; 30:1572-8.
13. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the
treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-77.
14. Swartz HM, Dunn J. The difficulties in comparing in vivo oxygen measure-
ments: Turning the problems into virtues. Adv Exp Med Biol 2005; 566:295-
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15. Weibel ER. Oxygen and the History of Life. In: The Pathways for Oxygen.
Cambridge MA, Harward University Press 1984, pp 1-30.
Part C
Clinical Considerations
6
Blood Gases and
Acid-Base Balance
SK Jindal, N Singh and R Agarwal
BASIC CONCEPTS
INTRODUCTION
Assessment of arterial oxygen tension (PaO2) and content is
essential not only for assessment of tissue oxygenation but also for
guiding and monitoring oxygen therapy. Since PaO2 is basically
the function of ventilation and other respiratory processes, it is
always interpreted in conjunction with PaCO2 and the acid-base
status. Following parameters are required for interpretation of
blood gas measurements:
Arterial Oxygen Tension (PaO2)

PaO2 indicates the partial pressure of dissolved oxygen present in
the blood. In a healthy adult breathing air at sea level (760 mm
Hg), PaO2 is about 97 mm Hg. It decreases with age and approaches
80 mm Hg in a 60-year old man. There is a fall of about 10 mm Hg
for every 10-year of age thereafter. A PaO2 of 80 mm Hg in an
adult is fairly acceptable at sea level as it does not affect the oxygen
saturation of blood.
PaO 2 depends upon two important factors, FiO 2 and
atmospheric pressure. Therefore, both are considered while
interpreting PaO2.
Inspired Oxygen Concentration (FiO2)

PaO2 depends upon alveolar oxygen tension (PaO2) which is
directly proportional to the fractional concentration of oxygen in
90 Oxygen Therapy
the alveolar (i.e. inspired) air. The alveolar oxygen tension (PaO2)
can be determined from the alveolar air equation:
PaCO 2
PAO2 = FiO2 (PB–PH2O) –
R
(PB = Barometric pressure; R = Respiratory gas exchange ratio,
i.e. CO2 output/O2 uptake)
40
On room air (at sea level), PAO2 = 0.21 (760 – 47) –
0.8
= 100 mm Hg
As the FiO2 is increased, the PA O2 (hence PAO2) increases.
Therefore, in a person breathing 40 percent oxygen, PAO2 = 0.4
40
(760–47) = 235 mm Hg.
0.8
Atmospheric Pressure (PB)

Atmospheric pressure is constant (760 mm Hg) at sea level. It
decreases at high altitude. PB increases below sea level. This fact
assumes significance in sea divers and those working in deep
mines.
Atmospheric pressure is purposefully increased for manage-
ment of some specific disease states when oxygen is administered
under hyperbaric conditions. Therefore, at two atmospheric
pressures (i.e. 2 × 760 mm Hg) in a patient administered 40 percent
oxygen.
40
PAO2 = 0.40 (1520 – 47) – = 540 mm Hg
0.8
Alveolar-arterial Oxygen Pressure Gradient

Oxygenation is affected by changes in ventilation. Hyperven–
tilation “blows off” some CO2 (thereby increasing PAO 2) and
hypoventilation causes CO2 retention (lowering PAO2). Measure-
ment of the gradient between alveolar and arterial oxygen tension
(PA O2 – PaO2 ) therefore gives a clear idea about the oxygen
exchange within the lung. A gradient of 10-15 mm Hg can be
normally observed in a healthy individual. The gradient increases
by 3 mm every decade after 30 years of age. The gradient is greater
in the elderly, both during air and oxygen breathing. An increase
Blood Gases and Acid-Base Balance 91
in this value indicates impairment of oxygen transport in the lungs.

Since alveolar PO2 is always higher, the gradient can never be
negative. A negative value indicates defective measurements.
Relationship of Total Ventilation to Alveolar Ventilation

The total ventilation (V) of minute ventilation (MV) consists of two
components: i, amount of ventilation taking part in gas exchange
in alveolar ventilation (VA); ii, the volume not taking part in
ventilation, i.e. MV = VA + VD.
We also know that the arterial carbon-dioxide tension depends
directly on the VA; PaCO2 α 1/VA .
Therefore, PaCO2 shall depend on MV provided the VD is
relatively constant. In a normal healthy person, the physiological
dead space is generally unchanged. A decrease may occur during
exercise. Therefore, arterial carbon dioxide tension is either normal
or decreased during exercise. In the presence of an adequate
cardiopulmonary reserve, increase in minute ventilation due to
any cause can result in a decreased PaCO2 provided the VD is
unaltered. If there is an increase in PaCO2 in the presence of
hyperventilation, a dead space producing disease (e.g. COPD)
should be suspected.
Relationship Between Carbon Dioxide and pH

There occurs a fall in pH of 0.10 units for every 20 mm Hg increase
in PaCO2 and a rise in pH of 0.10 units for 10 mm Hg decrease in
PaCO2. The normal pH is 7.4 at a PaCO2 of 40 mm Hg. An increase
in PaCO2 to 50 mm Hg shall cause a fall in pH to 7.35. Similarly a
decrease in PaCO2 to 30 mm Hg shall increase the pH to 7.5.
Blood Bicarbonate Level and Acid-Base Status

Kidney plays an important part in homeostasis by excreting or
retaining bicarbonate in accordance with the acid-base status of
body.
The subject of acid-base balance is interlinked with both oxygen
physiology and therapy. It is therefore, important to be familiar
with the subject. The main aim of acid-base regulatory mechanisms
is to protect pH from alterations induced by continuous formation
of acid end products of metabolism.
92 Oxygen Therapy
NORMAL CHEMISTRY
Atom
We have already defined atom as the smallest unit of an element.
It is further composed of smaller particles which may be either
charged or uncharged. The uncharged neutrons and positively
charged protons form the nucleus of the atom. Most of the mass of
the atom is contained in its nucleus. The number of protons in the
nucleus is the atomic number of the atom. The sum of numbers of
protons and neutrons is the atomic weight. Around the nucleus,
there are negatively charged electrons moving in different orbits.
In the natural state of an element, the number of protons is the
same as that of electrons. When one or more electron/s is/are either
removed or added to the outermost orbit, the state is said to be
ionized.
Solutions
A solution is a homogenous mixture of two or more substances in
a liquid form. It consists of a solvent, the major portion in which
one or more solutes are dispersed. A solute is said to be ionized
(dissociated state) when there is an excess or deficit of electrons in
the outer orbits of its atoms. In other words ionized substances can
readily donate or accept ions from other substances. Strong acids,
strong bases and salts exist in the ionized state, therefore, they are
highly dissociated (or reactive). All ions have electrical charges;
those with net positive charges are cations and those with net
negative charges anions.
One of the important ion which is critical for maintenance of
cellular metabolism is the hydrogen ion. Its concentration is
normally maintained at a constant value. Any significant shift in
[H+] is injurious for cell health. The concentration of hydrogen ions
[H+] is very small in water which dissociates very weakly.
Acids and Bases

An acid is a substance capable of providing a hydrogen ion (Proton
donor) while a base is capable of accepting or removing a hydrogen
ion from a solution (Proton acceptor). This can be expressed as:
HA —————— H+ + A–
(Acid) (Base)
For example, carbonic acid dissociation can be expressed as

H2CO3 → H+ + HCO3–
(Acid) ← (Base)
Strong acids are capable of donating and strong bases of
accepting many [H+] to or from a solution. Weak acids and weak
bases can donate or accept a varying degree of [H+].
Based on [H+], acidosis and alkalosis are defined as conditions
in which [H+] are above or below the normal range.
The concentration of hydrogen ions in physiological solutions
in the body including tissue fluids and blood is very small. It is
difficult to express the actual small numbers. Therefore, these are
expressed in terms of negative logarithm to the base 10 of the [H+],
denoted by the symbol of pH (“puissance hydrogen” – in French:
negative logarithm of hydrogen ion activity).
pH = log 10 [H+]
Most blood levels of H+ concentration lie between 1 × 10–7 mole/
L (pH 7) and 1 × 10–8 mole/L (pH 8). The average value for H+ in
blood is 0.4 × 10–8 mole/L (pH 7.4).
The pH is maintained normal by 4 main mechanisms: buffer
activity; exchange of ions between two major fluid compartments;
respiratory and renal regulation.
Buffer System
A buffer system is defined as a substance which prevents extreme
changes in free H+ concentration in that solution. This is important
in body systems to maintain stabilization of free H+ concentration
(whenever the cells are subjected to a significant increase or
decrease in the number of H+ ions, the buffer system will neutralize
the changes and allow the cellular function to continue).
A buffer consists of a combination of a weak acid (or a base)
and the salt of that acid (or base). There are a number of buffers in
the body in blood and extracellular fluid such as the hemoglobin,
bicarbonate, phosphate ions and serum proteins. In terms of
buffering capacity, the carbonic acid – bicarbonate system is the
most important. Disturbances in this system result in most acid
base disturbances.
Na+OH– + H+HCO3– → Na+HCO3– + H2O
94 Oxygen Therapy
Henderson-Hasselbalch Equation
The equation expresses the state of acid-base balance and the
dependence of pH of the blood on bicarbonate – carbonic acid
buffer.
H2CO3 ———————H+ + HCO3–
By looking at just one component of the system, i.e. carbonic
acid to HCO3– relationship, we know the hydrogen ion activity
secondary to dissociation of H2CO3. This in turn is governed by
inter-relationship of all the blood acids, bases and buffers.
The equation is expressed as:
Base
pH = pK + log
Acid
pK represents the pH value at which the solute is 50 percent
dissociated. In other words pK represents the pH at which
maximum buffering capacity can be achieved for that particular
reaction. If the ‘base’ in the above equation be (HCO3–) and the
‘acid’ (H2CO3), and the pH equalled the pK, there would be equal
amounts of bicarbonate ions and carbonic acid. Since the amount
of H2CO3 depends upon the dissolved CO2 (solubility S x PCO2),
the equation can be expressed as:
[HCO3– ]
pH = pK + log
S × PaCO2
pK = 6.1
S = 0.03
In clinical terms, it can be said that pH shall vary directly with
bicarbonate concentration (regulated by the kidney), and inversely
with PaCO2 (regulated by the lung). Any disturbance of the acid-
base balance or the function of kidney or the lung is likely to affect
the pH. Normal blood pH has a narrow range between 7.35 to 7.45
(average 7.4).
We can use pH measurements to indicate the H+ concentration
and PaCO2 measurement for respiratory function. Bicarbonate
measurement done in the clinical biochemistry laboratory
represents standard HCO3– which reflects the nonrespiratory or
metabolic component of acid-base change.
The “actual” HCO3– concentrations are directly calculated from
the Henderson-Hasselbalch equation if pH and PaCO2 are known.
But the use of actual plasma HCO3– level is complex. One needs to
know its range during acute hypercapnia for titration at various

levels of PaCO2 and limits of secondary compensatory responses
during chronic hypercapnia. More commonly, we use the method
of “base excess” of Astrup and Siggaard-Anderson. Base excess is
defined as the number of multi equivalents of acid or base needed
to titrate 1 liter of blood to pH 7.40 at 37°C while PaCO2 is held
constant. This method obviates the problem of bicarbonate shifts
from blood to extracellular fluid. The HCO3 value obtained by this
method after actually increasing PaCO2will be higher than in blood.
The method requires the use of a slide rule or a normogram chart
to calculate HCO3–. For quick calculation, it can be assumed that at
PaCO2 held constant at 40 mm Hg, 7 mEq of acid or base are
required to change pH by 1 unit (0.10). For example, if the base
deficit be –7, the predicted pH is 7.3. At base excess of +7, the
predicted pH is 7.5.
Base excess (or deficit) is a true reflection of non-respiratory
component of acid-base-status. But it must be emphasized that base
excess is not a measurement but a calculation. It shall be reliable
only if the pH and PaCO2 measurements are accurate.
Blood Acids
Carbonic acid is the most important acid for our purpose. It is
produced by dissolution of CO2 in H2O. This is a slow process.
Therefore, only 5 percent of CO2 produced in the tissues which
enters the blood, remains in plasma. Most of CO2 enters the red
blood cells where the presence of hemoglobin and the enzyme
carbonic anhydrase facilitate its transport. The enzyme does not
exist in plasma. Therefore, very little CO2 reacts with water to form
H2CO3. In plasma, the dissolved CO2 is about 1000 times greater
than the concentration of H2CO3 (the dissolved CO2 exerts pressure
according to Henry Law, which is measured as PaCO2). But it is
not possible to differentiate between dissolved CO2 (dCO2) and
carbonic acid. Both these functions are added to give “total
dissolved CO2”. The total dissolved CO2, at BTPS can be calculated
by multiplying the PaCO2 with the solubility coefficient (S) which
is 0.0301. Total dissolved CO2 = (0.0301) × PaCO2.
Blood acids can be classified as (i) Volatile, i.e. those which are
capable of changing from liquid to a gaseous state and vice versa
(e.g. carbonic acid). These are derived from aerobic oxidation of
glucose and fatty acids and are controlled by the ventilatory process
96 Oxygen Therapy
by the lungs; (ii) Non volatile (fixed): they are produced during
protein metabolism, e.g. dietary acids, lactic and keto acid. These
are regulated by the kidney, and to a lesser extent by the liver. The
kidney helps by reabsorbing the filtered bicarbonate load and
excreting the fixed acids. Increase in acid load may occur in the
presence of renal failure (renal acidosis), tissue hypoxia (lactic
acidosis) and impaired glucose metabolism (ketoacidosis).
Blood Bases
Plasma bicarbonate is the most important base. It is primarily
regulated in the kidney. The presence of carbonic anhydrase in
the renal tubular cells catalyzes the production of HCO3– and H+
ions. There is absorption of a HCO3– ion in the blood for each H+
ion secreted in the urine in the renal tubules. The H+ is attached to
either the urine HCO3– phosphate or ammonia and secreted in the
urine.
The time required for the kidneys to affect the blood pH (by
conserving HCO3–) takes some hours. On the other hand, the
respiratory mechanism to alter pH is rapid and takes only a few
minutes.
Intracellular acid and extracellular potassium (K+) concentration
also influence the acid-base balance. Movement of K+ from within
the cell to plasma takes place in exchange for a H+ moving into the
cell, thereby adding a HCO3– in the plasma. Chloride ion (Cl–) is
also exchanged at a renal tubular level. The total electrolytes, i.e.
cations (e.g. Na+ + K+) and anions (Cl– + HCO3–) must remain in
electrical balance. If the cations are normal, a reduction in Cl–
necessitates an increase in HCO3–.
ALTERATIONS OF ACID-BASE STATUS

The acid-base status of a patient is determined by blood gas studies
which provide information about pH, PaCO2 and HCO3– (Table
6.1). Alterations in the acid-base status can occur due either to
metabolic or respiratory disturbances. It is PaCO2 which is directly
affected in respiratory and HCO3– in case of metabolic problems.
Therefore, pH can be expressed as:
Renal Function
pK =
Pulmonary Function
Table 6.1: Abnormalities of pH, PaCO2 and HCO 3– in different

acid-base disturbances
Acid-Base State pH PaCO 2 HCO3– Base Excess

(mm Hg) (mEq/L)
Normal 7.35-7.45 35-45 22-28 Normal
Respiratory Acidosis
Acute Decreased Increased Decreased Normal
Partly compensated Decreased Increased Increased Increased
Fully compensated Normal Increased Increased Increased
(Acidic)
Metabolic Acidosis
Acute Decreased Normal Decreased Decreased
Partly compensated Decreased Decreased Decreased Decreased
Fully compensated Normal Decreased Decreased Decreased
(Acidic)
Respiratory Alkalosis
Acute Increased Decreased Normal Normal
Partly compensated Increased Decreased Decreased Decreased
Fully compensated Normal Decreased Decreased Decreased
(Alkalotic)
Metabolic Alkalosis
Acute Increased Normal Increased Increased
Partly compensated Increased Increased Increased Increased
Fully compensated Normal Increased Increased Increased
(Alkalotic)
pH DISTURBANCES: THE CONCEPT OF COMPENSATION

Oxygen diffuses across alveolar capillary membrane 20 times more
slowly than CO2. Therefore, PaO2 is lower in arterial blood than
PAO2 (alveoli). In case of CO2, there is no alveolar-arterial gradient.
A. As discussed earlier, pH depends on PaCO2, i.e. on alveolar
ventilation. Therefore,
• Respiratory acidosis is present when PaCO 2 exceeds
45 mm Hg
• Respiratory alkalosis is present when PaCO2 is below
35 mm Hg.
However, PaCO2 alone does not define the nature of the
respiratory disturbance – whether primary or secondary
(compensatory) to a primary metabolic derangement.
B. pH also depends on HCO3–. Therefore:
• Metabolic acidosis is present when [HCO3–] is less than 22
mEq/L
98 Oxygen Therapy
• Metabolic alkalosis is present when [HCO3–] exceeds 28

mEq/L
[HCO3–] alone does not define the nature of metabolic alteration–
whether primary or secondary.
It is important to remember that physiologic compensation for
any alteration, i.e. homeostasis, is never complete, since this would
eliminate the very stimulus for compensation itself. Therefore,
when the primary event is a fall in pH, whether of respiratory or
metabolic origin, arterial pH will remain on acid side of normal
after compensation, although it may be within the normal range.
Therefore, pH defines the primary abnormality. PaCO2 and
[HCO3–] indicate whether the primary event is respiratory or
metabolic and to what extent compensation has occurred.
Examples:
1. Arterial pH 7.35; PaCO2 32 mm Hg; HCO3– 17 mEq/L.
Since pH is on acid side – the primary disturbance must itself
be metabolic acidosis. Low PaCO2 indicates respiratory alkalosis
which must be compensatory, hence this is metabolic acidosis.
2. Arterial pH 7.42, PaCO2 30 mm Hg and HCO3– 20 mEq/L. Here
pH is alkaline, so primary disturbance must be respiratory
alkalosis. Metabolic acidosis is compensatory.
In both examples, PaCO2 and HCO3– are almost identical yet
the cases represent two entirely different problems. It is the pH
which distinguishes (even though within the normal range).
CLINICAL CONSIDERATIONS AND INTERPRETATION

INTRODUCTION
Blood gas analyses are commonly performed especially in critically
ill patients to assess the adequacy of ventilation (including
oxygenation capacity of the cardiopulmonary system) as well as
the acid-base status. Arterial blood gas (ABG) analysis is an
important laboratory tool that can assist clinicians in timely
detection and management of metabolic and ventilatory disorders.
Arterial blood is used most frequently although peripheral venous
blood, mixed venous blood (from pulmonary artery) and capillary
blood are also utilized in specific situations. Before one proceeds
to ABG analysis, one should be familiar with conditions that can
invalidate or modify the results of this investigation.
CONDITIONS INVALIDATING OR MODIFYING ABG RESULTS

1. Delayed analysis: Consumption of oxygen and production of
carbon dioxide continues even after blood has been drawn out
of the body and is present inside the syringe. Therefore, samples
that are not iced quickly become invalid while iced samples
can maintain values for 1-2 hours. With a change in temperature
the PaCO2 increases at the rate of 3-10 mm Hg/hour, while
PaO2 decreases at a rate related to its initial value and are
dependent on oxygen saturation of hemoglobin (Table 6.2).
Table 6.2: Effect of temperature on the rate of change of ABG values
Parameter Change every 10 min at 37oC Change every 10 min at 4oC

pH Decreases by 0.01 Decreases by 0.001
PaCO2 Increases by 1 mm Hg Increases by 0.1 mm Hg
PaO2 0.1 vol % 0.01 vol %
2. Excessive heparin: Heparin is a weak acid and excess of heparin

has a dilutional effect on blood gas values. It causes a fall in
bicarbonate and PaCO2 values. Hence the syringe should be
completely emptied of heparin after flushing. The risk of
alteration of results increases with: a) Bigger size of syringe/
needle and b) Smaller volume of sample – the magnitude of
change can be as high as 25 units if 1mL sample is taken in a 10
ml syringe that contains 0.25 mL of heparin in the needle. Hence
syringes must be more than 50 percent full with blood sample.
3. Hyperventilation or breath-holding: This may lead to erroneous
laboratory results.
4. Air bubbles: Air bubbles have the composition of room air (PO2
and PCO2 of around 150 mm Hg and 0 mm Hg respectively). If
an air bubble is mixed with the blood sample, the PaO2 rises
and PaCO2 falls. Mixing and agitation of the sample in an
attempt to expel air bubbles often increases the available surface
area for diffusion and more erroneous results. One should
discard the sample if excessive air bubbles are present. A seal
with a cork/cap should be made immediately after taking the
sample.
5. Fever or hypothermia: Most ABG analyzers report data at normal
body temperature (37°C). In the presence of severe hyper/
hypothermia, values of pH and PCO2 that are reported at 37°C
100 Oxygen Therapy
can be significantly different from patient’s actual values. The

changes in PO2 values with temperature are predictable while
there are no significant changes in bicarbonate levels, oxygen
saturation and oxygen capacity/content as well as carbon
dioxide content values with changes in temperature. There is
no consensus regarding reporting of ABG values especially
those of pH and PCO2 after doing ‘temperature correction’.
Some advocate interpretation of values measured at 37°C, and
the reasons put forward include:
a. Most clinicians do not remember normal values of pH and
PCO2 at temperatures other than 37°C.
b. In patients with hypo/hyperthermia, body temperature
usually changes with time either per se or due to effect of
rewarming/cooling strategies. Hence if all calculations are
done at 37°C, it is easier to compare them.
c. Values other than pH and PCO2 do not change significantly
with changes in temperature.
Other people favor the use of nomograms to convert values at
37°C to patient’s temperature. Some analyzers calculate values
at both 37°C and patient’s temperature automatically, if entered.
Hence the patient’s temperature should be mentioned while
sending the sample and the laboratory should clarify whether
values being mentioned in the report are at 37°C or at patient’s
actual temperature.
6. WBC count: There can be marked increases in oxygen
consumption in patients with very high leukocyte/platelet
counts since 0.1 mL of oxygen is consumed per deciliter of blood
in 10 minutes in patients with normal leukocyte count. Hence
immediate chilling or preferably analysis is essential to avoid
erroneous results. An extreme form of this phenomenon is seen
in patients with leukemias where patients develop spurious
hypoxemia. This is called “leukocyte larceny”.
7. Type of syringe: Glass syringes are preferred to plastic syringes
as the PO2 values drop more rapidly in plastic syringes while
the pH and PCO2 values are unaffected. Other advantages of
glass syringes include:
a. There is usually only minimal friction of the barrel of the
syringe with the syringe wall.
b. Usually there is no need to apply force to pull back the

syringe barrel and hence there are lesser chances of air
bubbles entering the syringe.
c. Small air bubbles adhere to sides of plastic syringes and
can be difficult to expel.
Although glass syringes are preferred, the differences are
usually not of clinical significance and plastic syringes can be,
and continue to be used in clinical practice for blood gas
analysis.
8. Quality control and calibration: During analysis of an arterial
blood sample, pH, PCO 2 and PO 2 are measured while
bicarbonate levels are calculated. The Sanz (pH) electrode and
Severinghaus/Stow (PCO2) electrode are based on measure-
ment of voltages (potentiometric) and are known to have
‘balance drift’ (shifting of calibration points from baseline
though the same slope is maintained). On the other hand, the
Clark (PO2) electrode is based on measurement of amperage
(ampero-metric) and is known to undergo ‘slope drift’ (angle
of calibra-tion points changes though baseline remains same).
Recommen-dations for calibration of each electrode include
two-point calibration every eight hours and one-point
calibration every four hours.
INTERPRETATION OF ABG REPORT

Assessment of the type of acid-base disorder requires a minimum
of two and preferably all of the three parameters namely arterial
pH, PCO2 and plasma bicarbonate level while for a complete
analysis of an arterial blood gas sample one requires determination
of all of the following:
a. pH
b. PaO2
c. PaCO2
d. HCO3–
e. Oxygen Saturation (SaO2)
f. Anion Gap (AG)
g. Calculation of ΔAG and HCO3– values
102 Oxygen Therapy
ASSESSMENT OF OXYGENATION STATUS

The normal value of PaO2 in healthy adults breathing room air at
sea level is around 97 mm Hg. This falls progressively with
increasing age (approximately 5 mm Hg per decade after 10 years
of age). At the age of 60 years, it is around 75 mm Hg and falls by
approximately 1 mm Hg/year thereafter till the age of 90 years. It
is also dependent upon both the concentration of inspired oxygen
(FiO2) and the partial pressure of gas in the atmosphere (Patm).
Hypoxemia is defined as PaO2 < 80 mm Hg while breathing room
air. Since most patients who need arterial blood gas monitoring
usually require supplemental oxygen therapy, it should not be
withheld or interrupted ‘to determine PaO2 on room air’. As a rough
guide, if PaO2 is less than 5 times the FiO2, patient is probably
hypoxemic on room air. Hypoxemia is classified as mild if PaO2
< 80 mm Hg, moderate if PaO2 < 60 mm Hg and severe if PaO2
< 40 mm Hg.
ASSESSMENT OF ACID-BASE STATUS

Bicarbonate (HCO3– )
It is a reflection of non-respiratory (metabolic) acid-base status but
it does not quantify the degree of abnormality of buffer base or
actual buffering capacity of blood. There are two commonly used
terms with respect to bicarbonate measurement:
• Standard HCO3– : HCO3– levels measured in laboratory after
equilibration of blood PCO2 to 40 mm Hg (similar to routine
measurement of other serum electrolytes).
• Actual HCO3– : HCO3– levels calculated from pH and PCO2
directly.
Base Excess/Base Deficit

This is calculated from pH, PaCO2 and hematocrit and is expressed
as mEq/L of base above the normal buffer base range. A negative
base excess is also referred to as base deficit. It is a true reflection
of non-respiratory (metabolic) acid-base status. The base excess/
base deficit does not provide any extra information than those
provided by pH, PaO2, PaCO2 and HCO3– and thus will not be
discussed any further.
Acid-base status is described in three steps. These are:

1. Acidosis/Alkalosis
2. Respiratory/Metabolic
3. Compensated/Uncompensated
Acidemia is a reduction in arterial pH < 7.36 while alkalemia is
an increase in arterial pH >7.45. On the other hand, acidosis is the
presence of a process which tends to reduce pH by virtue of gain
of hydrogen ions (H+) or loss of HCO3–, and alkalosis is the presence
of a process which tends to increase pH by virtue of loss of H+ or
gain of HCO3–.
Respiratory processes are those which lead to acidosis (PaCO2
> 44 mm Hg) or alkalosis (PaCO2 < 36 mm Hg) through a primary
alteration in ventilation and resultant excessive elimination or
retention of CO2 while metabolic processes lead to acidosis (HCO3–
< 20 mEq/L) or alkalosis (HCO3– > 28 mEq/L) through their effects
on kidneys and the consequent disruption of H+ and HCO3– control.
Compensation is the normal response of the respiratory system
or kidneys to a change in pH induced by a primary acid-base
disorder. In the presence of acidosis or alkalosis, regulatory
mechanisms occur which attempt to maintain the arterial pH in
the physiologic range (Tables 6.3 and 6.4). These processes result
in the return of pH towards, but generally just outside the normal
range. Disturbances in HCO3– (metabolic acidosis or alkalosis) result
in respiratory compensation while changes in CO2 (respiratory
acidosis/alkalosis) are counteracted by renal compensation.
• Renal compensation—kidneys adapt to alterations in pH by
changing the amount of HCO3– generated/excreted. Full renal
compensation takes 2-3 days
• Respiratory compensation—alteration in ventilation allows
immediate compensation for metabolic acid-base disorders.
Table 6.3: Characteristics of primary acid-base disorders
Disorder Primary changes Compensatory

response
Metabolic acidosis ↑ [H+] ↓ pH ↓ HCO3– ↓ PCO2

Metabolic alkalosis ↓ [H+] ↑ pH ↑ HCO3– ↑ PCO2
Respiratory acidosis ↑ [H+] ↓ pH ↑ PCO2 ↑ HCO3–
+
Respiratory alkalosis ↓ [H ] ↑ pH ↓ PCO2 ↓ HCO3–
104 Oxygen Therapy
Table 6.4: Renal and respiratory compensations to primary

acid-base disturbances
Disorder Compensatory response

Metabolic acidosis PCO2 ↓ by 1.3 mm Hg per 1.0 mEq/L ↓ in HCO3–
Metabolic alkalosis PCO2 ↑ by 0.7 mm Hg per 1.0 mEq/L ↑ in HCO3–
Respiratory acidosis HCO3– ↑by 1.0 mEq/L per 10 mm Hg ↑ in PCO2
(Acute)
Respiratory acidosis HCO3– ↑ by 4.0 mEq/L per 10 mm Hg ↑ in PCO2
(Chronic)
Respiratory alkalosis HCO3– ↓ by 2.0 mEq/L per 10 mm Hg ↓ in PCO2
(Acute)
Respiratory alkalosis HCO3– ↓ by 4.0 mEq/L per 10 mm Hg ↓ in PCO2
(Chronic)
Simple and mixed acid-base disorder: Simple acid-base disorder

is a single primary process of acidosis or alkalosis whereas a mixed
acid-base disorder is when more than one acid-base disorder are
present simultaneously.
Stepwise Approach to ABG Analysis (Fig. 6.1)

• Determine whether patient is alkalemic or acidemic using the
arterial pH measurement
• Determine whether the acid-base disorder is a primary
respiratory or metabolic disturbance based on the PCO2 and
serum HCO3– level.
• If a primary respiratory disorder is present, determine whether
it is chronic or acute (based on clinical history and examination).
• In metabolic disorders, determine if there is adequate compen-
sation of the respiratory system. In respiratory disorders,
determine if there is adequate compensation of the metabolic
system
• Determine patient’s oxygenation status (PaO2 and SaO2)
• If a metabolic acidosis is present, determine the anion gap and
osmolar gap
• In high anion gap acidosis, determine the change in anion gap
(ΔAG) and bicarbonate (ΔHCO3–) in order to assess for the
presence of coexisting metabolic disturbances
• In normal (non) anion gap acidosis, determine the urinary anion
gap which is helpful to distinguish renal from non renal causes.
• In normal (non) anion gap acidosis, also determine the urinary
osmolal gap which determines the urinary ammonium
Fig. 6.1: Approach to interpretation of ABG in presence of normal or

near normal respiratory acid-base disorders
excretion versus the excretion of an unmeasurable anion

coupled with hydrogen ion.
Respiratory alkalosis is the most common of all the four acid-
base disorders (23-46%) followed by metabolic alkalosis. Respi-
ratory acidosis was seen in 14-22 percent of patients in a review of
almost 8000 ABG analysis in one ICU. Attention to the presence
and severity of hypoxemia should always assume priority while
analyzing a patient who is suspected to have a respiratory acid-
base disorder.
Respiratory Alkalosis
Respiratory alkalosis results from increased alveolar ventilation
with resultant washout of CO2 from the body.
Causes of Respiratory Alkalosis

1. Central respiratory stimulation: It is secondary to direct
stimulation of the respiratory center by a variety of causes. These
include structural causes like head trauma, brain tumor,
cerebrovascular accident and non-structural causes like pain,
anxiety, fever, pregnancy, drugs like salicylates and voluntary
hyperventilation.
106 Oxygen Therapy
2. Peripheral respiratory stimulation: It is related to hypoxemia

induced stimulation of the peripheral chemoreceptors and
hence reflex stimulation of the respiratory center. The causes

include: pulmonary V Q imbalance, pulmonary diffusion
defects, pulmonary shunts, high altitude and hypotension.
3. Intrathoracic structural causes: These include reduced
movement of chest wall and diaphragm, reduced compliance
of lungs and irritative lesions of conducting airways.
4. Mixed/Unknown mechanisms: Drugs (nicotine, progesterone,
thyroid hormone, catecholamines, xanthines), cirrhosis,
bacterial sepsis, heat exposure, mechanical ventilation, some
cases of metabolic acidosis (metabolic component treated).
Manifestations of Respiratory Alkalosis

1. Neuromuscular: These are related to cerebral arterial
vasoconstriction and associated decrease in cerebral blood flow
and include changes in higher mental status like decreased
intellectual function, lightheadedness and confusion. Other
manifestations are related to neuromuscular irritability and
include circumoral and extremity paresthesias, muscle
twitching, cramps, hyperreflexia and even tetany and seizures
in severe cases. Syncope and strokes can also occur (the latter
usually more frequent in patients with sickle cell disease).
2. Cardiovascular: These are related to coronary vasoconstriction
and include tachycardia with near normal blood pressure, chest
tightness and even angina, ECG changes (especially ST
depression) and ventricular arrhythmias. Individuals with
normal coronary vessels can also develop hypocapnia related
coronary vasospasm; the cardiovascular manifestations of
hypocapnia do not necessarily imply the presence of underlying
coronary artery disease.
3. Gastrointestinal: Nausea and vomiting (related to cerebral
hypoxia).
4. Biochemical abnormalities: These include decreased levels of
tissue carbon dioxide, phosphate, calcium and increased levels
of chloride.
Homeostatic Response to Respiratory Alkalosis

In acute respiratory alkalosis, immediate response to fall in CO2
(and H2CO3) is release of H+ by blood and tissue buffers, which
reacts with HCO3– and causes a fall in HCO3– as well as a fall in the
elevated pH. The HCO3– level usually does not fall less than
15 mEq/L. Other changes include cellular uptake of HCO3– in
exchange for chloride (Cl–). The steady state is reached in 15
minutes and persists for 6 hours after which the kidneys increase
excretion of HCO3–. Again the HCO3– level usually does not fall less
than 15 mEq/L. The new steady state after initiation of renal
compensation is reached in 1 to 3 days. The time of onset of
hypocapnia and progression from acute to chronic respiratory
alkalosis may not always be apparent in clinical practice.
Treatment of Respiratory Alkalosis

Respiratory alkalosis by itself is not a cause of respiratory failure
unless the work of increased breathing cannot be sustained by
respiratory muscles. Management involves treatment of the
underlying cause and administration of oxygen if hypoxemia is
co-existent. Usually, the extent of alkalemia produced is not life-
threatening. However, if pH increases more than 7.55, the patient
may need to be sedated/paralyzed and/or put on mechanical
ventilation.
Pseudo-respiratory Alkalosis
This refers to arterial hypocapnia seen in the presence of respiratory
acidosis in some cases of profound circulatory shock, especially in
patients who have markedly reduced cardiac output as well as
pulmonary blood flow but whose alveolar ventilation is relatively
preserved. This includes patients undergoing cardiopulmonary
resuscitation. The reduced pulmonary perfusion has a two pronged
effect: (a) the total amount of CO2 that can enter the pulmonary
vascular bed is limited and so is the quantity that can diffuse out
into the alveoli and finally get excreted out of the body. This leads

to increased venous hypercapnia, and (b) there is increased V Q
ratio as well as increased transit time of blood entering the
pulmonary vascular bed and this leads to increase in the quantity
of CO2 that is extracted from the pulmonary blood. This in turn
108 Oxygen Therapy
leads to reduced PaCO2 (arterial eucapnia/hypocapnia). Thus, even

though the arterial CO2 is reduced, there is an overall gain of CO2
in the body because of reduced CO2 excretion, and this is a typical
feature of respiratory acidosis. The acidemia seen in the venous
blood of such patients may also be contributed by coexistent
metabolic acidosis. The arterial pH in the presence of co-existent
metabolic acidosis in these patients can be mildly acidic, normal
or even alkaline.
Another problem commonly observed in these patients is
normal/near normal PaO2 and arterial oxygen saturation though
tissues suffer oxygen deprivation. Hence, in a patient with
circulatory failure, blood gas monitoring must include sampling
of mixed (or central) venous blood to rule out pseudo-respiratory
alkalosis. The treatment consists of treating the underlying disorder
and improvement in systemic hemodynamics with an aim of
increasing both cardiac output and pulmonary blood flow.
Respiratory Acidosis
Respiratory acidosis results from CO2 retention either due to
abnormalities with the peripheral apparatus responsible for
elimination of CO2 from the body or because of problems with the
control of the process of respiration and resultant inadequate or
ineffective alveolar ventilation.
Causes of Acute Respiratory Acidosis

Disorders of excretory components of respiration
1. Perfusion: Cardiorespiratory arrest and other cardiac causes
leading to reduced cardiac output, pulmonary thrombo-
embolism (end-stage).
2. Ventilation: Acute airway obstruction, severe pneumonia, acute
respiratory distress syndrome, severe pulmonary edema,
restriction of lung/thorax/chest wall, pneumothorax, flail chest,
muscle weakness (severe hypokalemia, myasthenic crisis),
failure of mechanical ventilation.
Disorders of control components of respiration
1. Central nervous system: Drugs (anesthetics, sedatives), central
sleep apnea syndrome, trauma.
2. Spinal cord and Peripheral nerves: Drugs causing skeletal
muscle paralysis (succinylcholine, curare, pancuronium and
allied drugs, aminoglycosides), neurotoxins (botulism, tetanus,

organophosphorus compounds), Guillain-Barré syndrome,
trauma (cervical cord injury, phrenic nerve injury).
Causes of Chronic Respiratory Acidosis

Disorders of excretory components of respiration
1. Ventilation: Chronic obstructive pulmonary disease, advanced
ILD.
2. Restriction of lung/thorax/chest wall: Fibrothorax, kyphoscoliosis,
muscle weakness (muscular dystrophy, polymyositis).
Disorders of control components of respiration
1. Central nervous system: Obesity-hypoventilation syndrome,
brainstem infarcts, myxedema, chronic sedative abuse.
2. Spinal cord and Peripheral nerves: Poliomyelitis, amyotrophpic
lateral sclerosis, diaphragmatic paralysis.
Manifestations of Respiratory Acidosis

1. Neuromuscular: These are related to cerebral arterial vasodila-
tation and consequent increase in cerebral blood flow. The
manifestations depend upon the rate of rise of PCO2. In acute
hypercapnia, these include altered behavior and sensorium
(ranging from anxiety and even frank delirium in some cases
to lethargy, stupor and coma in others). Asterixis may be
observed in these cases. Chronic hypercapnia on the other hand
is associated with headache, tremors, myoclonic jerks and focal
deficits. Papilledema and abnormal deep tendon reflexes may
be apparent on examination.
2. Cardiovascular: These are related to coronary vasodilatation
and include tachycardia and predisposition to ventricular
arrhythmias. This is related more to associated hypoxemia than
to hypercapnia per se. Increased sensitivity to digitalis is also
observed in these cases.
3. Biochemical abnormalities: These include increased levels of
tissue carbon dioxide, phosphate and calcium, and increased
levels of chloride.
Homeostatic Response to Respiratory Acidosis

The immediate response to a rise in CO2 levels (and hence carbonic
acid) is that blood and tissue buffers take up H+ ions, carbonic acid
110 Oxygen Therapy
dissociates and HCO3– increases along with a rise of the acidic pH.
The steady state is reached in ten minutes and lasts for eight hours.
The PCO2 of cerebrospinal fluid changes rapidly to match PaCO2.
Hypercapnia that persists for more than a few hours induces an
increase in cerebrospinal fluid HCO3– that reaches maximum levels
by 24 hours and partly restores the cerebrospinal fluid pH. After 8
hours of the onset of respiratory acidosis, kidneys generate HCO3–
and a new steady state is reached in approximately 2-3 days. The
alveolar gas equation is represented as PAO2 = FiO2 × (PB – PH2 O ) –
PaCO2 /R, where PAO 2 is alveolar PO2, FiO2 is the fractional
concentration of inspired air, PB is the barometric pressure, PH 2 O is
the water vapor pressure and R is the respiratory quotient. It follows
that with all other variables remaining constant, PAO2 (and hence
the PAO2) is inversely proportional to the PaCO2. Thus a rise in
PaCO2 leads to an obligatory hypoxemia in patients who are
breathing room air. However this rise in PaCO2 is generally limited
to an approximate level of 80 to 90 mm Hg because higher PaCO2
levels are associated with PAO2 levels that are incompatible with
life. Thus, as mentioned earlier, correction of hypoxemia and not
hypercapnia or acidemia is the primary aim of treatment of
respiratory acidosis since the former is the main determinant of
survival.
Treatment of Respiratory Acidosis

The main aim is to ensure adequate oxygenation while taking care
to avoid inadequate oxygenation in an attempt to prevent
worsening of hypercapnia by suppression of hypoxemic respiratory
drive. Again one should make attempts to correct the underlying
disorder. Rapid decrease in chronically elevated PCO2 should be
avoided to prevent development of post hypercapnic metabolic
alkalosis that can lead to arrhythmias and seizures. An adequate
intake of chloride is usually helpful in this setting.
Alkali (bicarbonate) therapy is used rarely in acute condition
only if acidemia is directly inhibiting cardiac functions and never
in chronic respiratory acidosis. Another disadvantage of using
bicarbonate in respiratory acidosis is the fact that bicarbonate would
be converted to carbonic acid and hence CO2. The respiratory
system would have additional load of excreting more carbon
dioxide. In fact, there is likely to be a paradoxical acidosis as the
condition which has led to hypercapnia (or respiratory acidosis)

makes the respiratory system unable to excrete CO 2. Other
problems with alkali therapy include decreased alveolar ventilation
by a decrease in pH mediated ventilatory drive and volume
expansion.
METABOLIC ACID-BASE DISORDERS

Overview of Acid-Base Physiology
The acids in the body are in the form of either volatile or non-
volatile acids. The normal metabolism produces 15,000-20,000
mmol of CO2 per day. According to the Henderson-Hasselbach
equation, pH = pK + log base/acid or pH = 6.1 + log HCO3–/H2CO3
or pH = 6.1 + log HCO3–/ 0.03 [PCO2] implying that H+ = 24 ×
PCO2/HCO3–. From the equation one can see that free H+ will be
produced if CO2 is not eliminated. Around 50-100 mEq/day of
non-volatile acids are produced daily. The primary source is from
metabolism of sulfur containing amino acids (cystine, methionine)
and resultant formation of sulfuric acid. Other sources are non
metabolized organic acids, phosphoric acid and other acids. The
range of ECF [H + ] variation is very small as it exists in
concentrations of 36-44 nanomole per liter, and pH (intracellular
and extracellular fluid, including blood) is maintained in a narrow
range to preserve normal cell, tissue and organ function.
The intracellular pH is normally maintained at around 7.2. This
is to keep important metabolic intermediates in ionized state and
limit their tendency to move out of cells. Most intracellular enzymes
taking part in cellular metabolism have pH optimally close to this
value. DNA, RNA and protein synthesis is increased at a slightly
higher pH. This maintenance is done with the help of plasma
membrane H+/base transporters that are activated in response to
acidemia. The pH of extracellular fluid is normally maintained at
around 7.4 to keep pHi in optimal range as well as enable optimal
binding of hormones to receptors and optimal activity of enzymes
present in blood.
The regulation of arterial pH is achieved through various means:
1. Buffers: Presence of buffer systems minimizes the change in pH
resulting from production of acid and provide immediate
protection from acid load. Main buffer system in humans is
HCO3– + H+ ⇔ H2CO3 ⇔ H2O + CO2.
112 Oxygen Therapy
2. The respiratory system: Elimination of volatile acid (CO2) is

achieved with the help of the respiratory system. Respiratory
centers in the brain respond to changes in pH of CSF and blood
to affect ventilatory rate. Ventilation directly controls the
elimination of CO2.
3. The kidneys: They help to retain and regenerate HCO3– thereby
regenerating the body buffers with the net effect of eliminating
the non-volatile acid load. H+ secretion takes place either in
combination with ammonia or phosphate or as free urinary H+;
the latter giving only a minimal contribution. On the other hand
HCO3– reabsorption takes place primarily in the proximal tubule
(around 90%) but some amount also occurs in the distal tubule.
Factors affecting H+ secretion/reabsorption of HCO3– include
CO2 concentration, pH, aldosterone, potassium concentration,
ECF volume and chloride levels in the blood.
Anion Gap (AG)

This has traditionally been used to assess acid-base status especially
in the differential diagnosis of metabolic acidosis while ΔAG and
Δ HCO3– have been used to assess mixed acid-base disorders. AG
is based on the principle of electroneutrality:
Total Serum Cations = Total Serum Anions
Na+ + (K+ + Ca+ + Mg+) = HCO3– + Cl– + (PO4– + SO4– + Protein
+ Organic acids)
Na+ unmeasured cations (UC) = HCO3– + Cl– + unmeasured
cations (UA)
Na+ – (HCO3– + Cl–) = UA – UC
Na+ – (HCO3– + Cl–) = AG
The normal value of AG was previously taken as 12 ± 4
mEq/L. However with changes in the methods of measurement
of Na+, Cl– and HCO3– (flame photometry in the past, and use of
ion-specific electrodes at present), there has been a shift of Cl– value
to a higher range and the revised normal value of AG is now taken
as 8 ± 4 mEq/L.
Limiting Factors for Anion Gap

1. Laboratory variations: Variations in the normal reference range
of components of AG should be taken into consideration and
each institution should assign a normal range for AG based on

these values.
2. Inherent errors in calculation: Limits for each component is
normally valid for 95 percent of the population. The probability
of false positive determination for each variable (Na+/Cl–/
HCO3–) is thus 0.05. Hence the probability of false positive
determination for AG is 3 times 0.05 that is 0.15.
3. Hypoalbuminemia: Patients with low serum albumin can have
high AG acidosis but the measured AG may be normal because
albumin has many negative surface charges and accounts for a
significant proportion of AG. Severe hypoalbuminemia may
exhibit a normal value of AG as low as 4 mEq/L. Therefore in
severe hypoalbuminemia, if the measured AG is normal, one
must suspect an additional metabolic cause for increased AG.
As a rough guide, for every 1 gm/dL decrease in serum
albumin, the AG correspondingly decreases by 2 mEq/L.
4. Alkalosis: In alkalemic patients with pH > 7.5, AG may be
increased due to metabolic alkalosis per se and not because of
additional metabolic acidosis. The reasons proposed for the
same include:
a. surface charges on albumin become more negative in
alkalemic conditions (due to loss of protons) and this leads
to increased unmeasured anions.
b. associated volume contraction leads to hyperproteinemia,.
c. induction of glycolysis and resultant hyperlactatemia.
5. Hypercalcemia: There is a fall in AG as expected because of an
increase in UC except in paraneoplastic hypercalcemia where
for unknown reasons, the AG does not change significantly.
6. Drugs: Lithium and polymyxin cause a fall in AG by increasing
the UC while carbenicillin and other penicillin group of
antibiotics can cause an increase in AG since they act like UA.
7. Clearance of anions: Patients with expected increased AG
metabolic acidosis may have a measured normal AG because
of clearance of added anions, e.g. patients with diabetic
ketoacidosis in the early stages who have adequate clearance
of ketones may have a normal AG as also those in the recovery
phase.
8. ΔAG – Δ HCO3– relationship: This has been used to assess mixed
acid-base disorders in setting of high AG metabolic acidosis as
follows:
114 Oxygen Therapy
ΔAG/ΔHCO3– = 1 → Pure High AG Metabolic Acidosis

ΔAG/ΔHCO3– > 1 → Associated Metabolic Alkalosis
ΔAG/ΔHCO3– < 1 → Associated normal AG Metabolic Acidosis
This is based on the assumption that for each 1 mEq/L increase
in AG, HCO3– will fall by 1 mEq/L. However non-bicarbonate
buffers especially intracellular buffers also contribute to buffering
response on addition of H+. This becomes more pronounced as the
duration of acidosis increases. Hence Δ AG/ΔHCO3– may be more
than 1 even in the absence of metabolic alkalosis. Also, all added
anions may not stay in the extracellular component and those that
diffuse inside cells could lead to a lesser rise in AG than expected.
Hence ΔAG/ΔHCO3– may be less than 1 even in states expected to
have high AG metabolic acidosis. Hence strict use of AG to classify
metabolic acidosis and of the ΔAG/ΔHCO3– relationship to detect
mixed/occult metabolic acid-base disorders can be associated with
errors because of the possibility of change of AG by factors other
than metabolic acid-base disturbances. Use of sequential AG
determinations and observation of temporal profile of AG is more
important than any single value. Modifications and alternatives
that have been proposed for AG include:
1. AG/ΔHCO3– = 1-2 → Pure High AG Metabolic Acidosis
ΔAG/ΔHCO3– > 2 → Associated Metabolic Alkalosis
ΔAG/ΔHCO3– < 1→ Associated normal AG Metabolic Acidosis.
2. Use of Corrected AG.
Corrected AG = Calculated AG + 2 (Albumin in gm/dL) + 0.5
(PO4)3– in mg/dL.
Metabolic Acidosis
Metabolic acidosis results from either bicarbonate loss (renal/
gastrointestinal), decreased renal acid secretion or increased
production of non-volatile acids (ketoacids, lactic acid, poisons or
exogenous acids). Metabolic acidosis has traditionally been
classified as high anion gap or normal anion gap though as
mentioned earlier due to the inherent limitations of the anion gap,
this classification itself has been a subject of intense debate. The
causes of high AG metabolic acidosis includes ketoacidosis
(diabetic, alcoholic, starvation), lactic acidosis (Type A- Inadequate

oxygen delivery to cells; Type B-Inability of cells to utilize oxygen;
Type C-Abnormal bowel flora with production of D-lactic acid),
drugs and toxins (salicylates, methanol, ethylene glycol,
paraldehyde, toluene, isoniazid, iron), renal failure, rhabdomyo-
lysis. The causes of normal AG metabolic acidosis include
bicarbonate loss, diarrhea, pancreatic or biliary drainage, renal
tubular acidosis, ketoacidosis (during therapy), post-chronic
hypocapnia, renal failure, parenteral nutrition (HCl containing
aminoacid solutions), HCl therapy (during treatment of severe
metabolic alkalosis) and ureterosigmoidostomy.
Manifestations of Metabolic Acidosis

• Attenuation of cardiovascular responsiveness to catecholamines
and impaired cardiac contractility leads to a fall in cardiac
output, arterial blood pressure as well as hepatic and renal blood
flow. Arteriolar dilatation, venoconstriction and centralization
of blood volume also occur as does increased pulmonary
vascular resistance. Sensitization to re-entrant arrhythmias
leads to reduction in the threshold for occurrence of ventricular
tachycardia and ventricular fibrillation.
• Compensatory hyperventilation occurs and can ultimately lead
to occurrence of muscle fatigue and dyspnea if accompanied
by concomitant reduction in the strength of respiratory muscles.
• Cerebral symptoms result from inhibition of metabolism and
cell volume regulation and include mental status changes
(somnolence, obtundation and coma).
• Metabolic changes include increased metabolic demands,
insulin resistance, increased protein catabolism, reduction in
ATP synthesis and hyperkalemia (secondary to cellular shifts)
Evaluation
This includes clinical profile of the patient along with arterial blood
gas analysis and determinations of AG (serum and/or urinary)
and osmolal gap (plasma and/or urinary). The urinary AG is based
on the principle of electroneutrality, like the serum AG.
116 Oxygen Therapy
Total Urine Cations = Total Urine Anions

Na u + K u + ( NH 4u and other UCu) = Cl –u + UAu
( Na u + K u ) + UCu = Cl –u + UAu
( Na u + K u ) – Cl –u = UAu– UCu
( Na u + K u ) – Cl –u = AGu
Determination of the urinary AG helps to distinguish between
gastrointestinal and renal causes of bicarbonate loss. It estimates
urinary NH 4 which is elevated in GI losses but low in renal losses
(as in cases of distal RTA). Hence a negative UAG (average –20
mEq/L) is seen in the former condition while a positive value
(average + 23 mEq/L) is seen in the latter.
The plasma osmolal gap is given by the formula POsmCalc =
2[Na+] + [Glucose]/18 + [BUN]/2.8. Normally the measured
plasma osmolality is more than the calculated value by up to 10
mOsm/kg. However if the difference is more than 15-20 mOsm/
kg, it suggests the presence of abnormal (osmotically active)
substance (s) – usually an alcohol.
The urine osmolal gap is based on the same principle as the
plasma osmolal gap wherein the UOsmCalc = 2[( Na u ) + ( K u )] +
[Glucu]/18 + [UUN]/2.8. If the measured urinary osmolality is
more than the calculated value it signifies that excretion of NH4 is
occurring with a non chloride anion (e.g. hippurate). The urinary
NH4 concentration is usually around 50 percent of the osmolal
gap.
Treatment
1. When to treat? The effect of severe acidemia on cardiac function
is the most important factor that determines patient survival.
Metabolic acidosis is rarely lethal in the absence of cardiac
dysfunction. The contractile force of the left ventricle in fact,
increases as pH falls from 7.4 to 7.2. However, when pH falls
below 7.1, profound reduction in cardiac function occurs and
the LV contractile force falls by as much as 15-30 percent. Hence
most recommendations favor the use of base only when pH is
less than 7.1.
2. How to treat? Treatment of metabolic acidosis includes treat-

ment of the underlying cause. If the pH is less than 7.1,
bicarbonate therapy is given to raise the pH upto 7.2. The
quantity of HCO3– to be administered is calculated as follows:
0.5 × ideal body weight (kg) × HCO3– deficit (mEq/L).
The volume of distribution (Vd) of bicarbonate is around 50
pecent in normal adults. However, in severe metabolic acidosis
can increase up to 70-80 percent in view of intracellular shift of
H+ and buffering of H+ by bone and cellular buffers.
3. Why not to treat all patients? Bicarbonate administration was
considered the cornerstone of therapy of severe acidemia for
more than a century based on the assumption that it would
normalize intra as well as extracellular fluid pH and reverse
the deleterious effects of acidemia on organ function. However,
studies contradicted this and showed little or no benefit from
rapid and complete or over correction of acidemia with
bicarbonate. The adverse effects of bicarbonate therapy include:
• CO 2 production from HCO 3 – decomposition leading to
hypercarbia especially when the pulmonary ventilation is
impaired
• Myocardial hypercarbia can lead to myocardial acidosis and
this can lead to impaired myocardial contractility and decreased
cardiac output, systemic vascular resistance and coronary artery
perfusion pressure which can precipitate myocardial ischemia
especially in patients with underlying heart disease
• Hypernatremia as well as hyperosmolarity can result and this
can lead to volume expansion and a fluid overload state
especially in patients with congestive heart failure
• Intracellular (paradoxical) acidosis can occur especially in the
liver and CNS (because of increased CSF CO2 levels)
• Increased gut lactate production, reduced hepatic lactate
extraction and thus increased serum lactate can result
• Reduced ionized calcium and reduced oxygen consumption.
Correction of Acidemia with other Buffers

• Carbicarb: It has been used in the treatment of metabolic acidosis
after cardiac arrest and during surgery. However data on its
efficacy in humans is limited.
118 Oxygen Therapy
• Tris-hydroxy-methyl-aminomethane (THAM) –
THAM or trometamol is a biologically inert amino alcohol of
low toxicity. It has capacity to buffer CO2 and other acids in vivo as
well as in vitro. It has a pK at 37°C of 7.8 while bicarbonate has pK
of 6.1 making it a more effective buffer in physiological range of
blood pH. It can accept H+/CO2 and generate HCO3– and reduce
PaCO2.
R–NH2 + H2O + CO2 ⇔ R–NH3+ + HCO3–
R–NH2 + H+ + La– ⇔ R–NH3+ + La–
It is rapidly distributed in the extracellular fluid except RBCs
and liver cells and is excreted by the kidneys in the protonated
form (NH3+). It is effective as a buffer in closed or semi-closed
system (unlike bicarbonate which requires an open system to
eliminate CO2). It is effective in states of hypothermia. Side effects
include tissue irritation and venous thrombosis especially if it is
administered through a peripheral vein. This is seen more with
THAM base with a pH of 10.4. THAM acetate with a pH of 8.6 is
well tolerated and does not cause tissue or venous irritation. Large
doses can cause respiratory depression and hypoglycemia. The
initial loading dose of THAM acetate (0.3 ml/L sol) is calculated
as follows: Lean body weight (kg) × Base Deficit (mEq/L). The
maximum daily dose is around 15 mmol/kg. It is indicated for use
in severe acidemia (pH < 7.1) in the following clinical settings:
induced acute hypercapnia (apneic oxygenation during
bronchoscopy and organ collection from organ donors), ARDS with
permissive hypercapnia, acute severe asthma with severe
respiratory acidosis, diabetic ketoacidosis, renal failure, salicylate
intoxication, cardiopulmonary resuscitation (after restoration of
cardiac function). It is also recommended for use in the
perioperative period (cardioplegia during open heart surgery,
during liver transplantation, chemolysis of renal calculi, raised
intracranial tension due to cerebral trauma).
Metabolic Alkalosis
Metabolic alkalosis is a common acid-base disorder and its
frequency has been reported to be as high as 50 percent of all acid-
base disorders. Severe metabolic alkalosis is associated with
significant mortality – mortality rate of around 45 percent when
the arterial blood pH is more than 7.55 and around 80 percent when
it is more than 7.65.
In most cases, the temporal profile in the development of
metabolic alkalosis is characterized by the presence of initiating
and maintenance phases. Factors that lead to initiation of the
process of metabolic alkalosis include either gain of bicarbonate or
loss of hydrogen ions. The latter can occur either from the
gastrointestinal tract due to diarrhea or loss of gastric acid (Ryle’s
tube aspiration or vomiting) or from the kidneys, common causes
being use of diuretics (thiazide) or mineralocorticoid excess.
Bicarbonate gain on the other hand may result from excess intake
of alkali as in milk-alkali syndrome or during overzealous attempts
at correction of metabolic/respiratory acidosis with bicarbonate.
Some cases of metabolic alkalosis are caused by volume contraction
or hydrogen ion shifts. The latter may be seen in hypokalemia and
refeeding.
A maintenance phase is also usually present in most cases of
metabolic alkalosis because the kidneys generally excrete alkaline
loads quickly and easily and significant metabolic alkalosis can
only occur in the setting of impaired bicarbonate excretion. The
latter can occur in the setting of volume depletion leading to a
reduced GFR as well as cases of mineralocorticoid excess that leads
to increased reabsorption of bicarbonate.
Classification
Metabolic alkalosis has traditionally been classified by the response
to volume/saline replacement therapy as either saline responsive
or saline unresponsive.
1. Saline responsive (volume/chloride depletion): gastric losses
(vomiting, removal of gastric secretions through nasogastric
tube), diuretics, diarrheal states, post-chronic hypercapnia.
2. Saline unresponsive (volume replete): primary aldosteronism
(adrenal adenoma, adrenal hyperplasia, adrenal carcinoma,
idiopathic), secondary aldosteronism (adrenal corticosteroid
excess, severe hypertension), tumors (e.g. renal cell carcinoma),
apparent mineralocorticoid excess (enzyme deficiencies–11β
and 17α hydroxylase), drugs (licorice, carbenoxolone), Liddle’s
120 Oxygen Therapy
syndrome, Bartter and Gitelman syndromes and their variants,

bicarbonate administration (overzealous attempt at correcting
metabolic/respiratory acidosis).
3. Miscellaneous: penicillin and related drugs (carbenicillin,
ampicillin etc), hypercalcemic states (malignancy related
hypercalcemia, milk-alkali syndrome).
Clinical Manifestations
Symptoms of metabolic alkalosis per se are difficult to distinguish
from those of chloride, potassium or volume depletion. In fact the
latter are usually more apparent than those directly attributable to
alkalosis.
• Cardiovascular manifestations result from arteriolar constric-
tion and resultant reduction in coronary blood flow and include
reduction in anginal threshold and predisposition to refractory
supraventricular and ventricular arrhythmias (especially if pH
is more than 7.6).
• Reduction in cerebral blood flow leads to mental status changes
(stupor, lethargy and delirium) and neuromuscular irritability
(related to low ionized plasma calcium) manifested as tetany,
hyperreflexia or even seizures.
• Compensatory hypoventilation may be seen leading occa-
sionally to hypercapnia and hypoxemia.
• Stimulation of anerobic glycolysis and organic acid production,
reduction in plasma ionized calcium concentrations, hypo-
kalemia (secondary to cellular shifts), hypomagnesemia and
hypophosphatemia may be seen.
Clinical Evaluation
In addition to clinical profile and ABG analysis, urinary chloride
and potassium measurements before therapy are useful
diagnostically. A low urinary chloride (<10 mEq/L) is seen in
alkalotic states where chloride depletion predominates (except
when the cause is use of chloruretic diuretic). It tends to remain
low until chloride repletion is nearly complete. Urinary potassium
concentration of >30 mEq/L with a low serum potassium level
suggests renal potassium wasting due to either intrinsic renal
defect, diuretic use or high levels of circulating aldosterone. A
urinary potassium concentration of <20 mEq/L with a low serum
potassium level suggests extra-renal potassium loss.
Management
Correction of severe alkalosis should be attempted when the arterial
blood pH exceeds 7.55. The immediate goal of therapy is modera-
tion and not full correction of alkalemia (reducing plasma
bicarbonate levels and pH to less than 40 mEq/L and 7.55
respectively). Most cases of severe metabolic alkalosis have volume
depletion and respond to administration of saline. Treatment of
the underlying cause responsible for volume and/or chloride
depletion is equally important. While replacing chloride deficit,
selection of accompanying cation (Na+ /K+/H +) depends on
assessment of ECF volume status, presence and degree of associated
K+ depletion, presence, degree and reversibility of reduction of
glomerular filtration rate. Patients with volume depletion usually
require replacement of both NaCl as well as KCl.
Depletion of both chloride and extracellular fluid volume
This is the most common scenario, and administration of isotonic
NaCl (150 mEq/L) in these cases causes simultaneous correction
of both chloride and ECF volume deficits. The quantity of isotonic
saline required to correct volume deficits as well as metabolic
alkalosis may be as high as 3-5 L in patients who have obvious
manifestations of volume contraction. After ECF volume has
returned to normal or near normal, isolated chloride deficit can be
replaced by calculating the total body chloride deficit as follows:
0.2 × BW (kg) × Desired [Cl–] – Measured [Cl–] (mEq/L). One should
also replace continuing losses of fluid and electrolytes. Correction
of Na+, K+ and Cl– deficits and associated prerenal azotemia
promotes HCO3– excretion and alkaline diuresis with a return in
plasma HCO3– towards normal.
Depletion of chloride with increased extracellular fluid volume
Administration of normal saline in these cases is not recommended
for obvious reasons. Chloride deficit should therefore be corrected
by use of KCl unless hyperkalemia is present or there is concomitant
fall in GFR and hence hampered ability to excrete K+ load.
Administration of acetazolamide accelerates bicarbonaturia
especially if natriuresis with a high sodium excretion rate is
required simultaneously or if high serum potassium is present.
Monitoring is needed to detect associated kaliuresis and
phosphaturia. GFR must be adequate and this therapy is
contraindicated if serum creatinine is more than 4 mg/dL.
122 Oxygen Therapy
Depletion of chloride with increased ECF volume and hyperkalemia

Neither Na+ nor K+ can be used as the accompanying cation while
replacing Cl– in these cases. However, severe metabolic alkalosis
that requires immediate treatment can be given Hydrochloric Acid
(HCl). The amount of HCl (given as 0.1 or 0.2 M sol) that is needed
to correct alkalosis estimated as: 0.5 × BW (kg) × Desired [Cl–]–
Measured [Cl–] (mEq/L). Continuing losses must also be replaced.
Use of 50 percent of body weight as Vd is done with an aim of
correcting alkalosis in both ICF and ECF and restoring buffers at
both sites. Half correction is given since immediate goal of therapy
is correction of severe alkalemia and not complete normalization
of serum pH. Hydrochloric acid has sclerosing properties and must
be administered through a central venous catheter (placement
confirmed radiologically to prevent leakage of HCl and sloughing
of perivascular tissue). Infusion rates are normally less than 0.2
mmol/kg BW/hr with a maximum rate of 25 mEq/hour.
Hydrochloric acid can also be infused after adding it to amino acid
solutions, fat emulsion or dextrose solutions containing electrolytes
and vitamins without causing adverse chemical reactions. In such
cases administration can be done through a peripheral vein.
However frequent measurement of ABG and electrolytes is
required. Ammonium chloride can also be used and can be given
into a peripheral vein but the rate of infusion should not exceed
300 mEq/24 hr. It is contraindicated in the presence of renal or
hepatic insufficiency where worsening of azotemia and
precipitation of acute ammonia intoxication leading to coma
respectively, can occur with its use.
In the presence of renal failure or severe fluid overload state in
CHF, dialysis with or without ultrafiltration may be required to
exchange bicarbonate for chloride and correct metabolic alkalosis.
Usual dialysates for both hemodialysis/peritoneal dialysis contain
high concentrations of bicarbonate or its metabolic precursors and
hence their concentrations must be reduced. In patients with
unstable hemodynamics, continuous renal replacement therapy
using NaCl as replacement solution can be done.
Proton pump inhibitors can be administered to reduce gastric
acid production in cases of chloride depletion metabolic alkalosis
resulting from loss of gastric H+/Cl– (e.g. pernicious vomiting,
requirement for continual removal of gastric secretions, gastrocys-
toplasty, etc). In such cases, metabolic alkalosis is likely to persist
and replacement of pre-existing deficits is hampered by ongoing

losses.
Treatment of volume replete/saline unresponsive metabolic alkalosis
In cases of mineralo–corticoid excess, elimination of the source is
essential to achieve permanent correction of metabolic alkalosis.
In cases where removal of the source is not possible, treatment
should be aimed at blocking the action of aldosterone (or any other
mineralocorticoid that is in excess) till definitive treatment is
attempted. Potassium sparing diuretics, especially spironolactone,
are useful since they help to reverse the adverse effects of
mineralocorticoid excess on sodium, potassium and bicarbonate
homeostasis. Restriction of sodium and addition of potassium to
diet are also helpful both in treatment of metabolic alkalosis as
well as control of hypertension. Treatment of milk-alkali syndrome
involves cessation of alkali ingestion as well as of calcium.
Treatment of the underlying cause is required in cases of metabolic
alkalosis due to malignancy related hypercalcemia. Chloride and
volume repletion may also be required in cases where multiple
mechanisms for alkalosis (including vomiting and reduced GFR
due to volume depletion) are present.
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7
Blood Gas Monitoring
Chandana Reddy, R Agarwal
INTRODUCTION
Monitoring of arterial blood gases is fundamental to respiratory
critical care and oxygen therapy. It is important to recognize gas
abnormalities before the appearance of clinical symptoms or signs.
A patient may look pink and appear to be oxygenated well but,
may have a low PaO 2 values on blood gas measurements.
Therapeutic interventions are required after careful monitoring of
blood gases. Blood sample is obtained from the radial artery for
this purpose. Venous sample though easy and safer to obtain, is
not helpful for blood gas monitoring. Blood sample from any artery
represents the sample from the left ventricle. On the other hand
venous sample is affected by the metabolism, blood flow and many
other factors of different tissues. However central venous samples
have been shown to correlate well with arterial samples with
respect to pH, PCO2 and base excess in mechanically ventilated
trauma patients to reach clinically reliable conclusions. But central
venous sample cannot substitute arterial samples for resuscitation
and management. This chapter will review the technical aspects
of both invasive (arterial blood gas analysis) and non-invasive
(pulse oximetry and capnography) blood gas monitoring.
INVASIVE TECHNIQUE
Arterial Sampling
Radial artery is the most commonly used site to obtain a sample
for arterial blood gas analysis. This is because the radial artery is
Blood Gas Monitoring 127
superficial and easily accessible. Moreover, there is a good collateral

vascular network minimizing the risk of vascular interruption in
case of complications such as vascular spasm, intraluminal clotting
or periarterial hematoma formation which can compromise the
blood supply. Radial artery can also be fixed against the radius
bone for obtaining sample, and compressed in case of continued
ooze. If none of the radial arteries are available for sampling, other
sites such as dorsalis pedis, femoral and brachial arteries should
be tried.
It is important to ensure adequate collateral circulation before
performing an arterial puncture. In case of the upper extremity,
this can be done with the help of a simple and reliable test, the
Allen’s maneuver. In this, the hand is clenched to form a fist;
pressure is applied to obstruct the radial and ulnar arteries at the
wrist. The hand is then relaxed (but not fully extended) when the
palm and finger are seen to blanch. Thereafter, the pressure from
ulnar artery is removed. The thumb and index finger get flushed
within 15 seconds, followed by flushing of the entire hand. This is
a positive Allen’s test indicating adequacy of collateral circulation
i.e. ulnar artery alone is capable of supplying the hand. If the test
is negative, it implies the inability of ulnar artery to supply the
entire hand. In this situation, the radial artery should not be used
for arterial puncture.
In an uncooperative or unconscious patient who cannot clench
the first, the test is done in a similar fashion by obstructing both
the arteries, raising the patient’s hand above the level of the heart
until balancing occurs. The hand is then lowered below the level
of the heart and pressure removed from the ulnar artery.
Technique for Arterial Puncture

The process is explained to the patient, both radial and ulnar arteries
palpated and Allen’s test applied.
1. A 20 or 21 gauge needle and a glass syringe is taken and 0.2 mL
(just enough to smear the inner aspect of the syringe) of 1000U/
mL heparin is drawn into the syringe. Errors in PaO2 of up to
6 percent in two minutes and 16 percent in 30 to 60 minutes
due to exhange of O2 from plastic syringes have been reported.
Hence, glass syringes are generally preferred to plastic syringes
unless analysis is done immediately.
128 Oxygen Therapy
2. The wrist is stabilized in the position in which maximum

pulsations are felt.
3. The skin is sterilized at the puncture site and a small skin wheal
is raised with a local anesthetic.
4. The radial artery is then punctured keeping the needle at a
minimum angle of about 30-40 degrees to the artery; slowly
advance the needle in one plane. Once the artery is punctured,
the blood will enter the syringe.
5. If the needle has completely gone through the artery, its tip is
slowly withdrawn until it is once again in the lumen as indicated
by the free flowing blood through the needle.
6. After the required amount (2-4 mL) of blood has filled the
syringe, the needle is withdrawn and firm pressure is applied
at the puncture site for a minimum of two minutes. The pulse
distal to the pressure site is palpated to ensure arterial patency.
7. The syringe is then held vertically and air bubbles removed.
The needle is then replaced by a syringe cap, the syringe rolled
between palms of hand and immersed in a bag of ice and sent
to the laboratory.
Arterial Cannulation
Most patients requiring critical care need repeated arterial
punctures, and many intensivists prefer indwelling arterial
catheters/cannulae to repeated punctures. With the availability of
an arterial cannula, samples can be immediately and as repeatedly
drawn as required. It is also useful in patients whose cardiopul-
monary status is unstable. The pre-analytical errors related to
improper sampling, handling and storage are minimal with
samples obtained from arterial cannulae. In addition, the arterial
cannulae can be used for systemic blood pressure monitoring and
to obtain blood samples for other numerous clinical estimations
such as electrolytes, urea, creatinine, etc.
However, arterial cannulation is not without risks. There is an
increased incidence of diminished or absent blood flow through
the cannulated artery. This is often reversible, although necrosis
and loss of tissue have been reported in some cases. Local infection
and systemic sepsis can also occur. But the incidence is believed to
be no more than that with venous cannulation. Another method
to obtain arterial blood especially in infants and young children is
the arterialized earlobe capillary blood sample (ELCS) which shows

strong agreement with arterial blood pH and PaCO2. Simultaneous
measurements of oxygen saturation through pulse oxymetry may
also improve the accuracy of ELCS for PaO2 assessment.
Measurement Techniques
Measurement of blood pH, PaO2 or PaCO2 is done with the help of
an electrode. It consists of an anode and a cathode immersed in an
electrolyte solution. The flow of electrons (electric current) occurs
from one point to another in response to a potential difference
between the two points. The difference called voltage is measured
with a voltmeter. The voltage can be varied predictably with the
help of an electric device called potentiometer. A brief account of
the different electrodes used for blood gas analysis is described
below. Both pH and CO2 electrodes employ a measuring chemical
half-cell of silver-silver chloride solution (to measure small potential
differences accompanying pH changes) and a reference half-cell
to supply a constant reference voltage.
Oxygen Analysis
There are several techniques to analyze oxygen in the dissolved
form which include manometric and volumetric measurements,
chemiluminescence method, gas chromatography, physical
methods using paramagnetic properties of oxygen and electro-
chemical techniques. It is the membrane covered oxygen electrode
employing the principle of polarography which is most useful and
employed in clinical laboratories.
Polarographic electrode for O2 (Clark electrode) utilizes the
principle of chemical reduction of oxygen, i.e. oxygen is dissolved
in an aqueous medium and exposed to a polarizing voltage at a
cathode wherein the following reaction takes place- O2 + H2O + 4
electrons (e’) → 4 OH–. The electrode consists of a silver anode and
a platinum cathode. The silver anode is immersed in a potassium
chloride solution. The chloride ion will react with silver anode to
form silver chloride producing a constant flow of electrons. The
adjacent platinum cathode reacts chemically with oxygen to form
hydroxyl (OH–) ions. This reduction reaction uses the electrons.
The amount of oxygen reduced is strictly proportional to the
number of electrons used in the cathode reaction. The change in
130 Oxygen Therapy
electron flow (i.e. current) between the anode and the cathode is
measure of the amount of oxygen.
The electrode system is covered by a polypropylene membrane
which allows a slow diffusion of oxygen from the blood from into
the electrode. The membrane is a slow diffusion membrane to
prevent oxygen depletion during the measurement. The ease with
which oxygen molecules can pass through the membrane depends
upon its permeability coefficient expressed in terms of the number
of moles of the gas passing through a specific area and thickness at
a given temperature and pressure difference across the membrane.
A galvanic electrode has also been used for oxygen analysis. It
is based on a principle similar to the Clark electrode. The voltage
for cathode reduction is produced internally by the galvanic cell.
The cathode is usually composed of gold, the anode of lead and
the electrolyte solution is potassium hydroxide.
Some of the technical difficulties in using the polarographic
method of gas analysis include the alteration in the electrolyte layer
thickness, changes in electrolyte concentration causing dryness,
deposition of silver on the platinum cathode, artifacts due to the
presence of gas bubbles in solution and changes in the sensitivity
of the membrane. The response time, i.e. the time required in
sensitivity of the membrane or the time required for the output to
change following a change in the partial pressure of oxygen, of the
electrode depends upon the membrane thickness and the
permeability coefficient. The average 97.5 percent response time
for a 1 mL teflon membrane covered electrodes is 10 seconds while
for 1 mL polypropylene it is close to 40 seconds.
Calibration of the electrode is done with an oxygen
concentration of 0 percent and either of 12 percent or 20 percent.
The calibration of gases for PO2 and PCO2 are generally combined
for purposes of conveniences and economy.
PCO2 Electrode
PCO2 is measured with the help of Severinghaus electrode. It
utilizes the principle of Henry’s law, i.e. the amount of the gas
(CO2) diffusing across a semipermeable membrane is directly
proportional to the pressure gradient, i.e. PCO2 in contact with the
membrane. The PCO 2 electrode consists of a silicon elastic
membrane containing a measuring half-cell (silver-silver chloride)
and a similar reference half-cell. It is calibrated each time with a
gas mixture containing 5 percent and 10 percent CO2 concen-

trations. As stated earlier, gas mixture of 5 percent CO2 plus
12 percent or 20 percent O2 (remainder nitrogen) and 10 percent
CO2 plus 90 percent N2 can be used to calibrate both O2 and CO2
electrodes.
pH Electrode
The modern pH electrode is an ultra-micro Sanz electrode
consisting of a pH sensitive glass rolled into a fine capillary tube
which draws in a very small quantity of blood to be tested. It
maintains anaerobic and thermostatic conditions essential for pH
measurement. It is important to know the pH of the buffer solution
in the measuring half-cell for purposes of calibration. When the
measuring half-cell contains the buffer solution with pH of 7.384
the difference between the two half cells is 0.554 pH units and a
33.5 mv potential difference is predicted. Thus the voltmeter
measures 33.5 mv and a slope potentiometer sets the display at
7.384. Two point calibrations are generally sufficient.
NON-INVASIVE BLOOD GAS MONITORING

Blood gas analysis requires repeated arterial punctures or
cannulation. Several non-invasive methods have emerged in the
last quarter of a century as fairly reliable alternatives to arterial
sampling.
Oximetry
Oximetry involves the assessment of arterial oxygen saturation.
The concept of pulse oximetry is based on 3 principles (Fig. 7.1).
1. Spectrophotometry: Every substance has a unique absorbance
spectrum, and the different types of hemoglobin have different
absorption spectra. The currently available pulse oximeters
consist of a probe containing two small, high intensity
monochromatic light emitting diodes (LEDs) that are activated
alternatively, and emit light at 660 nm (red) and 940 nm
(infrared) wavelengths. These two wavelengths are used
because oxyhemoglobin and hemoglobin have different
absorption spectra-oxyhemoglobin absorbs less light than
deoxyhemoglobin in the ultraviolet region, while the reverse
occurs in the infrared region.
132 Oxygen Therapy
Fig. 7.1: Oximetry-light of known wavelength is passed through the finger tip and
measured by the photodetector after absorption by the vascular bed and other
tissues (or the finger tip)
2. Lambert-Beer law: The absorption of light as it passes through

a solution is proportional to the concentration of those molecules
within the solution which have the vibrational frequencies on
sympathy with the wavelength of the light.
3. Optical plethysmography: The presence of a pulsatile signal
generated by the arterial blood that is relatively independent
of the non pulsatile venous and capillary blood and other
tissues. Two components of light absorption are associated with
pulsatile blood flow-a constant component due to absorption
by skin, subcutaneous tissue, venous blood and a pulsatile
component due to absorption by the pulsating arterial blood.
Comparing the peak and the trough absorbencies, the
contribution from non arterial sources becomes irrelevant.
Using changes in absorption during each pulsation the pulse
oximeter eliminates the constant component.
Co-oximeter, on the other hand, operates using four different
wavelengths, and can measure total hemoglobin, oxyhemoglobin,
carboxyhemoglobin, and methemoglobin, and expresses each as a
percentage of the total hemoglobin in a given sample of blood.
The value reported by a Co-oximeter is commonly termed fractional
saturation and is equal to the amount of oxyhemoglobin expressed
as a fraction of the amount of total hemoglobin, i.e. the total of all
the active and inactive forms of hemoglobin with respect to
the oxygen-binding capability (oxyhemoglobin × 100)/(total
hemoglobin + oxyhemoglobin + carboxyhemoglobin + methemo-
globin).
Pulse oximeters use only two wavelengths, and therefore,
cannot distinguish between the relative concentrations of each type
of hemoglobin derivative present in the blood. A pulse oximeter
thus measures the functional saturation, i.e. the relative concentration

of oxyhemoglobin expressed as a fraction of the total amount of
hemoglobin able to bind oxygen, namely, the ratio of the
concentration of oxyhemoglobin and the concentrations of
oxyhemoglobin and deoxyhemoglobin. The ratio of absorbencies
at these two wavelengths is calibrated empirically against direct
measurements of arterial blood oxygen saturation (SaO 2) in
volunteers, and the resulting calibration algorithm is stored in a
digital microprocessor within the pulse oximeter to give the
estimated patients’ oxygen saturation (SpO2). At 85 percent SaO2,
the amount of light absorbed by hemoglobin and oxyhemoglobin
is about the same. Hence the normalized amplitudes of the red
and infrared signals are equal (i.e. R/LR = 1.0).
In healthy volunteers, oximeters commonly have a mean
difference (bias) of less than 2 percent and a standard deviation
(precision) of > 3 percent when SaO2 is 90 percent or above.
Comparable results have also been obtained in critically ill patients
with good arterial perfusion. Accuracy of pulse oximeters
deteriorates when SaO 2 falls to 80 percent or less. Most
manufacturers report accuracy to within ± 2 percent for SpO2
70 percent to 100 percent, and ± 3 percent for SpO2 50 percent to
70 percent, with no reported accuracy below 50 percent saturation.
There can also be a delay between a change in SpO2 and the display
of that change, and this depends on the signal averaging time,
circulation time, and the site of the oximeter probe. In general, finger
probes are slower (24-35 sec) than earlobe probes (10-20 sec).
Limitations
Pulse oximeters have several limitations, which need to be
considered while interpreting SpO2.
1. They estimate the arterial oxygen saturation (SaO2) and not the
arterial oxygen tension (PaO2). Pulse oximeters measure SaO2
that is physiologically related to arterial oxygen tension PaO2
according to the oxygen hemoglobin dissociation curve. It is
known that because of the sigmoid shape of the oxygen
dissociation curve, large changes in PaO2 may occur in the upper
and lower horizontal portions of the curve with minimal
changes in the SaO2. The oxygen-hemoglobin dissociation curve
is flattened at saturation values <90-95 percent and errors of
134 Oxygen Therapy
only a few percent in SaO2 measurements could easily represent

a large and significant error in the oxygen tension values.
Therefore, pulse oximeters are not accurate enough to safeguard
against hyperoxia in neonates at risk of retrolental fibroplasia.
Factors that affect the oxygen hemoglobin dissociation curve
such as pH, temperature, PaCO2 affect the relationship between
oxygen saturation and PaO2. Pulse oximeters also give us no
information regarding the acid-base or the ventilatory status
of the patient and hence should not be used as an alternative to
blood gas monitoring.
2. Low perfusion states such as hypotension, vasoconstriction,
hypothermia or cardiopulmonary bypass and cardiac arrest,
produce a signal that is too small to be processed and may make
it difficult for the sensor to distinguish a true signal from
background noise. Increased venous pulsations as seen in right
heart failure can lead to artificially lower SpO2 readings.
3. The presence of abnormal hemoglobins can lead to erroneous
pulse oximetry measurements. At 940 nm, carboxyhemoglobin
has minimal light absorption, while at 660 nm its absorption
coefficient is similar to oxyhemoglobin thus in the presence of
elevated carboxyhemoglobin levels, oximetry overestimates the
SpO2. Methemoglobin contributes to light absorption at both
660 nm and 940 nm. As the concentration of methemoglobin
increases, red and infrared light absorptions increase driving
the ratio towards unity which correlates with a saturation of 85
percent. The difference in the optical absorbance of adult and
fetal hemoglobins is too small (<3%) to affect the clinical
accuracy of pulse oximetry measurements.
4. Nail polishes, specifically blue, green or black colors have light
absorbance near 660 nm and affect the measured SpO2 leading
to falsely low readings. Most studies indicate that the
concentration of hemoglobin does not affect the pulse oximeter
reading until the hematocrit reaches values less than 10 percent.
Polycythemia, on the other hand does not affect SpO2. A number
of dyes and pigments can interfere with the accuracy of pulse
oximetry. Hyperbilirubinemia has not been shown to affect
SpO2 and in one study, bilirubin levels up to 30.6 mg/dL did
not affect the accuracy of pulse oximeter.
5. The readings of pulse oximeters may be affected by high

frequency radio interference from electrocautery units and high-
intensity light sources such as infrared, xenon and fluorescent
lamps. Motion artifact continues to be a significant source of
error and false alarms.
Clinical Applications
Pulse oximetry is a non-invasive, relatively inexpensive way to
measure and continuously monitor oxygen saturation (Fig. 7.2).
Pulse oximetry is widely used during anesthesia, surgery, critical
care, hypoxemia screening, exercise, and transport from the
operating room to the recovery room and in the emergency room.
The availability of small, lightweight optical sensors makes SpO2
monitoring especially applicable for preterm neonates, pediatric
and ambulatory patients. Easy application, fast response time of
pulse oximeter helps in monitoring patients during procedures like
bronchoscopy, endoscopy, cardiac catheterization, exercise testing,
and sleep studies. They are commonly used during labor and
delivery for both the mother and infant. In critically ill patients
non-invasive monitoring can decrease the distress caused by
Fig. 7.2: A common pulse oximeter used to continuously monitor SaO2

136 Oxygen Therapy
repeated arterial punctures, and assist in titrating the FiO2 and

ventilatory settings. Continuous monitoring also provides
information on trends in the patient’s condition, to assist the
clinician in assessing the response to therapeutic procedures.
Hypoxemia is detected more frequently and early during anesthesia
and in the recovery rooms with the use of pulse oximetry.
Bronchospasm, atelectasis, and bradycardia can be detected more
frequently in the group monitored by pulse oximeters. It is also a
valuable tool in palliative and supportive care for patients with
end stage diseases to determine the need to prescribe or to withhold
oxygen therapy.
Generally, the accuracy of most non-invasive pulse oximeters
is acceptable for a wide range of clinical applications. Pulse
oximetry has replaced transcutaneous oxygen tension monitoring
in neonatal intensive care. Intrapartum fetal oxymetry is also shown
to compare well with fetal scalp blood gas assessment in neonatal
management.
Recognizing the above-mentioned limitations and applying
appropriate corrective interventions are essential to optimize the
clinical use of pulse oximeters. To overcome some of the limitations
of pulse oximetry from finger, ear or toe where the pulsatile flow
is more easily compromised, esophagus has emerged as another
alternative site for continuous monitoring in cases of poor
peripheral circulation.
Transcutaneous Oxygen Measurement

Partial pressure of oxygen in blood perfusing the skin (PtcO2) has
been used as an estimate of arterial PO2. This can be done using a
modified Clarke electrode which uses a platinum cathode and a
silver anode in a potassium chloride solution. Oxygen diffuses from
the skin across the membrane to the electrode and reacts with the
electrons provided by the anode. The resulting current generated
is proportional to the PaO2. Gas exchange at the skin surface is
dependent on the cutaneous blood flow and metabolism.
Application of local heat (40-45°C) increases the local blood flow
and decreases the influence of cutaneous blood flow on PtcO2
measurement. Actual PaO2 rather than SpO2 is measured and hence
can be used to monitor hyperoxemia and prevent its complications
especially in neonates. Values are not affected by abnormal
hemoglobins. PtcO2 can be used to assess shunt in a patient on
supplemental oxygen, detect onset of hemodynamic instability and

limb ischemia. Oxygen reaches the surface after traversing the
epidermis. Skin also consumes oxygen, so there is always a gradient
between PtcO2 and PaO2. Response of PtcO2 electrode to a rapidly
changing PaO2 is slow. These problems are minimized in neonates
and infants in view of the thin skin with lower metabolism. Local
heating may lead to thermal injury to the skin and the site of the
electrodes may need to be changed frequently. Accuracy is affected
by low perfusion states, hemoglobin concentration, capillary
density and hydration of the epidermis. It has a potential role in
monitoring in neonates and infants in critical care, but in adults
the use of PtcO2 measurement is limited. Unpredictable correlation
of PtcO2 with PaO2, slow response characteristics and the need for
3 to 4 hourly site changes limit its use for monitoring during
anesthesia, exercise and sleep studies.
Transcutaneous PCO2 Measurement

Transcutaneous CO2 (PtcO2) measurement reflects PaCO2 in the
arterial blood in a similar fashion as the PtcO2 which reflects PaO2.
The electrode senses the PCO2 by monitoring changes in either the
pH of bicarbonate containing electrolyte solution or the infrared
absorption from a sample chamber. In view of a much higher
solubility of CO2 in the tissues, PtcO2 estimation is less dependent
upon cutaneous perfusion than PtcO2. Therefore heating the skin
to 40°C suffices. The electrode can be left in place for up to 48 hours
without the risk of thermal injury. Heating causes a temperature
dependent rise in the PCO2 and an overestimation of PaCO2.
Transcutaneous PCO2 measurement has been also employed
for apnea test. In brain dead patients, a PtcO2 of 60 mm Hg
accurately predicts a PaCO2 of 60 mm Hg allowing a reduction in
the duration of apnea test. Combined O2-CO2 electrodes are also
available. Since the OH– ions produced by O2 reduction accumulate
in these electrodes, there is a problem of change in the pH of the
electrolyte solution for PCO2 sensing. Some of the electrodes are
designed to consume the accumulated OH– ions preventing the
pH shift.
Capnography
Continuous waveform display of the changes in the concentration
of carbon dioxide throughout the ventilatory cycle is called
138 Oxygen Therapy
capnography. Capnography was developed in 1943 and introduced

to clinical practice in the early 1950s. Commonly, capnography
uses the principle of infrared light absorption (infrared spectro-
metry) or mass spectrometry. The first method depends on the
concept that CO2 strongly absorbs infrared light at a wavelength
of 4280 nm. This infrared radiation passes through the sample
chamber where it is absorbed by CO 2 and the remaining
unabsorbed radiation is focused onto a detector with a
semiconductor that creates an electrical signal. The concentration
of CO2 is directly proportional to the amount of infrared light
absorbed; and the higher the CO2 concentration in the gas mixture
the more infrared radiation is absorbed and less arrives at the
detector. This method allows for real time, continuous
measurement, and display of PCO 2 with a delay time of
approximately 0.25 second.
The end-tidal (PetCO2) CO2 monitors can be categorized as
mainstream or sidestream variety depending upon the gas
sampling technique. Mainstream analyzers are placed in the airway
circuit usually between the end of the endotracheal tube and the Y
connection. They provide continuous monitoring and the response
is rapid. They are heavy, may cause kinking or dislodgement of
the endotracheal tube and increase the dead space. The sensors
can be disrupted by humidity and secretions and heating is
required to prevent condensation. The second method is the
sidestream analyzer, in which the gas sample is aspirated from
the breathing circuit through a small bore tube to a remote analyzer.
Time delay, loss of expired tidal volume and clogging by
pulmonary secretions are the main disadvantages. It may also be
contaminated by ambient air.
The capnogram during expiration is normally divided into 3
phases (Fig. 7.3). The first phase (a) represents the gas from the
anatomical dead space (trachea) that is free of CO2. In the second
phase (b) the curve rises sharply as the alveolar gas that contains
CO2 mixes with the dead space. This represents emptying of rapidly
emptying alveolar spaces. As expiration continues (c) more and
more of the alveoli empty and CO2 concentration rises rapidly until
a plateau (d) that essentially represents alveolar gas, is reached
(phase 3). When inspiration starts the CO2 level drops sharply and
there is a rapid down-stroke of the curve to zero (e). The highest
CO2 tension measured during the plateau phase (i.e. the point at
Fig. 7.3: A normal capnogram (see text for details)
which the plateau ends just before inspiration) is referred to as the

end tidal CO2 concentration (PetCO2).
PetCO2 is commonly used to estimate PaCO2 quantitatively;
however the PetCO 2 is less than the PaCO 2, and in normal
individuals P (a-et) CO2 gradient ranges between 2 and 5 mm Hg.
This is because of the normal physiological dead space. The PetCO2
can be affected by changes in alveolar ventilation, CO2 production
(metabolism) and transport (perfusion). Capnography is helpful
in ensuring adequacy of pulmonary ventilation, assessing changes
in pulmonary blood flow and physiological dead space, and
detecting the addition of CO2 to the systemic circulation. PetCO2
can increase in conditions with increased production of CO2 (fever,
sepsis), decreased ventilation or equipment malfunction. Decrease
in PetCO2 with increase in the gradient can occur secondary to
increased dead space (as during hypotension, pulmonary emboli,
and cardiac shunts), incomplete alveolar emptying, decreased CO2
production or equipment malfunction.
PetCO2 can be used for continuous non-invasive monitoring of
PaCO2 as long as the capnogram waveform remains unchanged,
the temperature remains constant and the ventilatory and
cardiovascular functions are stable. A normal capnogram with a
large difference between PetCO2 and PaCO2 indicates substantial
physiologic dead space.
Capnography has been shown to be useful during intubation
to ensure tracheal rather than esophageal intubation. CO2 is
primarily eliminated from the lung and the concentration of CO2
140 Oxygen Therapy
in the stomach is negligible, so with tracheal intubation the PetCO2

is high (20-45 mm Hg) and remains so, whereas with esophageal
intubation the PetCO2 is usually zero and the waveform disappears.
Capnography is also helpful in recognizing disconnection from
ventilation system, accidental extubation and airway obstruction.
Capnography provides a simple, non-invasive, rapid continuous
monitor and can be helpful in patients undergoing elective surgery
under general anesthesia, patients receiving hyperventilation to
decrease intracerebral edema, and those requiring apnea
monitoring. It has also been helpful as a prognostic tool during
cardiopulmonary resuscitation (CPR). Sudden increase in PetCO2
indicates successful (CPR) with return of spontaneous circulation.
Falsely low PetCO2 can occur due to leaks in the sampling system
or circuit.
Capnographic waveform changes are also important and may
be characteristic of certain clinical situations; hence it is essential
to monitor the waveform tracing in addition to the numerical value
of PetCO2. An elevation of baseline indicates clinically important
rebreathing of exhaled air secondary to malfunction of expiratory
value or exhaustion of CO2 absorbent. Delayed up-stroke with
flattening of phase 2 and blurring of the distinction between phase
2 and 3 is seen in obstructive pulmonary diseases. Restrictive lung
diseases cause irregularity in the plateau due to uneven alveolar
emptying.
Capnography in the intensive care unit (Fig. 7.4) during
mechanical ventilation can help in detecting the development of
pulmonary emboli (rapid fall in PetCO2) or a pneumothorax
(inability to maintain a plateau). Capnography can also be used to
measure the physiological dead space using mixed expired CO2
tension (PetCO2). It can help in determining the best positive end-
expiratory pressure (PEEP) during mechanical ventilation. The
hypothesis is that PEEP decreases the dead space by recruiting
alveoli, whereas higher PEEP leads to over distention of the alveoli
that can increase the dead space. The smallest Pa-etCO2 gradient
coincides with the maximal recruitment of the alveoli without over
distention and the least shunt, and hence the PEEP level can be
adjusted while monitoring the Pa-etCO2 gradient in addition to
other parameters.
Capnography, however, cannot be reliably used for patients
wearing face masks and nasal cannulae. The readings should be
Fig. 7.4: Capnography instrument used in ICU
interpreted with caution in critically ill patients and should be

periodically confirmed by an arterial blood gas analysis.
BIBLIOGRAPHY
1. AARC Clinical Practice Guideline. Capnography/Capnometry during
Mechanical Ventilation- 2003 Revision and Update. Respiratory Care 2003;
48:534-9.
2. AARC Clinical Practice Guideline- Pulse Oximetry. Respir Care 1991;36:
1406-9.
3. Anderson CT, Breen PH. Carbon dioxide kinetics and capnography during
critical care. Crit Care 2000;4:207-15.
4. Caples SM, Hubmayr RD. Respiratory monitoring tools in the intensive
care unit. Curr Opin Crit Care 2003; 9:230-5.
5. Jubran A. Advances in respiratory monitoring during mechanical
ventilation. Chest 1999;116:1416-25.
6. Jubran A. Pulse oximetry. Intensive Care Med 2004;30:2017-20.
7. Kyriacou PA. Pulse oximetry in the esophagus. Physiol Meas 2006; 27:R1-
35.
8. Malinoski DJ, Todd SR, Slone S, Mullins RJ, Schreiber MA. Correlation of
central venous and arterial blood gas measurements in mechanically
ventilated trauma patients. Arch Surg 2005;140:1122-5.
9. Perkins GD, McAuley DF, Giles S, Routledge H, Gao F. Do changes in pulse
oximeter oxygen saturation predict equivalent changes in arterial oxygen
saturation? Critical Care 2003; 7:R67-R71.
142 Oxygen Therapy
10. Van de Louw A, Cracco C, Cerf C, et al. Accuracy of pulse oximetry in the
intensive care unit. Intensive Care Med 2001;27:1606-13.
11. Vivien B, Marmion F, Roche S, Devilliers C, Langeron O, Coriat P, et al. An
evaluation of transcutaneous carbon dioxide partial pressure monitoring
during apnea testing in brain-dead patients. Anesthesiology 2006;104:
701-7.
12. Vora VA, Ahmedzai SH. Pulse oximetry in supportive and palliative care.
Support Care Cancer 2004;12:758-61.
13. Wimpress S, Vara DD, Brightling CE. Improving the sampling technique of
arterialized capillary samples to obtain more accurate PaO2 measurements.
Chron Respir Dis 2005;2:47-50.
14. Wouters, PF, Gehring H, Meyfroidt G, et al. Accuracy of pulse oximeters:
the European Multi-Center Trial. Anesth Analg 2002;94(Suppl):S13-S16.
8
Hypoxemia and Goals of
Oxygen Therapy
SK Jindal
INTRODUCTION
The primary goal for oxygen therapy is to correct alveolar and/or
tissue hypoxia. Therefore, any disorder causing hypoxia is a
potential indication for oxygen administration. But the tissue
oxygen delivery depends upon an adequate function of cardiovas-
cular (cardiac output and blood flow), hematological (Hb and its
affinity for oxygen) and the respiratory (arterial oxygen pressure)
systems. Therefore, tissue hypoxia is not relieved only by oxygen
therapy-functioning of all the three organ systems need to be
improved.
HYPOXIA AND HYPOXEMIA

Hypoxia is defined as the “lack” of oxygen at the tissue level. Others
have used “dysoxia” to include disorders of oxygen metabolism.
Both are used interchangeably although dysoxia is a broader term
covering defects of oxygen utilization even in the presence of
normal oxygen tension.
Hypoxemia is loosely used in place of hypoxia although it
implies a low arterial oxygen tension below the range of normal
for that age. Since PaO2 is directly dependent upon alveolar oxygen
tension, hypoxemia results from either a reduction of inspired
oxygen concentration or diseases of the respiratory system.
Hypoxemia does almost always respond to oxygen therapy.
144 Oxygen Therapy
CAUSES OF HYPOXIA
Hypoxia results when the oxygen available for use by the tissues
is inadequate. It is broadly classified into hypoxemic (in the
presence of low PaO2, and normoxemic (in the presence of normal
PaO2).
Hypoxemic Hypoxia
A decrease in arterial PaO2 can occur from either a decreased
oxygen intake (i.e. low FiO2) or due to hypoventilation, ventilation
– perfusion mismatching, right to left shunting of blood or impaired
diffusion.
Causes of Hypoxemic Hypoxia

Decreased oxygen intake (FiO2): At high altitude the total barometric
pressure as well as the partial pressure of oxygen are low. Therefore,
both alveolar and arterial PO2 are also low. Pathological lowering
of FiO2 occurs when oxygen in the inspired air is diluted/replaced
by some other gas e.g. carbon dioxide, carbon monoxide or methane
in a smoke filled room or a mine. Oxygen intake also falls when
oxygen from the atmospheric air gets consumed by fire. These
pathological situations are acute and often fatal. In those who
survive, the effect on blood gases is rarely ever demonstrated. By
the time the blood sample is obtained, the subject is inhaling either
room air or oxygen, administered therapeutically.
Hypoventilation: Hypoventilation implies a fall in total minute
ventilation. If adequate air (therefore oxygen) is not inhaled, the
oxygen uptake and carbon-dioxide removal from pulmonary
capillary blood is impaired resulting in a fall of PaO2 and a rise in
PaCO2.
The relationship between alveolar ventilation and PaCO2 is
defined by the following equations.

KVCO
PaCO2= 2
(K = Constant)
V
A
It is implied that V A is halved, the PaCO2 doubles provided the

V CO2 (i.e. carbon dioxide produced) is unaltered.
In other words, in pure hypoventilation, the arterial PO2 and
PCO2 shall change in opposite directions by nearly the same
amount.
Hypoxemia and Goals of Oxygen Therapy 145
Example: In a 40 years old man, PaCO2 of 60 mm Hg and PaCO2

of 70 mm Hg indicate a change of 30 mm Hg on either side- a
decrease in PaO2 (from 90 mm Hg) and an increase in PaCO2 (over
40 mm Hg). If the change is not the same, it indicates the additional
presence of either a V Q abnormality or shunt. This distinction is
important in view of its therapeutic significance.
Pure hypoventilation shall occur when either the respiratory
center is depressed due to anesthetic or sedative drugs or there is
failure of neuromuscular control of respiration. In the presence of
a parenchymal lung disease, hypoventilation is often accompanied
by other disorders of gas exchange, i.e. V Q mismatch or right to
left shunting of blood.
Ventilation-perfusion mismatching: Some degree of V Q abnormality

is present in most lung diseases. An increase in the ratio, implying
“wasted ventilation”, is the most common cause of hypoxia. This
is clinically encountered in chronic obstructive pulmonary diseases
and pulmonary thromboembolism.
The V Q abnormality can be detected by calculating alveolo-
arterial oxygen gradient (P A O 2-PaO 2). This can be done by
determining PaO2 from arterial blood sample, and PAO2 from FiO2,
atmospheric pressure and PaCO2.
This can be easily understood by imaging lung as a two
compartments (A and B) model (Table 8.1). We can take example
of normal lung (model I) in which both compartments receive equal
and normal amount of ventilation and perfusion, and the other
example (model II) in which compartments receives less (or
inadequate) V A. Although the total V A in model II is the same as in
model I, the ratio of distribution of ventilation in the two
compartments A and B in model II is 2.3:1. Since the blood flow
(perfusion) is equal, the V Q ratios are different, i.e. 1.16 and 0.5
in the two compartments. The alveolar and hence arterial oxygen
and carbon dioxide tensions will be different in the two units. A
difference in PAO2–PaO2 occurs because the relative hyperventi-
lation of one compartment (A) does not fully compensate for the
hypoventilation of the other compartment (B). This is more so for
oxygen (than CO2) because of the sigmoid shape of oxygen
dissociation curve. While increased ventilation of unit A may help
to normalize the “hypercapnia” resulting from hypoventilation of
146 Oxygen Therapy
unit B, the hypoxia of hypoventilation (unit B) is not corrected by

hyperventilation of unit A. This causes a lowering of PaO 2
compared to PAO2 resulting in an P(A-a) O2 gradient.
Table 8.1: Change in relative ventilation of two compartments and its

effect on arterial blood gases and P(A-a)O2
Model I Model II
Normal Lung   abnormality
V/Q
A B Total A B Total
Ventilation 2.5 2.5 5.0 3.5 1.5 5.0
Perfusion 3.0 3.0 6.0 3.0 3.0 6.0
  ratio
V/Q 0.83 0.83 0.83 1.16 0.5 0.83
Arterial PCO2 40 40 40 35 45 40
Alevelor PO2 100 100 100 110 80 105
Arterial PO2 100 100 100 110 80 90
P(A-a)O2 0 0 0 0 0 15
(In both models FiO2 is 0.21, mixed venous PO2 and PCO2 are
presumed to be normal, i.e. venous PO2 and PCO2 of 40 mm Hg
and 46 mm Hg respectively).
In a true clinical condition, the arterial PO2 and PCO2 are affected
by the increasing V Q inequality. The PO2 falls continuously and
rapidly while the PCO2 rises gradually at first and more markedly
afterwards, as the inequality increases. Therefore, when V Q
inequality is marked, PCO2 is also increased. In fact, V Q shunt
more than 30 percent behaves clinically as right to left shunt.
Right to left shunt: Mixing of blood from the right with that of the
left heart, without getting oxygenated in the lungs can occur either
in the presence of a true right to left shunt or a V Q inequality.
The V Q defect involves the presence of areas in the lung which
are perfused but not ventilated, e.g. consolidation due to
pneumonia or pulmonary edema. The gas exchange in the normal
areas of the lung is unaffected, or may be slightly increased than
the normal. But there is nil or inadequate gas exchange in the blood
passing through the unventilated (or hypoventilated) areas, i.e.
shunting of venous (or unoxygenated) blood. Mixing of this
unoxygenated blood with that from the normal areas results in a
net lowering of PaO2. Often, there is no increase in PaCO2 because
the normal areas are able to eliminate the excess CO2 in the blood
from non-ventilated areas.
Hypoxia of V Q inequality is corrected by administration of

100 percent O2 while that due to shunt effect is not corrected. This
principle is used to identify the mechanism of hypoxia by
measuring the PO2 before and after administering 100 percent O2.
In the presence of venous admixture (shunt effect), the P(A-a) O2
difference increases after inhalation of 100 percent O2. The quantity
of shunt as a percent of cardiac output can be determined with the
help of shunt equation:
Q S C’c  C’a

Q T C’c  C v
 = Cardiac output, Q
Q  = Shunted blood, C ’ , C ’ and C are
S T c a v
oxygen contents of capillary, arterial and mixed venous blood

respectively).
On rough estimate, the P(A-a) O2 of 15 mm Hg on breathing
100 percent O2 indicates a shunt of about 1 percent of cardiac output.
A shunt of 2-3 percent of cardiac output is normally present on
breathing 100 percent O2. This occurs from the admixture of
unoxygenated blood from bronchial and mediastinal veins which
empty directly in to the pulmonary and thebesian veins emptying
into the left ventricle (Fig. 8.1).
Fig. 8.1: Schematic representation to show venous admixture: “normal” from

bronchial and other systemic veins (1 and 2) and “abnormal” from pulmonary
circulation from the non-ventilated lung areas (3)
148 Oxygen Therapy
Both the causes and the treatment approaches are different for
different types of hypoxemia (Table 8.2). The effect of oxygen
therapy is also different. It is therefore, important to identify the
mechanism of hypoxemia in an individual patient.
Table 8.2: Clinical examples, identification and therapeutic approach

to different causes of hypoxemia
Cause Clinical Identification Treatment approach

conditions criteria
General Response
to oxygen
therapy
1. Decreased High altitude Low PAtm and Suppor- Rapid
FiO2 fires, smoke history tive
2. Hypo- Neuromuscular Almost Venti- Initial
ventilation failure; CNS similar latory response
depression increase in good,
PaCO2 later
variable
3.  
V/Q COPD Increased Bron- Moderately
imbalance PAO2–PaO2 chial rapid
corrected by hygiene,
100% O2 broncho-
dilators
4. R to L shunt Pneumonia Not corrected Antibio- Variable
atelectasis, 100% O2 tics, diure-
pulmonary tics, PEEP
edema
5. Diffusion Interstitial Low VC, low Cortico- Moderately
defect disease DLCO steroids rapid
Diffusion defect: Diffusion of O2 is impaired when the alveolo-

capillary membrane is involved in either interstitial lung diseases
or emphysema. In clinical practice however, impaired diffusion is
not an important cause of hypoxemia. This is explained by the fact
that the red blood cell takes about 0.75 second (transit time) to
traversee the pulmonary capillary while it gets oxygenated (at rest)
within the first 0.25 second (Fig. 8.1). For the RBC to remain
unoxygenated, the blood velocity should increase by more than
three times (during exercise) to reduce the transit time to less than
0.25 second. Therefore, hypoxemia due to diffusion defect gets
manifest only on exercise unless the disease is far advanced when
oxygenation takes longer time and the blood velocity is also rapid.
This occurs when the capillary bed volume is reduced due to

progressive obliteration and destruction. The previously
unperfused capillaries are recruited, the blood flow velocity in the
remaining vessels increases i.e. the transit time is reduced and not
sufficient enough for uptake of oxygen by the red blood cells. This
is the mechanism for exercise-induced hypoxemia observed in
patients with ILDs.
Normoxemic Hypoxia
Tissue hypoxia occurring in the presence of normal PaO2 is referred
to as normoxemic hypoxia. It is difficult to measure in quantitative
terms but diagnosed by clinical signs, symptoms and indirect
laboratory parameters. It develops when the tissue demands for
oxygen are not supplied by the available oxygen stores. It is also
difficult to define the tissue PO2 below which the hypoxic damage
may occur.
Causes of Normoxemic Hypoxia

Tissue hypoxia is classified into one of the following types
depending upon the pathophysiology.
Circulatory (stagnant) hypoxia: There is inadequate supply of
oxygenated blood to the tissues.
a. Decreased blood flow: Cardiac failure, intravascular volume
depletion, hemorrhage, positive pressure ventilation, cardiac
temponade, pulmonary embolism, vasoactive states and drugs.
b. Altered blood flow: Seen in the presence of excess positive end-
expiratory pressure during mechanical ventilation, sepsis,
abnormal body temperature, drugs, thyroid dysfunction, etc.
The characteristic finding in these patients is the low central
venous PO 2 . Oxygen therapy does not help except when
administered under hyperbaric conditions in the presence of tissue
ischemia.
Cellular (histotoxic) hypoxia: Hypoxia may result from failure of
cellular metabolism or energy generation due to inhibition of
intracellular enzymes. This can occur in following circumstances:
a. Poisoning: Toxic agents such as hydrogen sulfide, cyanide or
carbon monoxide bind up cytochrome oxidase enzymes;
salicylates and dinitrophenol causes uncoupling of oxidative
150 Oxygen Therapy
phosphorylation and iron, steals electrons and O2 away from

ATP producing reactions-all resulting in histotoxicity and
hypoxia.
b. Altered oxygen diffusion: Decreased mitochondrial oxygen
consumption, edema, tissue ischemia and sepsis may lead to
decrease PO2 gradient.
c. Endotoxemia and septic shock.
d. Deficiencies: Thiamine Deficiency impairs Kreb’s cycle;
phosphate deficiency causes decreased ATP while copper
deficiency impairs cytochrome oxidase a1 and a3.
e. Miscellaneous: Tissue hypoxia may also result from abnormal
body temperature, thyroid dysfunction, ragged red cell disease
and liver disease.
Anemic hypoxia: Hypoxia due to deficiency of hemoglobin or altered
affinity of Hb to oxygen is called anemic hypoxia. This may occur
in the following conditions:
a. Hemorrhage and anemia
b. Altered P50, i.e. decreased O2 Hb affinity secondary to low levels
of 2,3 DPG in red blood cells, changes of pH and body
temperature, carbon monoxide poisoning and hemoglobino-
pathies.
c. Loss of Hb binding sites, e.g. carbon monoxide or cyanide
poisoning; methemoglobinemia.
Demand hypoxia: Hypoxia may also result where there is increased
demand or utilization of O2 by the tissues even though the O2
delivery is normal (or even more). This may occur during
conditions of excessive stress such as marked hyperpyrexia,
excessive exercise or thyrotoxicosis. Cardiac output is increased
but the mixed central venous PO2 is decreased due to excessive
tissue “extraction” (consumption) of oxygen.
SUMMARY
To summarize, oxygen is indicated whenever there is hypoxia with
or without hypoxemia. Hypoxemic hypoxia, demonstrable on
blood gas analysis results most often from diffuse pulmonary
diseases. Oxygen is clearly indicated in all such disorders. On the
other hand the presence of hypoxia in the absence of hypoxemia is
difficult to dcocument. Most such situations occur in sick patients
suffering from nonpulmonary illnesses in whom, uses and
indications for oxygen therapy should be carefully assessed.
BIBLIOGRAPHY
1. Bates DV, Macklem PT, Christie RV. Respiratory function in disease 1971.
WB Saunders, Philadelphia.
2. Calzia E, RaderMacher P. Alveolar ventilation and pulmonary blood flow:
  concept. Intensive Care Med 2003; 29:1229-32.
Their V/Q
3. Campbell EJM. Respiratory failure. Br Med J 1965, 1:1451.
4. Martin L. Respiratory failure. Med Clin N Am 1977; 61:1369.
5. Pierson D. Normal and abnormal oxygenation: Physiology and clinical
syndromes. Respire Care 1993; 38:587.
6. Squara P. Matching total body oxygen consumption and delivery: A crucial
objective? Intensive Care Med 2004; 30:2170-9.
7. Swensen EW, Finley TN, Guzman SV. Unilateral hypoventilation in man
during arrange alphabetically temporary occlusion of one pulmonary artery.
J Clin Invest 1961; 40:828.
8. Vincent JL, DeBacker D. Oxygen transport – The oxygen delivery controversy.
Intensive Care Med 2004; 30:1990-6.
9. Wagner PD Laravuso RB, UhlRR, et al. Continuous distribution of ventilation-
perfusion ratios in normal subjects breathing air and 100 percent O2. J Clin
Invest 1974; 54:45.
10. West JB. Ventilation perfusion relationships. Am Rev Respire Dis 1977; 116:
919.
9
Clinical Prescription
of Oxygen
SK Jindal
INTRODUCTION
Oxygen like a drug, is used for most of the indications discussed
later in this book. It is generally used as an additional supplement
to other forms of drug therapy. In many other diseases where
oxygen deficiency is a major abnormality, oxygen constitutes the
mainstay of therapy. But there are enormous errors committed in
its use. Oxygen is one of the most ill prescribed drug. Unlike the
prescription for a drug, oxygen is not prescribed with any degree
of careful consideration. Often, the prescription either includes a
single written word-oxygen, or merely a verbal mention of the order
to the staff nurse. It is generally left to the ward attendant or a
nursing student to administer oxygen to a patient. A review of
several indoor files and treatment charts of over a hundred patients
of general wards of our own hospital had revealed a gross
inadequacy regarding oxygen prescription. The prescriptions either
did not mention or lacked even the minimum instructions on
oxygen therapy. There was no clear indication for about 25 percent
of patients. There was no mention of the dose or concentration of
oxygen or the method of its administration. Similarly, the duration
of treatment and when was it discontinued was not stated in the
files.
Different types of errors of oxygen use are reported even from
more developed countries of the West. A report on assessment of
uses and misuses of oxygen in a hospital in Montreal had similar
findings. Oxygen prescription and/or delivery was associated with
significantly greater errors than those seen with antibiotics. In a
Clinical Prescription of Oxygen 153
recent study from Greece, 41 percent of 105 head nurses of seven

large district hospitals believed that oxygen was a gas that
improved patient’s dyspnea. There was no protocol for oxygen
therapy in most hospitals.
It is important to consider oxygen as a drug to get the maximum
benefit. It is important to have oxygen treatment protocols and
educational programmes especially for the nursing staff. A proper
oxygen prescription must specify the percentage of oxygen to be
delivered, flow in liters/min, source of oxygen and the method of
delivery. The type of delivery device to be used should be
mentioned. Finally, the duration should be specified and reviewed
every now and then.
It is true that all these guidelines vary with the underlying
disease and the clinical status of the patient. The clinical condition
is assessed best by the bed side examination of vital parameters
and the laboratory tests. Adequate monitoring is essential for
alterations in the prescribed modes of therapy. The instructions
with respect to domiciliary oxygen therapy need to be even more
precise and comprehensive.
KEY POINTS
Oxygen Concentration (FiO2) and Flow Rate
In general wards in most hospitals in India, it is not possible to
know of the exact oxygen concentration being delivered.
Frequently, one relies erroneously on the bubbling seen in the water
bottle connected to the delivery circuit. It can be best assessed by
the flow being administered and the method of delivery. FiO2 can
also be calculated if the flow rate and the type of mask are known.
The FiO2 required to be delivered depends upon the acuteness
of illness and severity of hypoxemia. In general, higher FiO2 is used
initially till the acute state is settled. One must avoid a high FiO2 of
over 0.6 for prolonged periods to avoid toxicity. Occasionally,
oxygen is administered at a very low flow rate of less than 0.5 L/
min at the opening of the nostrils. This is like “smelling” oxygen
which is more of a ritual than a therapy.
Source of Oxygen
Compressed gas cylinders continue to be used in most hospitals in
this country. Piped system with wall outlets from a central source
154 Oxygen Therapy
is available in several large hospitals. There is little option for the

physician to select the source than what is available in the hospital.
A knowledge of cylinders, regulators, flow meters and pressure
gauges is important for the physician for an efficient role. It is
important that regular and continuous supply is ensured. Pressure
gauges should be regularly checked to know of the contents of the
cylinder and replacement should be done before the supply is run
out.
Method of Administration
It is most important to choose an appropriate method of
administration depending upon the FiO2 requirement and the
patient’s convenience. The different types of devices include the
nasal catheters and cannulae, venturi and other types of face masks,
insulators and tents, tracheostomy masks and mechanical
ventilators.
Use of Humidifying Devices

Humidification is required in view of the dryness of oxygen which
produces drying of mucous membranes. It should be borne in mind
that humidification may also prove to be a source of cross infection
especially in the hospital setting when there are multiple users of
the facility.
Duration of Administration
The duration is determined by assessment of clinical response and
laboratory parameters. Monitoring parameters have been discussed
elsewhere. Needless to say that unnecessary prolongation of
therapy exposes the patient to oxygen toxicity. On the other hand,
premature discontinuation may cause hypoxia related
complications some of which may not be immediately discernible,
but manifest in the long run.
Monitoring of Oxygen Therapy

Both the nursing and the medical staff should be trained to monitor
oxygen therapy. Unfortunately, qualified respiratory therapists are
not yet routinely available in most hospitals in India. One has to
supervise the functioning of oxygen equipment and devices along
Clinical Prescription of Oxygen 155
with the patient’s response parameters. Proper orders should be

given regarding replacement of humidifiers, cylinders and delivery
devices. Continuation of therapy during the period when patient
is eating, or passing urine or stools should be ensured especially
for a sick patient. Oxygen is often discontinued during such periods
in the hospital. In fact, a sick patient may actually need higher
amounts of oxygen during periods of even a mild activity. It is
common for a enthusiast resident or respiratory physiotherapist
to put off the oxygen mask or cannula during examination or while
providing physiotherapy. In a sick patient, it is important that this
is not allowed to happen. Significant falls in O2 saturation have
been demonstrated during such periods. Similarly, over-
oxygenation may occur and toxicity results in the absence of careful
monitoring especially in patients with and underlying chronic lung
disease such as COPD.
Oxygen prescription for domiciliary use requires a careful
assessment regarding the indication of therapy. Variations persist
in the approach and indications of domiciliary oxygen prescription.
The current recommendations for its use in chronic obstructive
pulmonary disease is to adhere to the recent guidelines of the
American Thoracic Society and the European Respiratory Society
ensuring that the patients are assessed in a stable state or re-assessed
at least 2 months after an acute exacerbation. Proper instructions
and counselling regarding the devices and sources of delivery,
supervision and monitoring, daily duration and the total period of
therapy have to be clearly spelt out.
BIBLIOGRAPHY
1. AARC clinical practice guideline. Oxygen therapy in the home or alternate
site health care facility-2007 revision and update. Respir Care 2007;52:1063-
68.
2. Brokalaki H, Matziou V, Zyga S. Omissions and errors during oxygen therapy
of hospitalized patients in a large city of Greece. Intensive Crit Care Nurs
2004; 20:352-7.
3. Brougher LI, Blackwelder AK, Grossman GD, Satton GW. Effectiveness of
medical necessity guidelines in reducing cost of oxygen therapy. Chest 1986;
90:646-8.
4. Celli BR, Macnee W. ATS/ERS Task Force. Standards for the diagnosis and
treatment of patients with COPD: A summary of the ATS/ERS position paper.
Eur Respir J 2004; 23:932-46.
5. Fulmer JD, Snider GL. ACCP-NHLBI National Conference on oxygen therapy.
Chest 1984; 86:236-47.
156 Oxygen Therapy
6. Macnee W. Prescription of oxygen: Still problems after all these years. Am J

Respir Crit Care Med 2005; 172:517-8.
7. Mbamalu D, Banerjee A, Hinchley G, Idowu A. How much do new junior
doctors in emergency medicine understand about oxygen therapy? Br J Hosp
Med (Lond) 2007;68:156-7.
8. O’Neill B, Bradley JM, McKevitt AM. Prescribing practice for intermittent
oxygen therapy: A GP survey. Chron Respir Dis 2004; 1(3):139-42.
9. Petty TL. Misunderstanding concerning the proper clinical use of oxygen.
Ann Intern Med 1969; 70:645-6.
10. Small D, Duha A, Wieskopt B. Uses and misuses of oxygen in hospitalized
patients. Am J Med 1992; 92:591-5.
11. Snider GL, Rinaldo JE. Oxygen therapy in medical patients hospitalized
outside of the intensive care unit. Am Rev Respir Dis 1980; 122 suppl.
5:29-36.
12. Udwadia FE. Oxygen Therapy. Principles of Critical Care, Oxford University
Press, Delhi 1995; 229-38.
10
Oxygen Therapy for
Pulmonary Disorders
SK Jindal
INTRODUCTION
Hypoxia, a natural consequence of most diffuse lung disorders is
characteristically associated with hypoxemia. It is often demons-
trable by the presence of low PaO2 on blood gas examination.
Oxygen therapy is decided depending upon the type and chronicity
of disease and the degree of hypoxemia. Requirements for oxygen
are greater but for lesser duration in patients with acute illnesses
versus patients with chronic illnesses. Similarly, exacerbations of
chronic illnesses would require to be treated as acute conditions.
HYPOXEMIA DUE TO PULMONARY DISORDERS

Hypoxemia of both acute illnesses as well as acute exacerbations
of chronic disorders is labeled as acute (or acute on chronic)
respiratory failure. A variety of causes can lead to acute respiratory
failure (Table 10.1).
Presentation of acute respiratory failure is often sudden in onset
in a previously healthy person while it is generally gradual in a
patient with pre-existing chronic respiratory disease. There are
signs and symptoms of hypoxemia along with those of the
underlying and/or complicating disease. The general features
attributed to hypoxemia are restlessness, palpitation, sweating,
altered consciousness, headache, confusion and cyanosis. Blood
pressure may initially rise, but it falls as the severity of hypoxemia
worsens. Hypercapnia accompanies hypoxemia whenever there
is hypoventilation.
158 Oxygen Therapy
Table 10.1: Different causes of acute respiratory failure
A. Defective ventilation
i. Respiratory centre depression
Drugs such as narcotics, anesthetics and sedatives
Cerebral infarction
Cerebral trauma
ii. Neuromuscular disorders
Myasthenia gravis
Guillain-Barré syndrome
Brain or spinal injuries
Polio, porphyria, botulism
iii. Airway obstruction
Chronic obstructive pulmonary disease
Acute severe asthma
iv. Restrictive defects
Interstitial lung disease
Kyphoscoliosis, Ankylosing spondylitis
Bilateral diaphragmatic palsy
Severe obesity
B. Impaired diffusion and gas exchange
i. Pulmonary edema
ii. Acute respiratory distress syndrome
iii. Pulmonary thromboembolism
iv. Pulmonary fibrosis
  ) abnormalities
C. Ventilation-Perfusion (V/Q
i. Chronic obstructive pulmonary disease
ii. Pulmonary fibrosis
iii. Acute respiratory distress syndrome
iv. Thromboembolism
Diagnosis is made from the total clinical presentation of the

disease and the relevant investigations. Acute respiratory failure
is established by blood gas and pH determinations.
Considerations for Oxygen Therapy

Higher concentrations of oxygen are required initially during acute
respiratory failure. This is achieved by higher flow rates via a face
mask or a cannula. It is important to reduce the severity of
hypoxemia to prevent organ damage. Therapy is continuously
monitored with gas exchange parameters. In case hypoxemia is
not correctable, assisted ventilation may be required. It may also
Oxygen Therapy for Pulmonary Disorders 159
be stressed that correction of blood PaO2 is not the only objective

of therapy. Oxygen delivery to and its utilization by the tissues are
other major considerations. Therefore, all other factors responsible
for tissue delivery should be taken care of.
Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is the most
common disorder in which oxygen therapy is prescribed (Fig. 10.1).
Hypoxia in COPD results primarily from ventilation-perfusion
( V Q ) mismatch because of low V Q relationship (i.e. shunt
physiology). On the other hand, hypercapnia results from
numerous factors including airway obstruction, alveolar
hypoventilation, chronic respiratory muscle fatigue and central
hypoventilation. While some of the factors responsible for V Q
mismatch (e.g. infection, bronchospasm and airway inflammation)
are partially reversible, most other factors such as airway remo-
delling and established bronchiolar fibrosis are not. The end-
result is hypoxemia which is detrimental in many ways.
Hypoxemia leads to reflex pulmonary vasoconstriction and thus
worsens pulmonary hypertension. Oxygen administration is one
of most efficacious method of treatment of hypoxemia of COPD.
There is also evidence that it alleviates right heart failure caused
by cor pulmonale, enhances neuropsy-chological function,
improves exercise capacity and improves the performance of
Fig. 10.1: Chest radiograph in a COPD patient showing hyperinflation and bulla
(left) and increased retrosternal air space (right)
160 Oxygen Therapy
activities of daily living thus improving the overall quality of life.

Moreover, oxygen therapy, apart from cessation of cigarette
smoking, is the only strategy that has been shown to improve
survival in a patient with COPD.
The use of oxygen therapy in COPD can be divided into two
main categories: (i) oxygen therapy during hospitalizations of acute
exacerbations, and (ii) long-term domiciliary oxygen therapy,
which can be either ambulatory or non-ambulatory. Long-term
oxygen therapy (LTOT) is an effective but potentially expensive
and inconvenient intervention. It should be prescribed in COPD
only for patients, in whom there is evidence of benefit, especially
those with chronic hypoxemia related organ dysfunction.
Oxygen Therapy in Acute Exacerbations of COPD

Acute exacerbations of COPD can be clinically defined as
worsening of cough, expectoration and dyspnea along with
worsening ventilation-perfusion relationship and variable degrees
of fluid retention. It occurs due to an inadequate or inappropriate
maintenance treatment or an antecedent complication such as
respiratory tract infection, most commonly bacterial (e.g.
Pneumococcus, Hemophilus influenzae or Moraxella catarrhalis). Other
conditions like pneumonia, pulmonary embolism, cardiac
dysrhythmias, pneumothorax, congestive heart failure and use of
sedatives can also exacerbate the clinical and functional status of a
patient with COPD. In strict clinical sense, these conditions are
only mimics and not true acute exacerbation. All the conditions
listed above precipitate hypoxemia and hypoxia in patients with
COPD, and oxygen therapy is one of the most essential components
of management.
Oxygen therapy is started immediately on admission after an
arterial blood sample is obtained for assessment of blood gas
tensions. The goal of supplemental oxygen is to maintain a PaO2
of 55 to 60 mm Hg corresponding to SpO2 of 89-92 percent. A
common mistake committed by physicians, nursing staff and
occasionally the patient’s attendants is to increase the flow of
oxygen to improve oxygen saturation. However, one should not
forget that oxygen is a ‘drug’ and should be carefully administered
since excess oxygen is associated with numerous complications.
In a patient with COPD who has chronic type II respiratory failure
and hypercapnia, the ventilatory stimulus for hypercapnia is lost
and patients’ ventilatory drive is maintained by hypoxemia.

Administration of excess amounts of oxygen can blunt this
ventilatory drive with resultant hypercapnia and acute respiratory
acidosis superimposed on type II respiratory failure that could be
potentially life-threatening. Although not proven in the setting of
COPD, excess oxygen therapy has been shown to prolong hospital
stay probably because it can lead to generation of harmful reactive
oxygen species, which can exacerbate tissue injury. Excess oxygen
can also lead to hypercapnia by ventilation perfusion disturbances,
Haldane effect and by causing numerous areas of microatelectasis.
Another reason why PaO2 is not increased more than 60 mm
Hg is because it corresponds to an oxygen saturation (SaO2) of
around 90 percent; from the oxygen delivery equation we can
conclude that there is no benefit of increasing PaO2 above 60 mm
Hg except in situations of hyperbaric oxygen delivery.
Oxygen content = [1.34 × hemoglobin (gm/dL) × SaO2] +
[0.000031 × PaO2]
An important consideration in acutely ill patients is the type of
oxygen delivery device which is used. In acute situations, it is
always better to use high-flow devices as one can, to a reasonable
extent, guarantee the oxygen delivered. On the other hand, with
the use of a low flow device, oxygen delivery would not be
dependent on the patient’s minute ventilation. Once the patient
has been stabilized, one can shift to nasal prongs, as it proves more
comfortable for the patient.
How to Determine the FiO2 Required for An Individual Patient?

The appropriate FiO2 is selected with the help of alveolar gas
equation. We also know that the ratio of PaO 2 to P A O 2 is
independent of FiO2.
Example 1: A patient of COPD has PaO2 of 35 mm Hg and PaCO2
of 58 mm Hg on room air; what should be the FiO2 requirement to
bring PaO2 to 60 mm Hg?
PAO2 = [FiO2 (Patm minus PH2 O)] – (PaCO2/R)
= [0.21 (760 – 47)] – (58/0.8) = 77.3
PaO2/PAO2 = 35/77 = 0.45
To get the desired PaO2 of 60 mm Hg, the PAO2 must increase
for the same PaO2/PAO2 ratio, i.e.
35/77 = 60/ PAO2 (x) = 0.45
162 Oxygen Therapy
PAO2 (x) = 77 × 60/35

PAO2 = 133.3
The desired FiO2 (for PaO2 of 60 mm Hg) can be determined
again from the alveolar gas equation as above, i.e.
133 = FiO2 × 713 – (58/0.8)
FiO2 = 28.8
Example 2: A patient of COPD has been on domiciliary oxygen
with the help of a 28 percent Venturi mask. Following an episode
of infection, he deteriorates. The arterial blood gas sample shows
PaO2 of 35 mm Hg and PaCO2 of 60 mm Hg. What is the required
FiO2 to increase PaO2 to 60 mm Hg?
Initial PAO2 = 0.28 (713) – (60/0.8) = 125
PaO2/PAO2 = 35/125 = 0.28
35/125 = 60/x = 214 mm Hg
214 = (FiO2 × 713) – (60/0.8)
Desired FiO2= 40.5%
How to Manage CO2 Narcosis?

Small amounts of increases in CO2 are inevitable and are of no
clinical importance. The problem arises when FiO2 of 0.3 is not
able to correct hypoxemia and increases in FiO2 beyond 0.3 lead to
clinically significant hypercapnia and acute respiratory acidosis.
In such a situation, the patient requires mechanical ventilation,
either invasive or non-invasive. One should never hesitate to correct
hypoxemia for fear of hypercapnia, since the former is far more
dangerous than the latter. On the other hand, a common situation
could occur with a PaO2 of 75 and a PaCO2 of 70 mm Hg with pH
of 7.29 at a FiO2 of 0.35. In these situations one can safely decrease
FiO2 titrated by the PaO2 to PAO2 ratio formula.
PAO2 = (0.35 × 713) – 70/0.8 = 162
75/162 = 60/x = 129.6
Substituting the PAO2
129.6 = (x × 713) – 70/0.8 = 30%
Short-burst Oxygen Therapy (SBOT)

SBOT is a popular mode of treatment for COPD especially in this
country. Oxygen is administered after discharge of a patient
following admission for an acute exacerbation for variable periods
of time, mostly, in an unscheduled fashion either on an ‘as and

when required’ basis or for fixed periods. But there is lack of
evidence to support this treatment. In a recent report from
New Zealand, no improvements in health related quality of life or
reduction in acute health care utilization were observed in a
randomized double-blind, placebo-controlled study in patients of
COPD given cylinder oxygen, cylinder air or usual care following
discharge in three parallel groups.
Bronchial Asthma
Asthma is a disease of wide spectrum. Gas exchange in asthma is
affected when the disease is relatively severer. The airway
obstruction is diffuse, but non-uniform in severity. Ventilation in
different areas is reduced by a variable degree depending upon
the severity of obstruction. But the blood flow in the under-
ventilated areas is not similarly affected. There is thus mismatching
of ventilation to perfusion. Areas with severer obstruction have
lower V Q ratio vis-à-vis areas with milder airway narrowing or
normal ventilation. The V Q mismatch widens the (A-a) PO2
gradient and causes hypoxemia.
In spite of an impaired ventilation, CO2 retention is not an usual
feature. In the early phases, the arterial PCO2 is generally low. This
is attributable to an increase in the respiratory rate and the minute
ventilation. In later stages with persistent airway obstruction, the
respiratory muscles get fatigued. The effects are further
compounded by administration of sedatives or other drugs used
to reduce anxiety. All these factors adversely affect the respiratory
drive, hypoventilation ensues and CO2 gets accumulated. Even a
normal arterial PCO2 in the presence of hypoxemia and persistent
airway obstruction is also an indication of CO2 retention. In a more
advanced stage, the arterial PO2 may also rise, above normal and
result in CO2 narcosis.
Oxygen Therapy
Oxygen administration is an important component of management
of acute severe asthma. It should ideally start at home. In the
hospital, oximetry should be immediately done and oxygen given
if patient is hypoxemic. Arterial blood sample for PaO 2
measurements is not essential unless the patient does not respond
164 Oxygen Therapy
or deteriorates. Typically, a patient is likely to show mild

hypoxemia, hypocapnia and respiratory alkalosis during an acute
attack. Thus even a normal PaCO2 indicates imminent respiratory
muscle fatigue.
Oxygen is administered via a face mask or a nasal cannula at a
flow rate of 4-6 L/min to achieve an FiO 2 of 35-40 percent.
Humidified oxygen is important to avoid dryness of the respiratory
tract. Flow rate is adjusted to SaO2 of at least 92 percent and a PaO2
of about 60 mm Hg. Concurrently, bronchial hygiene, intravenous
fluids, nebulized bronchodilators and parenteral corticosteroids
are administered as per treatment protocol.
Oxygen improves hypoxemia and oxygen delivery to the tissues
including the respiratory muscles. It is a common fear that rapid
bronchodilation following active treatment with bronchodilators
in acute asthma may paradoxically worsen gas exchange and
V Q mismatch, precipitating hypoxemia. Concurrent O2 should
avoid this problem. It also reduces hypoxic pulmonary
vasoconstriction, thereby improving the pulmonary hypertension
present in an acute attack of asthma. Oxygen may also exert a
bronchodilatory effect on the severely constricted bronchi.
In case a patient continues to deteriorate, it is likely that CO2 is
being retained. An arterial blood gas analysis is essential at this
stage. As already stated, normal or high PaCO2 indicates the need
of aggressive therapy. Oxygen administration in this situation
carries the risk of blunting the hypoxia induced respiratory
stimulation, precipitating hypercapnia and narcosis due to CO2
retention. This is more commonly observed in patients of severe
COPD and respiratory failure but may be seen in severe asthma.
Endotracheal intubation and ventilatory assistance should be
instituted whenever such a situation is warranted.
Improvement following treatment is generally rapid in asthma
although complete resolution may take a longer time. Most patients
can be extubated after a few hours and continued on oxygen along
with other maintenance therapy until the acute episode is over.
Interstitial Lung Disease

Interstitial lung diseases (ILD) constitute an important group of
disorders responsible for hypoxemia and respiratory failure
(Fig. 10.2). A large number of parenchymal diseases included in
this category are characterized by infiltration and fibrosis of the
Fig. 10.2: Chest radiograph and high-resolution computed tomography

chest in a patient with idiopathic pulmonary fibrosis
lung interstitium responsible for impairment of gas exchange.

Idiopathic pulmonary fibrosis (IPF), also called as cryptogenic
fibrosing alveolitis (CFA) is the prototype and accounts for about
half the cases of ILDs. Other disorders included in this group are
those secondary to connective tissue disorders, such as the
progressive systemic sclerosis, rheumatoid arthritis and systemic
lupus erythematosis; pneumoconiosis, sarcoidosis, histiocytosis,
drug and radiation induced fibrosis, hypersensitivity pneumonias,
bronchiolitis obliterans and several other miscellaneous illnesses.
Abnormalities of Gas Exchange

Alterations in gas exchange in ILD are attributed primarily to both
ventilation-perfusion mismatch and impaired diffusion contributes
to hypoxemia only in specific situations like exercise. The V Q
mismatch results from small tidal volumes but high breathing
frequencies because of intrinsic stiffness of lungs. Ventilation is
preferentially distributed to areas of normal compliance but
diminished perfusion. The V Q ratio is therefore high. This gets
further worsened on exercise due to an increase in respiratory rate
and minute ventilation.
Following exercise, both the cardiac output and the blood flow
through the pulmonary capillaries are increased. Both these factors
add to the V Q mismatch. Thickening of lung interstitium may
also be responsible for impairment of diffusion of gases. This is
unlikely at rest since the transit time of blood through the
pulmonary capillaries is long enough to allow oxygen to diffuse
166 Oxygen Therapy
across. But following exercise, the diffusion limitation is also an

important factor in causing hypoxemia. The diffusion capacity for
carbon monoxide (DLCO) is therefore reduced. The typical blood
gas analysis in ILD reveals hypoxemia which may not be apparent
at rest but appears after exercise and worsens with increase in work.
The (A-a) PO2 is increased both at rest and during exercise. The
cardiovascular response to exercise is also inadequate.
There are large decreases in mixed venous PO2 which further
aggravate the (A-a) PO2 difference. Usually, there is no hyper-
capnia. On the other hand, PCO2 may actually be low because of
hyperventilation. In advanced cases, CO2 retention may also occur.
Oxygen Therapy
Acute respiratory failure in ILD is present at initial presentation in
case of a fulminant onset or during the course of an established
disease whenever there is an intercurrent insult such as an infection.
Oxygen administration in acute ILD is aimed at correction of
hypoxemia without any significant fear of causing hypercapnia.
Requirements of these patients are generally high and increase with
the severity of illness. Most cases would require higher concen-
tration at high flow rates. General principles apply for oxygen
administration.
Requirement for oxygen are likely to decrease once the acute
episode is controlled. Exercise induced hypoxemia, a disease
characteristic, is a more persistent problem. Long-term oxygen
therapy has been advocated for chronic ILD with resting
hypoxemia. Indications for exercise induced hypoxemia are not
clear. Not enough experience is available on this issue as yet. There
are no good retrospective survival data to suggest effectiveness of
domiciliary oxygen. There was only one unpublished randomized
controlled trial which showed similar mortality, quality of life and
physiological parameters in the oxygen treated and control groups
after 3 years. But there are anecdotal reports on the beneficial effects.
In our own experience, individual patients have done well.
Continued search for the supplemental role of LTOT is therefore
warranted.
Fig. 10.3: High-resolution computed tomography chest showing

extensive bilateral bronchiectasis
Bronchiectasis
Bronchiectasis is still a common problem in the developing
countries especially following chronic bacterial infections
(Fig. 10.3). Bronchiectasis as sequela to tuberculosis is another
important cause. It commonly results from destruction of the
muscular and elastic tissues of the bronchial walls. Bronchial
obstruction frequently predisposes and propagates bronchial
dilatation. It is generally a localized disease, but may involve large
areas of one or both the lungs. Allergic bronchopulmonary
aspergillosis is now being increasingly recognized as a cause of
patchy and diffuse bronchiectasis. Cystic fibrosis, a common cause
of bronchiectasis and hypoxia in the West is not unknown in India.
An extensive lung involvement may be responsible for chronic
hypoxemia and respiratory failure, obstructive defect on spirometry
is a common pulmonary function abnormality. Development of
pulmonary hypertension and chronic cor pulmonale occurs in a
minority of patients.
Acute or chronic respiratory failure generally results whenever
there is acute worsening - for example due to an infectious episode.
Oxygen for any such worsening is administered as for any other
hypoxemic condition. Hypoxic conditions in these patients may
also develop during sleep and exercise. Experience with long-term
168 Oxygen Therapy
domiciliary oxygen therapy is rather meager. It has been shown to

improve exercise performance in patients of cystic fibrosis with
extensive pulmonary disease. On similar basis, long-term oxygen
administration should benefit patients with extensive bron-
chiectasis and chronic respiratory failure of any cause.
In a retrospective study on the impact of first ICU stay for
respiratory failure in 48 cases of bilateral bronchiectasis, both prior
use of long-term oxygen therapy and age of over 65 years were
independently associated with reduced survival at one year.
Possibly, those who required LTOT before admission in the ICU
had more extensive disease than others. There is no prospective
controlled trial to show either the benefit or the risks of LTOT at
home.
Respiratory Tract Infections

Both upper and lower respiratory tract infections may be
responsible for respiratory distress and/or hypoxemia (Fig. 10.4).
Acute laryngitis with or without tracheitis, especially in infants
and young children may cause respiratory stridor and a picture of
acute upper airway obstruction. Lower respiratory tract infections
include bronchitis, bronchiolitis and bronchopneumonia. Acute
infection in chronic obstructive pulmonary disease is a common
cause of worsening and precipitation of respiratory failure in an
otherwise stable patient of chronic obstructive pulmonary disease.
Fig. 10.4: Chest radiograph showing right upper lobe consolidation

Pneumonia is the most important lung function which confronts

not only the pulmonologists but intensivists, physicians and
surgeons of all specialities and superspecialities. A severe
pneumonia in particular is a life-threatening condition requiring
urgent management. While antibiotics and other anti-infective
agents are the mainstay of treatment, oxygen plays an important
role in supportive therapy. It was Sir William Osler who had first
recognized the state of imperfectly oxidized blood in pneumonia
although he disfavored the use of oxygen for its treatment because
of the fear of toxicity. George Holtzapple was the first to publish a
case report in 1885 on use of oxygen, along with its physiological
basis for treatment of lobar pneumonia. But it is likely that oxygen
for this purpose was used even earlier. Later, during and after the
World War I, oxygen was found to relieve symptoms of hypoxemia
in patients of poisonous gas inhalation as well as those of severe
pneumonias. Thereafter, oxygen has acquired an essential place
in the therapy of severe pneumonias.
The spectrum of pneumonias which require oxygen therapy is
wide. It may vary from the community acquired infections to
nosocomial ventilator associated pneumonias and pneumonia in
the immunosuppressed patients. All kinds of pneumonias, acute
exacerbations of chronic airway obstruction and sepsis may require
supplemental oxygen. It is the severity of pneumonia, the extent
of lung involvement and the presence of hypoxemia rather than
the etiology of infection which determine the role of oxygen.
Severity is the strongest predictor of death and readmission from
pneumonias. This is particularly so in case of children. Hypoxemia
occurs commonly and earlier in diffuse interstitial and broncho
pneumonias for example in some forms of viral pneumonias.
Pneumocystis jirovecii pneumonia in patients with acquired
immunodeficiency syndrome (AIDS) or in those on immuno-
suppressive therapy following organ transplantation, is another
important cause of acute respiratory failure and hypoxemia.
Oxygen in these patients is required to achieve a normal or
oxygenation status at the start of therapy. Most patients may shown
improvement following oxygen administration through mask or
cannulae. But more serious patients especially those who have
developed a picture of ARDS will need intubation and assisted
respiratory support. The general principles and methods of oxygen
170 Oxygen Therapy
therapy are similar to those for any other cause of acute respiratory
failure.
Pneumothorax and Pneumomediastinum

The presence of air in the pleural cavity (pneumothorax) is a
common clinical condition which can occur both spontaneously
and secondarily to chest trauma, or to an underlying lung disease
(Fig. 10.5). Pneumothorax can cause respiratory distress when
sudden and severe or in the presence of a diffuse lung disease with
compromised lung function. Pneumomediastinum is relatively
uncommon and generally insignificant. In an occasional case
however, it can cause cardiovascular collapse due to cardiac
compression similar to situation seen in cardiac temponade.
Hypoxemia in both conditions can occur only if the lung function
is already compromised. Oxygen therapy is essential to treat
hypoxemia.
Supplemental oxygen has been also used to absorb air from
both pleural and pericardial cavities. Resolution of experimental
injury induced pneumothorax in white rabbits was shown to be
fast in the group administered 60 percent FiO2 than 40 percent
FiO2 or air. It was suggested that the practice of administration of
supplemental oxygen to patients with asymptomatic pneumo-
thorax should be continued even in the presence of an ongoing
Fig. 10.5: Chest radiograph showing left sided pneumothorax

pleural air leak. This follows the basic principle of gas absorption
which depends upon the difference in the pressure gradients and
the solubility of the gas. Administration of 100 percent oxygen
causes denitrofication of blood. The PN2 in the blood in the
capillaries on the pleural surfaces approaches zero while the PO2
in fully oxygenated blood is about 100 mm Hg, the total gas pressure
in the blood is therefore significantly lower than that of pleural air
(Table 10.2). This high gradient of pressure between the two
adjoining surfaces increases the rate of absorption by several fold.
Normally air is absorbed from pleural space at a rate of 1.25 percent
per day. Supplemental oxygen increases this process four-fold.
Air leaks from the respiratory passage can result in presence of
air in the subcutaneous tissue (subcutaneous emphysema) and
mediastinum. Air can occasionally track down to the peritoneum.
Air leaks can also occur in the joints, middle ear cavity, paranasal
sinuses and other sites in decompression sickness seen in deep sea
divers. Supplemental oxygen therapy can be employed for
absorption of any abnormal presence of air. The basic principle of
treatment in all those conditions remains the same. Hyperbaric
oxygen is however the treatment of choice in decompression
sickness.
Administration of oxygen in a hyperbaric chamber is likely to
achieve an early denitrofication of blood and an efficient pressure
gradient required for absorption of air. This however is not
routinely recommended. Supplemental oxygen therapy for
treatment of these conditions with supplemental oxygen is feasible
only when the amount of air is mild or moderate. Drainage remains
the method of choice in cases of presence of large amounts of air.
Table 10.2: Shows difference in gas pressures (mm Hg) between pleural air
(in pneumothorax) and capillary blood during normal air and on supplemental
100 percent O2 breathing
Pneumothorax Pleural cavity Capillary blood

Breathing room air On 100% O2
PN2 (mm Hg) 570 570 0
PO2 (mm Hg) 143 40 100
PCO2 (mm Hg) 0 46 46
PH2O (mm Hg) 47 47 47
Total Pressure (mm Hg) 760 703 193
Pressure Gradient
(mm Hg) 57 567
172 Oxygen Therapy
Kyphoscoliosis
Deformation of the spine characterized by antero-posterior
displacement (kyphosis), lateral angulation (scoliosis) or both
(kyphoscoliosis) is a common problem in minor forms. Severer
forms may result in restriction of lung expansion and diminished
ventilation. Chronic respiratory failure may develop in patients
with marked reduction in vital capacity. Additional factors such
as tobacco smoking, responsible for chronic airway obstruction may
further hasten this process. Development of pulmonary hyper-
tension and chronic cor pulmonale usually precede the onset of
chronic respiratory failure. Acute worsening may occur following
a lower respiratory tract infection or during pregnancy.
Oxygen therapy is an important component of management of
these patients after the development of respiratory failure. Oxygen
administration at rest or with exercise has been shown to minimize
dyspnea and prevent exercise induced desaturation in patients with
moderately severe kyphoscoliosis and chronic ventilatory failure.
Nocturnal non-invasive ventilation instituted for months or years
at home for severe kyphoscoliosis is shown to improve quality of
life and sleep quality.
Temporary improvement in oxygenation and resting arterial
PCO2 were shown with institution of intermittent positive pressure
breathing (IPPB). These changes may last for upto 4 hours following
acute IPPB treatment and may persist for upto 9 months after
prolonged IPPB therapy. Non-invasive positive pressure venti-
lation (NIPPV) with continuous positive airway pressure (BiPAP)
has now replaced the old traditional method of IPPB. Intubation
and assisted ventilation is required in cases of acute respiratory
failure refractory to treatment with NIPPV and other conservative
methods.
Sleep Apnea Syndrome

Arterial desaturation occurs during periods of apnea and hypopnea
during sleep. No desaturation is however demonstrable during
the awake periods unless a patient has developed respiratory
failure due to other associated problems or complications. Positive
pressure therapy delivered through nasal mask is the treatment of
choice.
Although there is limited evidence to suggest the usefulness of

oxygen administration to improve ventilation and abolish an apneic
episode, this remains largely an unproven benefit. In fact, there is
a theoretical basis to believe that oxygen may prolong the period
of apnea by delaying the arousal threshold. It may also result in
more severe hypoventilation. Therefore, oxygen may neither
prevent the sleep disturbance nor the excessive daytime sleepiness.
Unlike, chronic obstructive pulmonary disease, there is no improve-
ment in the quality of life in sleep apnea syndrome on long-term
oxygen use. But oxygen therapy does improve the arterial
oxygenation during sleep. Therefore, it does help to avoid cardio-
vascular complications of arterial desaturation. It may also help in
alleviation of symptoms related to obstructive sleep apnea. It is
sometimes considered as a safe treatment option in patients who
fail to comply with CPAP therapy.
Interestingly, sleep apnea may improve at high altitude due to
the ventilatory stimulation induced by hypoxia. But there is little
work on this subject on low landers with sleep apnea syndrome
on ascent to a high altitude. On the other hand, the nocturnal
desaturation as well as its complication may actually deteriorate
at high altitude. Supplemental oxygen will be required in all such
patients to prevent complication such as cardiac arrhythmias and
excessive daytime fatigue.
Pulmonary Hypertension and Cor Pulmonale

Pulmonary hypertension is defined as the elevated resting
pulmonary vascular pressure of more than 30/15 mm Hg or the
mean pressure of more than 20 mm Hg in an adult. There are a
number of clinical conditions which determine the etiology and
the type of pulmonary hypertension. It is frequently classified as
secondary, when the underlying cause is definitely identifiable, or
primary in the absence of a known etiology. Idiopathic or primary
pulmonary hypertension is a progressive disease of unknown
etiology which eventually leads to the development of congestive
heart failure. Presence of a chronic lung disease such as chronic
obstructive pulmonary disease, interstitial lung disease or a severe
chest wall abnormality such as kyphoscoliosis frequently gives rise
to pulmonary hypertension and right ventricular enlargement, a
condition known as pulmonary heart disease or chronic cor
pulmonale (Fig. 10.6). The most important cause of pulmonary
174 Oxygen Therapy
Fig. 10.6: Chest radiograph showing bilateral enlarged pulmonary

arteries in a patient with COPD
hypertension is a passive increase which occurs when the left atrial

pressure rises secondary to left ventricular failure or mitral stenosis.
Other common causes of secondary pulmonary hypertension
include a hyperkinetic pulmonary circulation (e.g. severe anemia,
thyrotoxicosis, large arteriovenous fistula), thromboembolic due
to occlusion of distal pulmonary arterioles, or dietary pulmonary
hypertension from chronic ingestion of certain toxins and drugs,
e.g. lead and alkaloids. Dietary form may mimic primary
pulmonary hypertension.
Alveolar hypoxia itself is an important cause of pulmonary
hypertension. Although there is passive increase in pulmonary
arterial pressure due to an elevated chronic pulmonary venous
and capillary hypertension in presence of a chronic lung disease,
alveolar hypoxia also induces reflex pulmonary vasoconstriction
which raises pulmonary vascular pressures. This is commonly seen
in cases of chronic cor pulmonale secondary to a chronic lung
disease or respiratory centre depression, e.g. primary alveolar
hypoventilation syndrome. Pulmonary hypertension in subjects
living at high altitudes is another important clinical condition of
interest which is attributable to the presence of hypoxic conditions.
Pulmonary pressures are shown to revert to normal if they live at

sea levels for several years. It is obvious therefore, that hypoxia is
an important cause of pulmonary hypertension.
Oxygen has a dual role in patients of pulmonary hypertension
especially those with alveolar hypoxia. Oxygen therapy abolishes
hypoxemia and also diminishes hypoxic pulmonary vasoconstric-
tion, thereby lowering the degree of pulmonary hypertension.
Treatment with 100 percent oxygen is shown to act as a selective
primary vasodilator in patients with pulmonary hypertension
regardless of primary diagnosis, baseline oxygenation or right
ventricular function. It is one of the important component of
management of pulmonary hypertension secondary to chronic lung
or chest wall disease (chronic cor pulmonale) or chronic alveolar
hypoventilation syndromes. (Details of this role have been
discussed in chapter on chronic obstructive pulmonary disease).
There is hardly any role of oxygen in management of other forms
of pulmonary hypertension except in patients with documented
resting hypoxemia.
Pulmonary Thromboembolism
Arterial hypoxemia in pulmonary thromboembolism is common
but not a definitive finding. It is generally related to the degree of
occluded pulmonary circulation – the more massive the pulmonary
vascular obstruction, the more severe is the hypoxemia (Fig. 10.7).
Fig. 10.7: Spiral computed tomographic pulmonary angiography showing filling

defects in both the major pulmonary arteries
176 Oxygen Therapy
A major pulmonary artery embolism may induce hypoxemia due

to the associated V Q abnormality or the presence of pulmonary
edema. Hypocapnia is common due to hyperventilation. Occa-
sionally, hypercapnia may be seen when pulmonary embolism
occurs in a patient with marked ventilatory insufficiency. Similarly,
a patient on controlled mechanical ventilation who is unable to
hyperventilate following pulmonary embolism is likely to show
hypercapnia.
Pulmonary infarction is likely to occur in only about 10 percent
of cases of pulmonary embolism. This is attributed to the fact that
the area devoid of the pulmonary circulation continues to get
oxygen from the alveolar air as well as through the anastomotic
channels from bronchial vascular circulation which are shown to
open up immediately following pulmonary arterial occlusion.
Oxygen therapy therefore, has a dual purpose in pulmonary
embolism, i.e. to correct arterial hypoxemia as well as to possibly
prevent the extent of pulmonary infarction by enriching local
oxygen supply to the lung tissue through both the alveolar air and
the expanded bronchopulmonary vascular anastomoses. Oxygen
with a FiO2 of 1.0 is routinely administered via nasal cannulae or
masks. Mechanical ventilatory support may be required to improve
oxygenation in a patient with massive pulmonary embolism,
pulmonary hypertension and shock when the condition so
demands.
Pulmonary vascular occlusion due to air, fat emboli, amniotic
fluid emboli, septic emboli or other materials (e.g. tumor tissue,
talc, trophoblastic tissue, etc.) are some special forms seen in specific
pathological conditions. Objectives and principles of oxygen
administration are generally similar in these patients. But in cases
of air embolism, oxygen has been used to absorb the embolism as
a ‘primary’ method of treatment. Use of 100 percent oxygen and
hyperbaric oxygen therapy have been successfully employed for
this purpose.
Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is the clinical
syndrome characterized by severe dyspnea, refractory hypoxemia
and bilateral radiographic opacities, occurring acutely in a patient
following severe trauma, sepsis, bronchopneumonia or other
respiratory and systemic catastrophies (Fig. 10.8). Different

parameters have been used to define ARDS at different times. Since
1994, the definition proposed by the American European
Consensus Conference Committee has been used more commonly.
This definition recognizes a gradation of severity of clinical lung
injury. Patients with less severe hypoxemia (defined by a PaO2/
FiO2 ratio of 300 or less) are considered to have acute lung injury
(ALI), while those with more severe hypoxemia (PaO2/FiO2 ratio
< 200) are labeled as ARDS. The definition is especially helpful to
decide on the mode of oxygen therapy—most patients with ALI
can benefit from oxygen administration through cannula or mask.
On the other hand, hypoxemia of patients with ARDS is mostly
refractory and requires assisted respiratory support for
oxygenation.
The major objective of oxygen therapy in ALI is to maintain an
adequate tissue oxygenation and not to achieve a normal or high
PaO2. Even a small rise in PaO2 is sufficient to increase the arterial
oxygen content to a satisfactory level. This is because these changes
take place on that portion of the oxyhemoglobin dissociation curve,
Fig. 10.8: Chest radiograph showing bilateral confluent alveolar opacities

178 Oxygen Therapy
where the relationship between PaO2 and oxygen saturation of

arterial hemoglobin, therefore the oxygen content, is quite steep.
In fact, a low blood hemoglobin level is likely to more adversely
affect the oxygen content than a low PaO2 level.
Oxygen therapy in these patients is initiated by a nasal cannula
or a mask and its effects are monitored on oximetry or on
measurements of blood gas tensions. This is not generally successful
in patients of ARDS with a FiO2/PaO2 ratio of < 200. These patients
would require a high alveolar pressure (Palv) achieved with the
help of assisted ventilation. An initial FiO2 of > 0.6 is used as a
temporizing measure but all attempts are made to decrease the
FiO2 as soon as possible. Subsequent management involving
adequate oxygenation requires a balance of maintaining FiO2 and
Palv (or PEEP) to achieve a satisfactory PaO2 (actually arterial
oxygen content) but avoiding the risks of high levels of both FiO2
and the Palv.
Although the total duration of ARDS as well as the outcome of
therapy are significantly determined by the underlying etiology
and the presence of concurrent complications, the oxygen therapy
does not depend upon the cause of ARDS. Requirements for oxygen
continue to increase with the severity of ARDS. But a high FiO2
administered for a longer period heralds the onset of oxygen
toxicity resulting in damage to the alveolo-capillary membrane and
a picture resembling that of severe ARDS. It is therefore, necessary
to limit FiO2 to safer levels of up to 0.6. However, limiting alveolar
pressure takes precedence over limiting oxygen administration
since the risks of a high Palv are greater than those of high FiO2.
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11
Oxygen Therapy for Non-
Pulmonary Disorders
INTRODUCTION
Oxygen is used for a variety of medical and surgical disorders.
Most of these conditions do not show any demonstrable hypo-
xemia. Many of the non-pulmonary disorders in this category have
doubtful indications for oxygen therapy. But there are several other
diseases characterized by tissue hypoxemia for which oxygen has
a genuine role to play.
MEDICAL DISORDERS
Ischemic Heart Disease
Oxygen is administered to patients with coronary ischemia on the
premise that there is arterial and/or tissue hypoxia which can be
reverted with oxygen administration. In fact this is a routine
practice in all patients with acute myocardial infarction. Some
degree of cardiac dysfunction and pulmonary congestion is present
in most patients with acute myocardial infarction even though there
is no arterial hypoxemia. Although oxygen administration may
prove to be useful to improve cardiac muscle and tissue oxygena-
tion and relieve breathlessness, excess administration of oxygen
can lead to systemic vasoconstriction and increased afterload. Also,
it is better to avoid arterial puncture for obtaining blood gas
samples, injury to skeletal muscles during the puncture may cause
release of enzymes which are measured to assess myocardial
infarction.
184 Oxygen Therapy
Myocardial Infarction with Complications

Some people advocate the use of 100 percent O2 for patients with
complicated infarction such as with congestive heart failure or
cardiogenic shock. Oxygen is administered to increase the oxygen
content and delivery to the tissues. It might also improve
myocardial oxygenation and contractility. There is more definite
and urgent indication in the presence of left ventricular failure with
pulmonary congestion and/or edema.
Although inhalation of pure oxygen may not cause pulmonary
toxicity for a few hours, it is not without complications when
prolonged. Therefore, FiO2 should always be guided by PaO2
measurements and administration of 100 percent O2 need not be
prolonged.
Uncomplicated Ischemic Episodes

The role of oxygen during uncomplicated episodes of angina or
myocardial infarction is largely supplemental. Usually there is no
demonstrable fall in arterial PaO2. In such a situation, O2 therapy
can be useful only if the FiO2 is high enough to cause a significant
increase in the amount of oxygen dissolved in plasma. Such an
FiO2 is difficult to achieve in the ambulatory setting. Oxygen is
administered to prevent or treat mild hypoxemia. It is also
debatable whether oxygen administration when given in higher
concentrations of 40 percent or more reduces the extent of
myocardial infarction. There is some evidence to suggest that the
short-term use of oxygen transiently reduces the magnitude and
extent of ECG abnormalities. This is supported by the observations
of experimental studies that an FiO2 of 0.40 reduces the myocardial
creatinine phosphokinase activity, amount of myocardial necrosis
and infarct extension in dogs with ligated coronary arteries; FiO2
of 1.0 had no advantage over FiO2 of 0.4. Even in documented
myocardial infarction, the electrophysiological evidence of
myocardial ischemia could be diminished.
On the other hand, there is lack of clear supporting clinical
evidence. Results of a double blind clinical trial show that there
were no clinically significant advantages in mortality or the indices
of morbidity such as the use of analgesics, incidence of arrhythmias
and systolic time intervals in the oxygen treated group. In fact, the
incidence of sinus tachycardia and the levels of serum asparate
Oxygen Therapy for Non-Pulmonary Disorders 185
aminotransferase levels in this group were higher. No definite

conclusion could be drawn on the use of O2 in reducing acute
myocardial ischemia in a recent systematic review. In another
search of literature, the addition of hyperbaric O2 therapy was
reported to reduce the risk of major adverse cardiac events and
some dysrhythmias. It is implied therefore that O2 therapy in these
patients should be given with caution. Thus supplemental oxygen
should be administered only to patients with arterial oxygen
desaturation (SaO2 less than 90 percent).
Cardiac Failure
Peripheral tissues as well as the internal organs suffer from hypo-
perfusion and hypoxia even though the arterial PO2 is normal.
Oxygen therapy raises tissue oxygen content to maintain the organ
function. Maintenance of an adequate BP and pharmacological
treatment of heart failure is essential to obtain benefit of oxygen
administration. Oxygen therapy is an important constituent of basic
care for acute decompensation of heart failure.
Home oxygen therapy has also been used for severe cardiac
failure. Long-term oxygen therapy is primarily used on nocturnal
basis. In a study of 22 patients of severe heart failure, the treatment
was shown to improve functional capacity after 3 months of therapy
in patients with or without sleep disordered breathing. But no
improvements were seen in either the day time sleepiness or in
sleeplessness at night or sleep related breathing problems.
Similarly, the cardiac function and the health related quality of life
parameters did not improve. There are other reports which
demonstrate significant improvements with nocturnal oxygen
therapy in quality of life as well as in sleep disordered breathing
and left ventricular function in chronic heart failure.
Cerebrovascular Disorders
Eubaric hyperoxemia was shown to improve neurological and
neuropathological outcomes in experimentally induced cerebral
infarction in rats. Maximum benefit was obtained by continuous
therapy. In another study, it was also shown that 100 percent
oxygen, administered within 30 minutes of experimentally induced
stroke in rats salvaged ischemic brain tissue especially in the
cerebral cortex. In humans, high flow O2 therapy was associated
186 Oxygen Therapy
with transient improvement of clinical deficits and MRI

abnormalities in select patients with acute ischemic stroke.
Supplemental oxygen administration is also used in acute stroke
to reduce long-term disability and mortality. But a recent study
demonstrates that O2 therapy is given to most patients of ischemic
stroke without any clear indications. In a large RCT of 550 patients,
no benefit was seen in patients receiving routine oxygen therapy,
and is thus not routinely recommended.
There are several reports on use of hyperbaric oxygen (HBO)
for treatment of neurological diseases and cerebral stroke. HBO is
shown to reduce cerebral edema and intracranial tension. It may
therefore, decrease the extent of brain infarction by improving the
mitochondrial dysfunction. It also diminishes the neurological
deficit and post infarction sequelae. HBO is also reported to
accelerate neurological recovery after spinal cord injury. But most
of the studies suggest that the clinical role of hyperbaric oxygen in
the treatment of cerebral ischemia or any subgroup of stroke
patients is uncertain. No such support has been found in a
systematic search of the Cochrane Stroke Group Trials Register.
Oxygen has been found useful in the treatment of cluster
headaches. It is administered at 7 to 8 L/min for about 10-15
minutes via a face mask. Significant relief is demonstrable in about
75 percent of patients. The effect is attributed to cerebral
vasoconstriction due to oxygen administration.
OTHER MEDICAL DISORDERS

Problems of Oxygen Transport
Oxygen is carried in hemoglobin and plasma when an adequate
blood flow is maintained. Abnormalities of hemoglobin, low
intravascular volume and/or inadequate blood flow can result in
poor oxygen transport and tissue hypoxia. All those states are
therefore potential indications for oxygen administration.
Chronic anemias are well tolerated by most patients who do
not need oxygen. Perhaps the tissues get acclimatized to the low
oxygen supply. Most physicians in this country would recall
patients with hemoglobins of around 5 gm percent carrying on
with routine activities. On the other hand, acute anemia resulting
from a massive bleeding or intravascular hemolysis is tolerated
poorly. Administration of high concentration of oxygen is required
as a short-term measure. Adequate blood replacement is required

for a more definitive treatment.
Role of oxygen for conditions associated with hemoglobin
abnormalities such as methemoglobinemia or sickle cell disease is
not fully established. Oxygen is temporarily useful in acquired
methemoglobinemia especially when severe. This is generally seen
following toxic exposure to drugs or chemicals such as nitrates,
nitrites, sulfonamides and chlorates.
Oxygen is reported to diminish the number of sickle cells in
the presence of HbS (sickle cell disease). In fact it has been observed
that the number of sickle cells in arterial blood is lower than the
venous blood and that administration of 100 percent oxygen
reduces sickling. Oxygen has therefore, been used to treat acute
sickle cell crises but the results are discouraging. In the presence of
pneumonias which are common in sickle cell anemia, oxygen is
administered to treat hypoxia. Hyperbaric oxygen has been tried
with some success.
One important form of acquired hemoglobin abnormality
where oxygen is of definite help is carboxyhemoglobinemia
(COHb) resulting from acute carbon monoxide poisoning. Affinity
of carbon monoxide to hemoglobin is several times more than that
of oxygen. To displace carbon monoxide, one needs to administer
100 percent oxygen which reduces the half-life of COHb from about
320 minutes to 60 to 80 minutes. Oxygen under hyperbaric
conditions is much better as it reduces the half-life of COHb to 20
to 25 minutes. Carbon monoxide poisoning is one of the absolute
indications for hyperbaric oxygen therapy.
Problems of Blood Volume and Cardiac Output

Oxygen transport and delivery to the tissues will also be inadequate
whenever there are problems with either the total blood volume
or the cardiovascular system. While acute blood loss may occur
following an accident or a massive bleeding, plasma is lost in
conditions associated with dehydration or burns. In view of a
relatively small amount of oxygen carried in the dissolved form,
loss of plasma shall not cause any significant change in the oxygen
content of the blood. But in view of the diminished volume and
hypotension, oxygen delivery is greatly impaired. Administration
of oxygen is of limited value in such conditions.
188 Oxygen Therapy
Similarly, cardiovascular diseases responsible for alteration in

the heart rate, preload, after load and myocardial contractility
adversely affect the oxygen supply. Such problems may arise in
conditions associated with hypovolemia, sepsis, myocardial
dysfunction due to ischemia or myocarditis and pulmonary
thromboembolism. Oxygen therapy is useful as a supplement to
the primary treatment of the disease. It should be administered in
a higher concentration of 60 to 100 percent for a short period of a
few hours. Prolongation of such treatment is likely to cause
problems of oxygen toxicity without accruing any significant
benefit.
PALLIATIVE CARE
Patients with terminal illnesses and advanced cancers have
dyspnea as a common problem. This could be attributed to
pulmonary pathophysiological changes due to cancer, concurrent
cardiopulmonary disease and general systemic manifestations.
Oxygen is frequently used in these patients with malignancies or
other end stage diseases to reduce breathlessness. A telephone
survey had revealed that over 80 percent of physicians would
prescribe oxygen for breathlessness or hypoxemia in palliative care
settings. Oxygen is commonly observed to diminish the anxiety
and discomfort associated with respiratory distress. It may also
help in providing some non-specific relief from pain of metastatic
malignancy. There are very few randomized controlled trials on
the palliative role of domiciliary oxygen. In a recent study on 38
patients of primary or secondary lung cancer, oxygen and air were
shown to ease the symptom of dyspnea regardless of the patient’s
arterial oxygen saturation. It was suggested that a trial of 15 minute
therapy at 4 L/min should be given to identify patients who are
likely to benefit from the treatment. It was also suggested that
benzodiazepines might potentiate the effect of oxygen.
The issue of palliative role of oxygen for breathlessness of
advanced COPD, heart failure and cancer was examined by the
Working Party of the Association of Palliative Medicine Science
Committee. The Committee suggested the need to tailor the O2
use to the individual and a formal assessment of its efficacy to
reduce breathlessness and improve quality of life for that individual
patient. In India in particular, it is also comforting for the near and
dear ones of a dying patient to see that oxygen – the ambrosia is

being provided before the final death.
SURGICAL INDICATIONS FOR OXYGEN THERAPY

Abnormalities of gas exchange in surgical patients are present in
not only those with lung diseases but also others, both during the
surgical procedure and in the postoperative period. Oxygen is
routinely administered during anesthesia and surgery. Oxygen
administration is also employed during endoscopic and
interventional procedures even in the absence of anesthesia
especially in patients with history of respiratory disease. Pre-
oxygenation helps to reduce anxiety of interventional stress, besides
the improvements in oxygen reserves. Pulmonary complications
especially infection, atelectasis and thromboembolism are frequent
in postoperative patients. This is especially so in patients who are
smokers, obese, aged (over 60 years) and/or with a pre-existing
lung disease. Hypoxemia with or without CO2 retention may occur
because of the problems of ventilation-perfusion relationship and/
or hypoventilation. Oxygen along with other forms of treatments
is required in all such patients with complications.
Perioperative Oxygen Therapy

The perioperative preconditioning with oxygen improves its partial
pressures in various organs and subcutaneous tissues. It is shown
to reduce the rate of postoperative wound infection by half,
decrease the occurrence of postoperative nausea and vomiting and
improve the outcome of various surgical procedures such as the
laparoscopic and open abdominal anastamotic surgery and liver
transplantation. Oxygen concentrations between 30 and 100 percent
are commonly employed but 80 percent inspired O2 fraction is
shown to be optimal. The practice is simple, inexpensive and well
tolerated without any significant side effects.
On similar basis, oxygen is also used for women in labor in an
attempt to increase the available oxygen from the mother to lessen
fetal distress. But there is hardly any data to support this prophy-
lactic use of oxygen. In a recent Cochrane database series, only
two studies were found on prophylactic use of oxygen in labor
and the results were quite conflicting and inconclusive.
190 Oxygen Therapy
Postoperative State
Immediate
Mild to moderate hypoxemia is common in the first few hours after
general anesthesia especially when abdominal or thoracic surgery
has been done. This is attributed to maldistribution of ventilation
and increased physiological shunting. Central and peripheral
ventilatory depression due to residual effects of anesthetic and pain
relieving drugs, shivering after anesthesia and some degree of
diffusion defect may also contribute to hypoxemia. The effects of
this hypoxemia are likely to be serious in the presence of pre-
existing risk factors or preoperative low arterial oxygen tension.
Such patients would require oxygen therapy for several hours
depending upon the levels of PaO2 and other clinical parameters.
If PaO2 measurements are not available, all such patients are given
oxygen until fully awake and vital signs are normal and stable.
Most patients require only small increases in FiO2 administered
with nasal cannulae at flow rates of 5 to 6 L/min.
Oxygen for patients with significant cardiopulmonary disease
and after pulmonary or cardiothoracic surgery is continued until
blood gas estimations indicate that this is not required. In patients
undergoing peripheral surgery, oxygen is generally not required
unless complications occur. In a recent study, patients receiving
supplemental perioperative oxygen had a significant reduction in
the risk of wound infection.
Late
As stated earlier, pulmonary complications are frequent following
surgery. Indication for oxygen during this period depends upon
the presence of a complication and the severity of hypoxemia. Prima
facie, oxygen has no prophylactic role to prevent the occurrence of
a complication. Its role should be considered in the total therapeutic
armamentarium of a particular problem.
BIBLIOGRAPHY
Ischemic Heart Disease
1. Bennett M, Jepson N, Lehm J. Hyperbaric oxygen therapy for acute coronary
syndrome. Cochrane Database Syst Rev 2005; 18:CD004818.
2. Brostrom A, Hubbert L, Jakobsson P, Johansson P, Fridlung B, Dahlstrom U.
Effects of long- term nocturnal oxygen treatment in patients with severe heart
failure. J Cardiovasc Nurs 2005; 20:385-96.
3. Emerman CL. Treatment of the acute decompensation of heart failure: Efficacy

and pharmacoeconomics of early initiation of therapy in the emergency
department. Rev Cardiovasc Med 2003; 7:S13-20.
4. Fillmore SJ, Shapiro M Killip T. Arterial oxygen tension in acute myocardial
infarction: serial analysis of clinical state and blood gas changes. Am Heart J
1970; 79:620-9.
5. Madias JE, Madias NE, Hood WB Jr. Precordial ST segment mapping: II.
Effects of oxygen inhalation on ischemic injury in patients with acute
myocardial infarction. Circulation 1976; 53:411-7.
6. Maroko PR, Radvany P, Braunwald E. Reduction of infarct size by oxygen
inhalation following acute coronary occlusion. Circulation 1975; 52:360-8.
7. Nicholson C. A systematic review of the effectiveness of oxygen in reducing
acute myocardial ischemia. J Clin Nurs 2004; 13:996-1007.
8. Rawles JM, Kenmure ACF. Controlled trial of oxygen in uncomplicated
myocardial infarction. Br Med J 1976; 1:1121-4.
9. Rotsztain A, Shugoll GI, Lloyd RA. Hypoxemia in acute myocardial infarction
and in coronary insufficiency. Am J Med Sci 1973; 266:253-60.
10. Sakakibara M, Sakata Y, Usui K. Effectiveness of short-term treatment with
nocturnal oxygen therapy for central sleep apnea in patients with congestive
heart failure. J Cardiol 2005; 46:53-61
11. Sasayama S, Izumi T, Seino Y, Ueshima K, Asanoi H. Effects of nocturnal
oxygen therapy on outcome measures in patients with chronic heart failure
and cheyne-stokes respiration. Circ J 2006; 70:1-7.
12. Valencia A, Burgess JH. Arterial hypoxemia following acute myocardial
infarction. Circulation 1969; 40:641.
Cerebrovascular Disorders
13. Al-Waili NS, Butler GJ, Beale J. Hyperbaric oxygen in the treatment of patients
with cerebral stroke, brain trauma, and neurologic disease. Adv Ther 2005;
22:659-78.
14. Bennett MH, Wasiak J, Schnabel A, Kranke P, French C. Hyperbaric oxygen
therapy for acute ischemic stroke. Cochrane Database Syst Rev 2005;
20:CD004954.
15. Carson S, McDonagh M, Russman B, Helfand M. Hyperbaric oxygen therapy
for stroke: A systematic review of the evidence. Clin Rehabil 2005; 19:819-33.
16. De La Morandiere KP, Walter D. Oxygen therapy in acute stroke. Emerg
Med J 2003; 20:547.
17. Flynn EP, Auer RN. Eubaric hyperoxemia and experimental cerebral
infarction. Ann Neurol 2002; 52:566-72.
18. Helms AK, Whelan HT, Torbey MT. Hyperbaric oxygen therapy of cerebral
ischemia. Cerebrovasc Dis 2005; 20:417-26.
19. Kudrow L. Response of cluster headaches to oxygen inhalation. Headache
1981; 21:1.
20. Pancioli AM, Bullard MJ, Grulee ME, Jauch EC, Perkis DF. Supplemental
oxygen use in ischemic stroke patients: does utilization correspond to need
for oxygen therapy? Arch Intern Med 2002; 162:49-52.
21. Ronning OM, Guldvag B. Should stroke victims routinely receive
supplemental oxygen? A quasi randomized controlled trial. Stroke 1999;
30:2033-37.
192 Oxygen Therapy
22. Singhal AB. A review of oxygen therapy in ischemic stroke. Neurol Res
2007;29:173-83.
23. Singhal AB, Benner T, Roccatagliata L. A pilot study of normobaric oxygen
therapy in acute ischemic stroke. Stroke 2005; 36:797-802.
24. Singhal AB, Dijkhuizen RM, Rosen BR, Lo EH. Normobaric hyperoxia reduces
MRI diffusion abnormalities and infarct size in experimental stroke.
Neurology 2002; 58:945-52.
Miscellaneous Medical Problems

25. Booth S, Kelly MJ, Cox NP, Adams L, Guz A. Does oxygen help dyspnea in
patients with cancer? Am J Respir Crit Care Med 1996; 153:1515-18.
26. Booth S, Wade R, Johnson M, Kite S, Swannick M, Anderson H. The use of
oxygen in the palliation of breathlessness. A report of the expert working
group of the Scientific Committee of the Association of Palliative Medicine.
Respir Med 2004; 98:66-77.
27. Fulmer JD, Snider GL. American College of Chest Physicians – National Heart,
Lung and Blood Institute Conference on Oxygen Therapy. Arch Intern Med
1984; 144:1645-55.
28. Lai YL, Chan CW, Lopez V. Perceptions of dyspnea and helpful interventions
during the advanced stage of lung cancer: Chinese patients’ perspectives.
Cancer Nurs 2007;30:E1-8.
29. Snider GL, Rinaldo JE. Oxygen therapy in medical patients outside the
intensive care unit. Am Rev Respir Dis 1980; 122:29-36.
30. Stringer E, McParland C, Hernandez P. Physician practices for prescribing
supplemental oxygen in the palliative care setting. J Palliat Care 2004;
20:303-7.
Surgical Indications
31. Belda FJ, Aguilera L, deLaAsunicion JG, et al. Supplemental perioperative
oxygen and the risk of surgical wound infection. A Randomized Controlled
Trial. JAMA 2005; 294:2035-42.
32. Fairley HB. Oxygen therapy for surgical patients. Am Rev Respir Dis 1980;
122:37-44.
33. Fawole B, Hofmeyr GJ. Maternal oxygen administration for fetal distress.
Cochrane Database Syst Rev 2003; (4):CD000136.
34. Garcia-Botello SA, Garcia-Granero E, Lillo R, Lopez-Mozos F, Millan M,
Lledo S. Randomized clinical trial to evaluate the effects of perioperative
supplemental oxygen administration on the colorectal anastomosis. Br J Surg
2006; 93:698-706.
35. Kabon B, Kurz A. Optimal perioprative oxygen administration. Curr Opin
Anesthesiol 2006; 19:11-8.
36. Leigh JM. Postoperative oxygen administration. Br J Anesth 1975; 47:108.
37. Rehder K. Anesthesia and respiratory system. Can Anesth Soc J 1979;26:
451-62.
38. Tallach RE, Ball DR. Routine pre-oxygenation. Anesthesia 2004; 59:943-5.
12
Long-Term Oxygen Therapy
Long-term oxygen therapy (LTOT) is now a popular mode of

therapy for a variety of respiratory disorders. When LTOT at home
was first introduced it was largely limited to patients with COPD
and chronic respiratory insufficiency. Subsequently, the indications
continued to expand to include almost any chronic respiratory
disease characterized by hypoxemia. In fact domiciliary oxygen is
also useful in those patients who do not demonstrate hypoxemia
such as those with breathing disorders during sleep or exercise.
Hypoxemia in such patients is absent when they are alert and
awake, but gets precipitated during sleep or exercise. Some of the
common conditions for which LTOT has been used with variable
degrees of benefit include COPD, interstitial lung disease,
bronchiectasis, cystic fibrosis, kyphoscoliosis, sleep apnea
syndrome, severe cardiac failure and other causes of chronic
breathlessness. More important than the underlying disease are
the other selection criteria required to be fulfilled for LTOT.
SELECTION OF PATIENTS
All patients with chronic hypoxemic lung disease are potential
candidates for long-term oxygen therapy. Following guidelines are
used to select patients for instituting the treatment:
1. A definitive documented diagnosis responsible for chronic
hypoxemia.
2. An optimal medical treatment should be in effect.
3. Patient in a stable condition.
194 Oxygen Therapy
4. Oxygen administration should have been shown to improve

hypoxemia and provide clinical benefit.
It is important to ensure that the patient is compliant with the
general medical regimen and follows instructions, such as to quit
smoking. Continued smoking not only aggravates the disease
process but also reduces the full physiological benefits of oxygen
and poses inherent safety risk of accidental fires.
Following specific indices are used while prescribing long-term
oxygen.
1. At rest, in non-recumbent position, the PaO2 of 55 mm Hg or
less.
2. Patients with PaO2 of more than 55 mm Hg are considered in
the following conditions:
a. Patient on optimal medical treatment, with demonstrable
hypoxic organ dysfunction, such as secondary pulmonary
hypertension, cor pulmonale, polycythemia or CNS
dysfunction.
b. When there is a demonstrable fall in PaO2 below 55 mm Hg
during sleep, associated with disturbed sleep pattern,
cardiac arrhythmias or pulmonary hypertension. These
patients may be benefited by nocturnal oxygen therapy.
c. When there is demonstrable PaO2 fall during exercise and
oxygen administration is shown to improve exercise
performance, duration or capacity. These patients may
benefit by oxygen during exercise. They may also be
administered supplemental oxygen before and after the
exercise.
It is important to mention that PaO2 (of 55 mm Hg or less) is
not the only guide to prescribe oxygen. It is the presence of a chronic
hypoxemic pulmonary disease. Healthy people living at an altitude
of 10,000 feet or more do not require oxygen. They are able to
acclimatize to even severe degrees of hypoxemia. In fact man has
survived without oxygen even at the top of Mt. Everest (altitude
29028 ft). It is a patient with a chronic pulmonary disease who
loses the ability to adapt, who needs long-term oxygen.
BENEFITS
Long-term oxygen therapy is definitely shown to benefit patients
with COPD. It has been used on other chronic pulmonary
hypoxemic diseases as well. There is however a limited experience.
Long-Term Oxygen Therapy 195
In COPD, it improves survival, and the quality of life. Exercise

tolerance is increased and cognitive mental function improved.
Some other conditions where LTOT has been used include
idiopathic pulmonary fibrosis, severe heart failure, extensive
bronchiectasis and severe kyphoscoliosis. In our experience of its
use in chronic interstitial pulmonary fibrosis and respiratory
insufficiency, breathlessness was significantly reduced and patients
were more comfortable at home. There was an appreciable
reduction in pulmonary hypertension and right ventricular failure
attributable to supplemental domiciliary oxygen therapy when
added to the optimal medical regimen.
INDICATIONS
There is evidence in literature to support the role of long-term
domiciliary oxygen therapy in stable COPD; however, the role of
oxygen therapy in patients who have only nocturnal hypoxemia
or hypoxemia during exercise only, is logical but not well supported
by evidence from the literature.
Long-term Oxygen Therapy in Patients Who Have Daytime

Resting Hypoxemia
Two landmark studies, i.e. the Medical Research Council (MRC)
trial and the nocturnal oxygen therapy trial (NOTT) have shown
that continuous long-term oxygen therapy can improve survival
in patients with COPD and resting daytime hypoxemia (Fig. 12.1).
The results of both the randomized controlled trials are
summarized below:
Nocturnal Oxygen Therapy Trial (NOTT)

A total of 1,043 patients from six centers in the United States were
screened for inclusion in the study. Only 203 patients were finally
included; others were excluded because of many reasons including
major concomitant diseases and patients who had previous oxygen
therapy or PaO2 greater than 59 mm Hg. The study was not blinded.
One hundred and two patients with hypoxemic COPD were
randomly allocated to nocturnal oxygen therapy and 101 to
continuous oxygen therapy. The oxygen source was an oxygen
concentrator, liquid oxygen or compressed gas (flow 1-4 L/min).
196 Oxygen Therapy
Fig. 12.1: Graph showing increased survival in patients receiving LTOT
The mean age was 65.7 years in the nocturnal oxygen therapy group
and 65.2 years in the continuous oxygen therapy group. Most
patients were male, 80.4 percent in the nocturnal oxygen therapy
group (82 percent used oxygen for 13 hours or less) and 77.2 percent
in the continuous oxygen therapy group (56 percent used oxygen
for 19 hours or more). The mean PaO2, PaCO2, FEV1, were 51 mm
Hg, 43 mm Hg and 29 percent respectively, and were not different
between the two groups.
There was a significant difference in survival in favor of the
continuous oxygen therapy group, and the overall mortality in the
nocturnal oxygen therapy group was 1.94 times that of the
continuous oxygen therapy group. The continuous oxygen therapy
group also showed improvement in stroke volume index,
pulmonary vascular resistance and pulmonary artery pressure but

not in other hemodynamic parameters compared to nocturnal
oxygen group.
Medical Research Council (MRC) Oxygen Therapy Trial

Eighty-seven patients with a diagnosis of COPD with hypoxemia
(PaO2 40-60 mm Hg) and right failure were randomized to receive
continuous oxygen therapy (15 hours a day) or no oxygen. The
study was not blinded. The treatment group received oxygen
therapy for at least 15 hours a day at a flow-rate of a minimum of
2 L/min. The mean age, FEV1, PaO2, PaCO2, were around 58 years,
0.7 liters, 50 mm Hg and 54 mm Hg respectively. There was an
improvement in survival in the group receiving oxygen therapy
(Peto Odds Ratio 0.42, 95 percent CI 0.18 to 0.98) but only beyond
500 days of treatment. Although, the mortality was improved in
female patients for the oxygen-treated group from the
commencement of treatment, the numbers were too small for any
meaningful interpretation. Although the total pulmonary resistance
and the pulmonary artery pressure increased in the control group,
this was not statistically significant but suggested benefit from
oxygen therapy.
Data from these two trials clearly showed that there was a
survival benefit with continuous oxygen therapy but none with
nocturnal oxygen therapy alone. Recent studies have also shown
that LTOT can decrease hospitalization in patients with COPD.
Importantly, oxygen should be taken for as long as possible as
hypoxemia related pulmonary vascular changes could occur
rapidly. In fact there is some data to show that these changes can
occur in less than three hours. The current widely accepted
indications for LTOT in COPD are summarized below (Box 12.1).
On the other hand, there is no justification for the prescription
of LTOT in patients with mild hypoxemia defined as PaO2 between
56-65 mm Hg. In a recent study by Gorecka et al, 135 patients with
Box 12.1: Indications for oxygen therapy in patients with chronic obstructive
pulmonary disease
• PaO2 ≤ 55 mm Hg
• PaO 2 56-59 mm Hg plus either pulmonary hypertension or hematocrit
≥ 55%
198 Oxygen Therapy
COPD who had severe airflow limitation (FEV1 less than one liter)
with PaO2 of 56-65 mm Hg, were randomly allocated to a control
(n = 67) or LTOT (n = 68) group. The patients were followed every
three months for at least three years or until death. There were no
significant differences in survival rates between patients treated
with LTOT and controls, nor did longer oxygen use (over 15 hours
per day) improve outcome. Younger age, better spirometric values,
and higher body mass index predicted better survival. It can be
therefore concluded that domiciliary oxygen treatment does not
prolong survival in patients with COPD with moderate hypoxemia.
It is the airway limitation which seems to determine survival in
this group of patients.
Initiation and reassessment of LTOT: Patients with COPD who have
FEV1 less than 40 percent and/or pulmonary hypertension should
be routinely screened for LTOT. Before prescribing LTOT, the
indication should be confirmed on atleast two occasions two to
three weeks apart with a resting arterial blood gas analysis
performed on room air. Patient should be stable on maximal and
optimal medical therapy including a complete pulmonary
rehabilitation program. Smoking cessation should be strictly
enforced. The oxygen flow rate should be set to maintain a PaO2 >
60 mm Hg during waking and at rest; usually 1-2 L/min through
nasal prongs would generally suffice. The oxygen flow rate should
be increased by 1 L/min during sleep, exertion and air travel.
The goal of LTOT should be confirmed by performing an arterial
blood gas analysis after one to two months of initiating oxygen
therapy, and documenting a PaO2 > 60 mm Hg; a repeat blood gas
analysis also helps in assessment of the hypercapnic response to
oxygen therapy. Patients with significant hypercapnia with oxygen
therapy may also require domiciliary non-invasive pressure
support ventilation.
Oxygen Therapy in Patients Who Have No Daytime Resting

Hypoxemia But Develop Hypoxemia During Sleep
The role of oxygen therapy, in patients who have no daytime
hypoxemia but are hypoxemic during sleep only, is controversial.
Patients with COPD can experience prolonged episodes of oxygen
desaturation during rapid eye movement sleep, and studies have
shown that nocturnal hypoxemia can exacerbate pulmonary
hypertension in patients with COPD but recent studies have

challenged this finding. Although it seems logical to administer
oxygen in patients with nocturnal hypoxemia, the current literature
does not support this fact. Data is insufficient to make general
recommendations, and further studies are needed. The current
practice is to rule out concomitant obstructive sleep apnea in
patients with COPD and those who have got nocturnal symptoms,
and to intensify medical management (smoking cessation, inhaled
corticosteroids, long-acting beta-2 agonists anticholinergic agents
and pulmonary rehabilitation). If the patient is found to have
nocturnal without daytime hypoxemia, oxygen therapy in this
subgroup of patients may be indicated if the patient has evidence
of chronic hypoxia-related sequelae like polycythemia or
pulmonary hypertension. Another subgroup of patients whose
oxygen saturation repeatedly falls below 88 percent for more than
one-third of the night may also benefit from nocturnal oxygen
therapy.
Oxygen Therapy in Patients Who Have No Daytime Resting

Hypoxemia But Develop Hypoxemia During Exercise
Intermittent oxygen therapy can be used in patients for indications
described above, where the benefits of LTOT are well known. The
benefits of pulmonary rehabilitation on exercise capacity and
quality of life in COPD patients support the use of ambulatory
oxygen in all patients on LTOT to allow them to achieve their full
potential in terms of reduced mortality from continuous oxygen
therapy. The role of intermittent ambulatory oxygen therapy in
patients, who do not fulfill the criteria for LTOT, is controversial.
There is evidence to show an improved exercise tolerance and
improved quality of life in patients who use intermittent oxygen
therapy prior to exercise. On the other hand, some studies do not
show significant benefit. There are a few studies, which have shown
benefit even with room air itself, and the hypothesis is that the
cold effect of the air probably helps in resolution of dyspnea. Thus
the evidence from the available literature is inadequate on the role
of intermittent oxygen therapy, and more studies are required to
amicably solve this issue.
In the absence of any definite data, intermittent oxygen therapy
may be prescribed in individual patients in whom the benefits
(dyspnea, exercise capacity) have been definitely proven by an
200 Oxygen Therapy
exercise test (complete incremental exercise testing, six-minute

walk test, shuttle test) especially in those patients awaiting lung
transplantation or lung volume reduction surgery, to maintain an
increased level of fitness prior to surgery.
Oxygen Therapy for COPD During Air Travel

This topic is dealt in detail in Chapter 14.
Modern aircraft are pressurized to cabin altitudes up to 2438 m
(8000 ft) although this limit may be breached in emergencies. At
2438 m (8000 ft), the PaO2 will be equivalent to that of breathing 15
percent oxygen at sea level. In a healthy individual, the PaO2 at
2438 m (8000 ft) will generally fall to 53-64 mm Hg. This may
exacerbate hypoxemia in patients with COPD, especially those who
are hypoxemic at sea level. There are three common methods of
assessing the requirement for oxygen therapy during air travel,
the so-called pre-flight hypoxia testing.
1. Six-minute walk test: Although not specifically evaluated for
the purpose of pre-flight hypoxia testing, failure to complete
the task in terms of distance or time, or moderate to severe
respiratory distress recorded on a visual analogue scale, will
alert the physician and the patient to the possible need for in-
flight oxygen.
2. Prediction equations: Another method is the use of prediction
equations that have been derived from patients with COPD
who have had measurements of PaO2 in a hypobaric chamber,
while breathing FiO 2 at 15 percent. The accuracy can be
improved by inclusion of FEV1 in the equation. These equations
are reliable to establish upper and lower thresholds for “no in-
flight oxygen required” (SpO2 >95%) or “in-flight oxygen
needed” (SpO2 <92%). One commonly used prediction equation
is given below:
PaO2(Alt) = 0.519 × PaO2 ground (mm Hg) + 11.855 × FEV1
(L) – 1.760
3. Hypoxia challenge test: The ideal test is to expose the subject to
hypoxia in a hypobaric chamber. The facility for this testing is
not widely available. A surrogate is to administer FiO2 at
15 percent and measure the PaO2. Although not validated, a
PaO2 less than 50 mm Hg predicts requirement of in-flight
oxygen therapy.
In practice, oxygen is generally prescribed on the basis of the

prediction equations as the six-minute walk test is cumbersome
and hypoxia testing is not routinely available in developing
countries.
In conclusion, oxygen therapy in COPD has several definite
benefits such as improvement in survival, improvement in
intellectual functioning, decrease in pulmonary vascular resistance
and pulmonary arterial pressure, decrease in red cell mass and
diminution in the complications of polycythemia; other potential
benefits include increased exercise capacity, decrease in dyspnea,
improved quality of life and decrease in hospitalization. In view
of these benefits, oxygen therapy now occupies a key role in the
long-term management and rehabilitation of patients with COPD.
OXYGEN DOSAGE
Most of the COPD patients are prescribed low flow concentrations
at 1-2 L/min. Higher flow rates are required for some of the
patients, especially those with other chronic respiratory diseases.
The treatment is guided by PaO2 which should be maintained at
60 mm Hg or so (SaO2 of 85-90%). During the period of exercise,
sleep or other activities, the flow rate may be increased by another
1-2 L/min. While continuous therapy is required for patients who
show hypoxemia at rest, intermittent treatment during specific
periods may be used for patients who demonstrate intermittent
hypoxemia.
SUPPLY SOURCES
There are three main types of systems commercially available for
supply of oxygen at home: compressed gas cylinders, liquid oxygen
and oxygen concentrators.
Compressed Gas Cylinder

The commonly used gaseous system in the home consists of H or
K cylinders containing compressed oxygen. A pressure regulator
and a flow meter are required to adjust the amount delivered to
the patient. When continuously used at 2 L/min, each cylinder
will last about 2½ days necessitating frequent fillings. They are
also heavy giving an unsightly look to the bedroom. Moreover,
regulation of pressure and flow require some effort and additional
202 Oxygen Therapy
help. For the present, compressed gas cylinders are most commonly
used for domiciliary use in India because of the lower costs and
relatively easy availability in even small towns compared to the
other systems. Gas cylinders also form a good back up facility in
case of a failure of other systems. Portable D and E cylinders are
available for ambulatory use. Aluminium cylinders are also
available. These are lighter in weight than the cast iron cylinders.
They are better suited for portability, but are costlier.
Liquid Oxygen System (LOX)

The LOX system for use at home is a smaller version of the bulk
liquid system used in the hospitals. The reservoir (stationary) unit
contains about 70 to 90 pounds of oxygen in the liquid state at -
273oF. It lasts for 4½ to 10 days at a continuous flow rate of
2 L/min. The vessel is about 3 to 4 feet tall and about 18 inches in
diameter. The internal pressure is about 22 to 50 psi which can
generate flow rates of 0.25 to 15 L/min. In addition to the stationary
unit, there is a light weight portable unit which can be carried by
the patient on the shoulder for ambulatory and outdoor activities.
The portable units are designed to be filled from the stationary
reservoir unit with safety.
There is a minor loss of gaseous oxygen from the liquid gas
units at a rate of about 1 lb/day. Therefore, the units should not be
stored in a small and closed space to avoid gaseous accumulation
posing a fire hazard.
Liquid gas system is more practical but expensive. It is not easily
available in this country as yet.
Oxygen Concentrator
It is an electrical device that provides oxygen from the atmospheric
air. It employs a molecular “sieve” that filters out the nitrogen
molecules, water vapour and other trace gases. It can deliver 85
percent to 90 percent oxygen at flow rates of upto 4 L/min. The
polymeric membrane concentrators can deliver 30 to 40 percent
oxygen at flow rates of upto 10 L/min.
A concentrator is ideal for use at home. It obviates the need of
regular filling of the tank. Its initial cost is high but the running
cost is negligible. Proper maintenance of equipment and
replacement of filters is required. A back up source of oxygen
supply (e.g. compressed oxygen cylinder) is necessary in case of a

power failure.
There is generation of some noise and heat that some patients
may find bothersome. This can be avoided by placing the
concentrator in an adjacent room and using a longer oxygen tube.
This may increase the back pressure necessitating the use of a
pressure compensated flow meter to assure accurate oxygen flow.
DELIVERY DEVICES
Devices used to deliver oxygen include cannulae, prongs and
masks. Those are essentially the same as used in the hospitals
(Chapter 20). Nasal cannulae and prongs are preferred because of
the cosmetic reasons. It is easy to conceal oxygen tubing by applying
it to ordinary thick rimmed frames of eye-glasses (“Oxyspecs”).
Different kinds of “oxyspecs” and other devices are now commer-
cially available for this purpose.
There is no difference in the type of delivery devices used with
different types of oxygen sources.
Humidification is not essential at flow rates of less than
4 L/min unless the patient complains of dryness of the nose or
mouth, nasal irritation or crusting. Humidifier is a potential source
of infection and needs regular cleaning and disinfection. Disposable
humidifiers significantly increase the costs.
OXYGEN-CONSERVING DEVICES
Oxygen therapy on long-term basis is a costly proposition. Many
patients tend to conserve oxygen by reducing the flow as well as
the duration of administration. Moreover, the standard oxygen
supply devices allow the flow of oxygen both during inspiration
and expiration. In fact it is only 15 to 20 percent part of respiratory
cycle during inspiration which delivers the oxygen to the alveoli
effectively. A lot of oxygen delivered to the patient is therefore,
wasted in the surroundings.
Several methods have been devised to conserve oxygen in the
recent years. It is possible to save upto 50 percent oxygen with
some of these methods. There are three types of devices
commercially available for this purpose.
204 Oxygen Therapy
Reservoir Oxygen Delivery

With this method, oxygen which is stored during exhalation in a
reservoir (appx. 20 ml) becomes available at the beginning of
inhalation. There are two types of reservoir cannulae in use:
Pendant Reservoir (Oxymizer Pendant)

The reservoir coupled to the nasal prongs consists of a collapsing
chamber that hangs at the chest. It saves oxygen between 2:1 to 4:1
over continuous flow oxygen therapy.
“Moustache Configured” Oxymizer

The reservoir sits right on the face thus being noticeable and
cosmetically unsightly. Its efficiency is similar to that of pendant
reservoir.
Both the reservoirs provide equivalent oxygen saving at flow
rates of 0.5 L/min. But the pendant reservoir can be operated at
0.25 L/min to achieve the oxygen saturation similar to those of a
flow of 1 L/min with a steady flow delivery system. The reservoirs
maintain a saving of 3:1 to 4:1 over steady flow during exercise as
well.
Recently, a pendant which allows pursed lip breathing has been
described. It combines oxygen saving mechanism of the pendant
with that of pursed lip breathing. It increases the efficiency of
oxygenation to about 7:1 compared with standard steady flow
systems.
Electromechanical Pulsing Devices

The electromechanical demand devices deliver oxygen only during
inhalation. Delivery of oxygen during exhalation is saved. It consists
of a box shaped unit attached to the outlet of the oxygen source
and a solenoid valve which opens on sensing the decrease in
pressure as the patient inhaled. A “pulsed” volume of 15 to 35 ml
of oxygen is delivered each time. It reduces the amount of oxygen
usage by 35 to 75 percent producing a saving of about 7:1 compared
with continuous flow system.
Electronic demand devices are also available for use with
portable cylinders as well as with piped-in-oxygen system in the
hospitals. Some of the demand devices available in the Western
market include Pulsair, DO2 S and Oxymatic, etc. They significantly

add to the costs and produce a “clicking” sound at the bed side.
Both these factors make it unacceptable to many of the patients.
Transtracheal Catheters
It is a narrow lumen catheter which resembles an angiocatheter. It
is inserted directly into the trachea. Oxygen is delivered through a
tubing attached to a small fitting at the neck. There are several
reasons to believe that it is more effective.
1. Oxygen is delivered ahead of the nasopharynx bypassing some
of the anatomical dead space.
2. The upper airways serve as a reservoir towards the end of
expiration.
3. The oxygen delivered is not diluted with atmospheric air prior
to entering the respiratory tract.
Transtracheal catheters are useful for patients receiving very
high liter flows. They save oxygen by an efficiency factor of 2:1 to
3:1. Its efficiency can be further enhanced by combining it with
pulsed oxygen delivery.
Intratracheal catheter is more acceptable to the patient since
the look is not unsightly. There is nothing on the face and it can be
easily hidden beneath the collars. Moreover, there is no nasal or
auricular irritation, it does not get dislodged during sleep.
There is a small risk of infection and subcutaneous emphysema
when the catheter is introduced. It can get plugged with mucus
and thick secretions. It should therefore be cleaned on daily basis.
Some of the transtracheal catheters available commercially are
Heimlich Microtrach, the SCOOP catheter and the intratracheal
oxygen catheter (ITOC). The ITOC is implanted through a
subcutaneous tunnel from the chest wall to the trachea. It is of
more permanent nature.
Patients with transtracheal catheters should have conventional
cannulae at home for use in an emergency when the transtracheal
catheter gets blocked due to kinking or plugging.
RISKS OF LONG-TERM OXYGEN THERAPY

There are three types of risks associated with long-term use of
oxygen—physical, functional and cytotoxic.
206 Oxygen Therapy
Physical Risks
Since oxygen supports combustion, the tanks are potential risks of
fire hazard and tank explosion. In fact these risks are rather small.
It is highly desirable that smoking is stopped with its use. The
supply source (such as a cylinder) should not be kept in a small
closed room to avoid accumulation of the vented gas.
The other minor risks of oxygen therapy include the injury to
the nose and face from catheters and masks. Dryness and crusting
may occur from dry, nonhumidified gas.
Functional Risks
Oxygen therapy may accentuate hypoventilation in patients with
COPD. This may induce hypercapnia and carbon dioxide narcosis
(Chapter 10). In practice, with low flow oxygen therapy, the risk is
rather small. Therefore, chronic carbon dioxide retention is not
considered a contraindication for long-term oxygen therapy. It has
been suggested that arterial pH is a better guide to monitor therapy
than PaCO2. Patients with carbondioxide retention also tolerate
and benefit from long-term oxygen as long as pH does not show
acidemia.
Cytotoxic Damage
Long-term oxygen can cause structural damage to the lungs. Both
proliferative and fibrotic changes of oxygen toxicity have been
shown at autopsy on COPD patients treated with long-term oxygen.
But there is no significant effect of these changes on clinical course
or survival of these patients. Most of the structural damage
attributable to hyperoxia results from high FiO2 administration in
acute conditions.
Oxygen for Air Travel

Patients with COPD and other chronic hypoxemic conditions
require supplemental oxygen during air travel (Chapter 14).
Ambient pressure in the commercial aircrafts is maintained to that
of an altitude of 8500 feet or less. But this may be inadequate for
patients with chronic hypoxemic lung disease. Personal oxygen
supply equipment is generally not allowed on the aircrafts.
Requirement of oxygen during travel, therefore, must be
communicated before hand and inquiries made about the available

supply facilities. It is quite likely that precise oxygen supply
required by the patient, may not be feasible during travel.
PERSPECTIVES OF DOMICILIARY OXYGEN USE IN INDIA

Long-term oxygen therapy is picking up in the country. This is
much more so in larger metropolitan cities where both the facilities
and the expertise are more easily available.
An organized domiciliary oxygen and rehabilitation pro-
gramme is yet to establish at most places in India. In spite of the
several limitations, we have used home oxygen therapy in COPD
and other chronic lung diseases since 1970s. On an average, 10 to
12 new patients are recruited in the programme every year.
Our criteria are quite restrictive. Before deciding on prescribing
the therapy, it is important to assess the educational and
psychological status of the patient (and the family), social
background, place of residence, income and employment position.
Availability of an organized supply of O2 is lacking and the costs
are high. Feasibility of supply is poor and is much more so in rural
areas and small towns. Occasionally, patients even from smaller
towns have succeeded in overcoming difficulties. One such patient
from a distant city who could afford and organize domiciliary
oxygen and assisted ventilation at home had useful prolongation
of life for about two years.
COPD remains the chief indication for LTOT in our experience.
Some other conditions include idiopathic pulmonary fibrosis,
chronic bronchiectasis, kyphoscoliosis and post pneumonectomy
pulmonary hypertension and respiratory insufficiency. Most
patients had relied on commercial oxygen supply. In fact, some
patients from smaller towns had used oxygen tanks procured from
vendors using oxygen for welding and other industrial purposes.
In spite of an irregular and inadequate treatment employed by
the patients, significant benefits were reported. There was
subjective improvement in general well-being and alertness, relief
in sleep disturbances, morning headaches and fatigability. On
investigation, there was an improvement in mean lung function
parameters, cardiac size and pulmonary hypertension assessed on
chest roentgenography.
Some of the important problems stated by most of the patients
related to difficulties of procurement and costs. There are limited
208 Oxygen Therapy
sources of supply. Moreover, the medical expertise and advice to

supervise domiciliary treatment is lacking. Patients’ resources to
afford the treatment are also scanty. There are no clear guidelines
available regarding reimbursement of costs on oxygen and the
apparatus—a facility available to government and several other
private/public sector employees for other treatments. One does
expect that most of the difficulties shall resolve in due course of
time.
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13
Oxygen Therapy in the
Intensive Care Unit
AN Aggarwal
INTRODUCTION
Not all critically ill patients in an ICU require supplemental oxygen.
The need is determined by a combination of clinical indicators and
laboratory parameters. In patients admitted to the ICU, reliance
on clinical features alone can be hazardous, as several clinical
features of inadequate oxygenation are non-specific and can be
seen in several other medical conditions commonly encountered
in critically ill patients. For instance, cyanosis could result from
inadequate tissue perfusion due to hypotension, rather than
hypoxemia per se. Similarly, other commonly described mani-
festations of inadequate oxygenation such as dyspnea, tachypnea,
altered sensorium, arrhythmias, etc. are also otherwise commonly
seen in critically ill patients. Such clinical information therefore
needs to be interpreted in the context of more objective measures.
ASSESSMENT OF NEED FOR SUPPLEMENTAL OXYGEN

Non-invasive monitoring of oxygen saturation (SaO2) by pulse
oximetry and arterial blood gas (ABG) analysis are the two most
common ways of objective assessment for supplemental oxygen.
In contrast to other patients admitted to a health care facility,
interpretation of pulse oximetry readings and/or ABG reports from
critically ill patients is complicated by several disease and patient
related factors. Pulse oximetry, although a simple and widely
available technique, gives inconsistent results in patients with
212 Oxygen Therapy
hemodynamic instability, especially in conditions associated with

hypotension or low pulse volumes. The technique is also not of
much use in patients with altered hemoglobin (such as carbon
monoxide poisoning, methemoglobinemia). In chronically
hypoxemic patients, compensatory mechanisms such as
polycythemia, shift of oxygen-hemoglobin dissociation curve and
increased oxygen extraction allow better tissue oxygenation even
at lower levels of blood oxygenation, and this must be taken into
consideration when deciding on oxygen therapy once these patients
are admitted to the ICU with a disease exacerbation.
Measurements of both SaO2 and PaO2 can be normal despite
substantial tissue hypoxia associated with anemia, low output
cardiac states, and disorders resulting in failure of tissue to utilize
oxygen. Under such circumstances, one needs to be guided by tissue
oxygenation rather than blood oxygenation. Two independent
procedures—measurement of mixed venous oxygen saturation and
gastric tonometry—have been developed to assess tissue
oxygenation in critically ill patients. Gastric tonometry is an indirect
method to assess adequacy of splanchnic perfusion and ischemia.
Mixed venous oxygen saturation ( ScvO2) is measured invasively
through a catheter placed in the superior vena cava, and reflects
the amount of oxygen left over in blood after body tissues have
removed whatever oxygen they need. A low ScvO2 value suggests
that the cardiac output and level of oxygenation are insufficient
for meeting the metabolic demands of body tissues. Routine
measurement of ScvO2 has recently been suggested as a component
of the ‘early goal directed therapy’ in critically ill patients.
INDICATION AND UTILITY OF OXYGEN IN

CRITICALLY ILL PATIENTS
Oxygen, like any other drug used in the ICU, works best only if
given when necessary, and in the correct dosages. Failure to realize
this, and considering supplemental oxygen as a universal panacea,
is likely to lead to over prescription of oxygen. This not only adds
to the cost of ICU care, but also instills a false sense of security in
the clinician’s mind, without actually contributing anything
positive to patient outcome.
Before prescribing oxygen to an acutely ill patient, one should
ensure that the airway is sufficiently patent to be able to deliver
oxygen to the lungs. This might require endotracheal intubation
Oxygen Therapy in the Intensive Care Unit 213
or tracheostomy before oxygen supplementation is actually started.

Oxygen should always be started and titrated based on an objective
evaluation of patient’s oxygenation status. In certain emergency
situations (such as cardiac or respiratory arrest, or acute onset
respiratory distress or hypotension) oxygen supplementation can
be initiated empirically while detailed clinical and physiological
evaluation is being carried out. Even under these circumstances,
arterial blood gases (ABG) should be analysed as quickly as
possible, not only to assess level of hypoxemia, but also the acid-
base status. In general, oxygen therapy is necessary for any patient
in the ICU with documented arterial hypoxemia (PaO2 less than
60 mm Hg).
Hypoxemia results from several mechanisms in critically ill
patients managed in any ICU. Increasing the partial pressure of
inspired oxygen (FiO2) can ameliorate only some of these defects
by raising the oxygen content in arterial blood. Oxygen therapy is
the essential cornerstone of management of respiratory failure of
several etiologies (such as acute respiratory distress syndrome,
exacerbations of asthma or COPD, etc.). When hypoxemia results
from ventilation-perfusion mismatch related to consolidated,
atelectatic, or otherwise disease lung zones, oxygen supplemen-
tation is generally helpful, although the exact response is
unpredictable and dependent on the quantum and distribution of
mismatched areas. Similarly, in patients with alveolar hypo-
ventilation, oxygen supplementation rapidly corrects hypoxemia,
but the primary aim must be to correct the underlying cause.
However, oxygen therapy is of lesser benefit if there is a problem
with blood circulation (e.g. severe hypotension, vascular blockade,
large right to left shunt) or if hypoxia occurs at tissue level (e.g.
severe anemia); under these circumstances, oxygen therapy can at
best provide some additional time to the clinician while the
underlying disorders are being tackled.
Oxygen therapy is generally begun at high FiO2 levels for most
patients in the ICU. It is customary to start with 100 percent oxygen
in patients who have sustained a cardio-respiratory arrest. Patients
with acute hypoxemic respiratory failure generally require oxygen
at an initial FiO2 exceeding 0.50; this can then be titrated upward
or downward depending on clinical and physiological response.
For patients with hypercapnic respiratory failure (especially those
with a preexisting component of chronic hypoventilation), it is
214 Oxygen Therapy
advisable to begin with lower FiO2 levels to avoid worsening CO2

retention once the PaO2 is normalized. However, one must never
be overcautious in providing less than optimum FiO2 to these
patients, as hypoxemia is always more deleterious than hyper-
capnia.
OXYGEN DELIVERY IN THE ICU

There are three main components of oxygen administration in an
ICU - (a) the control component that includes regulators and
flowmeters between the source of high pressure supply and the
point of oxygen delivery to patient, (b) blending of oxygen and air,
and (c) administration of oxygen through devices such as masks,
etc.
Almost all well-equipped ICUs have continuous pressurized
oxygen and air supply available at each patient bed. The main
advantage of such a supply mode is that both oxygen and air can
simultaneously be fed into a oxygen blender and the output FiO2
can be precisely controlled. The centralized hospital source of such
supply could be variable, and these issues are discussed elsewhere
in this book (Chapter 23). In some resource-limited settings, oxygen
cylinders are used to provide oxygen. Patients requiring oxygen
through mask at low FiO2 can also be managed with oxygen
concentrators. Most ICUs have oxygen cylinders and/or
concentrators as a backup in case of failure of central oxygen supply.
Oxygen can be delivered to patients either non-invasively
through masks or cannulas, or as a component of assisted
respiratory support, either though non-invasive positive pressure
ventilation (NIPPV) or through conventional mechanical
ventilation after endotracheal intubation. The choice of method of
oxygen delivery depends entirely of the patient’s clinical condition.
Although the proportion of patients receiving oxygen as part of
assisted respiratory support is much higher in an ICU as compared
to other hospital areas, several patients can still be managed with
non-invasive oxygen supplementation.
OXYGEN SUPPLEMENTATION THROUGH MASKS

The principles and utility of oxygen supplementation through
masks and cannulas has been detailed elsewhere. A few important
points however should be remembered in the ICU scenario. Since
most patients in the ICU are quite sick with high ventilatory
requirements, and have primarily been referred there because
conventional therapy outside the ICU area proved ineffective, high
flow systems are generally more useful. Several patients also
require rather high FiO2, and hence delivery systems designed for
optimal use with low FiO2 (such as the nasal cannulas and simple
face masks) are not as effective. These systems may still have a
role in patients requiring lesser or loosely controlled FiO2. The best
systems for routine use are the Venturi masks, and they have several
advantages. They allow a fairly tight control over the FiO2 being
delivered; this helps clinicians to monitor patients well and to
precisely titrate amount of oxygen being supplemented.
A particular use of these masks is in patients with acute
exacerbation of COPD, where controlled oxygen supplementation
at a relatively lower FiO2 is necessary to maintain oxygenation at
slightly subnormal levels to prevent worsening of carbondioxide
retention. However, Venturi masks must be used carefully, using
oxygen flow rates recommended for the mask. It is a general
tendency to increase the oxygen flow rate to higher than that
recommended for a particular FiO2, in hope of improving oxygen
delivery to the patient. However, these masks work on the Venturi
principle, and increasing oxygen flow without changing the
entraining aperture size will lead to entrainment of more air,
leading to more than expected dilution. The resulting FiO2 reaching
the patient is unpredictable, and may even be less than the mask
setting.
Oxygen delivery through a mask can be improved by adding a
reservoir to the mask. Such a partial rebreathing circuit collects
the initial portion of the exhaled air coming from the anatomic
dead space into a reservoir, and delivers it to the patient during
the next inspiratory cycle. A high FiO2 of upto 0.6 can be delivered
through these masks.
OXYGEN SUPPLEMENTATION DURING NIPPV

NIPPV is a useful technique to assist ventilation through a tight
fitting nasal or full face mask in patients with acute respiratory
failure associated with COPD or sleep related breathing disorders,
as well as during weaning from conventional mechanical
ventilation. Several such patients will require supplemental oxygen
along with ventilatory support. NIPPV can be delivered either
216 Oxygen Therapy
through conventional mechanical ventilators or through portable

systems. While the former can provide precisely controlled FiO2
during conventional ventilation, they may not do so during NIPPV
due to presence of mask leaks, which invariably occur during
NIPPV. The portable systems compensate for mask leaks well;
however most of them do not have an oxygen control mechanism.
Supplemental oxygen is delivered by simply adding it to the
mask or circuit, and hence an accurately controlled FiO2 cannot be
achieved. The delivered FiO2 using these system is a complex
interaction between several factors such as the site of addition of
oxygen (whether into the mask or the circuit), position of exhalation
port (whether in mask or the circuit), and the level of inspiratory
and expiratory pressures used. When the exhalation port is located
within the mask and oxygen is directly added into the mask,
presumably much of the oxygen gets exhausted through the
exhalation port, because of the close proximity of the oxygen
entrainment site and the leak port. Adding oxygen distally into
the circuit allows more time for mixing than when the leak port is
in the mask. The highest oxygen concentration of oxygen is
generally achieved with oxygen added to the mask, with the leak
port in the circuit, and with the lowest settings of inspiratory and
expiratory pressures. However, the delivered FiO2 still remains
unpredictable. When a more precise oxygen delivery is needed, it
is desirable to use a conventional ventilator with an integrated
oxygen blender.
OXYGEN SUPPLEMENTATION THROUGH

CONVENTIONAL MECHANICAL VENTILATORS
Most of the currently available mechanical ventilators are capable
of delivering tightly controlled and high levels of FiO2 to intubated
patients. These machines have integrated microprocessor
controlled gas blenders for precise mixing of compressed oxygen
and compressed air, and allow delivery of a preset FiO2 for
continued and long periods. It is also possible to deliver high FiO2
(upto even 1.0) through such systems; a feat that no non-invasive
system can achieve in a sustained manner. It is no surprise that
mechanical ventilation is the cornerstone of our efforts to improve
oxygenation to a satisfactory level in patients with the most severe
forms of respiratory failure admitted to ICUs.
DANGERS AND COMPLICATIONS OF OXYGEN

THERAPY IN CRITICALLY ILL PATIENTS
Like any other pharmacologic agent, oxygen too is associated with
toxicity if used in higher than needed doses. Application of high
concentrations of oxygen for prolonged periods, which is often
necessary to reverse acute hypoxemia in the critically ill patients,
can lead to several physiologic and cellular alterations, and even
lung injury. The pathogenesis is largely linked to production of
cytotoxic free oxygen radicals that overwhelm the body’s natural
antioxidant defense mechanisms, resulting in accumulation of
reactive oxygen intermediates. The mechanisms resulting in oxygen
toxicity, and associated clinical manifestations, are detailed
elsewhere in this book. The dangers of pulmonary toxicity due to
oxygen, ranging from atelectasis to pro-inflammatory processes,
and the risks of prescribing oxygen for patients with chronic
obstructive pulmonary disease, are widely recognized. Despite this,
physicians themselves are sometimes responsible for aggravating
oxygen toxicity through their endeavor to try and normalize blood
oxygenation. It is well known that arterial oxygen saturation at a
PO2 of 60 mm Hg is about 90 percent, and beyond that any further
increase in PO2 (by increasing FiO2 further) does not result in a
proportionate improvement in oxygen saturation or tissue oxygen
delivery. Since patients in ICUs are perceived to be critically ill
and in need of oxygen, physicians often overprescribe oxygen.
Short-term exposure to high oxygen concentrations is tolerated
fairly well, and hence ICU patients needing short-term oxygen
supplementation (24-36 hours) are unlikely to develop oxygen
toxicity. Patients needing prolonged oxygen supplementation are
definitely at risk. Since there is hardly any treatment for oxygen
toxicity, the goal in an ICU setting should be at prevention of this
complication. Simple measures that are useful in the ICU setup
include (a) use of lowest possible FiO2 (preferably less than 0.5-
0.6) to achieve arterial PO2 of 55-60 mm Hg, and (b) judicious
upward titration of positive end-expiratory pressure (PEEP) in
ventilated patients to reduce their overall FiO2 requirement. In
addition, regular monitoring for manifestations of oxygen toxicity
should be undertaken. Several symptoms and signs of oxygen
toxicity such as restlessness, nausea, dyspnea, cough, retrosternal
discomfort, parasthesias, etc. are fairly non-specific in any critically
ill patient; nevertheless, oxygen toxicity should be a consideration
218 Oxygen Therapy
if such features appear freshly in any patient otherwise improving

on therapy. Worsening infiltrates on chest radiographs, or
increasing FiO2 and/or PEEP requirements may also be a pointer
to relatively severe pulmonary oxygen toxicity.
The other important issue with oxygen delivery systems in the
ICU is related to nosocomial infection. Under normal circum-
stances, low-flow oxygen systems do not present clinically
important risk of infection and need not be routinely replaced.
High-flow systems that employ heated humidifiers and aerosol
generators, particularly when applied to patients with artificial
airways, can pose important risk of infection. In the absence of
definitive studies to support change-out intervals, results of
institution-specific and patient-specific surveillance measures
should dictate the frequency with which such equipment is
replaced.
MONITORING OXYGEN THERAPY IN ICU

Patients admitted to ICUs and requiring supplemental oxygen are
usually quite sick, and are monitored frequently for their general
condition, vital signs and level of dysfunction of various organ
systems. Monitoring of oxygen therapy is an integrated component
of this management paradigm.
It is important to regularly check patient’s temperature, heart
rate, respiratory rate and respiratory effort to be able to assess a
patient’s ventilatory requirement. This in turn, will help in selecting
the oxygen delivery system and oxygen flow rate best suited for
the patient. For instance, a patient using nasal prongs may need to
be shifted to a high flow system if he starts hyperventilating after
developing fever in the ICU. More importantly, it is necessary to
periodically check the oxygenation status of these critically ill
patients. This is best accomplished by continuous non-invasive
monitoring through a pulse oximeter, supplemented by periodic
ABG measurements.
It is important to obtain an arterial blood gas analysis before
initiating oxygen supplementation. Once oxygen supplementation
(with or without mechanical ventilation) is started, ABG should
be repeated after about two hours (or earlier depending on clinical
condition) to establish efficacy of oxygen therapy. Subsequent
monitoring depends on patient’s clinical condition and level of
FiO2. In general, patients on low FiO2 need less frequent monitoring
than patients on high FiO2 or receiving mechanical ventilation.

Patients with hypercapnic respiratory failure may also require more
frequent monitoring. Once the patient is stabilized, ABG analysis
is perhaps needed only once a day, with intermittent or continuous
monitoring with oximetry in between. The goal of all such
monitoring is to try and keep FiO2 levels in a safe range to prevent
oxygen toxicity, and at the same time ensure a level of oxygenation
that does not put the patient to risk due to hypoxia.
Some patients may also benefit from monitoring of adequacy
of oxygen delivery to the tissues. Serum lactate, anion gap, base
excess, and pH may be used to assess the severity of metabolic
acidosis and shock. However, these are global measurements and
are not sensitive to regional hypoperfusion. The adequacy of
systemic or global oxygen delivery is most commonly assessed
directly by measuring the oxygen content of arterial and mixed
venous blood, estimating cardiac output, and then calculating
oxygen delivery. Gastric tonometry, which measures gastric PCO2
and calculates gastric intramucosal pH, was developed based on
the principle that fluid in a hollow organ can be used to measure
the gas tension of the surrounding tissue. This index is an indirect
measure of splanchnic perfusion and oxygenation.
A recent advance in the initial management of critically ill
patients with severe sepsis has been the concept of “early goal
directed therapy”. The protocol involves intensive monitoring of
these patients using central venous oxygen saturation. This is an
indirect marker for the quantum of tissue extraction of oxygen,
and the goal is to eventually get a central venous oxygen saturation
value exceeding 70 percent with supportive therapy (such as
volume resuscitation, blood transfusion, inotropic support, etc.).
In addition to the patient, the oxygen delivery systems in the
ICU also need to be monitored. This ensures that results of clinical
and laboratory monitoring are interpreted in a correct perspective.
All oxygen delivery systems should be checked at least once per
day. Mechanical ventilators should be periodically calibrated with
respect to oxygen blending and delivery.
DISCONTINUATION
Oxygen should be stopped once the critical illness leading to
hypoxemia has considerably resolved, and when arterial
oxygenation is adequate with the patient breathing room air (PO2
220 Oxygen Therapy
60 mm Hg, SaO2 > 90%). In patients without arterial hypoxemia

but at risk of tissue hypoxia, oxygen should be stopped when the
acid-base state and clinical assessment of vital organ function are
consistent with resolution of tissue hypoxia.
BIBLIOGRAPHY
1. Bateman NT, Leach RM. ABC of oxygen. Acute oxygen therapy. BMJ
1998;317:798-801.
2. Huang YC. Monitoring oxygen delivery in the critically ill. Chest 2005;128(5
Suppl 2):554S-560S.
3. Kallstrom TJ. AARC Clinical Practice Guideline: Oxygen therapy for adults
in the acute care facility - 2002 revision and update. Respir Care 2002;47:
717-20.
4. Leach RM, Treacher DF. The pulmonary physician in critical care. 2. Oxygen
delivery and consumption in the critically ill. Thorax 2002;57:170-7.
5. Lodato RF. Oxygen toxicity. Crit Care Clin 1990;6:749-65.
6. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early
goal-directed therapy in the treatment of severe sepsis and septic shock.
N Engl J Med 2001;345:1368-77.
7. Schwartz AR, Kacmarek RM, Hess DR. Factors affecting oxygen delivery
with bi-level positive airway pressure. Respir Care 2004;49:270-5.
14
Air Travel and
Oxygen Therapy
Ajay Handa
INTRODUCTION
Air travel is a common mode of transportation in the present day
society. It is the preferred mode of travel due to convenience and
time saving. The vast majority of people who travel by air are
healthy individuals but approximately 5-10 percent of them have
underlying illnesses including chronic respiratory diseases. The
prevalence of respiratory diseases is increasing worldwide and
most such patients would prefer to travel by air to avoid exertion.
Many patients consult their physician prior to planning air travel
for fitness and prescription of supplemental oxygen during flight.
Patients who have suffered from an acute medical problem in the
immediate period preceding air travel as well as those with
previous cardio-pulmonary diseases are particularly anxious and
need advice on oxygen supplementation. The knowledge of
changes in pulmonary physiology with altitude and aviation is
important to know for physicians to advise on fitness for flying
and in-flight oxygen supplementation for patients with chronic
respiratory diseases.
As altitude increases, the atmospheric pressure declines
logarithmically and the temperature decreases in a linear fashion.
The fall in partial pressure of oxygen with altitude can cause
hypobaric hypoxia during air travel. Commercial aircraft fly at
10,000-13,000 meters above sea level (ASL) and pressurization in
the cabin is maintained to keep the level at about 2,450 meters ASL.
For technical reasons the cabin altitude cannot be maintained lower
than 2,450 m. Breathing at this altitude (15.1% oxygen) causes the
222 Oxygen Therapy
PaO2 to fall to 53-64 mm Hg (SpO2 85-91%). This does not produce

any symptoms in healthy subjects but this stress may cause
significant hypoxemia and precipitate respiratory failure in patients
with chronic lung disease. Such patients need thorough preflight
evaluation and are to be recommended to use supplemental in-
flight oxygen. Most authors consider using supplemental oxygen
below arbitrary level of PaO2 of 50 mm Hg.
Another physical effect of ascent to altitude is the expansion of
gases due to decrease in the ambient pressure (Boyle’s law). The
expansion of gas trapped in close cavities such as middle ear,
intestine can cause discomfort. The gas within a non-
communicating bulla will expand by 30 percent at 2450 m ASL
and can rupture to cause complications such as pneumothorax,
pneumomediastinum and air embolism. The patients of COPD with
large bullae are at increased risk for pneumothorax during air travel
and are advised to avoid air travel due to the absence of medical
care in flight. Due to risk of developing respiratory distress,
pneumothorax is the only absolute contraindication for travel by
air. The analysis of in-flight emergencies from various studies has
shown that respiratory problems account for 2-10 percent of all
medical emergencies, and together constitute the third leading
cause after cardiac and neurologic diseases. The overall fatality
rate is 0.107-0.38 per million passengers.
PREFLIGHT ASSESSMENT
The aim of preflight assessment is to identify those likely to develop
significant hypoxemia. The important categories include patients
who are oxygen dependent as well as others with cardio-respiratory
illnesses. Patients with severe COPD, asthma, previous venous
thromboembolism, recent pneumothorax and pulmonary
tuberculosis are at high risk for deterioration during air travel.
Patients with congestive cardiac failure may also develop
worsening during air travel. But travel on commercial airlines is
fairly safe after 2 weeks of myocardial infarction without the
requirement for supplemental oxygen. Preflight assessment should
include detailed medical screening and counselling. The three
methods usually adopted for pre-flight evaluation for oxygen
supplementation include 50 m walk test, use of prediction equations
and the hypoxia challenge test.
Air Travel and Oxygen Therapy 223
Airline medical authorities traditionally use the 50 m walk test

for screening passengers. Those who are able to walk 50 m are
considered fit to fly. The test is a crude assessment of cardio-
respiratory status.
Nomograms and equations for predicting PaO2 at altitude using
blood gas parameters and spirometry at ground have been
developed from studies in COPD patients exposed to hypoxia
(Box 14.1). In clinical practice, regression equations are most
frequently applied to predict fitness and requirement of on-board
oxygen. Predicted PaO2 values of less than 50 mm Hg are indication
of supplemental in-flight oxygen.
Box 14.1: Equations for calculating predicted PaO2 at 2450 m
PaO2 altitude = 0.84 + 0.68 (PaO2 ground)

PaO2 altitude = 0.295 (PaO2 Sea level) + 0.086 (FEV1% predicted) + 23.211
PaO2 altitude = 0.245 (PaO2 Sea level) + 0.171 (FEV1/FVC % predicted) + 21.028
The hypoxic challenge test is currently the gold standard for

preflight assessment. The subject is exposed to 15 percent oxygen
in nitrogen using non-rebreathing facemask, or body plethysmo-
graph. Commercially available venturi devices with nitrogen as a
source gas to lower inspired O2 tension has been also used for this
evaluation. Continuous monitoring with pulse oximetry and
electrocardiography is done to prevent severe oxygen desaturation
and detect cardiac arrhythmias. Arterial blood gas analysis is done
before and after the hypoxic exposure. The mean predicted altitude
PaO2 derived from these equations compares well with actual PaO2
obtained during the hypoxic challenge tests.
Considering the large numbers of patients with COPD who
travel by air and the limited availability of facilities for hypoxic
challenge testing, the British Thoracic Society guidelines
recommend that oxygen saturation measured by pulse oximetry
can be used to initially screen groups of passengers (Table 14.1).
Those passengers who have additional risk factors such as
hypercapnia, FEV1 < 50 percent predicted, lung cancer, restrictive
lung diseases, co-morbid cardiovascular or neurologic disease and
within 6 weeks of discharge from hospital for acute exacerbation
of lung disease shall require hypoxic challenge testing. Those with
initial SpO2 of less than 92 percent are advised in-flight oxygen
while those with SpO2 of between 92-95 percent are prescribed
hypoxic challenge test (Table 14.2).
224 Oxygen Therapy
Table 14.1: BTS recommendations for initial screening
Pulse oximetry Recommendation

SpO2 > 95% Oxygen not required
SpO2 92-95% without risk factors Oxygen not required
SpO2 92-95% with risk factors Hypoxic challenge test
SpO2 < 92% In-flight oxygen
The patients subjected to hypoxic challenge are categorized

based on the measured PaO2 after 20 min at FiO2 15 percent and
advised accordingly (Table 14.2).
Table 14.2: BTS recommendations after hypoxic challenge test
Blood gas report Recommendation

PaO2 >55 mm Hg Oxygen not required
PaO2 50–55 mm Hg Borderline, advised 50 m walk test
PaO2 <50 mm Hg In-flight oxygen (2 L/min)
PRESCRIBING IN-FLIGHT OXYGEN

Any passenger with a partial pressure of arterial O2 of less than 70
mm Hg at sea level at rest requires supplemental O2 during air
travel. Most commercial airlines will provide oxygen in-flight on
advance request by the passenger and on physician’s prescription.
Oxygen-dependent passengers must make additional arrange-
ments for use of supplemental oxygen not only during the flight
but at the airports as well. The expenses are usually required to be
borne by the traveler rather than by insurers.
The oxygen supply is usually provided from cylinders.
Therefore the rate of flow and duration must be specified so that
adequate amount of oxygen is available during the journey. The
flow rate of oxygen of 2 L/min is suitable for most passengers.
Those on long-term oxygen therapy (LTOT) are advised to increase
the flow rate 2 L/min above the usual flow rate.
Most airlines provide oxygen through simple facemask and
passengers are advised to carry their nasal prongs to prevent
rebreathing. The oxygen and cabin air inside the aircraft are devoid
of moisture and can lead to drying of tracheobronchial mucosa
and precipitation of bronchospasm. The airlines have to be
informed for humidified oxygen for patients with asthma and
COPD. In addition such patients must be advised to carry their
medications in their hand baggage for use in emergency situations.
Air Travel and Oxygen Therapy 225
Passengers must remember that the airline does not provide

oxygen during waiting periods and stopovers. Some airports
restrict oxygen use in the airport because of the risk of explosion.
Patients on long-term oxygen therapy cannot use their own
cylinders or concentrators, but may be able to take these items with
them as baggage for use at their destination. It is also important
for these patients to carry the medical documents and extra supplies
during the travel (Box 14.2).
Box 14.2: Guidelines for oxygen dependent patients prior to air travel
Obtain medical certificate of fitness to fly

Carry prescription of in-flight oxygen requirement
Inform the airlines while booking tickets and 48-72 hours before date of journey
Inform airlines need for oxygen before boarding and during stopovers
Preferably take nonstop flight to destination
Carry extra tubing and personal nasal cannula
Carry extra copies of prescriptions and medical certificate
Carry emergency supply of medications in hand baggage
CONCLUSIONS
For most passengers, air travel is safe and comfortable. Patients
who have cardio-respiratory diseases are at risk of significant
hypoxemia during air travel. However, most of these individuals
complete the journey uneventfully with supplemental oxygen. All
the present recommendations are based on results of the effects of
simulated hypoxia on patients with lung diseases. More investi-
gations are required on the effects of air travel on passengers with
lung diseases.
BIBLIOGRAPHY
1. Berg BW, Dillard TA, Rajagopal KR, Mehm WJ. Oxygen supplementation
during air travel in patients with chronic obstructive lung disease. Chest 1992;
101:638-41.
2. British Thoracic Society Standards of Care Committee. Managing passengers
with respiratory disease planning air travel: British Thoracic Society
Recommendations. Thorax 2002; 57:289-304.
3. Celli BR. ATS standards for the optimal management of chronic obstructive
pulmonary disease. Respirology 1997; 2:S1-4.
4. Cramer D, Ward S, Geddes D. Assessment of oxygen supplementation during
air travel. Thorax 1996; 51:202-3.
5. Dillard TA, Berg BW, Rajagopal KR, et al. Hypoxemia during air-travel in
patients with COPD. Ann Intern Med 1989;111:362–7.
226 Oxygen Therapy
6. Dillard TA, Moores LK, Bilello KL, et al. The pre-flight evaluation. A
comparison of the hypoxia inhalation test with hypobaric exposure. Chest
1995;107:352-7.
7. Gendreau MA, DeJohn C. Responding to medical events during commercial
airline flights. Current Concepts. N Engl J Med 2002;346:1067-73.
8. Gong H, Tashkin DP, Lee EY, et al. Hypoxia-altitude simulation test. Am
Rev Respir Dis 1984; 130:980-6.
9. Johnson AOC. Chronic obstructive pulmonary disease: Fitness to fly with
COPD. Thorax 2003;58:729-732.
10. Khilnani GC, Bhatta N. Air travel and supplemental oxygen in patients with
cardio-pulmonary diseases. J Assoc Physicians India 2002;50:811-5.
11. Lyznicki JM, Williams MA, Deitchman SD, Howe JP 3rd; Council on Scientific
Affairs, American Medical Associate. Medical Oxygen and Air Travel. Aviat
Space Environ Med 2000;71:827-31.
12. Mills FJ, Harding RM. Fitness to travel by air. I: Physiological considerations.
BMJ 1983;286:1269-71.
13. Mills FJ, Harding RM. Fitness to travel by air. II: Special Medical
Considerations. BMJ 1983;286:1240-1.
14. Roby H, Lee A, Hopkins A. Safety of air travel following acute myocardial
infarction. Aviat Space Environ Med 2002;73:91-6.
15. Stoller JK, Hoisington E, Auger G. A comparative analysis of arranging in-
flight oxygen aboard commercial air carriers. Chest 1999;115:991-5.
16. Vohra KP, Klocke RA. Detection and correction of hypoxemia associated with
air travel. Am Rev Respir Dis 1993;148:1215-9.
15
High Altitude Problems
INTRODUCTION
There is a gradual decline in the atmospheric pressure (Patm) as the
altitude increases. This relationship is almost linear. Patm is 760
mm Hg at sea level and falls to about 733 mm Hg at an altitude of
330 meters (e.g. Chandigarh) and 587 mm Hg at an altitude of
2150 meters (e.g. Shimla). While the fractional concentrations of
atmospheric gases remain the same, the partial pressures of all gases
(i.e. nitrogen and oxygen) fall proportionately. The low oxygen
pressure at high altitudes, i.e. atmospheric hypoxia is of great
clinical significance. Some of the problems at high altitudes are
recognized for centuries. Marco Polo had given the early
description of acute mountain sickness when he mentioned “the
Headache Mountains” in 1272 while crossing the Pamir mountains
of Asia. There are more than 140 million people living at moderate
to high altitude such as, Tibet, China, in the Himalayas and the
Andes in South America. Besides the natives of high altitudes, a
large number of low-lander people visit the mountains for tourism,
pilgrimage, military purposes and mountaineering.
The fall in oxygen pressure assumes a clinical significance
beyond an altitude of about 10,000 feet when the symptoms
attributed to hypoxia may appear. While the natives acclimatize
to the hypoxic conditions, the low-landers develop high altitude
problems on rapid ascent. A large spectrum of high altitude
pulmonary diseases is described. These include the acute mountain
sickness (AMS), high altitude pulmonary edema (HAPE),
pulmonary hypertension, chronic mountain sickness (CMS) and
228 Oxygen Therapy
high altitude cerebral edema (HACE) – an end stage of severe AMS.

The problems of hypoxia are even greater for those with chronic
lung diseases many of whom develop problems at even lesser
altitudes. Their requirements for oxygen are more both during the
stable state as well as during exacerbations.
OXYGEN FOR HIGH ALTITUDE SICKNESS

High altitude pulmonary edema and acute mountain sickness may
develop in low-landers ascending to high altitude for the first time
and in a minority of high-landers returning to the mountains after
a sojourn in the plains at low altitudes or sea level. The factors that
may exacerbate the problem include the rapidity of the ascent, the
altitude, physical exercise and cold. But not all people who visit
the mountains develop the problems. There is a variable individual
susceptibility.
High altitude pulmonary edema is life-threatening and requires
urgent treatment. A rapid descent to a lower altitude is essential.
Portable hyperbaric chambers for oxygen are employed for
mountaineering purposes. Short period of treatment are shown to
cause improvement in symptoms of AMS but no beneficial long-
term effects. There is a report of successful treatment of a severe
form of AMS in a 37-year old climber who developed HAPE at an
altitude of 7060 m on Mount Everest. He was treated for 2 hours in
a portable Ganow bag hyperbaric chamber with a bag pressure of
103 mm Hg using ambient air and the pulmonary edema had
resolved. Oxygen administration is immediately required pending
the descent to a lower altitude. Oxygen rapidly lowers the
pulmonary arterial pressure and relieves the condition. However,
this may not always succeed and some of the patients may fail to
respond. Oxygen is administered at the highest FiO2 possible to
achieve immediate relief. Successful treatment with low flow rates
is sometimes reported with efficient breathing circuits specifically
designed to conserve oxygen.
A symptom complex of acute mountain sickness varying form
headache, giddiness and blurring of vision to coma may develop
6-96 hours after ascent. It probably occurs secondary to cerebral
vasoconstriction and not to current hypoxia. In fact patients with
chronic lung disease characterized by alveolar hypoxia do not
develop symptoms resembling acute mountain sickness. Oxygen
alone has no role in the management of acute mountain sickness.
High Altitude Problems 229
In a recent report of the Air Force Research Laboratory on 1699

symptoms of altitude decompression sickness, most were relieved
on descent and ground level oxygen; only the serious, recurring,
delayed and refractory symptoms required hyperbaric oxygen
therapy.
Oxygen may however improve some of the symptom complex
of high altitude. Oxygen enrichment of room air was shown to
improve the sleep quality at 3800 m. Both high-altitude pulmonary
edema and acute mountain sickness are best prevented by a
planned, gradual ascent to high altitude. Short halts of 24-48 hours
at intermediate heights allow body adaptation to hypoxia avoiding
the high altitude problems.
CHRONIC MOUNTAIN SICKNESS OR

MONGE’S DISEASE
Monge’s disease develops due to chronic alveolar hypoxia in long-
term residents of mountains. It takes several decades to develop
and is characterized by chronic pulmonary hypertension and
secondary erythrocytosis that gives an appearance of robust health
with deep red lips, conjunctiva and cheeks. There are three different
groups of individuals who develop Monge’s disease:
1. Residents at sea level who move to the high altitude but are
unable to acclimatize (chronic soroche).
2. People with chronic pulmonary diseases like chronic obstructive
pulmonary disease (COPD), kyphoscoliosis that are known to
produce hypoxia at even sea level.
3. Permanent residents of high altitude who somehow loose the
acclimatization and develop chronic mountain sickness
(primary Monge’s disease).
Oxygen therapy has no place in the treatment of Monge’s
disease. It may lower pulmonary hypertension temporarily but will
not reverse the condition. Oxygen is however required for
respiratory insufficiency, which may occur in the second group of
patients i.e. those with chronic hypoxemic disorders. Oxygen
treatment in these conditions is administered on standard
principles as anywhere else. But early and more vigorous therapy
may be required.
230 Oxygen Therapy
OXYGEN FOR THE HEALTHY AT HIGH ALTITUDE

Arterial PaO2 alone in the absence of a chronic lung disease or end-
organ damage, is not an indication for oxygen administration. In
fact, PaO2 levels of 55 mm Hg or less are normal in most adults
living at an altitude of over 10,000 feet. Also, healthy individuals
may survive without oxygen at even much higher altitude. There
are reports on some of the climbers at the Mount Everest (height
29,028 feet) not using oxygen for several hours. A marked leftwards
shift of the oxygen-hemoglobin dissociation curve which favors
unloading of oxygen has been demonstrated as an adaptive process
to hypoxia in healthy and fit individuals.
BIBLIOGRAPHY
1. Apte NM, Karnad DR. Altitude hypoxemia and the arterial-to-alveolar oxygen
ratio. Ann Intern Med 1990;112: 547-8.
2. Barash IA, Beatty C, Powell FL, Prisk GK, West JB. Nocturnal oxygen
enrichment of room air at 3800 meter altitude improves sleep architecture.
High Alt Med Biol 2001; 2:525-33.
3. Bartsch P, Merki B, Hofstetter D, Maggiorini M, Kayser B, Oelz O. Treatment
of acute mountain sickness by simulated descent: A randomized controlled
trial. BMJ 1993; 306:1098-101.
4. Dillard TA, Rosenberg AP, Berg BW. Hypoxemia during altitude exposure.
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Hig Rada Toksikol 2002; 53:3-6.
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Environ Med 2004; 75:496-9.
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Medical Research Expeditionary. Efficient breathing circuit for use at altitude.
Wilderness Environ Med 2005; 16:101-3.
10. Rabold M. High altitude pulmonary edema: A collective review. Am J Emerg
Med 1989; 7:426-33.
11. Schoene RB. Pulmonary edema at high altitude. Review, pathophysiology
and update. Clin Chest Med 1985; 6: 491-507.
12. Singh I, Khanna PK, Srivastava MC, et al. Acute mountain sickness. N Engl J
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Adv Exp Med Biol 1999; 474:57-64.
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2004; 141:789-800.
Oxygen Use in Diving Medicine 231
16
Oxygen Use
in Diving Medicine
PS Tampi
INTRODUCTION
Divers are entirely dependent on the oxygen carried in their lungs
or their gas supply. Moreover, in diving, it is not always possible
to breathe adequately and comfortably, and the diver’s safety, work
capacity and equipment are impaired to the extent that his
breathing is limited. At higher atmospheric pressures (greater depth
of diving), oxygen itself causes acute oxygen toxicity which can
manifest with convulsions and can even kill the diver. Hence the
diver in his underwater environment has a paradoxical problem
with oxygen. To understand the diver’s narrow knife-edge between
fatal hypoxia and equally dangerous hyperoxia, calls for a thorough
understanding of physical properties of gases at sea level and
underwater.
PHYSIOLOGY
All organisms require oxygen for metabolism, but the oxygen in
water is unavailable to mammals, which includes divers, whales
and seals. The body obtains energy for life and activity from the
internal chemical reactions of oxidative metabolism, basically
comparable to combustion. The fuel for metabolism is provided
by food and is readily stored, but oxygen must be supplied to the
sites of metabolic reaction on a continuous basis matched to need.
At the same time, carbon dioxide (CO2) that is produced by this
reaction must be eliminated. If delivery of O2 or removal of CO2 is
impaired by environmental factors or the limitation of breathing
232 Oxygen Therapy
apparatus, the divers capacity for exertion will, accordingly be

limited. Life itself is threatened when exchange of O2 and CO2 is
severely restricted.
PHYSICS
The ambient pressure increases by one atmosphere for every 10 m
if depth in sea water an every 10 um of depth in freshwater.
At sea level, the weight of the atmosphere exerts a pressure
which will support a column of water 10 m high; thus, 10 m under
water the pressure on a diver is 200 kPa. According to Boyle’s law,
the volume of gas in a diving bell full of air at sea level is halved at
10 m, at 20 m the pressure is 300 kPa absolute and the gas is
compressed to one-third the volume. Also, since dry air is composed
of roughly 21 percent oxygen, 78 percent nitrogen and 1 percent
other gases, the partial pressure of oxygen at any depth will be 21
percent of the total pressure exerted by the air.
Gases dissolve in the liquid with which they are in contact.
Among the various gases in the air, nitrogen is fat-soluble and there
are several liters dissolved in our bodies at sea level. At 10 m depth
by breathing air, the partial pressure of nitrogen is doubled.
Consequently, once equilibration occurs there will be double the
numbers of nitrogen molecules as at sea level. Since oxygen in our
blood is largely bound to hemoglobin, and only partly dissolved
in solution, doubling the inspired partial pressure of oxygen only
doubles the dissolved component. The hemoglobin in arterial blood
is virtually saturated at an inspired partial pressure of oxygen of
21 kPa; increasing the partial pressure of oxygen, therefore has
little effect on the amount of oxygen bound to hemoglobin.
GASES USED IN UNDERWATER BREATHING

Air
This is the cheapest and most easily available gas to use for SCUBA
(Self Contained Underwater Breathing Apparatus) or surface
supplied diving. It can be compressed easily and is less likely to
produce a fatal mixture than gas mixing but has several
disadvantages. Nitrogen narcosis can result from high partial
pressures at depth which can affect the function of cell membranes.
At 30 m, only mild impairment of intellectual function may occur,
but this may progress to unconsciousness as the diver descends to

depths near 100 m.
During ascent or decompression, this large volume of highly
soluble, dissolved nitrogen from the tissues is liberated. If the
ascent/decompression is too rapid, large amounts of bubbles are
liberated from the supersaturated tissues and this can lead to the
well known “diver’s bends” (Caisson’s disease or Decompression
sickness). The recommended rate of ascent for most air divers is
not more than 10-15 m/min.
Nitrogen is a relatively dense gas and hence the work of
breathing at 30 m depth is twice as great as at the surface. A
breathing system using air must liberate the exhaust gas (low in
O2 and high in CO2 and N2), as bubbles can be a problem in covert
military operations and while defusing naval mines with acoustic
sensors.
Oxygen
To overcome the problems of nitrogen, several alternatives were
considered. Oxygen rebreathing systems allow divers to breathe
100 percent O2 but CO2 accumulation occurs and is removed by a
CO2 absorber. When pure O2 is breathed, much smaller amounts
of gas need to be carried and produce no bubbles. However, there
can be problems which can even be fatal. The fraction of inspired
nitrogen is zero in such a system. However, the diver’s body
contains several liters of dissolved nitrogen, which can as a
consequence of the pressure gradient, pass back to the lung and
into the counter-lung. O2 is consumed, CO2 is removed and
nitrogen accumulates, gradually reducing the percentage of O2 in
the counter-lung. This can lead to unconsciousness. Flushing the
system with pure O2 periodically can overcome this problem. But
high partial pressures of O2 can increase blood pressure and reduce
heart rate.
Pulmonary toxicity and eventually irreversible pulmonary
fibrosis can result from prolonged breathing of a gas with FiO2
>0.6, though this may take many hours or days. Acute O2 toxicity
can occur within minutes causing convulsions when PiO2 >160
kPa, and if underwater, is usually fatal. Breathing air with 21
percent O2 risks acute O2 toxicity at depths > 66 m; breathing 100
percent O2 there is a risk of convulsion at only 6 m.
234 Oxygen Therapy
TYPES OF DIVING
Breath-hold Diving
An average healthy person can hold his/her breath for about half
a minute. During the breath hold, the oxygen content of tissues
progressively decreases, but the breath hold is broken as a result
of carbon dioxide production from tissues and resulting acidosis
which stimulates the respiratory centre. With practice and special
training, one can learn to resist the stimulus to breathe during
breath holding. Hyperventilation, immediately prior to breath
holding can extend its duration. This is due to carbon dioxide
washout resulting in starting with a higher cerebrospinal fluid pH.
Here it is the hypoxic stimulus that triggers respiration before the
pH of cerebrospinal fluid falls enough to do so. Hence, it follows
that it may be possible to hold a breath for over 5 minutes by prior
hyperventilation on 100 percent oxygen, which would increase the
total oxygen content of blood considerably.
Hyperventilation before diving enables breath hold divers to
stay down longer but is very dangerous. The diver starts with a
low CO2 content, a high pH, and a normal O2 tension. During
descent to say, 30 m, the pressure increases 4-fold, compressing
the airspaces to one-fourth their surface volume (from TLC of 6
liters to 1.5 liters, near residual volume). The partial pressures of
O 2 and N 2 in the lungs also increase 4-fold and produce
corresponding increases in arterial and tissue gas tensions. During
diving, O2 is consumed and CO2 is produced. Due to preceding
hyperventilation, the diver does not feel the need to breathe until
the arterial O2 tension has fallen to levels which stimulate the
carotid chemoreceptors. As the diver ascends, hydrostatic pressure
is reduced 4-fold with a 4-fold reduction in O2 tensions in alveolar
gas, arterial blood, and tissues. The rapidly falling cerebral O2
pressure may be inadequate for consciousness to be maintained
and the diver could drown during ascent. Even coming to the
surface from the bottom of a 2 m deep pool can reduce the O2
pressure sufficient to cause loss of consciousness, and some fatalities
have occurred this way.
Surface Oriented Diving

Refers to those diving operators where the diver travels between
the surface and his worksite through the water column and without
being protected within a closed diving bell. Thus he may swim,

climb or be lowered in a basket or wet (or open) bell. The maximum
depth of such operation is usually 165 ft (50 m) and air is normally
the breathing gas.
Mixed Gas Diving

This is synonymous with bell diving, in systems used for diving
beyond 165 feet (50 m) but may also be used at shallower depths.
It is divided into two basic types of operations: bounce diving and
saturation diving procedures.
Bounce Diving Procedures

A bounce dive is one in which the diver’s exposure to the bottom
pressure is usually limited to about 30-60 minutes in order to
minimize their subsequent decompression period. This is achieved
with the help of a diving bell which is first lowered to the working
depth while maintaining internal atmospheric pressure. When the
divers are ready to go for work, the internal pressure is raised
rapidly by the divers until it reaches the external pressure at which
point the outer door falls open and the diver is able to venture out
of the bell. As soon as the diver finishes his work and returns to
the bell, the inner door is closed and the bell immediately risen.
Thereafter decompression is commenced.
Saturation Diving Procedures

For some tasks the need for longer dive durations and more
working divers necessitates the use of saturation techniques.
Saturation diving systems are much larger than bounce diving
systems because up to some 16 divers will be maintained under
pressure and for as long as 4 weeks. Such systems can operate 24
hours a day, and consequently, a larger surface support crew of
10-35 men working on a shift basis is also required.
Saturation diving gases: The gaseous mixture used in the saturation
diving and maximum depth are shown in Table 16.1.
236 Oxygen Therapy
Table 16.1: Shows the gaseous mixture used in saturation diving
Mixture Gas Maximum depth
Nitrogen-Oxygen 40 m
Helium-Oxygen 350 m
Helium-Oxygen-Nitrogen 650 m
Hydrogen-Oxygen Unlimited
a. Nitrogen-oxygen saturation dive: N2-O2 saturation dive basically

involves shallow depth of up to 40 m because of the narcotic
property of nitrogen. The oxygen partial pressure in the mixture
is kept at 0.2 to 0.43 kg for avoiding chronic O2 toxicity.
Advantages
1. Cheaper than helium.
2. Suitable for shallow depths of up to 40 m and excursions
possible up to 60 m.
3. No chance of pulmonary O2 toxicity.
4. Negligible risk of high pressure nervous syndrome (HPNS)
Disadvantages
1. Long decompression time would be required
2. Greater chances of decompression sickness
b. Helium-oxygen saturation diving: Helium is commonly used with
oxygen (heliox), even though helium is expensive and has a
high thermal conductivity, which potentiates heat loss and can
make hypothermia a serious possibility on deep dives. Helium
molecules are small so that the work of breathing is low even
at great depths. It is relatively insoluble in lipids, minimizing
bubble liberation on decompression. Its insolubility means that
it lacks narcotic effects, but this unmasks another problem of
diving deep, the high pressure nervous syndrome (HPNS).
This condition is characterized by tremors, irritability,
drowsiness and a depression of the alpha activity in the
electroencephalogram. The cause of HPNS is not settled but a
wide variety of gases including helium that are physiologically
next at normal pressures are anesthetics at higher atmospheric
pressures.
Advantages
1. Colorless, odorless, tasteless, light weight, non-toxic, non-
explosive inert gas.
2. Suitable for deep diving up to 600 m and more.
3. Low density gas.
4. Limited narcotic properties.
Disadvantages
1. Good conductor of heat (especially below 300 m) at least
five times as rapidly as air.
2. Voice distortion due to ‘Donald duck’ effect.
3. HPNS.
During heliox dives, the partial pressure of oxygen is
maintained at 0.35 to 0.43 kg for preventing chronic pulmonary
oxygen toxicity. The habitat is to be pressurized gradually to
avoid hyperbaric arthralgia and HPNS. Compression is kept
slow from 9 to 18 m/minute at shallow depth to 0.05 m at deeper
depths. The habitat temperature is regulated between 20-22
degrees Celsius. However, at depths greater than 300 m, the
temperature control gets more difficult in view of helium’s high
thermal conductivity and the temperature is to be maintained
at 31-32 degrees Celsius. The relative humidity is maintained
between 55 to 65 percent. Saturation excursion either deeper
or shallower can be carried out from a particular storage depth
of the habitat.
c. Trimix (helium-oxygen-nitrogen) saturation diving: In order to
prevent HPNS of heliox mixture, the narcotic property of
nitrogen is advantageously used in this mixture. In trimix, the
partial pressure of N2 is maintained below 1.5 kg. Trimix can
be used up to a depth of 600 m or more.
d. Hydrogen-oxygen saturation diving: The world’s helium resources
are gradually diminishing. Hence, there is a need to find gases
to take man down to even greater depths than have been
achieved with helium. Future deep diving operation will
depend upon the substitute of helium in the breathing mixture.
Hydrogen-oxygen saturation dive is still in an experimental
stage, but the diminishing supply of helium may make H2 - O2
mixture an attractive alternative in the future.
238 Oxygen Therapy
Advantages of Hydrogen
1. Colorless, odorless, tasteless gas and lighter than all gases
2. Being a low-density gas it offers lowest resistance to breathing
3. Diffuses faster than any other gas due to high diffusion
coefficient. H2 absorption and elimination from tissues is more
rapid and thereby reduces decompression time
4. Minimal narcotic activity based on the solubility
5. No HPNS
5. Can be obtained from electrolysis of water and is thus
potentially more abundant
6. Can be used for dives beyond 600 m.
Disadvantages
1. It is highly inflammable and explosive when the oxygen content
in the mixture exceeds 4 percent
2. High thermal conductivity like helium
3. Voice communication is as bad as in a helium dive
A young Swedish engineer, Arne Zetterstorm, made the first
successful dive using H2-O2 mixture to depths of 110 m and 160 m
in 1945. The French have conducted various experimental
saturation dives using H2-O2 mixtures starting from the first Comex
saturation dive- Hydrox I in 1972 at 60 m to Hydrox IX in 1989 to a
depth of 600 m. In the future, the deepest dives can be achieved by
using H2-O2 mixture.
DIVING PROBLEMS
Diving injuries are increasing because of a tremendous increase in
the popularity of SCUBA diving. Most diving emergencies are
related to changes in the behavior of gases due to pressure changes.
During descent, there is an increase in the partial pressure of gases
in the blood and tissues. Barotrauma may result especially from
compression of air present in the middle air, sinuses and lungs.
Medical problems may occur during or even after 24 hours of
diving. Pulmonary edema may result from an increase in the
hydrostatic pressure. Decompression results on ascent after re-
exposure to normal or lower ambient pressures when the gases
dissolved in the body fluids may bubble out and cause decompre-
ssion sickness which may present with varied clinical manifes-
tations.
An intensive medical fitness examination is important for deep

sea and military divers. Routine during medical examination
includes a pressure test in the hyperbaric chambers. Oxygen
tolerance tests under hyperbaric conditions is important for divers
who use oxygen rebreather devices.
BIBLIOGRAPHY
1. Bennett PB, Elliot DH (Editors). The physiology and medicine of diving (4th
ed). London: WB Saunders Company Ltd., 1993.
2. Bove AA, Davis JC. Diving medicine. 2nd edn. Philadelphia: WB Saunders,
1990.
3. DeGorordo A, Vallejo-Manzur F, Chanin K, Varon J. Diving emergencies.
Resuscitation 2003; 59:171-80.
4. Emerson GM. What you need to know about diving medicine but won’t find
in a textbook. Emerg Med 2002;14:371-6.
5. Kot J, Sicko Z. Delayed treatment of bubble related illness in diving – review
of standard protocol. Int Marit Health 2004; 55:103-20.
6. Sport Diving. The British Sub- Aqua Club diving manual, 11th edn. London:
Stanley Paul, 1993.
7. Strauss RH. Diving Medicine. Am Rev Respir Dis 1979;119:1001-23.
8. Tetzlaff K, Shank ES, Muth CM. Evaluation and management of
decompression illness – an intensivist’s perspective. Intensive Care Med 2003;
29:2128-36.
9. Weiss M. Standards on medical fitness examinations for Navy divers. Int
Marit Health 2003; 54:135-43.
10. Wilmshurst P. ABC of oxygen, Diving and oxygen. BMJ 1998;317:996-9.
17
Hyperbaric Oxygen Therapy
PS Tampi, SK Jindal
INTRODUCTION
Hyperbaric oxygen therapy (HBO2T) is the administration of
oxygen at a pressure greater than that at sea level, which is one
atmosphere. Hyperbaric medicine owes its origin to the problems
encountered by deep-sea, divers exposed to high pressure diving
sports, commercial or military expeditions at depths of 10 m or
more. In clinical medicine, this is simulated by exposing a patient
to hyperbaric atmosphere in a closed monoplace or multiplace
chamber. In either case, the partial pressure of oxygen (PaO2) will
approach 1500 mm Hg at a pressure equivalent of 33 feet of
seawater. A century of research in oxygen administration has
established that the effects are dose related, and the hyperbaric
environment merely provides the opportunity to give higher doses
than can be achieved at sea level.
HISTORY OF HYPERBARIC MEDICINE

Development of Hyperbaric Air Therapy
The British physician Henshaw used compressed air for medical
purposes in 1662 in an airtight room called a “domicilium” in which
variable climatic and pressure conditions could be produced, with
pressure provided by a large pair of bellows. According to
Henshaw, “ In times of good health, this domicilium is proposed
as a good expedient to help digestion, to promote insensible
respiration, to facilitate breathing and expectoration, and
consequently, of excellent use for the prevention of most afflictions
Hyperbaric Oxygen Therapy 241
of the lungs.” There is however, no account of any application of

Henshaw’s proposed treatment, and there were no further
developments in the field of hyperbaric therapy for nearly two
centuries.
In the nineteenth century, there was a rebirth of interest in
hyperbaric therapy in France. In 1834, Junod built a hyperbaric
chamber to treat pulmonary afflictions using pressures of two to
four absolute atmospheres (ATA). In 1837, Pravaz built the largest
hyperbaric chamber of that time and treated patients with a variety
of ailments. Fontaine, in 1877, developed the first mobile hyperbaric
operating theater, and by this time hyperbaric chambers were
available in all major European cities. Interestingly, there was no
general rationale for hyperbaric treatments, and prescriptions
therefore varied from one physician to another. During the second
half of the nineteenth century, hyperbaric centers were advertised
as being comparable to health spas. Junod referred to his treatment
as “Le Bain d’air comprimd” (the compressed-air bath). In 1855
Bertin wrote a book on this topic and constructed his own
hyperbaric chamber.
The first hyperbaric chamber on the North American continent
was constructed in 1860 in Oshawa, Ontario, Canada, just east of
Toronto. It was later shifted to New York, to treat nervous disorders.
The chamber that was built by Cunningham received the most
publicity, and was the most actively used in Kansas City in the
1920s. Cunningham claimed to have achieved remarkable
improvement in patients who were cyanotic and comatose.
Cunningham reasoned that a barometric factor was therefore
involved. However, one night a mechanical failure resulted in a
complete loss of compression and all his patients died. This tragedy
was a sobering lesson but ultimately did not deter Dr Cunningham.
His enthusiasm for hyperbaric air continued, and he started to treat
diseases such as syphilis, hypertension, diabetes mellitus, and
cancer. Its reasoning was based on the assumption that anaerobic
infections played a role in the etiology of all such diseases. In 1928,
Cunningham constructed the largest chamber ever built (five stories
high and 64 feet in diameter), in Cleveland. Each floor had
1 bedroom with all the amenities of a good hotel. At that time it
was the only functioning hyperbaric chamber in the world. The
Cunningham chamber was dismantled for scrap in 1937, which
242 Oxygen Therapy
brought to a temporary end of the era of hyperbaric air therapy for

medical disorders.
Development of Hyperbaric Oxygen Therapy

Oxygen was not “discovered” until 1775, when the English scientist
Joseph Priestley isolated what he called “dephlogisticated air”
(Chapter 1). Although hyperbaric air had been used as early as
1662, oxygen was not specifically added to early hyperbaric
chambers. The toxic effects of concentrated oxygen reported by
Lavoisier and Segiom in 1789 were reason enough for hesitation to
use it under pressure. Paul Bert, the father of pressure physiology,
discovered the scientific basis of oxygen toxicity in 1878. The
potential benefits of using oxygen under pressure for the treatment
of decompression sickness were first realized by Drager, who in
1917 devised a system for treating diving accidents. It was not until
1937 – the very year that Cunningham’s “air chamber” hotel was
demolished, that Behnke and Shaw actually used hyperbaric
oxygen (HBO2) signifying the arrival of the era of HBO2 therapy.
Rationale of Hyperbaric Oxygen

An increased atmospheric pressure increases the partial pressure
of O2 in the alveolar air and arterial blood provided the fractional
concentrations of oxygen remains the same. This is easily derived
from the alveolar air equation. Since the oxygen dissolved in the
plasma depends upon PaO2, the dissolved O2 content of blood is
also increased. This is independent of Hb levels of the blood.
Therefore, under hyperbaric conditions the total oxygen carrying
capacity of the blood is significantly more (Table 17.1). At 1
atmosphere (sea level) with a person breathing 100 percent O2, the
PaO2 is about 670 mm Hg and the total oxygen content of 18.7 mL/
dl. Increasing the pressure to 3 atmospheres, the PaO2 increases to
about 1700-1800 mm Hg and the total O2 content to 22 mL/dl. Of
this, about 25 percent (i.e. 5.5 mL/dL) is dissolved in plasma. This
in fact is equivalent to the total oxygen content of blood under
normal conditions at much lower Hb level of 4 gm percent.
Therefore under hyperbaric conditions, it is possible to maintain
adequate oxygen content of blood as well as delivery to the tissues
with a very low or no hemoglobin at all. However, it should be
remembered that the whole of the tissue oxygen requirements can
be met by dissolved oxygen only if PaO2 is around 2025 mm Hg.
Table 17.1: Shows the different components of oxygen content of the blood at
different atmospheric pressures at constant plasma hemoglobin of 14 gms/dL,
when breathing 100% O2
Pressure PaO2 (mm Hg) Dissolved O2 (%) Total O2 content

(atmospheres) (mL/dL)
1 670 11 18.7
2 1200-1300 18 20
3 1700-1800 25 22
Other Physiological Effects of Hyperbaric Oxygenation

Effect on PaCO2: An increased hemoglobin saturation of venous
blood reduces its ability to carry CO2, and results in carbon dioxide
accumulation (Haldane effect).
Vasoconstriction: Occurs due to increase in PaO 2 and has a
therapeutic value.
Angiogenesis: The mechanism by which this occurs is not known
but occurs only when oxygen is administered at more than 1 ATA,
and does not occur with 100 percent oxygen at 1 ATA.
Beneficial Effects of HBO

Hyperbaric oxygen administration achieves two principal
objectives:
1. It increases PaO2 and tissue PO2 to levels higher than those
obtained at 1 atmosphere. This has several potential therapeutic
benefits. The oxygen delivery to the tissues is increased, which
may promote healing; the phagocytosis and antibiotic action
on the microorganism are augmented. Hyperoxia induces
vasoconstriction, which reduces tissue edema. Finally, the
oxygen dissolved in the plasma is available to the tissues
without any increase required in the hemoglobin level. This is
not associated with any increase by blood transfusions.
Problems of increased blood viscosity are therefore, avoided.
2. There is an increase in the ambient pressure which increases
interstitial tissue pressures as well. This is used to treat
decompression sickness, which may occur in divers. Similarly,
presence of air or gas in the blood either injected accidentally
during some procedure or due to embolization can be absorbed
with HBO2 therapy.
244 Oxygen Therapy
Mechanism of Action of HBO2

i. HBO2 increases dissolved oxygen in the plasma, which
readily diffuses into the hypoxic tissues.
ii. Increased oxygenation results in vasoconstriction at the site
resulting in induced transudation, reduction in capillary
pressure and thereby reducing the tissue edema.
iii. The reduction in tissue edema reduces compression of the
cells thereby enhancing the reabsorption of fluid.
iv. With edema being less, barriers of diffusion are reduced and
oxygen diffusion to the tissues improves, resulting in
improvement in tissue functions.
v. Improved vascularization due to neovascularization results
in speedy recovery to tissues and gives way to tissue
regeneration.
vi. Oxide, hydro-peroxide and superoxide radicals of oxygen are
toxic, and interfere with cell metabolism of bacteria and
thereby destroy the bacteria.
vii. HBO2 modulates the immune system and helps in the faster
elimination of viruses.
viii. Bacterial killing effect of leukocytes is impaired in the hypoxic
state. Increased oxygenation will enhance the killing power
of leukocytes.
INDICATIONS
Enthusiasm with the use of HBO2 now is almost similar to what
was seen with use of normobaric oxygen in the 19th century when
its therapeutic applications were first discovered. But this
enthusiasm has helped to discover its beneficial role as an adjunct
in the treatment of diverse clinically conditions. Indications may
vary in different countries in different settings. Some of the more
definite indications are the decompression sickness, air embolism,
gas gangrene and carbon monoxide poisoning. The indications
apprised by the Undersea and Hyperbaric Medical Society are
rather limited and rely on the proof of efficacy of controlled studies.
Decompression Sickness
Decompression sickness occurs when the ambient air pressure is
allowed to lower rapidly after a prolonged exposure to a higher
pressure. This is commonly seen in the deep sea divers after
emerging from a diving juggernaut and occasionally in the aviators

or astronauts on reaching the outer atmosphere or space. Due to a
sudden lowering of pressure, the inert gases dissolved in body
fluids bubble out in both intravascular and extravascular compart-
ments resulting in multiple symptoms. The common clinical mani-
festations include musculo-skeletal pains, neurological symptoms
such as paresthesias and sensori motor deficits, nausea, vomiting,
nystagmus, tinnitus, sub-sternal pain, cough, dyspnea, hoarseness
of voice and occasionally shock and death.
Hyperbaric oxygen and recompression to about 60 feet
constitute the mainstay of therapy. Both steps help in the reduction
and resolution of the bubbles and maintenance of tissue
oxygenation. Increased occurrence of oxygen toxicity under higher
pressure conditions limits the duration of use of hyperbaric oxygen.
Relapse may occur after discontinuation of therapy. Short-term
observation especially in patients with neurological symptoms for
at least 6 hours is generally recommended. Some people advocate
the provision of observation units for about 24 hours after
hyperbaric therapy.
Air Embolism
Air bubbles may form in the venous circulation, due to sudden
decompression (e.g. decompression sickness) or more commonly
get introduced during central venous instrumentation, invasive
medical and surgical procedures, hemodialysis, chest trauma or
positive pressure ventilation, employing high levels of positive end
expiratory pressures (PEEP). These air bubbles finally end up in
the lungs causing obstruction of pulmonary circulation and
presenting a picture of pulmonary air embolism. It may occa-
sionally be fatal if a large pulmonary vessel gets blocked. Bubbles
may also form in the arterial circulation but are rare because of the
higher hydrostatic pressure in the larger vessels. Cerebral air
embolism is uncommon but more serious in nature.
Treatment of air embolism employs resuscitative and restorative
measures for pulmonary circulation through removal and/or
absorption of air from the pulmonary vessels. Attempts to remove
the air bubbles include the direct needle aspiration, Trendelenburg
position or removal through a central venous catheter. Adminis-
tration of 100 percent oxygen helps reabsorption of air. Hyperbaric
oxygen administration rapidly reduces the bubble size. Generally
246 Oxygen Therapy
50 percent O2 at a pressure of 165 feet is administered initially for

a few minutes followed by intermittent periods of 100 percent
oxygen at a lower pressure of 65 feet. A recent report on the use of
U.S. Navy Treatment suggests this use of oxygen filled monoplace
hyperbaric chamber as better tolerated and safer from oxygen
toxicity point of view than a multiplace chamber, for the treatment
of both decompression sickness and air embolism.
Gas Gangrene and Other Necrotizing Infections

There is an increased evidence to suggest a major role of HBO2 on
inflammatory cytokines and mediators. It is shown to cause
cytokine down-regulation and growth factor up-regulation. HBO2
therefore is likely to promote wound healing by suppressing
inflammation and facilitating repair. It also augments the
antibacterial action of leukocytes which gets otherwise inhibited
under hypoxic conditions and thereby improves the efficacy of
antibiotics. These effects have been shown in a few clinical trials
and clinical experience when used as an adjunct treatment for gas
gangrene, non-healing wounds (e.g. diabetic foot), osteomyelitis
and necrotizing fasciitis. It is also shown to shorten the treatment
with antibiotics for soft tissue infections.
Hyper-oxygenation in particular is valuable in gas gangrene
since it inhibits the growth of the causative anerobic micro-
organisms, i.e. clostridia and prevents formation of toxins
responsible for necrotizing myositis and myonecrosis. Reports on
the useful role of HBO2 are available for treatment of all kinds of
clostrial infections including necrotizing fasciitis of upper extre-
mities, orbital gas gangrene, recurrent crepitant cellulitis with
extensive subcutaneous emphysema. It has been also used in
patients with refractory mycoses, leprosy and other intractable
infections.
Carbon Monoxide Poisoning

Carbon monoxide (CO), a byproduct of incomplete combustion of
coal, is a poisonous gas. It is a common cause of death in miners
and other personnel working with coal furnaces in foundaries and
factories. CO poisoning in India occurs in people burning indoor
coal for heating and cooking during winter months in ill ventilated
houses. Deaths in this scenario are commonly reported in
individuals sleeping in closed rooms. Malfunctioning air condi-

tioning system in cabins have been occasionally blamed for CO
poisoning.
CO poisoning is generally insidious. Neurological complications
are most frequent. Some of the common symptoms include
headache, confusion, dizziness, nausea and vomiting. In more
serious forms, syncope, seizures and coma may precede death.
Cardiac arrhythmias and pulmonary edema may also occur.
CO has an affinity for hemoglobin almost 300 times that of
oxygen. Exposure to CO therefore quickly results in displacement
of oxygen and formation of carboxy hemoglobin (HbCO).
Treatment of CO poisoning needs to be prompt and aggressive.
A great degree of evidence supports that hypoxia occurs late in
CO poisoning. But the treatment of both the actually poisoned
persons as well as the environmental exposures are based on a
hypoxic theory of toxicity. Oxygen therapy is the mainstay of
therapy besides other supportive care. Oxygen accelerates the
dissociation of CO from hemoglobin and other heme proteins.
Oxygen with an FiO2 of 100 percent is administered with a high
flow and the response is quick provided the treatment is started in
time before any organ damage has occurred.
Hyperbaric oxygen has been used in a few trials. It rapidly
decreases blood COHb. It may also delay the occurrence of delayed
brain injury. But there is no conclusive evidence to support its use.
Firm guidelines regarding the use of hyperbaric oxygen cannot be
established from the available literature.
Adjunct to Treatment of Cancers

HBO 2 may improve the treatment of malignant tumors by
increasing the tumor sensitization to radiotherapy. A significant
improvement is reported with HBO2 followed by radiotherapy for
local tumors control, mortality for cancers of the head and neck,
and local tumor recurrences in cancers of head, neck and uterine
cavity. It also improves the response to photodynamic and
chemotherapy possibly by raising intra-tumoral oxygen tension.
It was also shown to improve survival in locally advanced breast
cancer undergoing neo-adjuvant chemotherapy. It may also
promote new vessel growth into areas with reduced oxygen tension
thereby promoting healing of radiation induced tissue injury.
248 Oxygen Therapy
Miscellaneous Conditions
• Plastic and reconstructive surgery: For non-healing wounds
including radiation wounds and venous leg ulcers, as an aid to
the survival of skin flaps with marginal circulation, as an aid to
re-implantation surgery, as an adjunct to the treatment of burns
•· Trauma: Crush injury, compartment syndrome, soft tissue sports
injuries
• Orthopedics: Non-union of fractures, bone grafts, osteoradio-
necrosis
• Peripheral vascular diseases: Shock, myocardial ischemia, aid to
cardiac surgery
• Neurological: Stroke, multiple sclerosis, migraine, cerebral
edema, multi-infarct dementia, spinal cord injury and vascular
diseases of the spinal cord, brain abscess, peripheral
neuropathy, radiation myelitis, vegetative coma
• Chronic pain from fibromyalgia syndrome, myofascial pain
syndrome, migraine and cluster headache
• Hematology: Sickle cell crises, severe blood loss anemia
• Ophthalmology: Occlusion of central artery of retina
• Gastrointestinal: Gastric ulcer, necrotizing enterocolitis, and
paralytic ileus, Pneumatoides cystoides intestinalis, hepatitis
• Otorhinolaryngology: Sudden deafness, acute acoustic trauma,
labyrinthitis, Meniere’s disease, malignant otitis externa
(chronic infection)
• Lung diseases: Lung abscess, pulmonary embolism (adjunct to
surgery)
• Endocrines: Diabetes
• Obstetrics: Complicated pregnancy – diabetes, eclampsia, heart
disease, placental hypoxia, fetal hypoxia, congenital heart
disease of the neonate
• Asphyxiation: Drowning, near hanging, smoke inhalation
• Aid to rehabilitation: Spastic hemiplegia of stroke, paraplegia,
chronic myocardial insufficiency, peripheral vascular disease.
CONTRAINDICATIONS
Contraindications for HBO2 therapy can be divided into the
absolute contraindication which include untreated tension
pneumothorax; and relative contraindication which includes upper
respiratory infections, emphysema with CO2 retention, sympto-

matic pulmonary lesions seen on chest X-ray, history of thoracic
or ear surgery, uncontrolled high fever, pregnancy, claustrophobia,
seizure disorders and malignant diseases.
COMPLICATIONS
The complications in the use of HBO2 are related to pressure
changes and the toxic effects of oxygen. They include barotrauma
to ear sinuses, or lungs. Trauma to ears or sinuses may be averted
with slow compression, the use of decongestants, patient education
and rarely myringotomy. Pulmonary barotrauma is very rare,
perhaps occurring 1 in 50,000 treatments. It can be prevented by
careful pretreatment screening for pulmonary blebs, air trapping
caused by bronchospasm or secretions, preexisting pneumothorax,
central lines and ventilatory support. Oxygen toxicity with
occurrence of grand-mal seizures are noticed beyond a depth of 3
ATA (66 feet or 20 m of seawater). Damage of lung tissue,
manifested by decrement in vital capacity and irritation to large
airways may occur due to oxygen toxicity following HBO 2.
Increased pressure causes increased gas density and airway
resistance. This produces an altered voice called the “Donald Duck
voice” and an increased awareness of breathing. Hypoventilation
may result especially in a patient with the underlying obstructive
lung disease. Increased partial pressure of nitrogen causes
symptoms of mild euphoria at pressure of 2.5 atmospheres
progressing to frank intoxication and decreased performance at
over 4 atmospheres. Accumulation of O2 may occur in the event of
an exposure for several days. Hyperpnea and occasionally
respiratory acidosis may result. Other toxic substances or
pollutants, which may continue to accumulate in a closed chamber
and reach toxic pressures, include alcohol (from disinfectant
solution), sulphur dioxide, hydrocarbons, carbon monoxide,
volatile substances and mercury vapors. A regular monitoring is
required for their concentrations. The nursing and medical
personnel looking after the patient in a hyperbaric chamber may
suffer from decompression sickness due to tissue bubble formation.
The risk is rather low because the chamber is kept warm; exposure
is short and decompression rate slow. Risk of an accidental fire is
greater in hyperbaric conditions. All inflammable material should
therefore be kept away. Refractive changes and cataracts in the
250 Oxygen Therapy
lens of the eye may occur as a complication of prolonged HBO2T.

Claustrophobia may be a problem in up to 10 percent of patients,
especially in the mono place chamber.
HYPERBARIC CHAMBERS
The main facility required for hyperbaric medicine is of course the
hyperbaric chamber itself. This is essentially a chamber constructed
to withstand pressurization so that oxygen can be administrated
inside at a pressure greater than at sea level. The size, shape and
pressure capabilities of the design chambers vary considerably.
The technical details of each model now available are provided by
the manufacturers and a classification of various types of chambers
is shown below:
Types of Hyperbaric Chambers

a. Monoplace chamber (Fig. 17.1)
b. Multiplace or “Walk-in“ Chambers (Fig. 17.2)
c. Mobile or portable
Monoplace: Transportable by air, sea or land
Multiplace: A chamber can be driven from place-to-place
d. Chambers for testing and training divers
e. Small hyperbaric chambers
f. For neonates
g. For animal experiments
Fig. 17.1: A monoplace hyperbaric chamber

Fig. 17.2: A multiplace hyperbaric chamber
TECHNIQUES OF HYPERBARIC OXYGENATION

The hyperbaric technician follows the prescribed instructions for
the hyperbaric physician about pressure, duration, and frequency
of treatment. Most of the treatments are given at pressures between
1.5 and 2.5 ATA, and the usual duration of a hyperbaric session is
60 minutes. Of this, 10 minutes are required for compression and
5 minutes for decompression if a pressure of 1.5 ATA is used. Thus,
the maximal oxygen saturation is maintained for about 50 min. In
the case of infections, the treatment duration is doubled. The
treatment sessions for most chronic conditions are given daily,
including on weekends.
World distribution of hyperbaric chambers: Some idea of the
quantity of hyperbaric medical facilities in the world can be
obtained by a review of the statistics regarding the distribution of
hyperbaric chambers in various countries. Accurate information
on this subject is difficult to obtain. The largest number of chambers
is located in Russia (over 1200). South Korea has the largest number
per million inhabitants (4.9 compared with 3.6 in Russia). Within
Europe, excluding Russia, Italy has the largest number of
installations (34.1% of the European total) and also the largest
number per million inhabitants (1.75). The number of hyperbaric
chambers per million inhabitants has risen progressively since 1968
in all countries except Germany, where the number has actually
declined. The fastest rise has been in China and Japan. The number
of chambers does not necessarily correlate with the number or the
252 Oxygen Therapy
number of treatments given. There is no separation of multiplace

and monoplace chambers in the statistics.
Hyperbaric chambers in India: As the medical professionals in
India are not all aware of the benefits of hyperbaric treatment, the
availability of such facilities is also considerably less in number in
India. Of 16 hyperbaric chambers in India, nine chambers are
available with defence services and seven chambers are with civil
hospitals in metropolitan cities. Of course, the hyperbaric chambers
available with the Defence services are also being utilized by the
civil population. But considering the magnitude of hyperbaric
chamber requirements in India for a billion population the
availability of chambers is grossly inadequate.
BIBLIOGRAPHY
1. Al-Waili NS, Butler GJ, Beale J, Hamilton RW, Lee BY, Lucas P. Hyperbaric
oxygen and malignancies: A potential role in radiotherapy, chemotherapy,
tumor surgery and phototherapy. Med Sci Monit 2005; 11: RA279-89.
2. Al-Waili NS, Butler GJ. Effects of hyperbaric oxygen on inflammatory response
to wound and trauma: Possible mechanism of action. Scientific World Journal
2006; 3:425-41.
3. Bennett M, Feldmeier J, Smee R, Milross C. Hyperbaric oxygenation for tumor
sensitization to radiotherapy. Cochrane Database Syst Rev 2005; 19:CD005007.
4. Bennett, PB, Elliot DH (Editors). The Physiology and Medicine of Diving
(4th edn). London, WB Saunders Company Ltd., 1993.
5. Davies JC, Hunt TK (Editors). Hyperbaric Oxygen Therapy. Bethesda, MD:
Undersea and Hyperbaric Medical Society, 1977.
6. Fukaya E, Hopf HW. HBO and gas embolism. Neurol Res 2007;29:142-5.
7. Lumb AB. Hyperoxia and oxygen toxicity. In: Nunn’s Applied Respiratory
Physiology. 5th Edition, Oxford, Butterworth-Heinemann 2000; 491-512.
8. Mayer R, Hamilton-Farrell MR, Van der Kleij AJ, et al. Hyperbaric oxygen
and radiotherapy. Strahlenther Onkol 2005; 181:113-23.
9. Moon RE, Camporesi EM. Clinical care at altered environment pressure. In
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2306.
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extremity. J Surg Orthop Adv 2004; 13:57-68.
11. Prockop LD, Chichkova RI. Carbon monoxide intoxication: An updated
review. J Neurol Sci; 2007.
12. Rhine DJ, Best T. Hyperbaric oxygen therapy in carbon monoxide poisoning:
Effects on neurological sequelae. CJEM 2000;2:22-24.
13. Sharma SN, Sapre GK, Kulkarni J, Alurkar VM, Ganjoo RK, Sundaram PM.
Hyperbaric oxygen therapy in multiple sclerosis. J Assoc Physicians India
1986;34:221-4.
14. Stoller KP. Hyperbaric oxygen and carbon monoxide poisoning: A critical
review. Neurol Res 2007;29:146-15.
15. Strauss RH. Diving Medicine. Am Rev Respir Dis 1979;119:1001-23.

16. Sugihara A, Watanabe H, Oohashi M, et al. The effect of hyperbaric oxygen
therapy on the bout of treatment for soft tissue infections. J Infect 2004;48:
330-3.
17. Tetzlaff K, Shank ES, Muth CM. Evaluation and management of decompre-
ssion illness – an intensivist’s perspective. Intensive care Med 2003; 29:2128-
36.
18. Trivedi DR, Rout VV. Role of hyperbaric oxygen therapy in the rapid control
of gas gangrene infection and its toxemia. Postgrad Med J 1990;36:13-5.
19. Wang C, Schwaitzberg S, Berliner E, Zarin DA, Lau J. Hyperbaric oxygen for
treating wounds: A systematic review of the literature. Arch Surg 2003;138:
272-9.
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year experience. Undersea Hyperb Med 2006;33:85-8.
18
Complications of
Oxygen Therapy
D Gupta, SK Jindal
INTRODUCTION
The complications and hazards associated with injudicious use of
oxygen are many. High concentrations of oxygen are used
indiscriminately for many conditions including chronic diseases.
Pre-hospital hyperoxia is a frequent problem encountered in
patients with acute exacerbations of chronic obstructive pulmonary
disease caused by excessive O2 administration by the ambulance
crew. Besides the physical hazards that are encountered in storage,
transport and use of oxygen, oxygen use itself can lead to certain
problems. Oxygen promotes combustion, thereby increasing the
risk of fire hazards. This is especially important for patients on
domiciliary oxygen use. Nasal and facial burns have been reported
in smokers on oxygen inhalation. Medical complications from
oxygen therapy can occur either from physiological disturbances
caused by excessive oxygen administration or from toxic damage
to the tissues by production of toxic oxygen radicals called reactive
oxygen species (ROS).
PHYSIOLOGICAL COMPLICATIONS
Suppression of Hypoxic Ventilatory Drive
This problem is seen in patients with chronic hypoxemia and
hypercapnia whose ventilation is primarily driven by hypoxia. A
typical example is a patient with chronic obstructive pulmonary
disease who in chronic state maintains a PaCO2 of about 40-50 mm
Hg. If such a patient is given oxygen at high concentrations, for
Complications of Oxygen Therapy 255
example during an acute exacerbation, his hypoxic stimulus is

abruptly relieved resulting in depressed ventilation. This causes a
dangerous rise in PaCO2 levels to 70-80 mm Hg. Such a complica-
tion is less likely in a chronic and stable patient or if oxygen is
delivered at low concentrations. Even a short-term high flow
oxygen as a driving gas in jet nebulizers in patients with COPD
and chronic respiratory failure can lead to a precipitous increase
in the carbon dioxide retention. It is recommended that 100 percent
oxygen should not be used for nebulization therapy in such
patients. Compressed air is employed instead.
This is not to say that oxygen should not be administered for
the fear of rise in CO2 retention. Oxygen is supplemented at a low
flow (e.g. 0.5 L/min), and increased slowly after 20-30 minute
interval to achieve a PaCO2 of around 50 mm Hg or SaO2 of 90
percent. PaCO2 may rise by 4-8 mm in this effort but this much
acidemia is not life-threatening and is more acceptable than a
prolonged hypoxemia. Of late, higher flow rates of oxygen are being
used along with non-invasive ventilation to prevent acute
hypercapnia.
Absorption Atelectasis
This is a complication seen in patients receiving very high FiO2s
(0.9-1.0). This results from the uneven ventilation. Oxygen which
replaces nitrogen in the poorly ventilated areas is absorbed more
rapidly and leads to atelectasis of such poorly ventilated segments.
This causes an increase in the alveolo-arterial oxygen gradient.
Although the clinical importance of such absorption atelectasis is
yet unknown in patients who require such FiO2 values nearing 1.0
because of profound hypoxemia, it should be known to all
physicians working in critical care units so as to differentiate this
relatively benign condition from more serious endobronchial
obstruction and pneumonic consolidation.
Effects on Circulation
Breathing 80 percent or more of oxygen at atmospheric pressure is
known to cause a mild increase in peripheral vascular resistance
and a slight decrease in cardiac output primarily as a result of mild
bradycardia. The bradycardia is vagally medicated since it is
reversed by atropine. There is also a slight decrease in the
256 Oxygen Therapy
pulmonary vascular resistance, particularly following hypoxia. A

transient immediate decrease in red blood cell volume, an increase
in blood volume and a decrease in hematocrit and serum albumin
are also seen with 100 percent oxygen. Spontaneous reversal may
occur with continued oxygen breathing.
Effects on Respiration
Inhalation of 100 percent oxygen causes about 10 percent decrease
in the minute ventilation in normal man; 95 percent oxygen
breathed over 3 hours has been shown to marginally decrease the
diffusion capacity.
The effects on circulation and respiration described above, are
minor and are generally clinically insignificant.
TOXIC EFFECTS OF OXYGEN

Fundamentally, oxygen acts at cellular levels in three ways: (a) It
acts as an electron acceptor; (b) It adds on directly to a substrate
aided by various enzymes; (c) It has a paramagnetic effect on the
electron movements in the neighboring atoms.
Oxygen at Cellular Level
Reactions Role of oxygen

A O2 + 2e´ O´2 + 2H+ H2O2
O2 + 4e´ 2 O´ + 4H+ 2 H2O2 Accepts electrons
B AH + O2 + 2e´ AOH + O´ Oxidation of the
substrate ‘A’ by
direct addition.
A + O2 AO2
In the sequential electron reduction of the oxygen molecules,

there are opportunities for production of oxygen free radicals. These
free radicals are highly reactive and when in excess, can upset
biological function. Ever since the biological discovery of super
oxide dimutase (SOD) in 1969 and the knowledge that neutrophils
(PMN’s) can elucidate superoxide radicals, several investigators
have focussed on the role of these radicals in various disease states.
Sequential Single Electron Reduction of Oxygen to Water
O2 + e´ O ’2 + e´ H2O2 + e´ OH + e´ H2O
Oxygen Superoxide Hydrogen Hydrogen Water
anion peroxide peroxide
As depicted in a simplified manner, addition of one electron to

O2 leads to formation of superoxide anion O′2 which is highly
unstable at neutral pH. It protonates to a weak acid perhydroxyl
radical (OH’2 ). OH2 is a stronger oxidant than O′2 and can react
with polyunsaturated fatty acids. Two electron reduction of O 2 or
single electron reduction of O′2 lead to formation of hydrogen
peroxide (H2O2). H2O2 is a stable oxidant. It is highly volatile and
lipid soluble, so can be excreted by the lungs. It is theoretically
possible to generate hydroxyl radical HO  by 3 electron reduction
of O2 molecule; but is formed only in the presence of certain
transition metals (Fe 2+ , Cu + , Mn 2+ ), metal chelates or
hematoproteins. O′2 and H2O2 can react in the presence of these
metals to generate hydroxyl free medical radical H O , a potent
oxidant.
The reactions involved are also known as iron catalysed Haber-
Weiss reaction or O′2 driven Fenton reaction and can be represented
as below:
Reactions Involved in Generation of HO Radicals
O´2 + Fe3+ + O2 + Fe 2+
H2O2 + Fe 2+ H O  +OH´ + Fe3+
O´ + H2O2 H O  + OH´ + O2
HO  is extremely reactive molecule and reacts with virtually

any organic molecule. Because of its high reactivity, it survives
only briefly at the site of production and its ill effects are mostly
dependent on its site of production rather than the amount, e.g.
even a small amount of HO  radical generated at sensitive sites
like DNA surface can lead to great biological dysfunction.
258 Oxygen Therapy
Other Free Radicals

The oxygen free radicals can lead to formation of several other
types of free radicals in the presence of organic/inorganic
substrates, e.g. HO  can initiate the lipid peroxidation and lead to
formation of lipid peroxi-radical (LOO). Iron enhances this lipid
peroxidation. Hematoprotein peroxidases like myeloperoxidase
(MPO) and eosinophilic peroxidase (EPO) can lead to formation
of potent oxidizing agents by combining with H2O2 in the presence
of halide (Cl′, Br′, l′) or pseudohalide ions (SCN′) by forming
hypochlorous (HOCl), hypoiodus (HOI) and hypobromus (HOBr)
acids which are potent oxidizing and halogenating agents.
Redox Cycling
Redox cycling is a process where production of oxygen metabolites
is enhanced in the presence of certain compounds such as paraquat,
adriamycin and nitrofurantoin. These substances first get reduced
and then combine with oxygen to generate the parent compound
and O′2 thereby setting up a self perpetuating cycle of reduction/
oxidation and O′2 generation.
Tissue Damage Due to Toxic Oxygen Metabolites

Under normal circumstances, about 5 percent of the oxygen
consumed during oxidative metabolism in the mitochondria is
converted to toxic O2 radicals. These are however, effectively
scavenged by several potent defence mechanisms available in the
tissues (discussed later). In situations of hyperoxia, increased
availability of oxygen leads to increased production of O2 free
radicals and tissue damage. Presence of other pathological
conditions such as hyperglycemia may further enhance the damage
from oxidative stress.
Tissue injury can result from several processes. They can initiate
lipid peroxidation and result in membrane defects. They can
activate the complement and coagulation cascades. The oxidative
stress can also induce depletion of cellular ATP levels, denaturing
of enzymes, imbalance in the protease-antiprotease balance and
damage to DNA. The reactive oxygen species may also act as
oxidative signalling in cells causing various gene expressions in
various leukocytes and cardiovascular system playing an important
role in cell death.
DEFENCE MECHANISM AGAINST TOXIC

OXYGEN METABOLITES
Several mechanisms exist in the body to overcome the oxidant
stress. Lungs are armed with a large number of endogenous anti
oxidant agents which act as first line of defence against a wide
variety of oxidants/reactive oxygen species.
Antioxidant Enzymes
Superoxide dismutase (SOD), the chief agent in this group, catalyses
the conversion of O′2 to H2O2 and O2. This reaction is enhanced
several thousand folds over the spontaneous dismutation of O′2,
H2O2 thus formed is decomposed to water by another enzyme
catalase.
The organic hydroperoxides (ROOH) are decomposed by
enzyme glutathione peroxidase (GPO), which uses glutathione
(GSH) as a reducing substrate and reduces the ROOH to water
and organic alcohol. In the process, glutathione is oxidized but is
recycled by glutathione reductase catalysed reaction. These
enzymes have different concentrations in different tissues. SOD
has maximum presence in the liver and the brain and least in the
lungs and the red blood cells (RBCs). Catalase has maximum
concentration in the liver and RBCs, moderate in the lungs and
the kidneys and least concentration in the brain and the skeletal
muscles, GPO activity is also maximum in the liver and least in
the skeletal muscle.
Other Free Radical Scavengers

Several other compounds have the ability to either block the free
radical mediated reactions or to directly scavenge these radicals.
Vitamins E (alpha tocopherol) has been shown to have antioxidant
properties in some experimental models. Similarly, beta carotene,
a vitamin A precursor can scavenge HO  and HOCl–.
Other compounds known to reduce the oxidizing potential of
toxic oxygen metabolites are glutathione, methionine and ascorbic
acid. Ascorbic acid can promote generation of which in turn can
catalase the formation of HO  radical. In plasma, the activity of
SOD, GPO and catalase is very low. Heavy metal chelators such as
transferrin and ceruloplasmin are the main defence mechanisms.
They chelate iron and prevent formation of HO . Ceruloplasmin
260 Oxygen Therapy
can in addition also react with O2 and convert Fe2+ to Fe3+, thereby
preventing Haber-Weiss reaction.
Several micronutrients are essential for proper functioning of
antioxidant enzymes. For example, selenium is essential for GPO.
The nutritional state of a particular cell therefore, is also an
important antioxidant defence.
Clinical Syndromes of Oxidant Injury

The oxidant injury is primarily seen in the lungs, eyes and central
nervous system, because these organs are most susceptible to
oxygen toxicity. Oxygen may also contribute to the pathogenesis
of cardiac dysfunction and gene damage. The tissue damage occurs
with hyperoxia, when production of toxic oxygen metabolites
exceeds their degradation by above mentioned antioxidant defence
mechanism. The clinical syndromes associated with hyperoxia can
be discussed for the sake of convenience under two broad headings,
i.e.
1. Normobaric hyperoxia
2. Hyperbaric hyperoxia
Toxicity of Normobaric Hyperoxia

Pulmonary toxicity is the major concern of oxygen therapy. Lungs
are the organs most severely affected by oxygen in adults. This is
coupled with the underlying disease state of the lungs, which had
necessitated the oxygen administration. The hyperoxia induced
pulmonary injury is a bimodal process from direct oxygen toxicity
and accumulation of inflammatory cells within the lungs.
Pulmonary oxygen toxicity may present with one of the
following three interrelated forms:
a. Tracheobronchitis.
b. Acute lung injury, i.e. acute respiratory distress syndrome
(ARDS).
c. Bronchopulmonary dysplasia (chronic lung injury).
The manifestations depend on the duration and concentration
of oxygen used. Tracheobronchitis is typically characterized by dry
cough and retrosternal pain. Experimental studies have shown
progressive damage to tracheobronchial tree on continued
exposure to 100 percent oxygen. Within 3 hours of exposure to
pure oxygen, the muco-ciliary clearance is decreased. This leads to
focal hyperemia, edema and redness of tracheo-bronchial tree

within 6 hours. Healthy volunteers have been shown to have
increased albumin and transferrin in their bronchoalveolar lavage
(BAL) fluids within 17 hours of exposure to 100 percent oxygen,
thereby indicating an alveolo-capilllary damage and exudation.
The chronic stage is characterized by fibroblastic activity, severe
pulmonary fibrosis and pulmonary dysplasia akin to that of several
other lung injuries.
Pathological changes in pulmonary parenchymal injury
progress in 3 phases. After a latent period of 24-72 hours, the earliest
change which occurs is the edema of the endothelial cells, followed
by damage to alveolar pneumocytes and exudation of edema fluid.
These cells get necrosed over the next few days with denudation
of basement membrane. Type I pneumocytes are more susceptible
to damage than type II pneumocytes. Type II pneumocytes
proliferate by day 6 after which the stage of pulmonary fibrosis
(third phase) is established and continues if exposure persists.
The pathogenesis of hyperoxic lung is attributed to the toxic
oxygen metabolites. The neutrophils are also responsible in part
in the whole process. Intense neutrophilic infiltration has been
demonstrated. The underlying disease of the lungs further adds to
the damage. It has been seen that the risk of oxygen toxicity is
minimum at FiO2 of < 0.5 even for prolonged periods. The best
policy is to keep the FiO2 below 0.6 as far as possible to achieve a
saturation of 90 percent. There is no great purpose of achieving a
high PaO2. Increasing FiO2 further increases the intrapulmonary
shunts without any significant additional therapeutic advantage.
The pulmonary oxygen toxicity manifests with worsening
hypoxemia in spite of a high FiO2. Chest roentgenogram would
show alveolointerstitial shadows depending on the extent of
damage. Both infective and vascular complications in the setting
of critical care unit, present similar clinical/radiological
appearances. Therefore, a careful differential diagnosis is required.
Bronchopulmonary dysplasia is an important complication of
supplemental oxygen in premature infants. It is characterized by
pulmonary fibrosis, leading to chronic respiratory disease and
insufficiency. Another important problem is the retinopathy of
prematurity characterized by vaso obliteration and neovasculari-
zation and retinal traction resulting in blindness. It is now believed
that lower O 2 saturation targets in preterm infants reduce
262 Oxygen Therapy
retinopathy of prematurity and pulmonary complications and may

improve growth.
Toxicity of Hyperbaric Hyperoxia

Hyperbaric oxygen (HBO2) implies administration of oxygen at
pressures more than the atmospheric pressure. This forms of
therapy is needed for clinical situations like decompression
sickness, carbon monoxide poisoning, burns, necrotizing fasciitis
and some other conditions. As is obvious, the oxygen availability
and concentration rise significantly with higher pressures. If oxygen
tension in lungs and brain are approximately 670 and < 80 mm Hg
on breathing 100 percent oxygen at 1 atmosphere; they rise to 3000
and 600 mm Hg respectively at 4-5 atmospheres. Brain has poor
antioxidant levels and cannot withstand such high oxygen
concentrations. Neurological toxicity is therefore the main problem
with HBO2. Since HBO2 is employed usually for very short periods,
the lung toxicity takes time to develop even at such high tensions.
Experimental animal studies have shown that 100 percent O2 at 5
atm is fatal within one hour versus several days’ survival at 1
atmosphere.
The first manifestation of neurological toxicity in man is the
occurence of seizures. The period of onset of seizures is reduced
progressively with increasing pressure. The overall neurological
effects of HBO2 vary from transient paresthesias to convulsions.
Ocular Toxicity
Retrolental fibroplasias is a unique toxicity of oxygen seen only in
premature infants with respiratory distress syndrome who require
ventilatory support and high concentration of oxygen. With the
use of HBO2, visual disturbances have also been reported, possibly
due to retinal ischemia.
MARKERS OF OXIDATIVE INJURY

Several markers which may indirectly indicate oxidative injury in
a critically ill patient have been identified.
End Tidal H2O2

Measurement of H 2O 2 in the expired breath ( EB H2 O 2 ) of the
intubated patients have revealed high values in patients with ARDS
when compared to controls. However, the specificity and sensitivity

of this measurement as an early marker for oxygen toxicity is yet
to be established.
Markers of Lipid Peroxidation

Several techniques have been evaluated to measure lipid
peroxidation.
Ethane and Pentane in Expired Breath

These volatile hydrocarbon gases are produced as side products
of oxidation of lipid hydroperoxides. They can be measured from
the expired gas by gas liquid chromatography. However, the tests
are cumbersome, requiring 60-90 minutes for equilibration. The
levels are also affected by several confounders such as nutritional
status and metabolic state of the individual. These gases are also
metabolized by liver, so levels expired with breath are subject to
variability. In a study in healthy volunteers pentane levels in an
expired breath were shown to increase 60-400 times after 30 minutes
of exposure to 100 percent oxygen.
Thiobarbituric Acid Test (TBA Test)

This is one of the oldest and most widely used test to detect lipid
oxygenation. This test has got high sensitivity. It essentially relies
on the formation of malondialdehyde (MDA) during lipid
peroxidation and the results are expressed as amount of MDA
produced per unit time.
TREATMENT OF OXYGEN TOXICITY

Oxygen toxicity is best prevented than treated. The understanding
of the various toxic radicals and their metabolism has opened up
several therapeutic options to counter the toxic effects. The basic
strategies for treatment consist of augmenting the antioxidant
defences, blocking the production of free radicals and reducing
the initiation of inflammatory reactions. Although none is
established, following modalities have been tried in various studies
and experimental models.
264 Oxygen Therapy
Exogenous Antioxidant Enzymes

SOD and catalase supplements have been tried. Human SOD
manufactured by recombinant DNA technology is now
commercially available. But these enzymes have a very short half
life (<5 minutes) and poor cell penetration. These problems can be
overcome by modifying these enzymes by polyethelene glycol
(PEG). PEG-SOD and PEG catalase are being developed to be used
by aerosolization or intravenous infusion in management of several
oxidant injuries.
Chelation Therapy
To block the Fe2+ medication production of HO radical, heavy metal
chelators have been tried in experimental studies. They are most
useful in preventing neurological toxicity since brain has high
concentration of free iron. Toxicity of iron chelators like
desferoxamine and risk of mobilizing body iron stores have limited
the clinical application of chelation therapy.
Enzyme Induction
Certain species such as the rats have been shown to induce SOD,
GPO and catalase activities on exposure to moderate oxygen
environment. Humans have failed to show such capabilities.
Experimental tools have been used to examine the possibility of
transreaction of human cells with genetically engineered plasmid
to express SOD, catalase and GPO.
Modulation of Inflammatory Response

Pentoxyfyllin that decreases the neutrophil function can decrease
neutrophil induced tissue injury. Similarly, monoclonal antibodies
against specific neutrophil molecules can prevent neutrophil
sequestration.
Cofactors
Glutathione (GSH) is a main cofactor in antioxidant pathways. GSH
helps in redox cycling of GPO and protects disulfide bonds of
proteins from oxidation. N-acetyl cysteine- a precursor of GSH has
been found to be useful in minimizing paracetamol induced liver
injury where GSH stores are depleted intracellularly. Modulation
of lipid peroxidation and provision of free radical scavengers are

also under investigations.
Most of the therapeutic approaches are still in their infancy.
Prevention of oxygen toxicity is the guiding principle in oxygen
therapy. One must not exceed the lowest possible concentration
necessary to correct tissue hypoxia.
BIBLIOGRAPHY
1. Baldwin SR, Simon RH, Grum CM, et al. Oxidant activity in expired breath
of patients with adult respiratory distress syndrome. Lancet 1986;1:11-4.
2. Bancalari E, Claure N, Sosenko IR. Bronchopulmonary dysplasia: Changes
in pathogenesis, epidemiology and definition. Semin Neonatol 2003;8:63-71.
3. Barber RE, Lee J, Hamilton WK. Oxygen toxicity in man. A prospective study
in patients with irreversible brain damage. N Engl J Med 1970;283:1478-89.
4. Cotes JE, Pisa Z, Thomas AJ. Effect of breathing O2 upon cardiac output,
heart rate, ventilation, systemic and pulmonary blood pressures in patients
with chronic lung disease. Clin Sci 1963;25:305.
5. Cross CE, Halliwell B, Borish ET, et al. Oxygen radicals and human disease.
Ann Intern Med 1987;107:526-45.
6. Davis WB, Remnard SI, Bitterman PB, et al. Pulmonary oxygen toxicity: Early
reversible changes in human alveolar structures induced by hyperoxia. N
Engl J Med 1983;309:878-83.
7. Eggers GWN, Palley HW, Leonard JJ, Warren JV. Hemodynamic responses
to oxygen breathing in man. J Appl Physiol 1962; 17:75.
8. Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest
2005;115:500-8.
9. Greenwald RA. Superoxide dismutase and catalase as therapeutic agents for
human disease: Critical review. Free Rad Biol Med 1990;8:201-210.
10. Jenkinson SG: Oxygen toxicity. J. Intensive Care Med 1988;3:137-52.
11. Kimura H, Sawada T, Oshima S, Kozawa K, Ishioka T, Kato M. Toxicity and
roles of reactive oxygen species. Curr Drug Targets Inflamm Allergy 2005;
4:489-95.
12. Morita S, Snider MT, Inada Y. Increased N-pentane excretion in humans:
Consequence of pulmonary oxygen exposure. Anesthesiology 1986;64:730-3.
13. New A. Oxygen: Kill or use? Pre hospital hyperoxia in COPD patients. Emerg
Med J 2006;23:144-6.
14. Pagano A, Barazzone-Argiroffo C. Alveolar cell death in hyperoxia-induced
lung injury. Ann N Y Acad Sci 2003;1010:405-16.
15. Rahman I, Biswas SK, Kode A. Oxidant and antioxidant balance in the airways
and airway diseases. Eur J Pharmacol 2006; 533:222-39.
16. Rolo AP, Palmeira CM. Diabetes and mitochondrial function: Role of
hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 2006;212:167-
78.
17. Sacknar MA, Landa J, Hirsch J, et al. Pulmonary effects of oxygen breathing:
A 6-hour study in normal men. Ann Intern Med 1975;82:40-3.
266 Oxygen Therapy
18. Saugstad OD. Oxygen for newborns: How much is too much? J Perinatol
2005; 25:S45-9.
19. Southorn PA, Powis G. Free radicals in medicine, I. Chemical nature and
biology reactions. Mayo Clin Proc 1988;63:381-9.
20. Speit G, Dennog C, Radermacher P, Rothfuss A. Genotoxicity of hyperbaric
oxygen. Mutat Res 2002; 512:111-9.
21. Thorn SR. Hyperbaric oxygen therapy. J Intensive Care Med 1989;4:58-74.
22. Weinberger B, Laskin DL, Heck DE, Laskin JD. Oxygen toxicity in premature
infants. Toxicol Appl Pharmacol 2002;181:60-7.
Part D
Special Issues
19
Alternate Oxygen Carriers
INTRODUCTION
The need for oxygen by the tissues suffering from hypoxia is intense
in the presence of a severe and critical illness. Administration of
oxygen through conventional means in such conditions is generally
insufficient. Higher concentration of oxygen especially with the
help of assisted ventilation may prove to be toxic. Search for
alternative strategies to carry oxygen to the tissues have alluded
investigators almost for a few centuries. Some of these therapies
seem promising and may occupy a more prominent position in
the near future.
BLOOD SUBSTITUTES
To improve oxygen delivery to the tissues, blood substitutes have
long been sought after. This is due to the fact that allogeneic blood
transfusion is associated with numerous adverse effects. Several
studies have suggested that routine blood transfusions increase
infectious complications, morbidity, mortality, and length of
hospital stay in critically ill patients, and the risk is directly
proportional to the number of blood transfusions. The adverse
effects are due to the fact that RBCs stored for more than 15 days
have a decreased ability to deform and unload oxygen in the
microcirculation. The decreased capacity to deform and the fact
that the aged RBCs undergo increased adhesion to endothelial cells
lead to impaired perfusion which predispose critically ill patients
270 Oxygen Therapy
to an increased risk of infections and organ dysfunction. Apart

from direct transmission of various infectious organisms, allogenic
blood transfusions also introduce a multitude of foreign antigens,
which lead to either immune activation (transfusion-associated
graft-vs-host disease, transfusion-related lung injury, alloimmuni-
zation and various autoimmune diseases) or tolerance induction
(predisposition to nosocomial and postoperative infections, cancer
recurrence, microchimerism and enhanced survival of allograft).
Another important reason for the need of blood substitutes is the
non-availability of allogenic blood in the setting of traumatic
hemorrhage because of the paucity of universal donor-type blood,
the length of time required for type and cross-matching, and the
limited blood bank inventory secondary to the short shelf-life of
red blood cells. Thus, there is a need for artificial oxygen carriers
which can be used as alternatives to allogeneic blood transfusions
to improve tissue oxygenation and function of organs with
marginal oxygen supply.
Artificial oxygen carriers may be grouped into hemoglobin-
based oxygen carriers (HBOCs) and perfluorocarbon emulsions.
Hemoglobin-based Oxygen Carriers

In HBOCs, the hemoglobin is either human (outdated human
blood), bovine or genetically engineered, modified to improve
oxygen off-loading by decreasing oxygen affinity, and to reduce
side effects. At present, hemoglobin solutions in clinical trials are
aqueous solutions, but the production of micro-encapsulated
hemoglobin particles (neo red cells) is also being planned. Also, it
appears that larger hemoglobin molecules (hemoglobin polymers
with a small residual hemoglobin monomer fraction) are better
tolerated probably due to the reduced penetration of these relatively
large molecules into the vessel wall.
There are safety concerns with HBOCs because early cell-free
hemoglobin preparations demonstrated significant nephrotoxicity.
Some of these solutions have been associated with pulmonary and
systemic hypertension, decreased cardiac output, and decreased
splanchnic perfusion. Cross-linking and polymerizing hemoglobin
subunits have reduced the incidence of nephrotoxicity, but
unwanted pressor effects have remained problematic. To
circumvent this, recent studies have evaluated the utility of
ultrapurified polymerized bovine hemoglobin as an oxygen-
Alternate Oxygen Carriers 271
carrying blood substitute. It has been well tolerated in humans

and improves oxygen delivery when compared with crystalloid
infusion. Other red cell substitutes under investigation include
polymerized, pyridoxylated, stroma-free human hemoglobin (has
similar oxygen transport and oncotic characteristics and does not
cause pulmonary or systemic hypertension) and oligomeric
hemoglobin solution derived from outdated human blood.
Perfluorocarbon-based Oxygen Carriers

Perfluorochemicals are chemically inert synthetic molecules that
have the ability to physically dissolve significant quantities of many
gases. Being hydrophobic, they are not miscible with water and
have to be emulsified for intravenous use. Of late, stable
perfluorocarbon emulsions with exceptionally small particles
(median diameter < 0.2 mm) have been manufactured. After
intravenous administration, the perfluorocarbon is taken up by the
reticuloendothelial system which determines their intravascular
half-life. Perfluorocarbon emulsions are well tolerated and at least
as successful to reverse physiologic transfusion triggers as
autologous blood. They are also well tolerated with minimal side
effects such as delayed febrile reaction and flu-like symptoms
related to the normal activity of phagocytic cells.
Perfluorocarbon emulsions may be used for augmented acute
normovolemic hemodilution wherein relatively low preoperative
hemoglobin levels are targeted during preoperative normovolemic
hemodilution and a perfluorocarbon emulsion is given to augment
oxygen delivery during surgery when low endogenous hemoglobin
levels are expected. The autologous blood is subsequently
retransfused in the postoperative period. The clinical experience
with perflubron has shown mixed results. Although ineffective in
the treatment of severe anemia due to hemorrhage, recent phase
III trials have shown that the use of perflubron emulsions was at
least as successful as autologous blood or colloids in treatment of
physiologic transfusion triggers in the setting of orthopedic and
genitourinary surgery. However, one phase III trial utilizing
perflubron (the latest perfluorocarbon) in the setting of cardiac
surgery were recently terminated due to untoward effects in the
perflubron arm. Additional uses of perfluorocarbon emulsions will
include treatments of disease states with compromised tissue
oxygenation such as cerebral or myocardial ischemia, air embolism
272 Oxygen Therapy
and emergency or trauma surgery as long as no allogeneic blood is

available.
EXTRACORPOREAL MEMBRANE OXYGENATION

Extracorporeal membrane oxygenation (ECMO) is a technique for
providing life support, in case the natural lungs are failing and are
not able to maintain a sufficient oxygenation of the body’s organ
systems. It is a modification of cardio-pulmonary bypass technique,
and involves connecting the patient’s circulation to an external
blood pump and membrane oxygenator. Basically, a catheter carries
blood to a pump, then to a membrane oxygenator, where exchange
of oxygen and carbon dioxide takes place. The blood then passes
through tubing back into either the venous or arterial circulation.
An anticoagulant or more recently, anticoagulated tubing is used
to prevent blood clotting in the external system. ECMO is a general
term and one basically should describe the vascular access used
(venovenous, venoarterial or arteriovenous); the proportion of
cardiac output pumped; and the ventilatory regimen of the natural
lung. The typical ECMO currently employed is a low-flow
venovenous bypass circuit, but occasionally cardiac support is also
an issue, and in such circumstances it can be changed to a
venoarterial setting. An alternative approach is to use a veno-
venous perfusion route with a blood flow of only 20-30 percent of
cardiac output combined with a low frequency mechanical
ventilation and additional oxygen insufflation called extracorporeal
CO2 removal (ECCO2R). The use of ECMO is associated with
numerous complications and can be classified into mechanical- and
patient-related groups. Mechanical complications include
oxygenator failure, tubing/circuit disruption, pump- or heat-
exchanger malfunction, and problems associated with cannula
placement or removal. Medical problems include bleeding,
neurological complications, additional organ failure, barotrauma,
infection and metabolic disorders. Extracorporeal membrane
oxygenation (ECMO) is used to treat respiratory or cardiac failure
that is unresponsive to all other measures but is considered to have
a reversible cause. It is most commonly used in the management
of severe (PaO2 <50 mm Hg with FiO2 = 1, PEEP e ≥ 5 cm H2O,
duration for more than 2 h) acute respiratory distress syndrome
(ARDS).
New concepts for miniaturized and highly integrated veno-

venous ECMO are being developed using the experience of already
evaluated mini-ECMO. Oxygenator and blood pump are coupled
reducing foreign surface area and priming volume and the blood
is warmed by the pump motor housing instead of a heat exchanger.
Another concept for a compact assist device is the implementation
insertion of oxygenators into the vena cava. The first device of an
intravascular oxygenator (IVOX) used the pressure difference
inside the vena cava for blood flow. Flow resistance of the device
in a low pressure vessel resulted in stasis as well as disturbed blood
flow around the fibers which achieved only low gas transfer rates,
and hence was abandoned for use. New concepts of intravascular
lung assist are being designed with a combination of a cross-flow
oxygenator and a intravascular microaxial blood pump to improve
blood flow and gas exchange. Using oxygenator with further
decreased flow resistance opens the opportunity to use the right
ventricle as driving force for blood flow.
Many questions, however, remain unanswered, especially in
adult patients; terminology, patient selection criteria, long-term
follow-up studies, and data from controlled studies. The question,
however, of whether ECMO can really complement the advanced
conventional treatment of adult ARDS is unanswered, and needs
evaluation by a randomized controlled trials. Current evidence on
the safety and efficacy of ECMO in adults does not appear adequate
to support the use of this procedure except in severe refractory
ARDS.
HELIOX THERAPY
Heliox is a gas mixture of helium (He) and oxygen which possesses
different physical properties than those of its constituent gases.
Helium, a colorless, odorless and tasteless gas is biologically inert
and nontoxic. With a density of 0.179 g/m3 and a viscosity of 201.8
μ poise, it has a low molecular weight and is lighter than oxygen,
therefore, reduces the density and viscosity of oxygen in a
concentration dependent manner, whenever mixed with oxygen
(Heliox).
It was in 1868 when a French astronomer Janssen noticed a
bright yellow line in the sun-spectrum during a solar eclipse which
was labeled as helium after the Greek god of the sun Helios by the
English astronomer Lockyer. It was much later in 1907 when the
274 Oxygen Therapy
same gas was identified on the earth. Its clinical use as a therapeutic
gas in mixture with oxygen (Heliox) was identified by Barach in
1934 since when several applications have been published from
time-to-time. Most of these applications accrue from several
respiratory benefits attributed to the physical properties of heliox.
Heliox is believed to increased the tidal volume, improve
ventilation and gas distribution within the lungs. It also reduces
the transpulmonary pressure required for ventilation and improves
the aerosol delivery as well. Airflow and diffusion of heliox in the
airways are smoother and faster than that of air or oxygen. All
these respiratory effects have potential clinical benefits in the
presence of severely obstructed air flow due to airway disorders.
Clinical Uses
One of the first applications of heliox comprised of its use for the
management of decompression illness in deep sea divers who work
for long periods. More importantly, it is used to manage conditions
such as acute severe asthma, acute exacerbations of chronic
obstructive pulmonary disease (COPD), upper airway obstruction,
croup, bronchiolitis and post-extubation stridor. Heliox with an
oxygen concentration of more than 20 percent (e.g. 30 percent O2
and 70 percent He or 40 percent O2 and 60 percent He) also serve
the purpose of oxygen supplementation in addition to the
improvements in airflow. It is therefore useful as a method of
oxygen administration.
Acute Asthma
An increased incidence of deaths from an extended occurrence of
non-responsiveness of acute asthma to most of the conventional
methods of treatment has continued to bother the clinicians.
Alternative methods of treatment have always aroused interest.
Helium, which was first described for management of asthma as
early as 1835, became a subject of several investigations since 1980s.
It got a push in 2002 when it was launched by BOC.
Heliox is used as a vehicle for nebulization in the presence of
severe airway obstruction of asthma. Drugs, such as salbutamol,
nebulized with heliox have a deeper penetration in the lungs and
a greater percentage of lung particle retention. Several investigators
have described its beneficial use in both children and adults with
moderate severe asthma exacerbation in causing a greater degree

of clinical improvement compared with the use of oxygen alone.
Heliox is also advantageous in both non-intubated and intubated
patients on mechanical ventilation.
Conclusive data on use of heliox is however inadequate. A
systematic review of seven randomized and non-randomized
prospective trials did not support its use in the emergency
department patients with moderate to severe acute asthma.
Another systematic review was done to examine the efficacy of
heliox on respiratory mechanics and outcome in acute asthma. The
authors on examining four randomized control trials concluded
that heliox might offer mild to moderate advantage in acute asthma
only in the first hour of use. It was not possible to conclude from
the available data whether heliox could avert tracheal intubation
or change other indices such as the hospital admission rates,
duration or mortality.

Heliox breathing is shown to be beneficial in COPD in several case
reports or small clinical studies. During an acute exacerbation in
non-intubated patients, it reduces the work of breathing and arterial
partial pressure of carbon dioxide more than with the conventional
treatment alone.
In intubated COPD patients ventilated with pressure support,
heliox is shown to reduce intrinsic PEEP, the number of ineffective
breaths, the magnitude of inspiratory effort and the work of
breathing. It may help in weaning from mechanical ventilation in
patients with high levels of PEEPi.– it reduces the work of breathing
at the end of weaning process in spontaneously breathing intubated
COPD patients recovering from acute exacerbations.
Sufficient data to support the role of heliox during acute
exacerbations of COPD in either avoiding mechanical ventilation
or in early weaning is not yet available. It also remains to establish
whether it can help in improving exercise tolerance, facilitate
emptying during expiration and relieve symptoms during
rehabilitation programmes. But it has no proven role in stable
COPD since no effect was demonstrable on dynamic hyper-
inflation with heliox breathing.
276 Oxygen Therapy
Critically Ill Children

Heliox has found several applications in critically ill children in
intensive care units. It reduces respiratory distress and use of
accessory muscles of respiration in young infants with acute
bronchiolitis. It may also be useful in prematurely born infants.
Its role as a better vehicle for nebulization of drugs (e.g. salbutamol)
in children with severe lower airway obstruction such as asthma
has been listed above. It may also be helpful to tide over an
emergency situation of upper airway obstruction from severe
laryngotracheitis or croup. Significant improvements in gas
exchange and an augmented clearance of carbon dioxide were
reported with heliox used along with high frequency jet ventilators
in a 5-month old infant with acute respiratory failure and persistent
hypercapnia.
Strong clinical evidence on efficacy of heliox in children is even
more sparse than in adults. Most of the reports are either anecdotal
or small and uncontrolled studies.
Heliox Administration
Heliox administration requires different specifications for devices
and accessories than those for oxygen. These include regulators
(both single stage and 2-stage), flow meters, masks, cannulae, tents,
hoods and artificial airways. Similarly, monitors and analysers are
important to assess and supervise the concentrations being
delivered. Most of these equipment normally used for oxygen
administration require careful adaptations and/or correction
factors for heliox administration. Both nebulizers and mechanical
ventilators required for its administration also require different
specifications. One, therefore needs to be careful for the potential
risks and hazards associated with the manipulations or the jury
rigging of available equipments.
One important potential hazard is the occurrence of anoxia due
to the possibility of administering a gas mixture with less than
< 21 percent oxygen. There is also a possible risk of delivering larger
volumes and inducing volutrauma during mechanical ventilation
especially with ventilators not meant for heliox administration.
Hypothermia has been reported in infants which results from a
high thermal conductivity of heliox.
In summary, it seems that heliox is there to stay and find wider

clinical applications in future. Consequently, appropriate and
dedicated equipment for its administration are likely to be
introduced to reduce the risks and obtain the maximum benefits.
BIBLIOGRAPHY
Blood Substitutes
1. Cohn SM. Alternatives to blood in the 21st century. Critical Care 2004;
8 (Suppl 2):S15-S17.
2. Cohn SM. Blood substitutes in surgery. Surgery 2000;127:599-602.
3. Kjellstrom BT. Blood substitutes: Where do we stand today? J Intern Med
2003; 253:495-7.
4. Spahn DR. Blood substitutes—Artificial oxygen carriers: Perfluorocarbon
emulsions. Crit Care 1999; 3:R93-R97.
5. Spahn DR, Leone BJ, Reves JG, Pasch T. Cardiovascular and coronary
physiology of acute isovolemic hemodilution: A review of non oxygen-
carrying and oxygen-carrying solutions. Anesth Analg 1994;78:1000-21.
6. Spahn DR, van Brempt R, Theilmeier G, et al. Perflubron emulsion delays
blood transfusions in orthopedic surgery. European Perflubron Emulsion
Study Group. Anesthesiology 1999;91:1195-1208.
Extracorporeal Support
7. Gattinoni L, Pesenti A, Mascheroni D, et al. Low-frequency positive pressure
ventilation with extracorporeal CO2 removal in severe acute respiratory
failure. JAMA 1986; 256:881-6.
8. Gerlach H. Extracorporeal ventilatory support. Eur Respir Mon 2002;20:
220-36.
9. Kopp R, Dembinski R, Kuhlen R. Role of extracorporeal lung assist in the
treatment of acute respiratory failure. Minerva Anestesiol 2006;72:587-95.
10. Pesenti A, Bombino M, Gattinoni L. Extracorporeal support of gas exchange.
In: Marini JJ, Slutsky AS, editors. Physiological Basis of Ventilatory Support.
New York, Marcel Dekker, 1998;997-1020.
Heliox
General
11. Barach AL. The use of helium in the treatment of asthma and obstructive
lesion of the larynx and trachea. Ann Intern Med 1935; 9:739-765.
12. Fink JB. Opportunities and risks of using heliox in your clinical practice.
Respir Care 2006; 51:651-60.
13. Gainnier M, Forel J-M. Use of helium-oxygen in critically ill patients. Crit
Care 2006; 10:241 (doi:10.1186/cc5104).
14. Hess DR, Fink JB, Venkataraman ST, Kim IK, Myers TR, Tano BD. The history
and physics of heliox. Respir Care 2006;51:608-12.
278 Oxygen Therapy
Asthma
15. Ho AM, Lee A, Karmakar MK, Dion PW, Chung DC, Contardi LH. Heliox
vs air-oxygen mixtures for the treatment of patients with acute asthma: A
systematic overview. Chest 2003;123:882-90.
16. Kim IK, Phrampus E, Venkataraman S, et al. Helium/oxygen-driven albuterol
nebulization in the treatment of children with moderate to severe asthma
exacerbations : A randomized, controlled trial. Pediatrics 2005;116:1127-33.
17. Kim IK, Saville AL, Sikes KL, Corcoran TE. Heliox-driven albuterol
nebulization for asthma exacerbations: An overview. Respir Care 2006;51:
613-8.
18. Reuben AD, Harris AR. Heliox for asthma in the emergency department : A
review of the literature. Emerg Med J 2004; 21:131-5.
19. Rodrigo GJ, Rodrigo C, Pollack CV, Rowe B. Use of helium-oxygen mixtures
in the treatment of acute asthma: A systematic review. Chest 2003;123:
891-6.
20. Wigmore T, Stachowski E. A review of the use of heliox in the critically ill.
Crit Care Resusc 2006;8:64-72.

21. Amdrews R, Lynch M. Heliox in the treatment of chronic obstructive
pulmonary disease. Emerg Med J 2004;21:670-5.
22. Diehl JL, Mercat A, Guerot E, et al. Helium/oxygen mixture reduces the
work of breathing at the end of the weaning process in patients with severe
chronic obstructive pulmonary disease. Crit Care Med 2003;31:1415-20.
23. Gupta VK, Grayck EN, Cheifetz IM. Heliox administration during high-
frequency jet ventilation augments carbon dioxide clearance. Respir Care 2004;
49:1038-44.
24. Hess DR. Heliox and non-invasive positive pressure ventilation: A role for
heliox in exacerbations of chronic obstructive pulmonary disease? Respir
Care 2006; 51:640-50.
25. Palange P, Crimi E, Pellegrino R, Brusasco V. Supplemental oxygen and
heliox: ‘new’ tools for exercise training in chronic obstructive pulmonary
disease. Curr Opin Pulm Med 2005;11:145-8.
26. Palm KH, Decker WW. Acute exacerbations of chronic obstructive pulmonary
disease. Emerg Med Clin North Am 2003; 21:331-52.
27. Pecchiari M, Pelucchi A, D’angelo E, Foresi A, Milic-Emili J, D’Angelo E.
Effect of heliox breathing on dynamic hyperinflation in COPD patients. Chest
2004;125:2075-82.
28. Rodrigo GJ, Pollack C, Rodrigo C, Rowe B. Heliox for treatment of
exacerbations of chronic obstructive pulmonary disease. Cochrane Database
System Rev 2002;(2):CD003571.
29. Tassaux D, Gainnier M, Battisti A, Jolliet P. Helium-oxygen decreases
inspiratory effort and work of breathing during pressure support in intubated
patients with chronic obstructive pulmonary disease. Intensive Care Med
2005; 31:1501-7.
Critically Ill Children

30. Cambonie G, Milesi C, Fournier-Favre S, et al. Clinical effects of heliox
administration for acute bronchiolitis in young infants. Chest 2006;129:
676-82.
31. Gupta VK, Grayck EN, Cheifetz IM. Heliox administration during high-
frequency jet ventilation augments carbon dioxide clearance. Respir Care
2004;49:1038-44.
32. Myers TR. Use of heliox in children. Respir Care 2006;51:619-31.
33. Piva JP, Menna Barreto SS, Zelmanovitz F, Amantea S, Cox P. Heliox versus
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obstruction. Pediatr Crit Care Med 2002;3:86-7.
20
Oxygen Delivery Devices
R Agarwal
INTRODUCTION
An oxygen delivery system is a device used to administer, regulate
and supplement oxygen to a subject to increase the arterial
oxygenation. In general, the system entrains oxygen and air to
prepare a fixed concentration required for administration. The
choice to use a particular system for an individual patient is
generally guided by the oxygenation status of the patient and
oxygen requirement as well as the disease and patient specific
characteristics.
AIR-OXYGEN MIXTURES
There are two mechanisms employed to facilitate air entrainment
to dilute oxygen viz. (a) Venturi tube and (b) Jet mixing.
Venturi Tube
It incorporates the principles of Venturi and Bernoulli; there is a
constriction in the tube to create subatmospheric pressure by the
accelerated flow velocity from the gas source. Air from the
surroundings gets entrained through the holes and the gas
delivered is a mixture of the source gas (O2) and entrained gas
(air) (Fig. 20.1).
Jet Mixing
In this system, the jet nozzle from which the gas flows is near the
entrainment port. When the gas flows from the pressure source,
Oxygen Delivery Devices 281
some of the velocity of the dynamic gas is transferred to the static

gas which is dragged into the moving gas to the outlet (Fig. 20.2).
Whenever there is a change in the pressure in the delivery circuit,
the amount of the entrained gas changes in the opposite direction
(Fig. 20.2).
FRACTION OF INSPIRED OXYGEN (FiO2)

Fraction of inspired oxygen (FiO2) is defined as the measurable or
calculable concentration of oxygen delivered to the patient. With a
tidal volume of 500 mL of air containing 105 mL oxygen, the FiO2
Fig. 20.1: Venturi tube for oxygen air delivery
Fig. 20.2: Jet mixing

282 Oxygen Therapy
is 0.21 (21 percent). If the entire tidal volume consists of oxygen,

FiO2 becomes 1 (or 100%).
FiO2 provides a consistent value of oxygen concentration being
administered. It gives no information on actual distribution within
the lung parenchyma or its uptake by blood.
How to Regulate FiO2?

In most situations, oxygen supplementation is dictated by the
disease state and other parameters. The following formula may be
used to calculate the total flow, air to oxygen ratio and air and
oxygen flow.
100% Oxygen (a) FiO2 – O2 concentration of

air (x-b)
Desired FiO2 (x)
(a-x)
O2 concentration of air (20 %) 100 – FiO2 desired
Example: For a desired FiO2 of 0.4 (i.e. 40%), the oxygen to air ratio
can be calculated as below:
100 20 (O2)
40 = 20/60 ratio
20 60 (air)
If the total flow is 20 L/min, the ratio of oxygen to air should be

1:3, i.e. O2 = 5 L/ min and air =15L/min.
For a precise FiO2 control, mechanical blending of pressurized
air and oxygen is achieved with the help of an air-oxygen blender.
Blenders help in controlling inlet pressures, balancing air and
oxygen pressures before mixing and metering of desired FiO2. The
oxygen and air travel from the inlet pressure alarm section to the
pressure balancing section and thence to the proportioning section,

where the air and oxygen are mixed according to the desired FiO2.
OXYGEN THERAPY DEVICES

Low-flow vs. High-flow Systems
Oxygen delivery systems are generally classified as low-flow or
variable-performance devices and high-flow or fixed performance
devices. Low-flow systems provide oxygen at flow rates that are
lower than patient’s inspiratory demands; thus when the total
ventilation exceeds the capacity of the oxygen reservoir, room air
is entrained. The final concentration of oxygen delivered depends
on the ventilatory demands of the patient, the size of the oxygen
reservoir and the rate at which the reservoir is filled. At a constant
flow, the larger the tidal volume, the lower the FiO2 and vice versa.
In contrast, the high-flow systems provide a constant FiO2 by
delivering the gas at flow rates that exceed the patient’s peak
inspiratory flow and by using devices that entrain fixed proportion
of room air. The commonly used oxygen delivery systems consist
of cannulae, catheters, masks and tubes adapted for different flow
rates (Table 20.1). The gas delivery devices can also be classified as
non-rebreathing or rebreathing systems. In the former, the exhaled
gases do not come into contact with the inhaled gas, whereas in
the latter, the exhaled gases are collected in a reservoir placed in
the expiratory circuit. A rebreathing circuit essentially results in
an increased accumulation of CO 2 which needs removal.
Rebreathing systems are generally meant for expensive anesthetic
gases which can be conserved.
Table 20.1: Commonly used oxygen delivery systems
Low-flow systems High-flow systems

Nasal cannulae and catheters Venturi masks
Face masks Non-rebreather reservoir masks with
Simple masks blending device and high-flow meters
Reservoir masks
– partial rebreather
– non rebreather
Endotracheal and tracheostomy Endotracheal and tracheostomy tubes
tubes with T-piece with mechanical ventilation
284 Oxygen Therapy
High-flow and Low-flow Systems vis-à-vis

High FiO2 and Low-FiO2
There is a tendency to confuse flow systems with oxygen
concentrations. However both are mutually exclusive in that a high-
flow system viz. Venturi mask can deliver FiO2 as low as 0.24,
whereas a low-flow system like non-rebreather mask can deliver
FiO2 as high as 0.8. Thus, if the ventilatory demand of the patient
is met completely by the system, then it is a high-flow system. On
the other hand, if the system fails to meet the ventilatory demand
of the patient, it is classified as low-flow system.
LOW-FLOW OR VARIABLE PERFORMANCE DEVICES

Nasal Cannulae
Nasal cannulae (also called nasal prongs) are the most widely used
oxygen delivery devices. They are well tolerated, inexpensive, easy
to use and do not interfere with activities like eating and speech. A
nasal cannula consists of two soft plastic prongs placed one cm.
into the nose and secured in place with the help of an elastic strap
(Fig. 20.3). They deliver a constant flow of oxygen to the
nasopharynx and oropharynx, which act as an oxygen reservoir
(approximately 50 mL). The gas flow through the catheter during
inspiration produces a Bernoulli’s effect in the posterior pharynx
causing entrainment of air through the nose. In a patient, with a
tidal volume of 500 mL, a respiratory rate of 20 breaths per minute
and an inspiratory-to-expiratory ratio of 1:2, a general relationship
between oxygen flow and FiO2 can be used i.e. for every one liter
per minute flow of oxygen, the FiO2 increases by 0.03-0.04 upto 6
liters per minute (Table 20.2). Flow rates above six liters per minute
are poorly tolerated. A high flow rate is uncomfortable since it dries
the nasal mucosa and should be avoided. As already explained
the FiO2 depends on the patient’s ventilatory demand and a
quadrupling of the respiratory rate can result in 48 percent decrease
in FiO2 and illustrates the limitation of all low-flow systems.
A miniature reservoir can be attached to the nasal cannula to
economize oxygen delivery. This fills with oxygen during
exhalation and is delivered during inhalation, and is more suitable
for ambulatory patients. Two commercially available reservoir
cannulae include the moustache cannula and the pendant cannula.
Fig. 20.3: Nasal Cannula
Table 20.2: Low-flow oxygen delivery systems
Delivery device Reservoir capacity Oxygen flow Approximate FiO2

(mL) (LPM)
Nasal cannula 50 1 0.21-0.24
2 0.24-0.28
3 0.28-0.32
4 0.32-0.36
5 0.36-0.40
6 0.40-0.44
Simple face mask 150-200 6-10 0.40-0.60
Reservoir masks 800-1000
Partial rebreather 8-10 0.35-0.80
Non-rebreather 8-10 0.40-1
LPM-liters per minute, FiO2-Fraction of inspired oxygen.
Nasal Catheters
These are soft plastic tubes with several holes at the distal end.
They use the nasal, oral and hypopharynx cavities as oxygen
reservoirs. The catheter is introduced through the nose and is placed
behind the uvula. These are always used with bubble humidifiers
as they bypass the nose. Although more secure than the nasal
cannula, it has the same shortcomings as nasal cannula and causes
more discomfort to the patient.
286 Oxygen Therapy
Face Masks
Face masks can be used to provide higher oxygen concentrations
than nasal cannulae as these masks increase the oxygen reservoir
above that of the upper airway. There are three common types of
face masks:
Simple Face Mask

This is a light weight plastic mask with oxygen inlet at the base
and holes at the side for exhalation (Fig. 20.4). It fits loosely on the
face and allows room air to be inhaled, if needed. In general, it
adds another 100-200 mL to the capacity of the reservoir (Table
20.2). A standard face mask delivers oxygen at flow rates between
6-10 liters per minute. The minimum flow rate of six liter per minute
is needed to clear exhaled gas from the mask and at low flow rates
carbon-dioxide can collect in the mask increasing the dead space.
Face masks have the same limitations as other variable
performance devices in that the FiO2 decreases with increasing
ventilatory demands, although they can provide higher FiO2 than
nasal prongs. Another disadvantage common to all face masks, is
that they have to be removed during drinking, eating and speech.
Fig. 20.4: Simple face mask

Masks With Reservoir Bags

The addition of reservoir bags to a standard face mask increases
the capacity of the oxygen reservoir to 800-1000 mL (Table 20.2).
They are divided into two types:
Partial rebreather face masks: These are named so because of the lack
of valve between the mask and the reservoir (Fig. 20.5). Gas from
the oxygen source enters the reservoir through tubing and as the
patient inhales, gas leaves the bag and enters the mask. As the
patient exhales, the first third of the exhaled gas fills the reservoir
bag and as the expiratory flow rate decreases, the last two-thirds
of the exhaled gas is vented through the one way valve in the
exhalation ports which also prevents air entrainment during
inhalation. The volume that fills the reservoir bag is roughly
equivalent to the patient’s anatomical dead space. The exhaled gas
in the reservoir bag has not participated in gas exchange and this
will have a high partial pressure of oxygen and low partial pressure
of carbon dioxide, and the patient inhales this gas mixture during
the next breath. Partial rebreathing circuits can deliver FiO2 of 0.6-
0.8 for oxygen flows of 6-10 L/min. The actual FiO2 depends on
the patient’s ventilatory demand and how snugly the face mask is
Fig. 20.5: Schematic diagram showing the principle of partial

non-rebreather mask
288 Oxygen Therapy
attached. One important point to remember is that the reservoir

bag should not collapse during inspiration which would suggest
an inadequate flow rate insufficient to meet the patient’s ventilatory
demand. This can increase the patient’s work of breathing as the
patient struggles against the one-way valve to entrain room air. A
minimum of 8 L/min should enter the mask to remove exhaled
carbon dioxide and to refill oxygen reservoir.
Non-rebreather face masks: These masks are similar to the partial
rebreather masks except that they have two sets of one way valves
(Fig. 20.6). One set, located between mask and reservoir allows
oxygen from the reservoir into the face mask but not in the other
direction. The other set of valves at the exhalation port prevent
room air from entering mask, however allowing gas to escape
during exhalation. Theoretically, these masks can deliver 100
percent FiO2, if the mask is tightly fit and the only source of
inspiratory gas is the 100 percent oxygen from the reservoir. In
practice, these masks provide FiO2 of 0.6-0.8 as the manufacturers
supply mask with one of the exhalation valve removed. The same
precautions as for the partial rebreather face mask, hold true for
these masks too in that the reservoir bags should not be allowed to
collapse during inspiration.
Fig. 20.6: Schematic diagram showing the principle of non-rebreather face mask
Reservoir bag masks are used in patients who decline invasive

ventilation and when non-invasive ventilation has failed or is
intolerable.
HIGH-FLOW OR FIXED PERFORMANCE DEVICES

The most commonly used fixed performance or high-flow oxygen
delivery device is air-entrainment or Venturi mask.
Venturi Mask (Air-entrainment Mask)

The Venturi mask comes with a color coded air entrainment device
that delivers a specific FiO2 at a specific flow rate (Fig. 20.7). The
entrainment device has various ports of restricted sizes through
which the oxygen flows at high velocities (Fig. 20.8). Air is entrained
at the jet site in direct proportion to the velocities with which oxygen
moves through the port. The mixing of air and oxygen is caused
by shear forces occurring at the boundary of the oxygen jet flow
which drags in room air and not by the lateral pressure at the jet
port. Table 20.3 shows the details of a commercially available air-
entrainment device (Adult MULTI-VENT, Hudson Respiratory
Care Inc. California). The air entrainment mask becomes a variable
performance device when total flow falls below 40 liters per minute
because the patient’s inspiratory demands are not met and air that
is drawn in around the mask dilutes the FiO2. Infact, a total gas
flow that is 30 percent greater than peak inspiratory flow is needed
to deliver a FiO2 at settings less than 0.3. Also, it is not possible to
Fig. 20.7: Commercially available Venturi mask

290 Oxygen Therapy
Fig. 20.8: Schematic diagram showing the principle involved

in the Venturi mask
deliver optimally humidified gases through these masks and

special adaptors are required for this purpose.
High-flow Non-rebreather Face Mask System

This system provides a constant oxygen flow with FiO2s varying
from 0.21 to 1. The device premixes air and oxygen at high
source pressures and delivers the gas at high flow rates of up to
100 L/min per minute with the help of a blending device and high
flow meters. This system is superior to two jet nebulizers fitted in
tandem with non rebreather face mask. This system is not
commonly available in India.
Other Oxygen Delivery Devices

Nasopharyngeal Oxygen
Nasopharyngeal oxygen (NPO) is a new alternative for post
anesthetic care and pediatric intensive care units. Even in adult
ICU setting, NPO administered by a fine catheter advanced into
the nasopharynx is better tolerated and as effective as face mask
oxygen in treatment of mild to moderate hypoxemia.
Table 20.3: Air-oxygen entrainment ratios of a commercially available device
FiO2 (%) Air: Oxygen ratio Recommended oxygen Total gas flow
(LPM) (LPM)
24 25.3:1 3 79
26 14.8:1 3 47
28 10.3:1 6 68
30 7.8:1 6 53
35 4.6:1 9 50
40 3.2:1 12 50
50 1.7:1 15 41
LPM-liters per minute, FiO2-Fraction of inspired oxygen
OxyArm is one such device for use in the postoperative period

after anesthesia. It is an “open oxygen” system that does not require
physical contact with the patient’s face. The device was found to
deliver adequate levels of oxygen for most patients in a recent study
on 60 patients who received oxygen via the Oxy Arm for the first 8
minutes after tracheal extubation after general anesthesia.
Transtracheal Catheters (TTC)

A transtracheal catheter is percutaneously placed into the trachea
through an incision in the cricothyroid membrane. This device is
mainly intended for long-term domiciliary use. The benefits of this
system include a significant conservation of oxygen, patient
comfort and an improved exercise tolerance. The conservation
benefit is achieved due to requirement of low flow rates; but the
mechanism of improved exercise tolerance is not clear. TTC has
been shown to be a potential alternative to nasal oxygen, continuous
positive airway pressure and tracheotomy for severe sleep apnea.
Endotracheal Devices
These devices include endotracheal and tracheostomy tubes which
can function as low-flow systems with T-piece and high flow
systems when connected to the mechanical ventilator.
Transtracheal augmented ventilation using high flows (> 10 L/
min) of a humidified air/oxygen blood can be used for outpatient
ventilatory support of patients with severe respiratory disease and
obviate the need of prolonged mechanical ventilation.
292 Oxygen Therapy
Oxygen tubing: The length of the delivery tubing is also an important

consideration, of particular importance in domiciliary care. An
increase in the length diminishes the flow depending upon the
delivery system. Traditionally, a tube length of upto 50 feet away
from the oxygen source is considered adequate. In a recent study,
it was concluded that flows of 1-2 L/min could be clinically
maintained with up to 100 feet of tubing. The flow delivery for a
particular oxygen source (i.e. oxygen concentrator) should be
checked for this purpose.
Oxygen connectors: A variety of connectors are used to attach tubing
to the oxygen source, humidifier and the delivery device. It is
important to have appropriate adapters to suit the fittings.
Connectors with universal application to fit to a oxygen hose, tubing
and adaptors of different diameters have the advantage of
convenience.
T- pieces and tracheostomy collars: They are meant for use with large
bore tubing in patients with artificial airways (i.e. endotracheal
tube or tracheostomy tube). Besides oxygen, additional humidity
can be provided with the help of a nebulizer. A particular type of
T-piece (ventilator elbow) is available for use for intermittent
positive pressure breathing (IPPB). It has a capped top port for
suctioning. The same may be reversed to fit tracheal adapters for
assisted ventilation. Another type of T-piece has got an opening
for suctioning which facilitates simultaneous aerosol therapy. A
T-piece may also be equipped with two unidirectional valves on
both sides of the piece. A gauge is incorporated to measure the
inspiratory or expiratory force. By occluding one port, the amount
of force can be measured.
Humidification
Humidity is defined as the presence of moisture (water vapor) in a
gas. The amount (mass) of water vapor is expressed in milligrams
per liter of gas. It can be expressed as percent saturation of air
(relative humidity), i.e. ratio between the mass of water actually
present (absolute humidity) and the maximum mass of water which
the gas can hold (fully saturated).
All gases get warmed and humidified in the upper respiratory

tract almost immediately after inspiration. There is complete
humidification by the time the gas reaches second or third tracheal
divisions. Humidification is essential to maintain the normal
function of the mucociliary mechanism of the tracheobronchial tree.
If the inspired gases are dry and humidification inadequate, there
is drying up of bronchial mucosa and impairment of mucociliary
clearance function. It is therefore, important to humidify the oxygen
being administered for therapeutic uses. This assumes even greater
importance when the conditioning system operative in the upper
respiratory tract gets bypassed because of the artificial airways such
as an endotracheal tube or tracheostomy.
Methods of Administering Humidified Oxygen

Humidification is achieved by either a humidifier or a nebulizer.
A humidifier is a device employed to increase the water vapor
content of the gas; a nebulizer is used to generate aerosols. Some
of the devices serve both the functions.
Humidifiers
The traditional humidifier used for oxygen administration in this
country consists of a glass bottle containing water through which
oxygen is passed before being delivered to the tube connecting the
nasal cannula/face mask (Fig. 20.9). This deploys the principle of
bubble diffusion. Its efficiency is increased by incorporating the
tube (submerged in water) with multiple perforations (Fig. 20.10).
The tube is immersed nearly to the bottom of the bottle. The gas
entering the tube is fractionated into small bubbles increasing the
surface area of the gas-liquid interface enhancing evaporation. The
humidity can therefore be increased to about 80 to 90 percent.
The same principle of bubble diffusion is employed in cascade
humidifier used in conjunction with mechanical ventilators. It
consists of a grid submerged in water. When the gas enters the
inlet tube (a) it is deflected from the water surface (b) through the
grid (c) and produces a foam (d) to provide a large surface area
and rapid evaporation (Fig. 20.11). To increase evaporation, the
temperature of the water is raised by a heated element (e). The
temperature can be controlled by a thermistor.
294 Oxygen Therapy
Fig. 20.9: Glass bottle (containing water) used for humidification of O2
Fig. 20.10: Bubble diffusion humidifier
Fig. 20.11: Cascade bubble diffusion humidifier CCaB

Another example of a heated humidifier incorporates a

saturated wick system. The gas passes through a heated chamber
containing a water saturated wick. The water level is maintained
by a reservoir feed system.
Nebulizers
Water can be converted in the inhalable aerosol or particulate form
with the help of a nebulizer (aerosol generator). As the gas is
inspired and gets warmed in the respiratory tract, the particulate
water is nebulized, simultaneously evaporates and gets inhaled.
Following types of nebulizers are available for use:
Jet nebulizers: Jet nebulization involves the introduction of high
pressure gas through a narrow orifice creating a high velocity jet
stream. It consists of a reservoir containing water, a high pressure
gas inlet with a restricted orifice, a liquid feed tube and an air
entrainment port. The high pressure gas introduced through the
orifice producing a jet effect creates subatmospheric pressure
(Bernoulli’s effect) adjacent to the liquid feed tube. Since the
pressure at the surface of water is atmospheric, the water is pushed
up the tube and the droplets get aerosolized by the jet stream. A
baffle is placed near the site of aerosolization to trap particles of
larger size which are therefore not allowed in the gas moving out
of the reservoir to the patient. The outgoing gas contains particles
with the required range of 20-40 m (Fig. 20.12).
Fig. 20.12: Jet nebulizer

296 Oxygen Therapy
Air entrainment port is required to dilute the high pressure gas

(oxygen) used for nebulization. This can be used to adjust the FiO2.
Because of the inherent restrictions involved with a jet, the
maximum oxygen flow that can be used with most such wall
mounted nebulizers is 14-16 L/min at 50 psig. When the total flow
to an aerosol mask is lesser than the patient’s inspiratory demand,
ambient air is inhaled through the exhalation port as well. This
causes a lowering of FiO2. This may happen at high FiO2 settings
(0.60 or more) when less air is entrained causing a decrease of the
total inspiratory flow. In such a situation, two nebulizers can be
connected to a single delivery system to provide adequate gas flow.
When a T-tube circuit is being used, the problem of dilution of
FiO2 is solved by adding a reservoir tube that is one and a half
times the patient’s tidal volume. The amount of air getting entrained
at a given FiO2 varies with changes in the delivery tube. Whenever
there is increased back pressure, the air entrainment is decreased
preventing the lowering of FiO2.
Nebulizers are used to humidify oxygen when an artificial
airway and T-tube systems are being used. These are the large
reservoir nebulizers. The small reservoir nebulizers with a capacity
of about 10 ml are generally used for limited periods for
administration of aerosolized drugs (e.g. bronchodilators). Some
of the nebulizers are fitted with heating mechanisms to increase
the humidify content.
Ultrasonic nebulizer: It uses sound vibrations instead of gas. It
consists of a power unit and a nebulizing unit. The power unit
utilizes standard alternating current converted into ultra high
frequencies of 1.35 and 1.4 megacycles/second. In the nebulizing
unit, the sound energy is passed on to a piezoelectric transducer in
the form of a small ceramic disc which starts vibrating. The
vibrations are transmitted to the couplant fluid. A diaphragm above
the couplant separates the nebulization chamber. The rapid
vibrations of the couplant break the nebulizer fluid into aerosol
particles. A propeller gas introduced through a large bore tube
carries the aerosol particles to the other end. Since the gas is required
only to carry the particles, only small volumes of the gas are needed
(Fig. 20.13).
The ultrasonic nebulizer has several advantages over a jet
nebulizer. The density of aerosol particles is as much as 10 times
Fig. 20.13: Ultrasonic nebulizer
the density produced by jet nebulizers. The aerosol output is more

e.g. up to 6 ml of water/min. The aerosol particles are relatively
homogenous in size. They are capable of supplying concentrations
of 44-74 mg/L of gas in a standard mist tent.
How to Calculate Humidity Deficit?

The amount of water vapor in a given volume of gas is determined
from the absolute and relative humidity. The humidity depends
upon ambient temperature (inspired air or oxygen).
The maximum water content of air at different temperatures is
known. At a room temperature of 22°C, the water content of fully
saturated air is 19.42 gm/L (at body temperature of 37°C, it is 43.9
gm/L. If the relative humidity of the room (at 22°C) is 50 percent,
the actual water content (absolute humidity) would be 19.42 × 0.5
= 9.71 gm/L.
To correct the humidity deficit to body humidity, the water
content shall increase by: (43.9-9.71= 34.19 gm/L).
In general, a healthy afebrile adult loses about 40 ml of water
per day from the respiratory tract. This is increased in febrile
patients and those with hyperpnea. During hyperpnea, the water
loss is as high as 400 mL/daily. This can cause systemic
disturbances of water balance besides the problem of local
dehydration of the tracheobronchial tree. It is therefore, important
to maintain the humidity of inspirited gases. During the states of
increased water losses and requirements, humidity content of
inspired gases is increased accordingly.
298 Oxygen Therapy
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21
Oxygen Therapy: Special
Considerations for Neonates
Anil Narang, S Venkatseshan
INTRODUCTION
Oxygen, perhaps, is the most used and abused ‘drug’ in neonatal
practice worldwide as well as in India today. Soon after its
discovery over two hundred years back, Priestly himself
conjectured that oxygen is a double edged sword, both beneficial
and hazardous to humans, a fact borne out by further experience
with its (mis) use. Oxygen was given to babies more than any other
medicinal product in the last 60 years. The free use of oxygen for
abolishing periodic breathing in the 1940’s led to a high incidence
of retrolental fibroplasias. The first, largest landmark trial on
oxygen use in neonatal medicine confirmed that although oxygen
was a good thing, it was quite possible to have too much of a good
thing. As a result, the environmental concentration of oxygen for
premature babies was generally restricted to 40 percent from that
time. However, it soon became clear that 40 percent oxygen was
insufficient in many cases of the respiratory distress syndrome and
led to a higher mortality rate. McDonald in a retrospective study
of preterm babies born in the 1940s showed an inverse relationship
between the incidence of retrolental fibroplasia and that of cerebral
diplegia. Thus the obvious benefits and the less obvious risks of
oxygen therapy are matters of great concern for neonatologists the
world over. Significant advance has been made in the recognition
of reactive oxygen species (ROS) mediated injury and the role of
hypoxia – reperfusion in the pathogenesis of lot of neonatal
illnesses. Recent advances in monitoring patient-oxygenation
Oxygen Therapy: Special Considerations for Neonates 301
together with a better understanding of the physiology of oxygen

transport in health and disease have considerably advanced our
knowledge in this area. The application of this knowledge, coupled
with the use of modern day technology available in this field, will
allow for a more rational use of oxygen in neonatal practice.
PHYSIOLOGY OF OXYGEN TRANSPORT

Partial Pressure of Oxygen (PO2)
Oxygen enters the blood by diffusion across the pulmonary
epithelium-vascular endothelium membranes according to oxygen
pressure differences between the alveolus (PAO2) and the plasma
(PaO2). The PO2 incidentally is the expression of the ‘activity’ of
oxygen molecules and quantitates the tendency of oxygen
molecules to escape the gas or fluid in which it is present and is
expressed as mm Hg. Physiologically, one can think of partial
pressure as a ‘driving force’ that determines the degree to which
oxygen will move from one compartment to another (e.g. plasma
to tissue). The alveolar PO2 is less than the atmospheric PO2 due to
dilution by CO2 and water vapor.
Oxygen Capacity
Oxygen dissolves in the plasma and binds to hemoglobin. The
amount of oxygen dissolved in the plasma is proportional to the
PO2. However with hemoglobin, the relationship is sigmoid
(See Fig. 4.1). At any PO2, more oxygen can be contained by
hemoglobin than plasma. The maximal quantity of oxygen that
can be carried by the hemoglobin is called the ‘oxygen carrying
capacity. Each gram of adult or fetal hemoglobin can combine
maximally with 1.37 mL of oxygen at 38°C.
Oxygen Content
Oxygen content (CaO2) is the total amount of oxygen present in a
given, volume of blood and is expressed in volumes percent. It
includes the oxygen that is combined with hemoglobin as well as
that dissolved in plasma (See also Chapter 4).
The largest portion (98%) of blood oxygen content is the oxygen
bound to hemoglobin. For a normal newborn with 20 gram
hemoglobin per 100 mL blood, hemoglobin would carry 268 mL
302 Oxygen Therapy
oxygen/L compared to only 4.5 mL/L of oxygen dissolved in the

plasma water.
Oxygen Saturation
The oxygen saturation of blood expresses the relationship between
the actual amount of oxygen bound to hemoglobin at a given PO2
and the oxygen carrying capacity of the same blood, i.e. it is the
percentage of the amount of oxygen bound to hemoglobin
compared to the maximally possible amount. Oxygen content
(CaO 2 ) can be calculated if oxygen saturation (SaO 2 ) and
hemoglobin content (Hb) are known.
Oxygen saturation (SaO2) of Hb and the amount of dissolved
O2 in plasma are directly related to the plasma oxygen partial
pressure (PaO2). Under this pressure, O2 diffuses into the red blood
cells where it reacts with the Hb to form a chemical compound
4O2 + Hb = Hb (O2)4. This relation is reflected by the oxygen -
hemoglobin dissociation curve. Binding of oxygen with Hb
activates further binding until it gets completely saturated. This is
due to the “heme-heme interaction” (cooperative binding). In other
words, the oxyhemoglobin dissociation curve relates the PO2 to
the oxygen saturation or to the amount of oxygen bound to
hemoglobin (See Fig. 4.1).
The position of the dissociation curve is an expression of the affinity
of hemoglobin for oxygen. In adult blood, complete saturation
occurs at a PaO2 of 90-100 mm Hg, whereas the dissociation curve
of fetal blood is shifted to the left and at any given PaO2 below 100
mm Hg, fetal blood binds more oxygen than does adult blood. The
shift is the result of a lower content of 2, 3 diphosphoglycerate
(DPG) in fetal Hb as well as a reduced sensitivity of HbF for 2, 3
DPG. The position of the curve (Hb-O2 affinity) is primarily
modified by four factors: Hydrogen ion concentration (H+), PCO2,
temperature and 2, 3 DPG concentrations (See Fig. 4.3). An increase
in these factors, decrease the affinity and vice versa.
Chronic hypoxic conditions are handled with increased HbO2
affinity in large variety of biologic situations. In these conditions,
the Hb structure is altered such that Hb affinity for O2 is increased,
resulting in higher O2 saturation and blood O2 content at relatively
lower PO2 values. Though the ability of fetal hemoglobin to carry
more oxygen at a given PO2 may be advantageous to extract more
oxygen from maternal blood, it reduces the ability of the

hemoglobin to unload the oxygen to the tissues as well. This is
clinically significant because the sick neonate’s blood will take up
more oxygen at an alveolar PO2 of 40 mm Hg, but the tissue PO2
will have to drop to a very low level in order to unload adequate
amounts of oxygen. The shift also makes clinical recognition of
hypoxia difficult as cyanosis will be observed at a very low oxygen
tension. In the fetus, umbilical venous PO2 is limited by the uterine
venous PO2 (35-40 mm Hg).
Cyanosis is first observed at saturations of 75-85 percent which
relate to oxygen tensions of 32-42 mm Hg in the fetal hemoglobin
dissociation curve, a level well below the value of adult blood and
approaching levels at which patho-physiological effects of hypoxia
occur. In contrast, the flattening of the upper portion of the S-shaped
dissociation curve makes it almost impossible to estimate oxygen
tensions accurately above 60-80 mm Hg from arterial oxygen
saturation.
Improved survival of low birth weight infants with severe
respiratory distress syndrome following exchange transfusion has
been known for some time. This is because infants given exchange
with fresh blood, show an increase in P50 (shift to right) and
2, 3-DPG, especially if citrate phosphate dextrose blood is used
which helps preserve the 2, 3 DPG for longer period. Thus
replacement by blood with higher 2, 3 DPG content and therefore
a more favorable ability to unload oxygen to the tissues would
appear to be of benefit, provided the risks of the procedure itself
can be tolerated by the infant.
In the thermoneutral zone, the oxygen consumption by the baby
is minimal yet sufficient to maintain the body temperature. Placing
the baby in an environmental temperature below the thermoneutral
zone, results in large obligatory increases in oxygen consumption.
However, if the baby is also hypoxic this response is abolished, i.e.
oxygen consumption does not increase and the infant’s body
temperature drops. This paradoxical hypoxic response to a
lowering of environmental temperature has been used as a means
to physiologically determine the presence of hypoxia. Though a
complicated test, its simple clinical counterpart would dictate that
a falling rectal temperature associated with a constant thermal
environment only slightly below the thermoneutral environment
should suggest the possibility of hypoxia. In addition, it has also
304 Oxygen Therapy
been shown that lowering the environment temperature also

lowers the PaO2 in healthy newborn infants.
The newborn has certain temperature stimulation zones
especially in the trigeminal area of the face. Thus the use of cold,
non-humidified oxygen via a face mask will result in large increases
in oxygen consumption even if the baby is in the thermoneutral
zone.
CLINICAL SIGNS OF HYPOXIA

Cyanosis
This is a late sign of hypoxia and in the newborn it appears at PaO2
of less than 40 mm Hg, well below the level at which pulmonary
vasoconstriction occurs. However, in an ill premature baby, the
peripheral circulation is slowed which may lead to a cyanotic
appearance when in actuality, the PaO2 is normal or high. On the
other hand, in very immature infants with little subcutaneous fat
nursed in a high oxygen concentration, one may observe a pink
skin probably due to direct diffusion from the atmosphere, while
the baby is actually hypoxemic. Guidelines to hypoxemia other than
skin color are also less reliable in the newborn.
Heart Rate
The newborn may react to hypoxemia by a deceleration rather than
acceleration in the pulse rate. A fixed heart rate of about 120/min
is seen in hypoxic babies.
Pulmonary Changes
Respiratory response to hypoxia varies between a fetus, a preterm
and a term neonate. Fetuses respond to hypoxia with a suppression
of ventilation, and this is more marked in growth retarded fetuses.
Very immature infants respond to hypoxia in a similar fashion to
fetuses. Otherwise neonates have a biphasic response with an initial
increase in ventilation followed by suppression. This response
disappears by 12-14 days of age and then the adult pattern is
established. However, hypoxic babies are tachypneic either due to
underlying cardiopulmonary disorder or due to the metabolic
academia secondary to the anerobic metabolism induced by
hypoxia. Hypoxia induces acute pulmonary vasoconstrictive
response due to pulmonary artery smooth muscle spasm. This

further aggravates the cyanosis both by decreasing pulmonary
blood flow and by intracardiac right to left shunting. The synthesis
surfactant is also seriously disturbed along with injury to the type
II pneumocytes (surfactant producing cells).
Thermoregulatory Disturbances
A fall in the deep body temperature (core) may prove an indication
of a fall in PaO2 to a level of approximately 50 mm Hg. Fat
thermogenesis is also affected by hypoxemia. In fact, skin
temperature over sites of brown fat is the first to drop in this
situation.
Metabolic Acidosis
Living organisms like humans are dependent on oxygen for energy.
In the key reaction in the aerobic metabolism of glucose (oxidative
phosphorylation), 38 moles of ATP are produced from each mole
of carbohydrate in the presence of adequate amounts of oxygen.
Anaerobic conditions are far less efficient yielding only two moles
of ATP in addition to causing metabolic acidosis. Hypoxemia
induced pulmonary vasoconstriction is further augmented by
acidosis. Together, this will compromise pulmonary blood flow
inducing further hypoxemia which in turn will compromise the
synthesis of lung surfactant.
Although the clinical guides to hypoxemia are poor, there are
no signs whatsoever of hyperoxemia and given the dangers of
hypoxemia and hyperoxemia, there is no substitute for proper
monitoring of oxygenation in the newborn.
OXYGEN TOXICITY
Oxygen may prove toxic either directly via oxidation of tissue or
indirectly through auto regulatory effects on blood flow. It also
causes injury by production of reactive oxygen species (ROS) that
interact with lung cell lipids. Oxygen induces both pulmonary
functional and lung parenchymal changes. It acutely reduces
ventilation and diffusing capacity as also induces pulmonary
vasodilatation. Absorption atelectasis may result in reduction in
vital capacity and increased intrapulmonary shunting. Surfactant
production is initially reduced, with reduction in both DPPC and
306 Oxygen Therapy
PG and so are mucociliary clearance, pulmonary alveolar

macrophage viability and function.
Continuous exposure to high concentrations of oxygen cause
endothelial and alveolar type I cell damage, leukocytic infiltration
with resultant lymphatic distension, alveolar hemorrhage and
edema eventually leading onto fibrosis.
O2 toxicity has been considered to be one of the factors leading
to the development of bronchopulmonary dysplasia (BPD).
Although human neonate has some antioxidant defenses like
glutathione peroxidase, which may even be greater than that of an
adult, other defenses, such as catalase are lower in the neonate
and even lower in the fetus. Oxidative stress affects a complex array
of genes involved in inflammation, coagulation, fibrinolysis,
extracellular matrix turnover, cell cycle, signal transduction and
alveolar enlargement. Hyperoxia also augments the transdifferen-
tiation of pulmonary lipofibroblasts to myofibroblasts (leads to
fibrosis) and increases apoptosis. Neonates, however, seem to more
resistant to pulmonary oxygen toxicity than adults.
The other disease related to oxygen toxicity is retrolental
fibroplasia or its more modern synonym, retinopathy of
prematurity (ROP). Though hypoxemia, hyper or hypocarbia and
prostaglandins have been implicated in its pathogenesis, there is
abundant clinical and epidemiological evidence incriminating
oxygen (hyperoxemia) as a major causative factor. It is evident that
careful control of oxygen administration reduces the incidence of
ROP but it has proved impossible to define a safe level of oxygen.
Current neonatal research is exploring the safe and upper limits of
arterial oxygen saturation.
Hyperoxemic reduction in local blood flow in multiple areas of
the central nervous system secondary to the vasoconstrictive action
of oxygen on the cerebral blood vessels have been demonstrated
and a number of brain lesions are attributed to this cause. Recently,
in autopsies of human infants exposed to hyperoxemia, a specific
lesion, pontosubicular necrosis has been demonstrated.
It is also known that hyperoxemia suppresses erythropoiesis
and predisposes to hemolysis. Anatomical changes in the renal
tubule and stimulation of the sympathoadrenal medullary system
are other purported toxic effects of oxygen.
It has been suggested that oxygen is toxic due to the production
of oxygen free radicals. Reactive oxygen species (ROS) are unstable
chemical compounds with only one unpaired electron in the outer

electron orbit. In the energy economy of the body, oxygen is the
ultimate electron acceptor. It is reduced by a series of four single
electron transfers to water, in which process superoxide radical,
hydrogen peroxide and hydroxyl radical are generated. In addition,
singlet oxygen is formed directly from the oxygen molecule. They
are thus highly reactive and can injure cell membranes by
peroxidation of the polyunsaturated free fatty acids, inactivation
of sulphydryl enzymes and damage to the nucleic acids.
One important oxygen radical generating system is the
hypoxanthine-xanthine oxidase system. Hypoxic neonates have
elevated concentrations of hypoxanthine in the tissues and when
simultaneously treated with oxygen, may produce oxygen radicals
far in excess of the body’s defense systems against free radicals.
A series of conditions in neonates may be caused by free
radicals, e.g. bronchopulmonary dysplasia, retinopathy of
prematurity, necrotizing enterocolitis, intraventricular hemorrhage
and patent ductus arteriosus. These conditions may constitute part
of the so called neonatal oxygen radical disease.
Protection against oxygen free radicals is accomplished by
protecting agents classified as scavengers (e.g. mannitol, superoxide
dismutase), antioxidants (e.g. Vitamin E, Vitamin C, and bilirubin),
repair agents (e.g. reduced glutathione) and antioxienzymes (e.g
catalase, glutathione peroxidase). Therapeutic strategies to reduce
oxygen toxicity would include aggressive treatment of infection,
aspiration and pulmonary embolization which contribute to
oxidant stress, to correct anemia, optimize cardiac output, treat
fever and provide good nutrition. If oxygen concentration cannot
be reduced to a FiO 2 < 0.6, it may be advantageous to add
continuous positive airway pressure (CPAP) or to ventilate.
Pharmacologic approaches to prevent oxygen free radical
diseases are mostly experimental and consist of strategies to reduce
free radical generation like xanthine oxidase, inhibition, calcium
channel blockers or to increase free radical elimination, like use of
allopurinol, N-acetyl cysteine and mannitol and perhaps the most
promising would be the use of cimetidine or intravenous
polyethylene glycol conjugated superoxide dismutase.
Vitamin A and its metabolites are important in lung
development and maturation. Vitamin A supplementation
attenuates hyperoxia induced lung injury in newborn rats.
308 Oxygen Therapy
Randomized controlled trials have shown that vitamin A

supplementation reduces BPD in infants. Inositol is required for
maturation of surfactant components and supplementation has
shown to reduce the incidence of BPD, ROP and IVH. Intratracheal
administration of Cu-Zn-SOD for ventilated animals has been tried
based on the observation that ventilated PT infants have reduced
levels of Cu-Zn-SOD. Chang et al performed a novel study by
continuous infusion of catalytic antioxidant – AEOL 10,113 during
100 percent O2 exposure and found that the histological changes
due to ROS were partially reversed.
OXYGEN AND RESUSCITATION

Standard guidelines for resuscitation of asphyxiated newborn
recommend use of 100 percent oxygen for assisted ventilation.
Recent evidence suggests that resuscitation with high concentration
of oxygen lead to excessive release of free oxygen radicals during
the post hypoxic reoxygenation phase. This has the potential to
cause cellular and organ damage. These observations initiated
several experimental studies to investigate the efficacy of room air
in neonatal resuscitation. Experimental studies in piglets have
indicated that outcome of resuscitation with room air is comparable
to the outcome of resuscitation with 100 percent oxygen.
Preliminary studies comparing room air with 100 percent oxygen
for resuscitation of the asphyxiated newborn have indicated that
room air is as effective as 100 percent oxygen. A recent multicentric
quasirandomized trial comparing the short-term efficacy of room
air versus 100 percent oxygen for resuscitation of asphyxiated
neonates has shown that room air was as good as 100 percent
oxygen for resuscitation of asphyxiated neonates. This trial has
stimulated the need for studies assessing the long-term effects of
room air resuscitation. As per the current neonatal resuscitation
programme (NRP) guidelines, term neonates should be resuscitated
with 100 percent oxygen and if oxygen is not available then room
air resuscitation can be carried out. Preterm neonates may
preferably be monitored with a pulse oximeter and based on that
the concentration has to be decided, which can be provided with
an oxygen blender.
INDICATIONS FOR OXYGEN THERAPY

Clinical conditions in which oxygen therapy is necessary in the
newborn include asphyxia neonatorum, common respiratory
problems like respiratory distress syndrome, meconium aspiration
syndrome, bacterial pneumonia and pneumothorax, shock, apneic
spells, congenital heart disease with right to left circulatory shunt,
persistent fetal circulation and many other respiratory problems.
Oxygen has also been used to differentiate the cause of cyanosis
in infants. Breathing of 100 percent oxygen- the hyperoxia test,
would help differentiate a defect of diffusion from right to left
shunting of blood; the hyperoxia - hyperventilation test is used to
differentiate cyanosis due to a congenital heart disease from that
due to persistent pulmonary hypertension of the neonate (PPHN).
Though breathing of 100 percent oxygen can expedite the
absorption of a pneumothorax, it is no substitute for emergency
relief of a tension pneumothorax by intercostal drainage and is
not recommended due to the direct and indirect effects of oxygen
toxicity.
Oxygen is an effective pulmonary vasodilator but if the inspired
oxygen concentration is reduced rapidly, the vasoconstriction
returns (flip-flop phenomenon) and then may not reverse.
Closure of a patent ductus arteriosus with high oxygen
breathing is generally temporary and the ductus tends to relax
when the stimulus is withdrawn and hence is no recommended.
A situation may arise where less O2 is used (relative hypoxia) to
keep the ductus arteriosus open (in duct dependent cardiac lesions).
Periodic breathing is abolished by oxygen enrichment but this
being physiological, such therapy is not warranted. Though oxygen
is needed in the treatment of a severe apneic episode and for a few
minutes thereafter, its continued use is contraindicated if there is
no ongoing hypoxia. If there is persistent hypoxemia between
apneic episodes, the number of apneic periods can be reduced
markedly if the oxygen concentration is increased slightly, but
careful monitoring is required to prevent hyperoxia.
Though hyperbaric oxygen therapy has not been successful in
the treatment of respiratory distress syndrome, it has been used
with success in promoting wound healing in neonates. Hyper
oxygenation of the mother has been shown to have a beneficial
effect on fetuses with intrauterine growth retardation and oxygen
has also been used successfully for “in utero resuscitation” of the
310 Oxygen Therapy
hypoxemic fetus. Further it has also been shown that significant

amounts of oxygen are absorbed through the newborn skin and it
has been suggested that transepidermal oxygen therapy can
usefully supplement oxygen delivery to very premature infants
with poor pulmonary gas exchange.
Oxygen administration has also been shown to improve right
ventricular performance in neonates with chronic lung diseases
and may help in the early detection of patients who can benefit
from long-term oxygen therapy. Such carefully supervised oxygen
therapy has been accomplished at home and so, at least in the West,
home oxygen therapy has permitted the safe, early discharge of
selected extremely low birth weight infants with chronic lung
disease.
METHODS OF OXYGEN ADMINISTRATION

The administration of oxygen to neonatal patients requires the
selection of an oxygen delivery system that suits the weight, age
and the need of the patient. Oxygen delivery systems can be broadly
divided in to low flow systems (variable performance) or high flow
(fixed performance) devices. Low flow systems provide fractional
concentrations of delivered oxygen (FDO2) that varies with the
patient’s inspiratory flow, whereas, high flow systems provide a
fixed FDO2.
Low Flow Systems

Nasal Prongs/Cannulas
Administration of oxygen through nasal prongs/cannulas in sick
neonates is not recommended. Newborns are obligate nose
breathers. The cannulae occlude the nostrils and increase the airway
resistance. However, it may be better to position the catheter across
the infant’s upper lip, with the distal end under the infant’s nose
and secure it by adhesive tape. Maximum flow should be limited
to 2L/min. The exact concentration of oxygen delivered by cannula
cannot be measured and flow rates are titrated by monitoring the
PaO2, tcPO2 or pulse oximetry levels and by evaluating the clinical
course. Excessive mucus drainage and mucosal edema are common
side effects. Even though FiO2 at the alveolar level is practically
not possible to measure, attempts had been made to measure the
FiO2 level at the hypopharyngeal level and nomograms have been
created to identify the flow requirements of air and oxygen to

provide the desired FiO2.
Oxyhood
Oxygen hoods are enclosure systems designed to surround the
head of the neonate to deliver a constant concentration of oxygen.
It is the simplest and most effective way to deliver oxygen to a
spontaneously breathing infant. However, the oxygen supplied has
to be prewarmed and humidified and the FiO2 inside the hood
should be monitored periodically. The hood should be of
appropriate size and flows >7 L/min is required to prevent carbon
dioxide accumulation.
Incubator Enclosure System

Closed incubators provide a warm environment. Supplemental
oxygen may be added to the incubators but oxygen concentration
may dangerously rise if left unmonitored.
Ventilatory Therapy
Mechanical ventilation of the neonate is an important therapeutic
modality for managing a sick neonate with respiratory failure.
Though indications would vary depending on the facilities,
generally a pH<7.25, PaO2<50 mm Hg and PaCO2>60 mm Hg on
a FiO2 of 0.6 would indicate the need for respiratory assistance.
Types of ventilatory support available are: application of conti-
nuous positive airway pressure (CPAP), intermittent mandatory
ventilation (IMV), High-frequency ventilation (HFV) and others.
OXYGEN MONITORING
In neonates undergoing oxygen therapy, there is only a fine line
dividing the therapeutic benefits of oxygen and its manifold toxic
effects. Therefore, the quality of respiratory care depends on the
tools available to measure the effects of such therapy. Recent
advances in electronic and computer technology have made
available an array of sophisticated and reliable instruments for
monitoring patient oxygenation.
312 Oxygen Therapy
FiO2 Monitoring
The FiO2 monitor/O2 analyzer is recommended for use in any area
where a continuous, accurate oxygen concentration is required for
neonatal oxygen therapy, e.g. intensive care, during anesthesia,
etc. It consists of an oxygen sensor – a thermal conductivity analyzer
type, a galvanic cell or a Clark electrode, which produces a voltage
that is proportional to the oxygen concentration at its detecting
surface. This data are fed into a microprocessor incorporating a
monitor. The monitor assembly contains sophisticated circuitry that
converts the sensor signal into a corresponding percent oxygen
display. FiO2 monitors should be employed to monitor inspired
oxygen concentration every hour/continuously in all infants
receiving supplemental oxygen.
Blood Oxygen Monitoring

Monitoring the partial pressure of oxygen in arterial blood is
mandatory in all infants undergoing oxygen therapy in order to
assess the adequacy of therapeutic interventions as well as to adjust
the respiratory support acutely, thus minimizing oxygen toxicity.
Intermittent Monitoring
In its most basic form this involves intermittent sampling of arterial
catheter, and in acute cases must be done at least four hourly. These
samples however yield discontinuous information about patient’s
oxygenation. The pain, crying and breath holding, which
accompany intermittent punctures, could affect the results.
Moreover, the frequent sampling and the associated blood loss may
be harmful especially for a preterm neonate. The delay in blood
sampling, plus the delay in obtaining the results, means that this
sort of analysis may be misleading. Despite these major
impediments to serial measurements, arterial blood gas values are
the most frequently ordered laboratory examinations in the
intensive care unit (ICU).
Continuous Monitoring
Continuous blood gas monitoring initially used electro-chemical
principles where blood gas electrodes (Clark type) were placed
inline. An indwelling intra-arterial polarographic electrode built
into the umbilical artery catheter has been used to continuously

monitor PaO 2 so also an indwelling saturation monitor (co-
oximeter). However there are many technical difficulties with their
usage and the list of catheter related complications is formidable.
More recently, electro-chemical principle has been replaced by a
more accurate and user friendly technique–Optode technology
(using Optical sensors).
Optode Technology
A further refinement in invasive blood gas monitoring has been
the development of the PO2 optode which works on the principle
of photoluminescence quenching. An optode is a sensor that
optically measures a specific substance. A chemical film is glued
to the tip of the optical cable and the fluorescent property of this
film varies with the varying concentration of the measured analyte.
The fluorescence in an oxygen optode is maximum when there is
no oxygen. When an oxygen molecule comes and collides with the
film, it reduces the fluorescence in proportion to the number of
colliding O2 molecules. Several recent studies have examined its
accuracy and it has been shown to function most precisely at low
PO2, a desirable feature. Thanks to its small diameter, the optode
sensor can be placed either extra-arterial (EABG) or intra-arterial
(IABG). Studies have shown that EABG is slightly better than the
IABG systems regarding the precision of PaO2 analysis.
Non-invasive Monitoring of Oxygenation

Transcutaneous PO2 Monitoring
The serious complications of invasive blood gas monitoring and
the realization of the inadequacy and fallacy of intermittent blood
gas monitoring led to the development of transcutaneous, non-
invasive, continuous monitoring of blood gases in the newborn.
The tcPO2 electrode is a miniaturized heated, redesigned Clark
electrode consisting of a platinum cathode and a silver reference
anode encased in an electrolyte solution and separated from the
skin by a membrane permeable to oxygen. The heating of the skin
arterializes the capillary blood and oxygen diffuses through the
membrane in to the electrode. There it is reduced by the cathode
thereby generating an electric current which is converted into
partial pressure measurements and displayed by the monitor. The
314 Oxygen Therapy
tcPO2 monitoring has received wide acceptance the world over.

Data show good correlation with PO2 values in healthy as well as
sick neonates. Improper probe placement and poor peripheral
perfusion are the two common conditions where the PO 2
measurement goes wrong. The tcPO2 monitor has been widely used
in ventilatory care facilitating maintenance of adequate
oxygenation as well as faster weaning; it provides an excellent
opportunity to have a continuous trend of oxygenation over the
previous hours/days, which significantly helps in clinical and
research activities. The tcPO2 monitor has also been used in the
diagnosis of right to left shunting by monitoring the preductal and
postductal oxygenation. The tcPO2 electrodes have been used in
monitoring maternal and fetal oxygen during labour. Side effects
are few and minor like local erythema, skin craters and blister
formation.
Pulse Oximetry
Pulse oximeter provides a safe and simple method of assessing
patient oxygenation. It has the advantages of being continuous,
non-invasive, and reliable with a rapid response time, self-
calibration and no risk of burns. It has the physiologic advantage
of indicating adequacy of oxygen supply to the tissues, and hence
the method is increasingly being used in neonatal intensive care
units. Pulse oximetry is used to measure hemoglobin oxygen
saturation and is based on the principles of plethysmography and
spectrophotometry. The monitor displays percentage saturation
of hemoglobin along with the pulse rate and pulse wave form.
Inspite of these many benefits, pulse oximeter may not work
well in the face of hypotension and shock. Recent advances in pulse
oximeter monitoring technologies (Masimo technology) which uses
the signal extraction technology (SET) to reduce the false alarms
following artifacts, has attempted to overcome these difficulties
but this still remains to be proven in clinical trials. If the heart rate
displayed by the ECG monitor correlates with the displayed pulse
rate on the saturation monitor within a five beat range, it ensures
adequacy of SpO2 readings in low perfusion states. Errors in pulse
oximeter recordings may occur due to the presence of abnormal
hemoglobins like methemoglobin and carboxyhemoglobin, dyes
like methylene blue and indigo carmine, artifacts like ambient light,
low perfusion and motion, venous pulsation, technological
problems like optical shunt, optical cross talk and electrical

interference.
Even after accounting for so many sources of error, the accuracy
of pulse oximeters is impressive. It has been suggested that the
SpO 2 be kept at 92±3 percent in sick neonates so that the
corresponding PaO 2 values are between 45-100 mm Hg. A
sensitivity-specificity analysis showed that the SpO2 range of 92±3
percent indicated a PaO2 range of 45-100 mm Hg with 100 percent
sensitivity and specificity. Hay et al recommended that the SpO2
range of >98 percent should be considered as a goal for achieving
and maintaining ‘normal’ blood oxygenation in newborn infants.
But till now the safe limits of saturation is controversial. A recent
national survey of pulse oximetry before and after 2 weeks of life
has shown that a saturation range ≤ 98 percent before 2 weeks and
≤ 92 percent after first 2 weeks of life led to a less number of severe
ROP cases requiring ablative surgery. However, some correlation
should be made between oxygen saturation and PO2 at lower (85-
90%) and higher (96-99%) saturation values before relying entirely
on pulse oxygen saturation determinations for oxygen and
respiratory management. Currently, randomized trials have been
planned to look for early infancy outcomes (ROP and neuro-
development) after a low (85-89%) vs. high (91-95%) target
saturations and the results of these studies may through some light
on this issue. Some hints on pulse oximetry can be found in
Table 21.1.
Table 21.1: Hints on SpO2 monitoring
Acute illness Chronic illness

Acceptable limits 87-95% 90-95%
O2 management Wean from O2 when baby Wean from O2 when baby
parameters stable and SpO2 stable and SpO2
consistently>95% consistently >95% 12-24 hrs
Blood gas SpO2 <85/>97% SpO2 <87 / >95 %

requirements consistently over consistently over an hour
15-30 min·
• Monitor whether ECG
heart rate is correlating·
• Watch for poor
peripheral perfusion
316 Oxygen Therapy
Other Methods of Assessing Oxygenation

Conjunctival PO2
A miniaturized Clark electrode has been made to fit inside a
polymethylmethacrylate ocular confirmer ring, and is directly
applied to the palpebral conjunctiva. This is thus a true tissue
oxygen monitor, does not need heating, has rapid equilibration
time and helps detect changes in carotid blood flow. However,
practical limitations are same as for any transcutaneous monitoring.
Potential for ocular damage had to be kept in mind.
Invasive Hemoglobin Saturation Monitoring

Mixed venous PO2 (P v O2) and hemoglobin and saturation (S v O2)
reflect global tissue oxygenation and the ability of the
cardiopulmonary system to transport sufficient oxygen to meet
body oxygen needs. Based on this physiologic argument,
continuous mixed venous oxygen monitoring using a fibreoptic
system with the catheter tip in the pulmonary artery has been
accomplished, although, it has not found wide acceptance in
neonatology.
Cytochrome aa3 Saturation Monitoring

Cytochrome aa3 is a distal enzyme in the oxidative phosphorylation
taking place in the mitochondria. Evaluating the redox state of this
enzyme, by illuminating with a NIROS-scope that emits near infra-
red light, has been used to follow trends in mitochondrial
oxygenation. The device, however, is not currently suitable for
clinical use owing to its size, expense and limited data as to its
accuracy. Nevertheless, it promises an exciting future for
monitoring oxygen continuously and non-invasively at its ultimate
destination, in living tissue.
GUIDELINES TO OXYGEN THERAPY

Oxygen is a drug and so should be given only for medical
indications as detailed earlier. Regardless of the mode of
administration, safe oxygen therapy should follow certain
guidelines. The following recommendations have been made in
accordance with the guidelines of the American Academy of
Pediatrics and the American College of Obstetricians and
Gynecologists.
1. No concentration of oxygen is safe. What is therapeutic for one

infant may be toxic to another. Therefore, mere FiO2 monitoring
is not adequate.
2. Give sufficient oxygen to maintain an arterial PO2 of 50-80 mm
Hg. If this is not possible, give just enough oxygen to alleviate
cyanosis.
3. Oxygen administration without some form of continuous
monitoring of infant’s oxygenation is not safe and so is not
recommended.
4. Administered oxygen should always be humidified (30-40
percent) and prewarmed to 31-34°C.
5. Inspired oxygen concentration should be measured near the
infant’s nose continuously or at least hourly and recorded. FiO2
monitors need 8-hourly calibration.
6. Always try to maintain a constant FiO2 so as to stabilize the
PaO2. All changes in FiO2 must be gradual to minimize the risk
of ‘flip-flop’ phenomenon.
7. Close monitoring and recording of clinical parameters like color,
respiratory effort, activity and circulatory response as also of
FiO2 concentrations and time of adjustments should be carried
out. This helps determine the need for oxygen therapy.
CONCLUSIONS
With the current state of our knowledge regarding oxygen’s uses,
hazards and dangers, it must be administered with extreme caution
in newborns. The administration must be done only when indicated
and it should be rigorously monitored to prevent life-threatening
complications. Oxygen concentration to be used during resusci-
tation needs further clarification regarding its long-term effects.
APPENDIX
Physical Constants of Oxygen
Chemical symbol O
International symbol (molecule) O2
Atomic number 8
Atomic weight 16
Molecular weight 32
Specific gravity at 70F (1 atmosphere) 1.1053
Contd…
318 Oxygen Therapy
Contd…
Density at 70 F and 1 atm 0.08281 cubic feet/lb
Boiling point at 1 atm –297.4 F (–183oC)
Melting point at 1 atm –361.1F
Critical temperature –181.1F (–118.4oC)
Solubility in water at 32 F 1/32
(vol of gas/vol of water)
Weight per gallon liquid at boiling point 9.55 lb
Critical pressure 715 psig
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Oxygen Therapy in Children 323
22
Oxygen Therapy in Children
Meenu Singh
INTRODUCTION
Oxygen is by far, the most frequently used intervention in the
management of the critically ill child; whether there is respiratory
disease or not. There is often, a casual attitude towards the
administration of oxygen. We, often, forget that oxygen has well
characterized and potentially toxic effects on the lungs and retina.
Oxygen therapy is the process of increasing the concentration of
oxygen in inspired air, to correct or prevent hypoxia. The primary
indication is the presence or risk of hypoxemia. The goal of oxygen
therapy is to supply adequate oxygen to the tissues. Reduced
oxygen in the blood is hypoxemia, whereas reduced oxygen to the
tissues is hypoxia.
THERAPEUTIC USES OF OXYGEN

In 1775, Priestley first wrote about the therapeutic use of oxygen.
“From the greater strength and vivacity of the flame of a candle, in
this pure air (oxygen) it might be conjectured, that it might be
particularly salutary to the lungs in certain morbid cases, when
common air would not be sufficient to carry off the phlogistic putrid
effluvium quickly enough. We may also infer from these
experiments that pure dephlogisticated air (oxygen) might be very
useful as a medicine.” The most enthusiastic early proponent of
oxygen therapy was Beddoes, who produced the first textbook of
oxygen therapy entitled Considerations on the Medicinal Use and
Production of Factitious Airs in 1796. This enthusiasm, however, was
324 Oxygen Therapy
tempered by its misuse and the toxic effects noted by Lavoisier in

1785, and, by the end of the 18th century, therapeutic use of oxygen
was in decline. Since then, interest in oxygen therapy has waxed
and waned, but research has continued to add to our understanding
of how oxygen works in the human body. The physiologic basis of
supplemental oxygen therapy and its complications in several
special conditions pertaining to children will be reviewed in this
article.
THE PHYSIOLOGY OF OXYGENATION

The use of oxygen by the body occurs by a relatively simple
physiological process. This process begins in the atmosphere, where
the partial pressure of oxygen (PO2) is approximately 160 mm Hg,
and ends at the mitochondria, where PO2 is only a few millimeters
of mercury. Partial pressure of oxygen decreases as soon as the
ambient gas reaches conducting airways because of its saturation
with water vapor. Once the inspired air reaches the terminal
respiratory units, gas exchange takes place. The blood in the
pulmonary capillaries leaving the alveoli contains approximately
the same PO2 as the gas phase of the terminal units. The PO2 in the
arterial blood is slightly lower because local matching of ventilation
and perfusion in normal lungs is imperfect and unoxygenated
blood is added to the pulmonary capillary blood from
postpulmonary shunt. Oxygen then is delivered to the systemic
capillaries and diffuses into the cells to support aerobic metabolism.
The bulk of molecular oxygen (90 percent) is consumed in the
mitochondria.
OXYGEN UPTAKE
Oxygen is taken up via respiration by the lung’s approximately
300 million alveoli, each of which is about 300 mm in diameter.
The huge surface area (approximately 75 m2) and the thinness of
the septa (< 0.5 mm thick) of the alveoli provide an extremely
efficient mechanism for the human body to take up oxygen from
the ambient air. With each inspiration, approximately 500 mL of
air enters the lungs (tidal volume). The surface area available for
exchange by body weight is larger in children in comparison to
adults which conforms to the metabolic demands of a growing
system. As the age increases, number of alveoli go on increasing
till about the middle of second decade of life.
Oxygen in the alveolar space continuously diffuses into the

pulmonary capillaries, where it binds the hemoglobin in the
erythrocytes and enters the systemic circulation. Each erythrocyte
traverses the pulmonary microcirculation in approximately three
quarters of a second. Within the first third of this brief transit time,
the hemoglobin becomes virtually completely oxygenated. At the
same time, carbon dioxide (CO2), formed constantly in the body
tissues, is removed continuously from the pulmonary capillaries
by ventilation. Slightly more O2 is removed from the alveolar space
than CO2 is added (normal respiratory exchange ratio = 0.8). The
efficiency of O2-CO2 exchange is determined primarily by the

ventilation-perfusion ( V Q ) relationship of the lung units. Low

V Q units and right-to-left shunt ( V Q = 0) are associated with
impaired oxygen uptake from the alveolar space, whereas high

V Q units and dead space ( V Q = infinity) result in inefficient
elimination of CO2 from the pulmonary arterial blood.
OXYGEN TRANSPORT
Once oxygen diffuses into the blood, it binds rapidly to hemoglobin.
The affinity of hemoglobin for oxygen increases with increasing
oxygen saturation, and the hemoglobin oxygen equilibrium curve
has a sigmoid shape. The amount of oxygen transported in the
blood to the peripheral tissues (oxygen delivery [DO 2 ]) is
determined primarily by hemoglobin concentration, its oxygen
saturation, and cardiac output (CO):
DO2 = 1.34 × CO × [Hb] × % sat + 0.0031 × PaO2
The amount of oxygen carried by hemoglobin is 1.34 mL/g. Given
the normal concentration of hemoglobin of 15g/100 mL and 100
percent saturation with oxygen (PO2 of 100 mm Hg), 100 mL blood
can transport approximately 20 mL of oxygen in combination with
hemoglobin (oxygen content). This is in contrast to the very low
amount of oxygen physically dissolved in the plasma (0.003 × 100
or 0.3 mL per 100 mL). Thus, without hemoglobin, one would need
a cardiac output of at least 80 L/min to support the normal resting
oxygen consumption of 250 mL/min. The sigmoid shape of the
hemoglobin-oxygen dissociation curve (See Fig. 4.1) also suggests
that when hemoglobin saturation is more than 90 percent (i.e., at
the plateau of the curve), additional oxygen does not enhance
326 Oxygen Therapy
oxygen delivery significantly because the percent saturation of

hemoglobin cannot exceed 100 percent. It simply increases the
amount of oxygen dissolved in the plasma.
A number of conditions can displace the oxygen-hemoglobin
equilibrium curve (See Fig. 4.3) to the right or the left of its normal
position (P50, or PaO2 at 50 percent saturation, of 27 mm Hg).
Increased 2,3-diglycerophosphate (2,3-DPG), acidosis, and
hyperthermia shift the curve to the right and facilitate the unloading
of oxygen in the peripheral tissues. In contrast, decreased 2,3-DPG,
alkalosis, and hypothermia shift the curve to the left and help
maintain oxygen saturation in the arterial blood.
OXYGEN CONSUMPTION
The mitochondria consume approximately 90 percent of the oxygen
used by the cell. Other subcellular organelles (lysosomes, nucleus,
cell membrane) use the other 10 percent. In the mitochondria,
molecular oxygen receives electrons from the respiratory chain and
is reduced to water. This reduction of oxygen is the primary
function of cytochrome c oxidase, the last enzyme in the electron
transport chain. High-energy phosphate compounds –for example,
adenosine triphosphate (ATP)–are generated by electron transport
in the process of oxidative phosphorylation. ATP provides most of
the energy for biologic function.
At the tissue level, the relationship between the transport and
the consumption of oxygen was described first by Fick in 1870.

According to the Fick principle, oxygen consumption ( V O2) of the
tissues can be calculated as follows:

V O2 = CO × (CaO2 – C v O2)
Where CO is cardiac output, CaO2 is arterial oxygen content, and
C v O2 is mixed venous oxygen content. Increased extraction of
oxygen from the blood leads to a lower C v O2 and frequently a
lower P v O2 (normal P v O2 is 35-40 mm Hg, with an oxygen
saturation of approximately 75%). Resting blood and oxygen supply
of various organs is shown in Table 22.1. As can be seen, brain
tissue and cardiac muscle extract much more oxygen from the blood
than do other organs. These two organs are most susceptible to
ischemia and hypoxia.
Table 22.1: Arterial oxygen pressure (PO2) and oxygen (O2)

content for venous blood of different organ systems
(CaO2-C vO2)
Organ system P vO2 (mm Hg) % Saturation C vO2 (ml/dl)
Brain 37 69 13.9 6.3
Heart 30 56 8.8 11.4
Intestine 45 80 16.1 1 4.1
Kidney 74 94 18.9 1.3
Skeletal muscle 32 60 12.2 8.0
Skin 75 95 19.2 1.0
RATIONALE FOR OXYGEN THERAPY

Supplemental oxygen usually is given to correct alveolar hypoxia
and arterial hypoxemia. The human body has only a negligible
reserve of oxygen, which amounts to approximately 1.5 L. This
would last for only 6 minutes in case of circulatory arrest (assuming
a body oxygen consumption is 250 mL/min). Hemoglobin contains
about half of the oxygen reserve (800 mL), whereas alveoli account
for about half of the remainder. In a gas volume of 3.5 L in the
alveoli, there is approximately 400 mL of oxygen. During a breath-
hold, this would last for about 1½ minutes. If 100 percent oxygen
has been breathed before the breath-hold, this can be extended to
10½ minutes. Other smaller reserves of oxygen are those bound to
myoglobulin (250 mL) and those dissolved in tissues (50 mL).
There are few clinical controlled trials documenting the
effectiveness of supplemental oxygen in acute hypoxia. The
rationale for starting supplemental oxygen under acute hypoxic
conditions is based on extensive clinical experience, which shows
that untreated hypoxemia leads to tissue hypoxia and irreversible
changes in vital organ function. As a general rule, supplemental
oxygen is indicated when arterial PO2 falls below 60 mm Hg or
hemoglobin saturation is less than 90 percent. Exceptions occur in
individuals adapted to high altitude who do not need oxygen even
if arterial oxygen pressure (PaO2) is less than 60 mm Hg. The
decision for using supplemental oxygen can be facilitated greatly
by understanding the physiologic mechanisms of hypoxemia and
the mechanisms of tissue hypoxia of the underlying conditions.
328 Oxygen Therapy
Physiologic Mechanisms of Hypoxemia

In general, arterial hypoxemia is defined as PO2 values less than
80 mm Hg in an individual breathing room air at sea level.
Hypoxemia usually indicates a defect in the gas exchange function
of the lung, although a normal PO2 does not exclude the presence
of lung diseases. A more sensitive index to detect the presence of
lung diseases is the alveolar-arterial O2 gradient (A-aDO2 ). A-a
DO2 can be calculated from the alveolar gas equation:
PAO2 = (PB – PH2O) × FiO2 – PACO2/R
A-a DO2 = PAO2 – PaO2
Where PAO2 is alveolar PO2; PB is barometric pressure (760 mm
Hg at sea level); PH2O is water vapor pressure (47 mm Hg at 37°C);
FiO2 is oxygen fraction in the breathing air (21% in room air); PaCO2
is alveolar PCO2 (frequently replaced by PaCO2); and R is the
respiratory exchange ratio (0.8). Normal A-a DO2 is age dependent
and is equal to the smaller of either 0.5 × age or 25.
There are five physiologic mechanisms of hypoxemia. They are
hypoventilation, ventilation-perfusion mismatch, right-to-left
shunt, diffusion impairment, and decreased mixed venous oxygen
content.
Hypoventilation
Hypoventilation decreases the arterial PO2 and increases the arterial

PCO2. If V Q distribution remains uniform, no alveolo-arterial
difference develops for either O2 or CO2. The common causes of
hypoventilation-associated hypoxemia are depression of the central
nervous system from anesthesia or narcotics and neuromuscular
diseases that affect respiratory muscle function. Although
hypoxemia caused by hypoventilation can be corrected by
supplemental oxygen, the primary treatment should be directed
to supporting alveolar ventilation.
Ventilation-Perfusion Mismatch

Ventilation-perfusion mismatch (low V Q regions) is the most
common cause of hypoxemia in lung disease. In children
pneumonias caused by infections or aspirations, foreign bodies or
mucus plugs in the bronchus are common causes of ventilation/

perfusion mismatch.
Right-to-Left Shunt
A shunt is defined as a region where there is blood flow from the

right heart to the left heart but no ventilation ( V Q = 0). Because
of the absence of ventilation in the shunt pathway, however,
hypoxemia resulting from right-to-left shunt cannot be corrected
by breathing 100 percent O2. Thus, breathing 100 percent O2 allows

V Q mismatch to be differentiated from shunt as the cause of
hypoxemia.
When a healthy person breathes 100 percent O2, an alveolar-
arterial PO2 difference of approximately 50 mm Hg usually can be
detected. This results from the presence of a physiologic shunt of
approximately 2 percent to 3 percent of the cardiac output. Most
of the physiologic shunt in normal subjects occurs distal to the gas
exchange units, that is, a “post-pulmonary shunt.” The main
sources of the normal postpulmonary shunt are bronchial and
mediastinal veins that empty into pulmonary veins and the
thebesian vessels of the left ventricle, which empty directly into
the left ventricular cavity. When shunting occurs in patients with
lung disease, it usually is accounted for by the perfusion of
nonventilated lung regions through relatively normal vascular
channels (intrapulmonary shunt). Sometimes, shunt flow may
occur through intracardiac communications, for example, a patent
foramen ovale, when the pressure in the right atrium is increased
because of pulmonary hypertension with right ventricular failure
(intracardiac shunt).
Diffusion Impairment
In normal subjects at rest, O2 equilibrates quickly between the blood
and gas phases in the alveolar region of the lung, and there is no
diffusion limitation. This is true for healthy persons at sea level
and at low altitude. During exercise at higher altitudes (>10,000
ft), the alveolar-arterial PO2 difference can increase in normal
individuals because of diffusion dysequilibrium as a result of low
ambient O2 and shortened capillary transit time. Exercise-induced
330 Oxygen Therapy
diffusion abnormalities in patients with lung diseases more

commonly result from a decrease in pulmonary blood volume in
combination with an increase in the rate of blood flow, thus
shortening the capillary transit time for the erythrocytes. Similar

to V Q mismatch, hypoxemia caused by diffusion impairment can
be corrected by having the individual breathe 100 percent oxygen.
Common causes of alveolo-capillary block in children are acute
respiratory distress syndrome (ARDS) and interstitial pneumonias.
Decreased Mixed Venous Oxygen Content

The O2 content of pulmonary artery (mixed venous) blood usually
has little effect on arterial PO2 in persons with healthy lungs. In

the presence of a substantial amount of either V Q mismatch or a
large right-to-left shunt, or both, the oxygen content in the mixed
venous blood has a considerable effect on arterial PO2. For a given

amount of V Q mismatch, the lower the mixed venous oxygen
content, the lower the arterial PO2. This mechanism of hypoxemia
is particularly important in critically ill patients with serious
cardiopulmonary diseases. The response to supplemental oxygen

clearly depends on the relative contribution of V Q mismatch and
right-to-left shunt to hypoxemia.
Causes of Tissue Hypoxia

A complex disturbance of cellular function can be produced by
hypoxia, primarily as a result of inadequate production of high-
energy phosphate compounds (e.g., ATP). When oxygen is
insufficient, glucose can only be metabolized anaerobically to
pyruvate and lactate. Organs that use large amounts of oxygen,
such as the brain and the heart, are more susceptible to hypoxia
(Table 22.1). When blood oxygen tension is reduced acutely,
symptoms and signs of cerebral hypoxia (impaired judgment,
motor incoordination, altered mental status) and cardiac hypoxia
(myocardial ischemia, arrhythmias) tend to manifest themselves
first. When hypoxia becomes more severe and prolonged, the
respiratory centers of the brainstem are affected, and death usually
occurs as a result of respiratory failure. The goal of supplemental
oxygen therapy thus is to prevent these detrimental consequences
of tissue hypoxia.
Although tissue hypoxia may be associated with a variety of

clinical conditions, there generally are four classic mechanisms that
cause it.
Hypoxic hypoxia results from an inadequate amount of oxygen
in the blood (i.e., reduced PaO2) caused by either lung disease or
decreased oxygen in the inspired air (e.g., at high altitude).
Supplemental oxygen may correct tissue hypoxia by raising the
oxygen tension in the blood in most cases (except in right-to-left
shunt).
Anemic Hypoxia
Anemic hypoxia results from a reduction in the oxygen-carrying
capacity of hemoglobin, which may be caused by severe anemia,
or the presence of dyshemoglobin states (carboxyhemoglobin,
methemoglobin), which decreases the affinity of oxygen for the
hemoglobin molecule. In anemia, PO2 remains normal, but the
absolute amount of oxygen transported per unit volume of blood
is diminished. Because the hemoglobin is well saturated with
oxygen, supplemental oxygen provides little benefit in augmenting
oxygen delivery to the tissues unless the PO2 in the arterial blood
is raised to very high levels. Carbon monoxide poisoning not only
decreases the oxygen-binding capacity of hemoglobin but also shifts
the hemoglobin dissociation curve to the left, impairing the
unloading of oxygen at the peripheral tissues. Oxygen is useful in
carbon monoxide poisoning because it displaces carbon monoxide
from hemoglobin and decreases the half-life of carboxyhemoglobin.
Stagnant Hypoxia
Stagnant hypoxia is a result of poor tissue perfusion, as may be
seen in severe cardiac failure, hypovolemic shock, cardiac arrest,
or peripheral vascular diseases. Tissue edema associated with poor
perfusion increases the distance through which oxygen has to travel
before it reaches the cells and contributes to localized hypoxia.
Supplemental oxygen is usually not helpful unless tissue perfusion
can be restored.
Histotoxic Hypoxia
Histotoxic hypoxia is an inability to use oxygen at the cellular level,
as in cyanide or sulfide poisoning. These chemical poisons produce
332 Oxygen Therapy
cellular hypoxia by inhibiting electron-transfer function by

cytochrome oxidase so that it cannot pass electrons to oxygen. The
oxygen that is delivered to the tissues by the blood is not extracted,
and as a consequence, the venous blood tends to have a high oxygen
tension. Obviously, supplemental oxygen has little benefit in this
case unless the underlying toxic process can be reversed.
Recognition of Hypoxemia
Traditionally in tertiary care settings, oxygen concentration in the
plasma (PO2) has been used to assess hypoxemia. But, this method
requires a blood sample and a laboratory. In the past 15 years or
so, the cutaneous measurement of oxygen through pulse oximeters
has nearly completely replaced the older techniques, particularly
in developed countries. Pulse oximeters, although relatively
expensive are very useful in the detection of early hypoxemia and
require little maintenance. A recent study reported use of pulse
oximetry to assess hypoxemia in critically ill children with
respiratory and non-respiratory illnesses. Depending upon the
altitude, hypoxemia can be defined accordingly by measuring
oxygen saturation (SaO2) percutaneuously. No universal definition
of hypoxemia exists. Investigators have defined hypoxemia from
<96.6 percent to <90 percent oxygen saturation at sea level and
<85 percent to <88 percent at higher altitudes. For simplicity, a
couple of on-going international multicentre clinical trials for
pneumonia therapy are using cut-offs of <90 percent at sea level
and <88 percent at higher altitude to define hypoxemia.
In most developing country situations, where facilities to
measure plasma concentration and oxygen saturation are not
available, most clinicians rely on clinical signs to identify
hypoxemia. Often standardized criteria and methods are not used
for providing oxygen therapy. The World Health Organization
(WHO) acute respiratory infection (ARI) control guidelines
recommend that where oxygen supply is scarce, it should be
provided to children with cyanosis and who are unable to drink.
Infants under 2 months of age with ARI are always considered a
priority. In presence of ample supply, oxygen should be provided
to children with severe lower chest in drawing, with a respiratory
rate of 70 breaths/minute or more or with restlessness (if improved
by oxygen). WHO guidelines were recently modified to include
lethargy/unconsciousness, head nodding, vomiting everything or
convulsions. A recent review of predictors of hypoxemia also

identified grunting and nasal flaring alongwith above-mentioned
signs. Reliance on a single clinical sign may not be optimal, as some
clinical signs like lower chest in drawing or fast breathing may be
sensitive but not very specific for identification of hypoxemia.
Whereas, other signs like cyanosis, inability to drink, grunting or
lethargy may be very specific, but not very sensitive. So it is better
to use a combination of signs. A study from Gambia prospectively
evaluated a combination of WHO recommended signs of inability
to feed or drink or cyanosis or respiratory rate of 70 or more breaths
per minute or severe chest in drawing and found them to be 80.9
percent sensitive and 62.5 percent specific for predicting
hypoxemia. This combination, which is fairly sensitive though not
highly specific, could be used in most developing country
situations.
METHODS OF OXYGEN ADMINISTRATION

Several methods are used to provide oxygen and the oxygen
concentration varies according to the methods used. Oxygen
concentration delivered to a child of 5 kg at a 1 L/min flow is 45-
60 percent with nasopharyngeal catheter, 35-40 percent with nasal
catheter, 30-35 percent with nasal prongs and 29 percent with head
box, whereas with face mask it is variable. WHO recommends three
low flow methods. It recommends using nasal prongs when giving
oxygen to young children. This method delivers adequate
concentration of oxygen safely to hypoxemic children. It also does
not require humidification. Where prongs are not available, nasal
catheters are an alternative. WHO guidelines recommend 0.5 L/
min oxygen flow for a child less than 2 months old (or less than 5
kg) and 1 L/min for above that age or weight. Where oxygen supply
is limited and adequate oxygenation is not achieved with prongs
or catheters, a nasopharyngeal catheter may be used as it achieves
the highest concentration. This requires trained staff, as a thin
flexible tube is passed through the nostril until the tip lies in the
patient’s throat, just beyond the soft palate. Before inserting the
catheter the distance for insertion can be measured from side of
the nostril to the front of ear. This method also requires
humidification as the catheter tip lies in the oropharynx. Nasal
prongs or nasal catheter require a higher flow of oxygen than
nasopharyngeal catheter. A few complications with the use of
334 Oxygen Therapy
nasopharyngeal catheter have been reported. When the patient

develops mucus in the nose, it requires cleaning. The catheters and
prongs should be cleaned once or twice every day. One study from
India has reported the use of oropharyngeal catheter for oxygen
delivery, delivery, but these results have not yet been replicated.
Use of facemask and head box for delivery of oxygen is
discouraged in less developed countries, because higher flows of
oxygen are required (4-5 L/min) and danger of carbon dioxide
accumulation exists if the oxygen flow is low. Head boxes are used
widely in developed countries for babies because they are tolerated
well and do not need humidification. But they require a mixing
device to ensure correct oxygen concentration. Because child’s
mouth and nose are close to the opening of the box, the actual
concentration inspired is lower than expected. The concentration
falls further when head box is opened. Furthermore, the oxygen
therapy has to be discontinued during feeding.
Limitations of Oxygen Therapy

The major limitation of oxygen therapy lies in the pulmonary
toxicity of increased alveolar oxygen tension. This is clearly related
to the duration and level of oxygen administration. An FiO2 0.6 for
more than 24 hours is definitely associated with lung damage;
whereas 4 or less can be given for prolonged periods.
Another feature that limits the usefulness of oxygen therapy in
pulmonary disease is the relationship between the FiO2 and the
resultant PaO 2 under conditions of varying or increasing
intrapulmonary shunting. This is akin to a certain amount of cardiac
output by passing the alveoli without getting oxygen from them.
The diseased alveoli do not allow oxygen to diffuse into the
capillaries that serve them. The amount of blood not getting
oxygenated is expressed as a shunt fraction. Once this is in excess
of 30 percent of the total cardiac output, oxygenation cannot be
maintained with less than 0.5 FiO2. With a greater than 40 percent
shunt, atmospheric oxygen alone will not be enough and some
other means of providing oxygen under pressure will be needed-
PEEP/CPAP/IPPV.
When air highly enriched with oxygen is supplied over a
prolonged period of time to the alveoli, the inert gas nitrogen gets
displaced and replaced by oxygen. Oxygen is absorbed out of the
alveoli and this may lead to a loss of volume in the alveoli resulting
in atelectesis. This is called the phenomenon of alveolar nitrogen
washout.
Oxygen administration for the correction of hypoxia can extend
from simple tubes and masks to life support systems like ECMO.
Oxygen administration to the non-intubated patients is elaborated
in this communication.
When to Stop Oxygen?

In severely hypoxemic children, the oxygen saturation may not be
corrected soon and the clinical signs may persist. When the child
is improving, oxygen could be withdrawn for a few minutes (nasal
catheter or prongs could be cleared at this time) and child should
be observed for about 10 minutes. Oxygen therapy is no longer
needed, if the child is comfortable without oxygen. If a pulse
oximeter is available, oxygen saturation can be monitored.
OXYGEN SOURCES
In most situations in developing countries, oxygen cylinders are
the main source of oxygen. They are expensive, bulky and difficult
to transport. A high pressure gauge is needed with individual
cylinders. Full cylinders contain oxygen at a pressure of 132
atmospheres or bars (2000 psi or 13,400 kPa). When the pressure
falls below 8 atmospheres or bars (120 psi or 800 kPa) the cylinder
is nearly empty. A flow meter must be attached to the regulator to
allow the precise flow of oxygen to the patient. One limitation of
individual cylinder is assessing the remaining quantity of oxygen
in order to prevent the risk of supply running out. Size and pressure
of the cylinder and oxygen flow per minute can be used to calculate
the remaining oxygen in the cylinder. Cylinders come in variable
sizes. For example size ‘D’ contains 340 liters, size ‘E’ contains 680
liters, size ‘F’ contains 1360 liters and size ‘G’ contains 3400 liters.
One can calculate how many hours the contents will last by using
the formula V/F/60, where ‘V’ is numbers of liters remaining in
the cylinder, ‘F’ flow of oxygen per minute (60 being minutes in an
hour).
Oxygen for cylinders is produced by cooling air until it liquifies,
and then distilling the liquid to separate pure oxygen from it.
Because of the very low temperatures required, below –180°C, this
336 Oxygen Therapy
process has a high-energy consumption and can only be done in

large manufacturing plants. It is an expensive process.
Oxygen cylinders are heavy and difficult to transport. The
cylinders have to be transported back to the bulk supply depot to
be refilled, as well as from the depot out to the point of use.
Transport is often unreliable in developing countries and expensive,
so there are often long periods when small hospitals in developing
countries have no supplies of oxygen.
Medical oxygen is very expensive in some developing countries
and may have to be imported, therefore consuming scarce foreign
currency. For instance, in Papua New Guinea, with bulk of large
(7600 liter) cylinders, a continuous flow of 1 L/min of oxygen costs
approximately US $ 6 per day, or US$ 2190 per year. This price
does not include the cost of transport, which is considerable for
rural areas, and it, may be even greater if small orders are placed
or small cylinders are used. For example it costs US$ 14 per day or
US$ 5110 per year for a continuous flow of 1 L/min from 440 liter
cylinders purchased in bulk. A recent article compared the cost of
oxygen from cylinders and from concentrators in Papua New
Guinea and found significant cost savings with the latter, ranging
from 25 percent in the smallest hospitals to 75 percent in large
district hospitals. A further study showed a significant cost saving
when oxygen concentrators for anesthesia were installed in all
district hospitals in Malawi. These savings were estimated by
comparing the costs of running the concentrators with those the
Ministry of Health of Malawi would have incurred if the same
amount of oxygen had been supplied with cylinders. The estimated
annual savings for oxygen amounted to about 1.27 percent of the
total health budget for that fiscal year. These promising results
need to be confirmed by further cost studies in other settings in
developing countries such as India.
Industrial oxygen is often much cheaper than medical oxygen
may be easier to obtain as the principle of manufacture is identical
to that of medical oxygen. Chemical impurities are unlikely in either
form. Industrial oxygen is therefore usually safe for medical use
and can be used instead of medical oxygen. If oxygen is obtained
from an industrial source however, hospital administrators or
persons incharge of oxygen supplies must make certain with the
manufacturer that the cylinders do indeed contain oxygen and have
not previously been used for other gases. The means of cylinder
identification must be agreed with the supplier before cylinders

are purchased.
OXYGEN CONCENTRATORS
Oxygen concentrators, developed in 1960s are widely used in the
industrialized world to provide oxygen at home to patients with
chronic lung disorders. Their success is attributed to provision of
oxygen at a low cost. WHO has identified some models that fulfill
the requirements for use in high temperature, humidity and
altitude. The use of such oxygen concentrators in district hospitals
in Papua New Guinea, Malawi, Mongolia and Egypt has been very
satisfactory. It was found to be economical way of delivering
oxygen. Although the initial cost (approximately US$ 1500) may
seem high, it is estimated that this cost is equivalent to 6-12 months
cost of oxygen supply for a typical district hospital. One oxygen
concentrator can provide low flow oxygen to up to four sick
children. Flow meters should also be attached to concentrator to
ensure adequate flow. Oxygen concentrator requires electricity to
run, but use with solar power has been reported.
Provision of oxygen optimally is a quality care issue. In resource
poor settings, there is a need to look for more cost-effective ways
of oxygen management. The use of oxygen concentrators and
provision of oxygen by nasal prongs or catheter can reduce the
cost of oxygen therapy tremendously. The use of pulse oximeter
can improve the care of critically ill children and provide cost
savings, especially if the oxygen source is cylinders.
An oxygen concentrator separates the nitrogen from the oxygen
in air. Most machines use an electrically powered compressor to
force compressed air through synthetic aluminium silicate (Zeolite),
which reversibly binds nitrogen. They deliver approximately 2-4
L/min of gas containing over 90 percent oxygen: the concentration
of oxygen is less at higher flow rates.
There have been recent improvements in the design and
manufacture of oxygen concentrators, making them more reliable/
smaller, lighter and cheaper. A working group established WHO
and the World Federation of Societies of Anesthesiologists has
drawn up requirements for concentrators to be used in adverse
conditions, which are based on the International standard for
oxygen concentrators. In order to meet the WHO specifications,
338 Oxygen Therapy
concentrators are required to operate at temperatures of upto 43°C.

A relative humidity of 90-95 percent and altitudes of upto 4000 m.
A vibration test, to simulate hazards of transport over rough terrain,
and a corrosion test are also specified. Machines meeting these
specifications are now being field-tested to assure their suitability
for use in developing countries. Their performance should be
closely monitored since to date there is relatively little experience
with their use in such settings.
Existing concentrators require a regular AC power supply of
about 300 watts from mains or a back-up generator. It is
recommended that an oxygen cylinder be kept in addition as a
back up in case of breakdown or power failure. Oxygen
concentrators are much more reliable now than they used to be.
Typically, all that is required for their regular maintenance is that
the users wash a filter each day and replace two other filters every
3 to 6 months. Skilled mechanical maintenance is needed at
intervals of about one year. Concentrators do malfunction
occasionally, and their repair can require considerable expertise;
worn parts on the compressor and valves may need replacement,
so that adequate stocks of filters and spare parts must be included
in the initial purchase. In Malawi, two technicians were trained
abroad for 3 months, six more received 4 weeks training locally,
and filters and spare parts were provided for 5 years. The
performance of the concentrators was monitored twice a year and
found to match the specifications for 26 months.
Some malfunctions cause oxygen concentrators to pump out
air rather than oxygen, so it is important to be able to test the oxygen
concentrations delivered, and not just check for a gas flow. The
models meeting the WHO specifications have a built-in device,
called an OCSI (Oxygen Concentration Status Indicator), which
measures the oxygen concentration just before the outlet. A warning
is given when the concentration is low, and the machines switch
off if the concentration of oxygen falls below 70 percent. In models,
which are not fitted with such a device, the concentration of oxygen
needs to be checked at regular intervals using a separate oxygen
analyzer. It is advisable to check the concentration of oxygen in
the models fitted with an OCSI as well, though less frequently
(twice a year, for example). The measurement must be carried out
about 10 minutes after switching the concentrator on, since this is
the average time taken by the machine to build up the desired (90-
95%) concentration of oxygen. Oxygen concentrators cost about

US$ 1500-2000 each; because cylinders of oxygen are so expensive,
concentrators can result in large savings in cost, but they should
only be used where there is a reliable electricity supply and
adequate maintenance and repair facilities. WHO recommends that
only models meeting the technical specifications mentioned above
be used in small hospitals in developing countries.
The management of hypoxemia in children can be improved
by ensuring that- i) health workers are aware that hypoxemia can
potentially lead to death and that it is assessed appropriately; ii)
oxygen is available to those who need it and iii) oxygen is delivered
efficiently and effectively for the required duration.
OXYGEN DELIVERY DEVICES

A low flow system provides FiO2 that varies with the patient’s
inspiratory flow rates, e.g. nasal cannula, simple mask, various
rebreathing masks. A high flow system provides fixed FiO2 at flows
that meet or exceed the patient’s own inspiratory flow require-
ments, e.g. Venturi systems. The patient’s own flow requirement
depend on the minute ventilation (MV) and I : E ratio. Normal
flow requirements are 3-4 times the MV and MV = Tidal Volume
(Vt) × Respiratory rate (RR). Average Vt is about 6 mL/kg.
Therefore a 5 kg child breathing at 60/min needs about 6-7 1/min
of the air oxygen mixture.
Nasopharyngeal Catheter
This is a thin flexible tube, which is passed through the nose until
its tip lies in the patient’s throat, just beyond the soft palate. A
catheter passed for a distance equal to that from the side of the
nostril to the front of the ear usually reaches that point in the
oropharynx. The tip of the catheter should be visible just below
the uvula when the mouth of the child is open. The nasopharyngeal
catheter is also known, in some places, as oropharyngeal catheter,
because its tip lies in the patient’s oropharynx.
The advantages of this method are that the lowest flow rate of
oxygen is required to achieve a given concentration in the airways,
the concentration is not reduced if the patient’s nostrils are blocked,
the catheter can easily be secured in place so that it is unlikely to
be dislodged, and there is no danger of hypercarbia (carbon dioxide
340 Oxygen Therapy
accumulation) if the oxygen is turned off or the tubing disconnects.

With a nasopharyngeal catheter, an oxygen flow of 1 L/min
delivers between 45 percent and 60 percent of oxygen to a 5 kg
child. When oxygen is supplied from a cylinder with a flowmeter,
the use of a nasopharyngeal catheter can result in considerable
savings over other methods of administration.
However, the gas should be humidified (to avoid drying of the
pharyngeal mucosa and reduce the likelihood of inspissated
secretions which can block the catheter and cause airway
obstruction), the catheter must not be pushed in too far (because
gastric distension may result), the flow rate must not be greater
that 2 L/min (because of the risk of gastric distension), and the
catheter must be taken out and cleaned at least twice a day (so that
mucus does not block the holes of the catheter). Some children
will cough and gag, or even vomit, when a nasopharyngeal catheter
is first put in. Some will deep on coughing and gagging, and the
catheter should then be withdrawn slightly. Occasionally, a
nasopharyngeal catheter will cause obstruction of the airways or
even apnea; continuous and skilled nursing care is needed to
prevent or treat these rare but potentially fatal complications. If a
nasogastric tube and a nasopharyngeal catheter are used at the
same time, they should be placed in the same nostril.
Nasal Catheter
This is a thin flexible tube which is passed through the nose and
ends with its tip in the nasal cavity, or just within the nasopharynx.
A catheter passed for a distance that is equal to the distance from
the side of the nostril to the inner margin of the eyebrow usually
reaches that point in the nasal cavity. The tip of the catheter should
not be visible when the mouth of the child is open.
Nasal catheter are not as economical as nasopharyngeal
catheters, when oxygen is supplied from a cylinder: they require a
higher flow to achieve a given concentration of oxygen in the
airways. They are usually well tolerated and unlikely to be
dislodged. Humidification of oxygen is not necessary. Like
nasopharyngeal catheters, they can become blocked with mucus;
accumulation of mucus can also cause airway obstruction. The risk
of displacement into the esophagus, and as a consequence the
potential risk of gastric distension, is smaller. If a nasogastric tube
and a nasal catheter are used at the same time, they should be
placed in the same nostril.
Nasal Prongs
This is a device for oxygen therapy ending in two short tapered
tubes (i.e., a fork or prong) designed to lie just with in the nostrils.
It is also called nasal cannula in some places and by some
manufacturers. Two soft prongs in the nostrils attached to the
oxygen source are attached to the face. The flow is directed to the
nasopharynx, which continues to do the work of humidification
and heat exchange. The maximum accepted flow is 2-4 L/min.
Irritation and nasal obstruction may occur but these are generally
well tolerated. In small premature babies, some inadvertent PEEP
may be generated and this device has been used after extubation
to provide some pressure, as when a very small size 2 or 2.5 mm
ETT is in place, the resistance with CPAP may be too high.
Nasal prongs are not as efficient as nasopharyngeal catheters
for giving oxygen: the inspired oxygen concentration is limited to
about 30-35 percent. The concentration delivered falls substantially
if the child breathes through the mouth (for example, when the
nose is blocked by mucus). Nasal prongs can be easily dislodged if
they are not fixed to the upper lip with a piece of tape. On the
other hand, nasal prongs are comfortable for the patient and there
is no danger of gastric distension. Also, humidification is not
required with nasal prongs. When used in combination with an
oxygen concentrator and a flow splitter, nasal prongs are the
cheapest method of oxygen administration.
Nasal cannulae are capable of delivering low-flow oxygen and
provide FiO2 in the range of 0.23 to 0.35. In general, 1 L/min of
nasal cannula oxygen flow is approximately equivalent to an FiO2
of 24 percent with each additional liter of flow, increasing the FiO2
by approximately 3 percent. Flow rates exceeding 4 L/min,
however, are not tolerated well because of drying of the nasal
mucosa. An advantage of a nasal cannula is that the patient can
eat and drink while receiving oxygen. Actual FiO2 for a given
oxygen flow, however, may fluctuate depending on whether the
patient breathes by mouth or by nose. Although nasal cannulae
usually are considered safe, complications, such as mucosal
342 Oxygen Therapy
perforation leading to submucosal emphysema with airway

obstruction, have been reported.
Mask
Simple Masks
A mask has perforations, which are exhalation ports. It fits the
person’s face without much discomfort. As children vary in size,
the most comfortable size must be sought and care must be taken
that there are not pressure points or eye damage. Precise FiO2 is
not the aim when using these masks (Table 22.2). By their nature,
they are used in conditions that are not severe.
Partial Rebreathing Masks

These are simple masks with an additional reservoir that allows
the accumulation of oxygen-enriched gas for rebreathing. A portion
of the exhaled volume from the anatomical dead space is rich in
oxygen. This is what enters the reservoir. Up to 60 percent can be
delivered but the pitfalls are similar to those of the simple mask.
Non-rebreathing Masks
These are like the above masks, but have a valve at the exhalation
port that allows only exhaled gases to enter the reservoir. It prevents
room air from being entrained. A well-fitting mask can provide
up to 100 percent oxygen. The oxygen percentages obtained with
different systems are summarized in Table 22.2.
Table 22.2: Oxygen percentages with different masks
Litres/min Simple Partial rebreathing Non-rebreathing masks

5 40%
6 45-50% 35% 55-60%
8 45-50% 60-80%
10 60% 80-90%
12 60% 90%
15 60% 90-100%
Air-entrainment or Venturi Masks

These are dilutional masks that work on the Bernoulli’s principle.
Oxygen is delivered through a narrow orifice at a high flow.
Negative lateral wall pressure is created in the tubing system. There

are openings (entrainment ports) near the nozzle that allow room
air to be sucked in, diluting the oxygen. Changing the size of the
nozzle, the flow rates, as well as ports, allows control of the amount
of oxygen.
The advantages of a venturi system include: (i) A high flow
device guarantees the delivery of a fixed FiO2; (ii) The high flow
comes from the air therefore saving on oxygen costs; (iii) Can be
used for low FiO2 also; (iv) Helps in deciding whether the oxygen
requirement is really increasing or decreasing; (v) Humidification
not needed; and (vi) Fairly cheap and reliable. Each device will
have a table on the package insert as a guide to flow rates required
by that particular device.
In children, the problem of fit and comfort is a daily issue.
Infants too large for oxyhoods and too small for masks are the usual
users. The average infant or even toddler is usually intolerant of a
mask and will keep pulling it off. In fact, the infant that remains
quiet when the mask is first fitted, is one that may be obtunded
from hypoxia or too tired too fight.
The Oxyhood
This is small baby’s friend. A clear transparent hood that has
enough room for the baby’s head to fit comfortably and allows
free neck and head movement without hurting the baby is the
correct hood size to use. At least 3-4 sizes are available and a unit
should keep one of each size. Too big a hood will dilute the oxygen
and too small a hood will discomfort and result in carbon dioxide
accumulation. Adequate flow of humidified oxygen ensures mixing
of delivered gases and flushing out of carbon dioxide. Oxygen
gradients can vary as 20 percent from top to bottom. Continuous
flow at 6 L/min avoids this problem. Cold air will cause heat stress
and condenses on the baby’s head, which will be mistaken for
perspiration.
Oxygen administration should be done without wasting time
and thought. Further therapy, amount, duration, etc. can then be
formulated. Between 0.4-0.6 FiO2 is adequate in most situations.
100 percent FiO2 needed only during resuscitation. However, if
needed, it should never be withheld for fear of toxicity.
If the patient is in obvious distress, a high flow system should
be used. If there is no distress or cyanosis, and vitals are stable, a
344 Oxygen Therapy
low flow device can be used. SpO2 monitoring is essential and

should be kept above 92 percent. An increasing requirement of
oxygen to maintain the same SpO2 is on ominous sign. Children
should be nursed in the manner that makes them most comfortable
and not by any preconceived notions. Mothers are often the best
administrators of oxygen. A frightened and agitated child so a little
time spent in explaining the situation may go a long way in
providing comfort. The indications for intervention are
summarized in Box 22.1.
Box 22.1: Indications for intervention
• Dropping SpO2
• Increasing FiO2
• Fatigue, confusion, agitation, drowsiness (ABG to look for PaO2,
PaCO2, acidosis)
• Poor respiratory effort
• Heart rate, BP fluctuations
Weaning: This is based on clinical and laboratory parameters. The

SpO2 levels are a boon in this phase and ABGs are usually not
needed. Abrupt cessation may precipitate rises in pulmonary
pressures in infants. The flow/concentration should be gradually
lowered while monitoring the child. Low flows and concentration
can continue without ill effects for a long time.
Oxygen therapy saves lives. There are side effects but the
advantages far outweight the risks. Hypoxia kills more people than
correctly delivered oxygen. Use oxygen but do not abuse.
EQUIPMENT FOR THE ADMINISTRATION OF OXYGEN

In large hospitals, oxygen pipeline systems are often used to deliver
oxygen to each bed. These are expensive, require complex and
difficult engineering and are therefore impractical for small
hospitals in developing countries. In these hospitals the traditional
solution has been to wheel cylinders of oxygen to the beds of
patients requiring treatment. The following sections describe and
discuss the equipment available to convey oxygen from the source,
a cylinder or a concentrator, to the patient.
Using Cylinders With Single Patients

Oxygen cylinders are filled with gas at a very high pressure. A
regulator, also known as a reducing valve, is needed to reduce this
pressure to a constant lower working pressure and to allow the

flow of gas to be controlled rather than determined by the pressure
remaining in the cylinder.
There are a number of different cylinder connectors; the
regulator must match the cylinder connector so as to be able to
connect with it. The most commonly found connectors are the pin-
index and the bull-nose, but others exist in different parts of the
world: handwheel, air liquid and American olive. Before ordering
a regulator, the user must check which type of connector is needed.
Regulators should include a high pressure gauge which
indicates the amount of oxygen remaining in the cylinder. Full
cylinders usually contain oxygen at a pressure of about 13,400 kPa
(132 atmospheres or bars, or 2000 psi). When the pressure falls
below 800 kPa (8 atmospheres or bars, or 120 psi), the cylinder is
nearly empty.
A flow control device must be attached downstream from the
regulator to allow the flow of oxygen to the patient to be precisely
set. There are two sorts of flow control devices:
a. Variable orifice flow meters, in which the flow is controlled by
a knob, which adjusts a needle valve. The flow is usually
indicated by a ball in a tube. For pediatric use it is desirable to
have a flow meter with a range of 0-2 dL/min, rather than the
0-16 L/min flow meters used for adults.
b. Fixed-orifice flow controllers, in which the flow is controlled
by a series of fixed-size openings using a control knob. Flows
of 0.5, 1, 1.5, 2, 4 and 5 L/min are usually available. Fixed-orifice
flow controllers are often sold already combined with a
regulator in a single unit.
Variable orifice flowmeters are widely used and those for adults
are readily available. Health workers are more likely to be familiar
with this sort o flow control device. They allow any flow at all to
be set that is within the range and limits of accuracy of the
instrument. Low-flow pediatric versions, however, are often more
expensive and difficult to obtain.
Fixed-orifice flow controllers are accurate at the flows for which
they are designed. They are more robust than variable orifice
flowmeters. For pediatric use they must be capable of delivering a
flow of 0.5, 1 and 2 L/min. Usually they offer other flows and a
range up to 5 L/min is desirable. They cannot give intermediate
flows between their fixed settings, but intermediate flows (say 0.8
346 Oxygen Therapy
L/min) are rarely prescribed, and with flowmeters such small

adjustments of flow are limited by the accuracy of the instrument
and the skill of the user.
Either type of flow control device is adequate. Variable orifice
flowmeters are more widely available, but new purchasers may
choose fixed-orifice flow controllers because of their robustness,
compactness and possible cost advantage. A regulator and a flow
control device in a single unit are less likely to get lost or damaged.
A sufficient length, usually about two metres, of non-crush
plastic oxygen delivery tubing must be used to link the oxygen
outlet to the nasal or nasopharyngeal catheter. Nasal prongs are
already supplied with a sufficient length of non-crush plastic
oxygen delivery tubing. Non-crush oxygen tubing can be easily
identified, because its cross-section is not a ring (the opening is
usually star shaped).
Using Concentrators with Single Patients

Oxygen concentrators operate at a low pressure. All the models
meeting the WHO specifications have built-in flow control devices
and can be fitted with humidifiers if desired. A suitable length,
usually about two metres, of non-crush plastic oxygen delivery
tubing is the only equipment needed to connect the oxygen outlet
to the catheter or prongs (which are already fitted with a sufficient
length of non-crush oxygen tubing).
Using One Oxygen Source for Several Patients

By far the best way of giving oxygen to several patients is to set
aside a part of the health center or hospital as the oxygen
administration area. Patients who need oxygen are moved to this
area. This arrangement is convenient for staff (the equipment is
permanently set up), it protects the equipment, and it concentrates
the sickest patients in one area. Either a concentrator, with a
cylinder back up, or a cylinder alone can be used as sources of
oxygen for the treatment of more than one patient. The equipment
needed varies depending on the source and is described in Part III
of this document.
Continuous Positive Airway Pressure

Continuous positive airway pressure (CPAP) commonly is
delivered by a tight-fitting mask with a continuous gas-flow rate
(usually 15-30 L/min at a specified FiO2) a reservoir bag, a one-

way valve, a humidifier, and an expiratory pressure valve. Many
patients, however, cannot tolerate a CPAP mask because of
claustrophobia, aerophagia, or hemodynamic instability. In these
patients, endotracheal intubation should be considered.
Humidification
If oxygen is to be given by nasopharyngeal catheter, a humidifier
is required downstream after the flow control device. For oxygen
delivered through nasal catheter or prongs, humidification is not
needed, since sufficient humidity is added by the nose when the
catheter or prongs are correctly placed. Humidifiers require care
and supervision, and their connectors are a potential source of leaks.
The water has to be boiled, needs to be replaced every day, and
may become colonized by bacteria. Humidifiers must be
periodically washed and dried.
Oxygen from cylinders or concentrators is completely dry. It is
important to humidify (add water to) oxygen being given by
nasopharyngeal catheter. If this is not done, the child’s pharynx
will become dry, sore and inflamed, and there may be an increased
risk of local infection. Humidification is not needed if oxygen is
given by nasal catheter or prongs, since sufficient humidity is added
by the nose when the catheter or prongs are correctly placed.
Heated humidifiers are expensive, difficult to operate, and need
electricity. Unheated bubble humidifiers, though less efficient, are
cheaper and much easier to use. They are not very efficient at high
rates of flow of oxygen, or if the gas is being given by an
endotracheal tube; however, they give acceptable results when low
flow rates are used in the tropics, where ambient temperatures are
high. The use of a humidifier carries the potential risk of bacterial
contamination and health workers need to be trained in methods
of preventing this.
The criteria used for selection of a particular method of oxygen
administration are different for different devices (Table 22.3).
In view of these criteria, and particularly in the interest of safety,
WHO recommends the use of nasal prongs for most children in
most such hospitals. Nasal prongs cannot achieve the higher
concentrations of oxygen in the airways that are achievable with a
nasopharyngeal catheter. These concentrations, however, are rarely
needed: almost all children with hypoxemia due to lower
348 Oxygen Therapy
Table 22.3: Criteria for the selection of an appropriate method of oxygen

administration to young children in small hospitals in developing countries
Criterion Nasal Nasal Nasopharyn- Headbox Face-

prongs catheter geal catheter mask
Safety High High Medium Low Low
Efficiency Medium Medium High Low Low
Simplicity High Medium Medium Low Medium
Tolerability High Medium Medium High Low
Availability Medium High High Low Low
respiratory tract infections can be well oxygenated using nasal

prongs at flow rates of 1 L/min or less. Nasal prongs are less
efficient than nasal and nasopharyngeal catheters, and a higher
flow of oxygen is needed to achieve a given concentration in the
airways. Efficiency, however, is important only when oxygen is
scarce and expensive, as is often the case with cylinders; it is a less
important concern with concentrators.
If nasal prongs are not available, a nasal catheter can be used.
This is preferred to a nasopharyngeal catheter in unsupervised
environments where safety is a major concern. Nasal catheters have
been used for many years in a large hospital in South Africa without
a single adverse effect being reported.
If the use of nasal prongs or nasal catheter does not provide
adequate oxygenation (i.e., if the clinical signs for which oxygen is
indicated persist), or if the oxygen supply is very limited, a
nasopharyngeal catheter can be used. This is the most efficient
method of oxygen administration, but owing to the risk of serious
complications it should only be used in places where skilled staff
are available for continuous monitoring of oxygen therapy. If the
nasopharyngeal catheter is adopted as the usual method in a
hospital, another method must be available for those children who
cannot tolerate the catheter or who develop serious complications.
MONITORING DURING OXYGEN THERAPY

Patient’s Clinical Status
Monitoring patients receiving oxygen therapy should begin with
a routine history and physical examination. Special attention should
be paid to symptoms and signs of hypoxia (dyspnea, diaphoresis,
restlessness, cyanosis, heart rate, respiratory rates, breathing
pattern, and mental status, and so on). Subjective relief of dyspnea

may indicate successful intervention. Conversely, paradoxical
movement of abdominal muscles and excessive use of accessory
muscles are warning signs of impending respiratory arrest.
Arterial Oxygenation
Because one of the major goals of supplemental oxygen is to correct
hypoxemia, arterial oxygenation should be measured periodically.
This can be achieved by measuring arterial PO2 by arterial blood
gas analysis or by monitoring arterial oxygen saturation by pulse
oximetry. Arterial blood gas analysis is invasive but provides
additional information such as pH, PCO 2 , and abnormal
hemoglobin states (carboxyhemoglobin, methemoglobin). Pulse
oximetry is non-invasive. Correlation between arterial oxygen
saturation (SaO2) measured by pulse oximetry and that measured
by co-oximetry is good in general, however, pulse oximetry is
reliable only if SaO2 values are between 65 percent and 90 percent.
Otherwise, it is inaccurate and overestimates the SaO2 at lower
values. Brown, red, and other colored nail polishes may reduce
the reading. Elevated bilirubin levels also may interfere with the
reading. Pulse oximetry does not detect the presence of
carboxyhemoglobin or methemoglobin. Thus, oxygen saturation
measured by pulse oximetry in carbon monoxide poisoning or
methemoglobinemia overestimates the true oxygen content of the
arterial blood. Arterial oxygenation should be maintained at an
arterial PO2 of at least 60 mm Hg or an oxygen saturation of at
least 90 percent using the lowest FiO2. Arterial oxygenation status
obtained by either arterial blood gas analysis or pulse oximetry
always should be interpreted in the context of the patient’s overall
clinical status.
Tissue Oxygenation
Biochemical Markers
The adequacy of tissue oxygenation may be tested indirectly by
monitoring the biochemical sequelae of tissue hypoxia. For
example, lactate accumulation may reflect an increase in anaerobic
metabolism induced by hypoxia. The accumulation of lactate in
350 Oxygen Therapy
the plasma, however, may not always indicate tissue hypoxia. The
plasma lactate level is known to increase in liver failure, where the
hepatic uptake of lactate is impaired, or in sepsis, where
hypermetabolism produces a large quantity of lactate.
Mixed Venous Oxygen Tension ( PvO 2) Or Saturation ( SvO2)
PvO 2 or SvO 2 does not always reflect tissue oxygenation status.

As can be seen by rearranging the Fick equation, PvO 2 and SvO 2
tend to decrease when SaO2 falls or decreased Hb concentration is
undercompensated by cardiac output. PvO 2 and SvO 2 may be
normal or high despite inadequate tissue oxygenation in diseases
such as sepsis and cirrhosis, in which shunting of arterial blood is
believed to occur in the peripheral tissues. Nonetheless, a low PvO 2
or SvO 2 should prompt proper reassessment of the patient’s
condition, especially if it is part of a rapidly deteriorating trend.
The reliability of PvO 2 and SvO 2 as hemodynamic or prognostic
indices tends to vary with the type of disease process. In cardiogenic
shock and with response to cardiopulmonary resuscitation, SvO 2
correlates with prognosis.
Tissue Oxygen Measurement

Because the ultimate goal of supplemental oxygen is to prevent or
correct tissue hypoxia, measuring tissue PO2 would be a more direct
assessment of tissue oxygenation. Various methods of measuring
tissue PO2 have been developed. These methods have been used
to assess and monitor tissue PO2 in various organs, such as skeletal
muscles, the brain, and the heart. Measurement of local tissue PO2
on the surface of various organs gives direct information on the
function of the capillary exchange area. These techniques, however,
are often cumbersome and sometimes labor intensive when used
routinely in clinical monitoring.
Adverse Effects of Oxygen Therapy

Oxygen therapy causes blunting of hypoxic pulmonary drive.
Respiratory depression worsens CO2 retention and respiratory
acidosis. The PaO2 of these patients should be maintained at 50 to
55 mm Hg with low-flow oxygen. The risk of tissue hypoxia in
these patients is relatively low at these levels of PaO2 because the

hemoglobin dissociation curve usually is shifted to the right, which
may facilitate unloading of oxygen molecules in the systemic
capillaries.
Pulmonary Oxygen Toxicity

Joseph Priestley, who discovered oxygen, first predicted the
adverse effects of oxygen: “….. for, as a candle burns out much
faster in dephlogisticated than in common air, so we might, as
might be said, live out too fast, and the animal powers be too soon
exhausted in this pure kind of air…..” In 1878, Paul Bert first
documented the central nervous system toxicity produced by
hyperbaric oxygen. Pulmonary oxygen toxicity was not discovered
ulntil 1899 by Lorraine Smith and retrolental fibroplasias of
prematurity until 1942 by Terry.
The development of pulmonary oxygen toxicity has been
attributed in part to the increased production of reactive oxygen
species (ROS), which overcomes the body antioxidant defenses.
Reactive oxygen species (superoxide [O2–], hydrogen peroxide
[H2O2], hydroxyl radical [OH] are derived from incomplete
reduction of molecular oxygen. ROS may react with many biologic
target molecules, including lipids, proteins, nucleic acids, and may
result in oxidative damages to cell membrane and structural
proteins, inactivation of enzymes, and altered cellular metabolism.
The pathologic response to prolonged exposure to oxygen
occurs throughout the respiratory system. The temporal sequence
of progressive histologic injury has been studied well in rodents
and nonhuman primates. The initial production of ROS damages
many biologic structures and causes a secondary cellular
inflammatory response. Pathologic descriptions of human oxygen
toxicity, however, have been limited because of the presence of
coexidting pulmonary diseases as well as variability in the
concentration-time profile of oxygen exposure. One of the earliest
findings after hyperoxic exposure appears to be an increase in
proteins in bronchoalveolar lavage fluid, which was noted after
an average of 17 hours of exposure. The increased proteins in the
lavage fluid are no longer present after a 2-week recovery period.
Pathologic changes at a later stage of oxygen exposure resemble
those found in subhuman primates, including alveolar epithelial
injury, endothelial cell injury, alveolar septal inflammation and
352 Oxygen Therapy
interstitial and alveolar edema. Clinically, the earliest mani-

festations of pulmonary oxygen toxicity in healthy humans are
cough and mild chest discomfort exacerbated by inspiration
suggestive of the development of tracheobronchitis. With
prolonged oxygen exposure, functional abnormalities develop,
including decreases in lung volumes, compliance, and DLCO
(diffusing capacity of the lung for carbon monoxide), as well as
impaired gas exchange.
Defining a “safe level” of oxygen exposure has been problematic
in part because of the limited data in lower primates and normal
humans. Baboons exposed to 60 percent O2 for 2 weeks show
evidence of pulmonary fibrosis 8 weeks later. In nonsmoking
human volunteers, inhaling 50 percent oxygen for a mean time of
44 hours has been shown to produce evidence of pulmonary
oxidant stress, as demonstrated by increase in lipid peroxidation
in the bronchoalveolar lavage fluid. In another study, mechanically
ventilated patients randomly assigned to receive 50 percent oxygen
showed significantly lower oxygenation after extubation than did
patients who were given the lowest possible FiO2. Thus, it seems
that an FiO2 of 0.50 or greater should be considered “toxic”.
Oxygen toxicity may be enhanced by many factors, including
drugs (bleomycin, paraquat), some pathophysiologic states
(hyperthermia, hyperthyroidism), prematurity of the newborn,
vitamin E deficiency, and protein deficiency. In the presence of
these conditions, pulmonary oxygen toxicity may develop even
after exposure to a “non-toxic” range of oxygen levels.
Although progress has been made in developing new
treatments for pulmonary oxygen toxicity, the efficacy of these
therapies has not been tested in clinical trials. Thus, the best strategy
for treating pulmonary oxygen toxicity is to prevent it from
developing by avoiding undue exposure to high concentrations of
oxygen for prolonged periods. The concentration of supplemental
oxygen should be maintained as low as possible to maintain an
optimal PO2.
SPECIAL APPLICATIONS OF OXYGEN THERAPY

High Altitude
A decrease in the PO2 in the breathing air is the main cause of
hypoxia at high altitude, where barometric pressure is lower. For
example, at 5500 m (18,000 ft), the barometric pressure decreases

by approximately 50 percent (379 mm Hg) and the PO2 in the
inspired air decreases from 160 mm Hg at sea level to 70 mm Hg.
At this altitude, the arterial oxygen saturation would drop from 97
percent at sea level to approximately 75 percent. This altitude also
happens to be the highest level of continuous human habitation.
Acute ascent from sea level to elevations higher than 2500 m
can produce headache, nausea, vomiting, and insomnia, which are
referred to as acute mountain sickness. The most severe forms of
acute mountain sickness may lead to high-altitude pulmonary
edema (HAPE) and high-altitude cerebral edema (HACE).
Hypoxia, which may result in inhomogeneous vasoconstriction and
hyperperfusion of unconstricted vessels, is believed to play an
important role in the pathogenesis of HAPE. Conversely, local
vasodilatation of cerebral vessels caused by hypoxia may increase
fluid leak from the capillaries into the brain tissue, contributing to
cerebral edema. The definitive treatment of HAPE and HACE is
descent. Supplemental oxygen may be a life-saving temporizing
measure.
Carbon Monoxide Poisoning

Carbon monoxide is the leading cause of death from accidental
poisoning. Carbon monoxide is absorbed and excreted primarily
by the lungs. On entry into the blood stream, it combines with
hemoglobin to form carboxyhemoglobin (COHb). The affinity of
carbon monoxide for hemoglobin is approximately 240 times
greater than that of oxygen, thus it interferes with O2 transport.
This causes a number of biochemical effects of carbon monoxide.
The formation of COHb not only decreases the binding sites
available for O 2 but also induces allosteric changes of the
hemoglobin molecules. The allosteric modification of the heme
group results in left shift of the oxygen hemoglobin equilibrium
curve. The combined effects on tissue oxygenation are greater than
would result from loss of oxygen-carrying capacity alone. In
addition, carbon monoxide also binds during hypoxia to the
reduced form of cytochrome c oxidase, the terminal enzyme of the
mitochondrial electron transport chain, thus blocking cellular
respiration during reoxygenation.
The symptoms and signs of carbon monoxide poisoning range
from dyspnea, headache, emotional changes, clumsiness to
354 Oxygen Therapy
respiratory depression, myocardial ischemia, arrhythmia,

confusion, and coma. Although the severity of clinical manifesta-
tions of carbon monoxide poisoning in general vary with COHb
levels, the correlation is not perfect. The emphasis should be placed
more on history and clinical features than on COHb values when
evaluating patients with carbon monoxide poisoning.
Immediate administration of supplemental oxygen is essential
in the initial management of carbon monoxide poisoning. Oxygen
helps dissociate carbon monoxide from hemoglobin and
counteracts hypoxemia. The half-life of COHb in patients breathing
room air is approximately 6 hours. With 100 percent oxygen, the
half-life is decreased to about 1.5 hours. With the application of
hyperbaric oxygen (2 ATA), the half-life is reduced further of 20
minutes. In mild carbon monoxide poisoning, treatment with
normobaric oxygen is frequently sufficient. Care should be taken
that the exhaled air (containing carbon monoxide) is not rebreathed
if oxygen is administered by a mask. For severe carbon monoxide
poisoning (COHb >25% or carbon monoxide <25% but with
neurologic signs or symptoms), hyperbaric oxygen should be the
treatment of choice.
Helium-Oxygen
Helium can be mixed with oxygen to form a low-density breathing
gas mixture. Helium-oxygen (Heliox) that contains 80 percent
helium and 20 percent oxygen has a density of approximately one
third that of air with only slight increase in viscosity. Because the
airway resistance to turbulent flow is related to gas density for a
given driving pressure, helium-oxygen mixtures may reduce
airway resistance and decrease work of breathing. Thus, helium-
oxygen mixtures may be used as a temporizing measure while
awaiting the resolution of the primary diseases or definitive
treatment of conditions associated with upper airway obstruction,
such as post-extubation stridor, tracheal stenosis or extrinsic
compression, and angioedema. Helium-oxygen mixtures have little
effect on lower airway obstruction, in which flow is less density
dependent.
There are limitations on the use of helium-oxygen has mixtures.
To effectively reduce gas density, the helium concentration in the
helium-oxygen mixture must be at least 60 percent, which limits
oxygen concentration in the gas mixture to a maximum of
40 percent. Helium-oxygen gas mixtures cannot be delivered by

nasal cannula. Flow meters that are calibrated for oxygen may
underestimate helium-oxygen mixtures are expensive and are not
widely available. Prolonged use of helium-oxygen mixtures (>24
hours) may result in hypothermia unless the gas is actively warmed
to body temperature because of the high thermal conductivity of
helium.
Nitric Oxide Inhalation Therapy

Nitric oxide (NO) is a reactive molecule produced endogenously
in the body by NO synthase from L-arginine. Since the first
description of NO as the endothelium-derived relaxing factor
(EDRF) mediating vasodilatation, NO has been shown to be
involved in a variety of biologic effects ranging from immu-
noregulation, neurotransmission, modulation of platelet function,
and leukocyte adhesion to intracellular and transcellular signaling.
In the environment, NO gas can be formed from incomplete
combustion, where it quickly is oxidized to nitrogen dioxide (NO2).
NO is lipophilic and has strong affinity for heme groups. The
affinity of NO for the heme group of hemoglobin is 1500-fold higher
than that of carbon monoxide, or 40,000-fold higher than that of
oxygen for the heme group. Such an avid reaction of NO with
hemoglobin in the blood, which leads to rapid “inactivation” of
NO, forms the physiologic basis for use of NO inhalation as a
“selective pulmonary vasodilator”.
The first clinical applications of NO inhalation therapy in
patients with acute respiratory distress syndrome (ARDS) was
reported in 1993. The results of this preliminary study showed that
inhaled NO is equivalent to intravenous prostacyclin in reducing
the pulmonary vascular resistance, but unlike prostacyclin infusion,
it does not produce any change in systemic hemodynamics. Arterial
oxygenation improved significantly, indicating a better ventilation-
perfusion matching. Although no severe side effects were noted
in this small study, concerns have been raised about the potential
toxicity of NO inhalation to the lungs, particularly in patients with
ARDS who frequently require high FiO2. The enthusiasm for NO
inhalation therapy in ARDS also is tempered by recent studies
showing that oxygenation improvement with inhaled NO is short-
lived (1-2 days).
356 Oxygen Therapy
It is known that NO is oxidized to NO2 by contact with O2 in a

dose and time-dependent manner. NO2 is a toxic gas that causes
bronchiolitis. Acute exposure to high concentrations of NO2 may
cause pulmonary edema and death. Long-term exposure to very
low concentrations of NO2 (0.3-1.0 ppm for 6 months) has also been
demonstrated to cause significant morphologic effects and
biochemical changes in the mouse lung. Although human data are
more limited, exposure to 2.3 ppm of NO2 for 5 hours in healthy
nonsmokers decreases the blood antioxidant activity (glutathione
peroxidase).
NO, being a free radical also may react with other oxygen-
derived free radicals, such as superoxide (O2–). The reaction
between NO and O2– is extremely rapid (nearly diffusion-limited).
The reaction product, peroxynitrite (OONO–), is a stronger oxidant
than NO or O2– and has been shown to produce oxidation and
nitration of biological molecules, such as proteins, DNA, and
membrane lipids. Although the toxicity of peroxynitrite in vivo has
not been proven directly, concerns over the potential adverse effects
of peroxynitrite are justified based on experimental evidence. More
research is needed to define how NO inhalation therapy interacts
with supplemental oxygen.
Home Oxygen Therapy

Similar to the practice adopted in adults, home oxygen therapy
has emerged as an attractive method of continued treatment in
children with chronic lung diseases such as cystic fibrosis and
bronchiectasis. Some of the other indications include bronchopul-
monary dysplasia, tracheomalacia, severe kyphoscoliosis, multiple
congenital anomalies and neurologic conditions, etc. Some of these
patients may require chronic domiciliary ventilatory assistance in
addition. There is very little data which conclusively supports the
beneficial role of long-term oxygen therapy. A recent Cochrane
Database System Review of 9 published studies on whether oxygen
therapy improved longevity on quality of life in cystic fibrosis
included only one on long-term oxygen therapy (128 participants).
No statistical significant improvement in survival was reported.
Sometimes, home oxygen has been used in for discharge from
emergency department of children admitted with acute bronchio-
litis and hypoxia. While nasal cannulae are more commonly
employed at home, some experience with transtracheal oxygen
catheters is also available which may serve as a method of

alternative administration.
BIBLIOGRAPHY
1. AARC Clinical Practice Guidelines. Resp Care 1991; 36:1410-3.
2. Bajaj L, Turner CG, Bothner J. A randomized trial of home oxygen therapy
from the emergency department for acute bronchiolitis. Pediatrics 2006;
117:633-40.
3. Balfour-Lynn IM, Primhak RA, Shaw BN. Home oxygen for children: Who,
how and when? Thorax 2005; 60:76-81.
4. Kindwall EP. Uses of hyperbaric oxygen in the 1990s. Cleveland Clin J Med
1992; 59: 517-20.
5. Mallory GB, Fullmer JJ, Vaughan DJ. Oxygen therapy for cystic fibrosis.
Cochrane Database Syst Rev 2005;19:CD003884.
6. Martin LD, James F. Principles of respiratory support and mechanical
ventilation. In: Rogers MC: Textbook of Pediatric Intensive Care. Baltimore
Williams and Wilkins, 1996;1:149-59.
7. Moss D, Bond P. Home oxygen therapy for children. Nurs Times 2002; 98:
37-9.
8. O’Brien JE, Dumas HM, Haley SM. Clinical findings and resource use of
infants and toddlers dependent on oxygen and ventilators. Clin Pediatr (Phila)
2002; 41:155-62.
9. Preciado DA, Thatcher G, Panitch HB, Rimell FL. Transtracheal oxygen
catheters in a pediatric population. Ann Otol Rhinol Laryngol 2002; 111:
310-4.
10. Simonds AK. Home ventilation. Eur Respir J Suppl 2003;47:38s-46s.
11. Vain NE, Prudent LM, Stevens DP, Weeter MM. Regulation of oxygen
concentration delivered to infants via nasal cannulas. Am J Dis Child 1989;
143:1458-60.
23
Oxygen Storage and
Supply in Hospitals
SK Jindal
INTRODUCTION
Oxygen is a natural gas available in plenty in atmospheric air. For
medical use, it is fractionated from air and stored. Commonly, it is
produced by cooling the air to a liquid from which it is fractionated
by distillation process, compressed and stored in cylinders. Strict
guidelines have been laid for bulk storage and transport for safety,
purity and uniformity.
Oxygen supply in the hospitals involves its procurement,
transport, storage and supply at the bedside. Because of the
problems involved in transport from the source of procurement,
several hospitals opt for the local production of oxygen and ensure
a central supply. An oxygen cylinder is the most conventional
method of storage of oxygen for supply in the hospitals. Liquid
oxygen containers and oxygen concentrators which have got
popular in the last two decades are safer and probably easier to
handle. Oxygen concentrators are being advocated as suitable
alternatives to cylinders in particular in the developing countries.
CYLINDERS
Oxygen cylinders are metal containers (Chrome-molybdenum
steel) made from seamless, brazed or welded tubing. The gas is
pumped at a pressure of approximately 2200 psig.
There are different sizes and shapes of cylinders. The size is
generally indicated by the type marked A, B, D, E, M, G, H or K
depending upon the diameter, height and weight. The filling
capacity varies with the size of the cylinder (Table 23.1).
Oxygen Storage and Supply in Hospitals 359
Table 23.1: Size and filling information of oxygen cylinders
Type Diameter (cm) Height (cm) Capacity (liters)

A 7.5 25
B 8.75 40
D 10.6 50 356
E 11.25 75 622
M 17.5 117.5 3028
G 21.25 137.5 5260
H and K 22.5 137.5 6900
All cylinders have uniform international color codes depending

upon the type of gas they contain. It is white for oxygen (green in
the United States). The cylinder contents are identified by
permanently attached labels naming the contents. Cylinders are
built as per standard specifications and marked permanently with
symbols and numbers on the shoulder or head. Cylinders and bulk
systems that have pressures higher than 200 psig are high pressure
systems while those with under 200 psig are low pressure systems.
Generally cylinders which are broad, squat and thick welded are
meant for service at low or moderate pressures. Narrow and thin
cylinders are intended primarily for high pressure service.
Transport of most compressed gases including oxygen is authorized
by most means of shipment, although local regulations may vary
from place-to-place.
COMPRESSED OXYGEN
Oxygen is a colorless, odorless and tasteless elemental gas. But in
liquid form, it is transparent, pale blue and slightly heavier than
water at temperature below –300 o C. Oxygen itself is non-
inflammable but supports combustion. Some of the combustible
materials such as the oils and grease burn with an explosive
intensity in the presence of oxygen.
As a compressed gas, the filling limit in the cylinder is 1800-
2400 psig at 70oC depending on the type of cylinder. In E type
cylinders it is about 2200 psig. The pressure within the cylinder
during normal usage is 75 psig.
The amount of gas in a cylinder is determined by the pressure.
At a given temperature, when the pressure is reduced to half the
original pressure, the cylinder will be approximately half full. The
content may also be determined by weight using weight volume
conversion factor.
360 Oxygen Therapy
In clinical practice, it is often important to know as to how long

a cylinder will last. This can be assessed by determining the K-
factor.
Volume of gas in a full tank (L)
K=
Pressure of a full tank (psig)
For an E type cylinder,
622 L
K = = 0.283 L/psi
2200 psig
To calculate the duration a cylinder shall last, K is multiplied
by the pressure on the gauge and divided by the flow rate of
administration.
K × Cylinder pressure
Time (min) =
Flow rate (L/min)
For example, if a full E type cylinder is being used at a flow rate
of 1.5 L/min, the duration it shall last =
0.283 × 2200
= 415 min (6.9 hrs)
1.5
K factor for O2 for cylinder D, G and H are 0.16, 2.41 and 3.14
respectively.
CYLINDER VALVES
There are two types of outlet valves for low pressure oxygen
cylinders conforming the Compressed Gas Association of USA
(CGA) recommendations:
Diameter Index Safety System (DISS)

It incorporates threaded connections for flow meters, pressure
gauges and regulators. There are different DISS connection
numbers for different gases. Each connection consists of a body,
nipple and nut. Only the properly mated and intended parts fit
with each other.
Pin Index Safety System (PISS)

It is used for cylinders of size E or less. There is a combination of
two pins projecting from the yoke assembly of the apparatus to fit
into the matching holes of the cylinder valve. Pin holes bored on
the face of the valve at various positions allow for alignment of
different gas mixtures (usually anesthetic gases).
Cylinder valve seals should ensure excellent sealing. A teflon
plastic seal for packing and a valve outlet washer (Gasloc seal) are
used for this purpose. Valve outlets should also be sealed against
dirt and foreign material. The valves should be regularly inspected
to ensure safety.
The Compressed Gas Association has laid several safety
standards and precautions. Greasy, oily and flammable material
should be kept away from oxygen system. Handling with oily
hands and lubrication of flow meters, regulators and gauges must
be avoided. Interchange of fittings meant for different gases should
not be done. The valve should be opened slowly and a reducing
valve should always be used to deliver gas from a cylinder.
GAS REGULATORS
Although the gas in a cylinder is compressed, it gets exposed to
the atmospheric pressure the moment the valve is opened. Sudden
decompression leads to an explosive outflow of the gas which needs
to be properly regulated. This is achieved by using a regulator.
Regulator is the device used to reduce the gas pressure in the
cylinder and control its outflow. It consists of a nipple connection
for the cylinder valve, measurement gauge/s and an exit.
Generally, there are two types of gauges attached to a regulator:
(i) Pressure gauge, nearer to the cylinder is meant to measure gas
pressure (psig) in the cylinder. This is an indirect estimation of the
gas volume; (ii) Flow gauge; required to indicate and control the
gas flow (L/min) out of the cylinder.
Regulators are typed depending upon the number of
mechanisms used to reduce the pressure and control the flow, as
single stage, double stage or three stage regulators. While one stage
regulator may be used for small cylinders with low pressure gas,
two and three stage regulators are better, reliable and more efficient
especially when the pressure inside the cylinders is high.
There are two types of mechanisms used in a regulator required
to reduce pressure.
362 Oxygen Therapy
Fig. 23.1: Variable type regulator
Variable (Fig. 23.1)

It is meant to obtain variable pressures in the regulator by turning
the screw. It consists of an inlet (a), an outlet (b), diaphragm (c),
adjusting screw (d), spring compression (e) and a safety valve (f).
On opening the cylinder valve, gas moves through the inlet nozzle
and moves the diaphragm if the outlet is open. When the outlet is
closed, the pressure builds up below the diaphragm to push it above
and close the inlet. The amount of compression applied on the
spring by the adjusting screw determines the amount of pressure
required for the diaphragmatic movement. Safety valve is meant
to release the gas if the pressure in the regulator exceeds the defined
limits.
Preset Regulator (Fig. 23.2)

Here the pressure is preset and cannot be varied by turning the
screw. The spring is connected to the chamber and calibrated to a
certain defined pressure. Whenever the pressure is exceeded, the
spring (and the diaphragm) moves up to close the inlet
While a one stage regulator has a single variable control, the
two and three stage regulators have both the preset and variable
controls. The first stage is preset to reduce the pressure at a fixed
level; second and third stages are adjustable.
Fig. 23.2: Preset type regulator
FLOW METERS
In most clinical situations oxygen administration is defined in terms
of flow, i.e. volume of gas per unit of time (L/min).
Flow meter is the device used to measure the flow. Flow meters
are integrated with regulators for use with gas cylinders.
Independent flow meters are available for oxygen outlets at
patient’s bedside. A flow meter utilizes the principles of physical
inter-dependence of the flow rate, the size of orifice through which
the flow is to occur and the pressure difference on either side of
the orifice. Since the flow depends on the viscosity and the density
of the gas passing through, they are important in measurement of
flow and calibration of the flow meters. By measuring the pressure
difference on either side of a pipe, we can calculate the volume
flowing through it every second if we know the density of the gas
and the area at cross-section.
There are two main types of flow meters commercially available.
Bourdon Flow Meter (Fig. 23.3)

It is in fact a pressure gauge recalibration in liters per minute (flow)
against a fixed orifice size. It consists of an inlet (a), a needle valve
at the inlet (b), a measuring dial (c) and an outlet of a fixed size (d).
The flow from the gas source entering the flow meter is controlled
364 Oxygen Therapy
Fig. 23.3: Bourdon flow meter
by an adjustable valve. As the gas enters the meter, it moves the

indicator needle. The size of the outlet orifice is fixed to allow a
known flow to pass through with each increment of pressure
difference.
Thorpe Tube Flow Meters

They are of two types:
Pressure Uncompensated (Fig. 23.4)

This type of flow meter does not indicate the actual flow of gas
past the restriction on the flow scale. The needle valve (b) is placed
between the gas source inlet (a) and the flow scale (c). The pressure
change occurs at (b) a metal float (f) riding at the inlet (a) moves
up and down with the flow. This is a type of dry bobbin type of
flow meter where the pressure on either side of the orifice is kept
Fig. 23.4: Thorpe flow meter pressure uncompensated
constant and supports the weight of the bobbin—a float. It is a

rotameter in which the float is forced up the calibrated tube by the
gas stream in which it moves freely without touching the sides.
The internal diameter of the tube is greater at the upper than the
lower end. As the gas flow increases, the pressure in the tube on
the float increases, which moves up allowing more gas to escape
to the outlet.
Pressure Compensated Flow Meter (Fig. 23.5)

In this type of flow meter, the flow indicated on the scale is what is
being delivered without restriction. The needle control valve is
positioned at the outlet of the flow tube. With the inflow of gas
and increased inlet pressure, the pressure between the top of
calibrated flow scale (c) and the outlet (d) changes. Since the gas
passing through the outlet orifice is less, the pressure above the
float is increased causing the float to drop.
OXYGEN SUPPLY AT BEDSIDE

There are three sources of oxygen supply to individual patients at
the bed side in a hospital.
Oxygen Cylinders
Most of the hospitals in this country rely on bedside oxygen
cylinders. This is a cheap and convenient method although it is
366 Oxygen Therapy
Fig. 23.5: Pressure compensated flow meter
not very efficient. There are difficulties of procurement, trans-

porting cylinders and changing connections in the wards. The ward
staff is usually inadequate and inexperienced and proper
instruments to change the regulators and flow meters are often
missing when required. The difficulties are even more at nights
and on holidays when the limited staff available on duty may find
it difficult to operate these tools manually.
Supplies are often interrupted. The system can be useful for
only a limited number of patients. There is also the additional
problem of maintaining sterilization, especially in Intensive Care
Units and Operation Theatres.
Centralized Oxygen Distribution System

This is the most efficient method of supplying oxygen in a modern
hospital.
Although the initial installation costs are high, it is cost effective

in the long run. It is almost mandatory for Operation Theatres,
Intensive Care Units, Emergency Wards and other areas where
serious patients requiring oxygen are cared for.
The system essentially consists of the following components:
a. Central oxygen storage/production
1. Compressed oxygen (manifold room, bulk tank)
2. Liquid oxygen tank
3. Central oxygen production with an oxygen concentrator
b. Supply line, usually copper pipes
c. Accessories: Alarm systems, control panels, oxygen outlets (wall
fittings) with terminal units, pendant and hose assemblies, flow
meters and adopters/connections.
Oxygen Storage
Compressed Oxygen
Manifold room: Multiple large cylinders of oxygen are grouped and

connected together with copper pipes and control panels at a central
place. From the cylinder room, the gas is pumped into the pipe
line to the required outlet points. The installation is tailored to the
requirements. It is fairly adequate for smaller units and hospitals.
Empty cylinders are continuously replaced to maintain the ade-
quate pressure.
Bulk oxygen tank: A bigger storage tank containing either com-
pressed or liquid oxygen may be used in place of a manifold system.
The storage system is usually built outdoor, but can be indoors.
From the main storage, oxygen is first carried to a station with a
reducing valve lowering the pressure to 50 psig. From there it is
carried to the service areas. This is especially useful in hospitals
where consumption of oxygen is greater.
Liquid Oxygen
A liquefied gas is defined as an element or a compound that has a
boiling point at relatively near atmospheric temperatures from
about – 30°F to 25°F or 30°F. The liquefied gas solidifies at cryogenic
temperatures (carbon dioxide is widely used in its solidified form
– “dry ice”).
368 Oxygen Therapy
Oxygen is used both as a non-liquified compressed gas and a

cryogenic fluid (liquefied form). It has a boiling point of –297°F.
To keep it in a liquefied form, the temperature is cooled down to
below the boiling point and stored with special insulated containers.
At low temperatures, it can be retained in the liquid form at
pressures of less than 75 psig or even at less than 1 psig.
The stationary storage tank for liquid oxygen is generally
located outdoors along with a standby supply of higher pressure
gaseous oxygen. Cryogenic storage system often includes
vaporizing units for converting cold fluid to gas at atmospheric
temperature and pressure. Liquid oxygen storage is compact and
occupies lesser space. It is more economical but the tank requires
regular refilling (as in case of compressed gas storage).
Oxygen Concentrator
The concentrator collects oxygen directly separated from the
atmospheric air and supplies to the storage tank. It is a very effective
method of oxygen supply. The initial cost of the equipment is
additional to the cost of the pipe line. It is however, cheaper in the
long run since no replacements are required for the oxygen tank.
The concentrator consists of the following parts (Fig. 23.6):
Compressor: Air is sucked from the atmosphere and compressed.
Zeolyte cylinders: The compressed air is passed onto cylinders
containing artificial zeolyte which absorbs nitrogen and separates
oxygen (with a small fraction of argon).
Fig. 23.6: Scheme of a medical oxygen concentrator

Storage tank: Oxygen is stored in the tank to maintain constant

supply to the pipe line. For auxiliary storage, refill cylinders may
be filled from the tank.
A cooling system is required to absorb the heat generated during
air compression. A simple water circulation system is adequate
for this purpose. In view of the noise generated during the process,
the system should be installed outside the main hospital building.
It should also be away from the hospital incinerator and other fire
sources. The system is easy to operate and run. Artificial zeolyte
needs replacement after 5 to 10 years depending upon the use. It
should be able to supply O2 of over 90 percent concentration.
There are several companies which manufacture and install the
equipment. While deciding to go in for the system, besides looking
into the costs and space, one should ensure the efficient functioning
of the machine and purity of the gas. It should also be equipped
with an oxygen analyzer to maintain accuracy, and alarms to
indicate falling oxygen concentration, pressure or processing.
Bedside Oxygen Concentrators

These are small concentrators supplying oxygen from the
atmospheric air. They are generally meant for domiciliary use.
Small nursing homes and hospitals with limited requirements may
also like to opt for such units.
General Problems and Precautions

The hospital oxygen system is associated with potential engineering
and supply risks. Damage to structures and other line mishaps
can result in interruption of supply and leakage. Malfunctioning
of pressure sensors; pressure unbalance and failure of vacuum seals
can cause supply problem. False alarms from calibration drifts are
not uncommon.
Although oxygen is not inflammable itself, it supports combus-
tion. Therefore, the storage as well as the supply lines should be
placed away from the fire sources. Smoking in the area should be
strictly prohibited. Fire extinguishing apparatus should be available
near the storage as a safety measure from accidental fires.
Reactions between oxygen and other compounds can occur
when there is sudden change in storage conditions. A sudden rise
in temperature of a compressed gas cylinder can result in gas
expansion and violent explosion. Controlled conditions should
therefore be ensured.
370 Oxygen Therapy
BIBLIOGRAPHY
1. Bancroft ML, duMoulin GC, Hedley-Whyte J. Hazards of hospital bulk oxygen
delivery systems. Anesthesiology 1980; 52:504-10.
2. Burton GG. Respiratory Care: A guide to respiratory therapy. JB Lippincott,
Philadelphia, 1984.
3. Deleris LA, Yeo GL, Seiver A, Pate-Cornell ME. Engineering risk analysis of
a hospital oxygen supply system. Med Decis Making 2006; 26:162-72.
4. Eubanks D. Comprehensive Respiratory Care: A learning system. CV Mosby.
St. Louis 1985.
5. Friesen RM, Raber MB, Reimer DH. Oxygen concentrators: A primary oxygen
supply source. Can J Anesth 1999; 46:1185-90.
6. Garcia L. Gas Therapy: In: Young JA, Crocker D. Principles and practice of
respiratory therapy. (2nd edition). Year Book Medical Publishers, Chicago,
117-43.
7. Keller RR. Long-term oxygen therapy: Advances and perspectives in technical
devices. Monaldi Arch Chest Dis 1999; 54:75-8.
8. McPherson SP, Spearman CB. Primary systems. In: Respiratory Therapy
Equipment, (2nd edition). CV Mosby, St Louis 1981;33-83.
9. Muhe L, Webert M. Oxygen delivery to children with hypoxemia in small
hospitals in developing countries. Int J Tuberc Lung Dis 2001; 5:527-32.
10. O’Neill B, Bradley JM, McKevitt AM, et al. Prescribing practice for intermittent
oxygen therapy: A GP survey. Chron Respir Dis 2004; 1:139-42.
11. Perrelet A, Zellweger JP, Talla I, Ndiaye Y, Gautier E, Gehri M. The oxygen
concentrator: An appropriate technology for treating hypoxemic children in
developing countries. Int J Tuberc Lung Dis 2004; 8:1138-41.
12. Schneider G. Oxygen supply in rural Africa: A personal experience. Int J
Tuberc Lung Dis 2001; 5:524-6.
13. Shrestha BM, Singh BB, Gautam MP, Chand MB. The oxygen concentrator is
a suitable alternative to oxygen cylinders in Nepal. Can J Anesth 2002;49:
8-12.
14. Stoller JK, Stefanak M, Orens D, Burkhart J. The hospital oxygen supply: An
“O2K” problem. Respir Care 2000; 45:300-5.
15. Young JA. Manufacture, storage and transport of gases. In: Young JA, Crocker
D. Principles and Practice of Respiratory Therapy. (2nd edition). Year Book
Medical Publishers, Chicago, 63-81.
Index
A Assessment of need for

supplemental oxygen 211
Acute respiratory distress syndrome Assessment of oxygenation status
(ARDS) 176 102
Air travel and oxygen therapy 221 Assessment of tissue oxygenation 80
preflight assessment 222 biochemical parameters 83
prescribing in-flight oxygen 224 blood lactate level 83
Air-oxygen mixtures 280 gastric tonometry 83
jet mixing 280 nuclear magnetic resonance
venturi tube 280 spectrometry 83
Alterations of acid-base status 96 sublingual capnography 83
Alternate oxygen carriers 269 clinical assessment 80
blood substitutes 269 physiological parameters 81
hemoglobin-based oxygen DO2/ V  O measurements 82
2
carriers 270 dual oximetry 82
perfluorocarbon-based mixed venous O2 saturation
oxygen carriers 271 (S v O2) 81
Ancient Greek concepts 6
Ancient Hindu concept of oxygen 5 B
Assessment of acid-base status 102
base excess/base deficit 102 Blood gas monitoring 126
pseudo-respiratory alkalosis 107 invasive technique 126
respiratory acidosis 108 arterial cannulation 128
arterial sampling 126
causes of acute respiratory
oxygen analysis 129
acidosis 108
non-invasive blood gas
causes of chronic respiratory
monitoring 131
acidosis 109
capnography 137
homeostatic response to 109
oximetry 131
manifestations of 109
Blood gases 89
treatment 110
basic concepts 89
respiratory alkalosis 105 alveolar-arterial oxygen
causes of respiratory pressure gradient 90
alkalosis 105 arterial oxygen tension (PaO2)
homeostatic response to 89
respiratory alkalosis 107 blood bicarbonate level and
manifestations of acid-base status 91
respiratory alkalosis 106 relationship between carbon
treatment of respiratory dioxide and pH 91
alkalosis 107 relationship of total
stepwise approach to ABG ventilation to alveolar
analysis 104 ventilation 91
372 Oxygen Therapy
C physiological complications 254

absorption atelectasis 255
Carbon dioxide transport 65 effects on circulation 255
carbon dioxide transport in blood effects on respiration 256
during rest and exercise 66 suppression of hypoxic
CO2 bound as bicarbonate 67 ventilatory drive 254
CO2 bound as carbamate 67 toxic effects of oxygen 256
dissolved CO2 66 oxygen at cellular level 256
effect of tissue metabolism and reactions involved in
blood flow on interstitial generation of HO. radicals
PCO2 69 257
physiology 65 sequential single electron
spectrum of pressure gradients reduction of oxygen to
during diffusion of CO2 68 water 257
transfer of CO2 across cell tissue damage due to toxic
membranes 69 oxygen metabolites 258
Chronic mountain sickness or Monge’s treatment of oxygen toxicity 263
disease 229 chelation therapy 264
Clinical considerations and cofactors 264
interpretation of blood gas 98 enzyme induction 264
Clinical prescription of oxygen 152 exogenous antioxidant
duration of administration 154 enzymes 264
method of administration 154 modulation of inflammatory
monitoring of oxygen therapy 154 response 264
oxygen concentration (FiO2) and Conditions invalidating for modifying
flow rate 153 ABG results 99
source of oxygen 153
use of humidifying devices 154
Clinical signs of hypoxia 304
D
cyanosis 304 Dangers and complications of oxygen
heart rate 304 therapy in critically ill
metabolic acidosis 305 patients 217
pulmonary changes 304 Diffusion 49
thermoregulatory disturbances 305 Diving problems 238
Complications of oxygen therapy 254 Domiciliary oxygen 10
defence mechanism against toxic
oxygen metabolites 259
E
antioxidant enzymes 259
clinical syndromes of oxidant Equipment for the administration of
injury 260 oxygen 344
ocular toxicity 262 continuous positive airway
other free radical scavengers pressure 346
259 humidification 347
markers of oxidative injury 262 using concentrators with single
end tidal H2O2 262 patients 346
markers of lipid peroxidation using cylinders with single
263 patients 344
Index 373
using one oxygen source for other oxygen delivery devices 290
several patients 346 endotracheal devices 291
Evolution of atmospheric oxygen 3 nasopharyngeal oxygen 290
Expression of gas volumes and transtracheal catheters (TTC)
pressures 25 291
flow of gases 26 venturi mask 289
flow through orifices 27 Hyperbaric oxygen 10
heliox 28 Hyperbaric oxygen therapy 240
thermal conductivity 28 complication 249
wave speed 28 history 240
Extra-corporeal membrane development of hyperbaric air
oxygenation 272 therapy 240
development of hyperbaric
F oxygen therapy 242
other physiological effects of
Fraction of inspired oxygen (FiO2) 281 hyperbaric oxygenation
243
G rationale of hyperbaric
oxygen 242
Gas laws 20 hyperbaric chambers 250
Bernoulli’s principle 23 types 250
Boyle’s law 20 indication 244
Charles’ law 21 adjunct to treatment of
Gay-Lussac law 21 cancers 247
general gas law 22 air embolism 245
Graham’s law 23 carbon monoxide poisoning
Henry’s law 23 246
Gas solution and tension 23 decompression sickness 244
gas gangrene and other
H necrotizing infections 246
miscellaneous conditions 248
Heliox therapy 273 Hypoxemia due to pulmonary
clinical uses 274 disorders 157
acute asthma 274 bronchial asthma 163
chronic obstructive oxygen therapy 163
pulmonary disease 275 bronchiectasis 167
critically ill children 276 chronic obstructive pulmonary
heliox administration 276 disease 159
High-flow or fixed performance oxygen therapy in acute
devices 289 exacerbations of COPD
high-flow non-rebreather face 160
mask system 290 consideration for oxygen therapy
humidification 292 158
humidifiers 293 interstitial lung disease 164
methods of administering abnormalities of gas exchange
humidified oxygen 293 165
nebulizers 295 oxygen therapy 166
374 Oxygen Therapy
kyphoscoliosis 172 face masks 286

pneumothorax and masks with reservoir bags 287
pneumomediastinum 170 simple face mask 286
pulmonary hypertension and cor nasal cannulae 284
pulmonale 173 nasal catheters 285
pulmonary thromboembolism 175
respiratory tract infections 168 M
Hypoxia 144
hypoxemix hypoxia 144 Metabolic acid-base disorders 111
causes 144 anion gap (AG) 112
normoxemic hypoxia 149 metabolic acidosis 114
causes 149 correction of academia with
other buffers 117
I evaluation 115
manifestations 115
Indication and utility of oxygen in treatment 116
critically ill patients 212 metabolic alkalosis 118
Indications for oxygen therapy 309 classification 119
Interpretation of ABG report 101
clinical evaluation 120
clinical manifestations 120
L management 121
Long-term oxygen therapy 193 overview of acid-base physiology
delivery devices 203 111
indications 195 Methods of oxygen administration
oxygen dosage 201 310
oxygen-conserving devices 203 low flow systems 310
electromechanical pulsing incubator enclosure system
devices 204 311
moustache configured nasal prongs/cannulas 310
oxymizer 204 oxyhood 311
pendant reservoir (oxymizer ventilatory therapy 311
pendant) 204 Methods of oxygen administration
reservoir oxygen delivery 204 333
transtracheal catheters 205 Modern history of oxygen 6
risks 205 Monitoring during oxygen therapy
cytotoxic damage 206 348
functional risks 206 adverse effects of oxygen therapy
oxygen for air travel 206 350
physical risks 206 arterial oxygenation 349
selection of patients 193 mixed venous oxygen tension
supply sources 201 (P v O2) or saturation
compressed gas cylinder 201 (S v O2) 350
liquid oxygen system (LOX) patient’s clinical status 348
202 pulmonary oxygen toxicity 351
oxygen concentrator 202 tissue oxygen measurement 350
Low-flow or variable performance tissue oxygenation 349
devices 284 biochemical markers 349
Index 375
Monitoring oxygen therapy in ICU Oxygen for non-pulmonary conditions

218 183
medical disorders 183
N cerebrovascular disorders 185
ischemic heart disease 183
Normal chemistry 92 other medical disorders 186
acids and bases 92 problems of blood volume
atom 92 and cardiac output 187
blood acids 95 problems of oxygen transport
blood bases 96 186
buffer system 93 palliative care 188
Henderson-Hasselbalch equation Oxygen for the healthy at high
94 altitude 230
solutions 92 Oxygen monitoring 311
blood oxygen monitoring 312
O continuous monitoring 312
intermittent monitoring 312
Oxygen and resuscitation 308
FiO2 monitoring 312
Oxygen concentrators 337
non-invasive monitoring of
Oxygen consumption (VO2) 76
oxygenation 313
calculated versus measured VO2
pulse oximetry 314
77
transcutaneous PO2
calculation of VO2 77
monitoring 313
factors influencing VO2 79
optode technology 313
causes of decreased VO2 79
other methods of assessing
causes of increased VO2 79
oxygenation 316
oxygen debt (VO2 deficit) 80
conjunctival PO2 316
O2 extraction ratio (O2ER) 77
cytochrome aa3 saturation
the DO2-VO2 curve 77
monitoring 316
Oxygen delivery (DO2) 72
invasive hemoglobin
calculation of DO2 72
saturation monitoring 316
factors influencing DO2 73
Oxygen sources 335
arterial O2 contents (CaO2) 73
cardiac output 74 Oxygen storage and supply in
steps involved in DO2 75 hospitals 358
cellular O2 supply 75 compressed oxygen 359
cellular O2 utilization 76 cylinder valves 360
Oxygen delivery devices 339 diameter index safety system
mask 342 (DISS) 360
non-rebreathing masks 342 pin index safety system (PISS)
oxyhood 343 360
partial rebreathing masks 342 cylinders 358
simple masks 342 flow meters 363
nasal catheter 340 Bourdon flow meter 363
nasal prongs 341 Thrope tube flow meters 364
nasopharyngeal catheter 339 gas regulators 361
Oxygen delivery in the ICU 214 preset regulator 362
Oxygen for high altitude sickness 228 variable 362
376 Oxygen Therapy
Oxygen supplementation during oxygen delivery, consumption

NIPPV 215 and extraction 63
Oxygen supplementation through oxygen delivery during
conventional mechanical exercise 64
ventilators 216 physiology 55
Oxygen supplementation through Oxygen use in diving medicine 231
masks 214 gases used in underwater
Oxygen supply at bedside 365 breathing 232
bedside oxygen concentrators 369 air 232
centralized oxygen distribution oxygen 233
system 366 physics 232
general problems and precautions physiology 231
369
oxygen cylinders 365
oxygen storage 367
P
compressed oxygen 367 Perspectives of domiciliary oxygen use
liquid oxygen 367 in India 207
oxygen concentrator 368 Physical properties of gases 16
Oxygen therapy 300 density 17
physiology 301 mass and weight 17
oxygen capacity 301 pressure 18
oxygen content 301 atmospheric pressure 19
oxygen saturation 302
partial pressure 19
partial pressure of oxygen
temperature 20
(PO2) 301
volume 16
Oxygen therapy 8
Pulmonary circulation 45
Oxygen therapy devices 283
distribution of perfusion 46
Oxygen toxicity 305
intravascular pressure 46
Oxygen transport 55
cellular use of oxygen 63 pulmonary driving pressure
combination of oxygen with 47
hemoglobin and transport transmural pressure 47
in circulation 56
Hb oxygen affinity 60 S
heme-heme interaction 57
Special applications of oxygen therapy
hemoglobin variants 57
352
oxygen combined with
carbon monoxide poisoning 353
hemoglobin 56
oxygen content 60 helium-oxygen 354
oxygen-hemoglobin high altitude 352
dissociation curve 58 home oxygen therapy 356
diffusion of oxygen from capillary nitric oxide inhalation therapy 355
blood into interstitium 62 State of matter 14
diffusion of oxygen from atom and element 14
interstitium into cells 62 atomic and molecular weights 16
diffusion of oxygen from the molecular movement 15
alveoli into the blood 56 molecule and compound 15
Index 377
Surgical indications for oxygen Types of diving 234

therapy 189 breath-hold diving 234
perioperative oxygen therapy 189 mixed gas diving 235
postoperative state 190 bounce diving procedures 235
immediate 190 saturation diving procedures
late 190 235
surface oriented diving 234
T
Techniques of hyperbaric oxygenation
251 V
Therapeutic uses of oxygen in children Ventilation 34
323 compliance 35
oxygen consumption 326 elastic properties of chest wall
oxygen transport 325
and lung-chest wall
oxygen uptake 324
interactions 38
physiology of oxygenation 324
recruitment 37
rationale for oxygen therapy 327
inertance 35
causes of tissue hypoxia 330
decreased mixed venous resistance 38
oxygen content 330 airway morphology 39
diffusion impairment 329 distribution of ventilation 43
hypoventilation 328 physical principles of gas flow
physiologic mechanisms of and resistance 40
hypoxemia 328 role of gravity 44
recognition of hypoxemia 332 total and alveolar ventilation
right-to-left shunt 329 42
ventilation-perfusion Ventilation-perfusion
mismatch 328 relationship 52

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Oxygen Therapy

JAYPEE BROTHERS MEDICAL

Surg Cdr (Dr) PS Tampi

Oxygen as a gas, has fascinated me since my early childhood which

therapy, oxygen use for non-pulmonary diseases, during air travel

Part A: General Introduction

Part B: Physiological Considerations

Part C: Clinical Considerations

12. Long-Term Oxygen Therapy .............................................. 193

Part D: Special Issues

EVOLUTION OF ATMOSPHERIC OXYGEN

2 million years when primitive man appeared. It has been explicitly

ANCIENT HINDU CONCEPT OF OXYGEN

In summary, it implied that the ‘vayu’ located in the ‘hrdya’

ANCIENT GREEK CONCEPTS

MODERN HISTORY OF OXYGEN

extraction technique to measure the content of these gases in the

help from James Watt—the inventor of steam-engine for storing

by excessive oxygen use or ‘oxygen free radicals’. Devison

oxygen to improve exercise tolerance was tried by Cotes in 1956 in

Ancient Hindu Concept

Ancient Greek Concept

7. Foster M. Lectures on the history of physiology. London, Cambridge

Modern History of Oxygen

Atom and Element

properties are lost and therefore, sub-atomic constituents of all

Molecule and Compound

Atomic and Molecular Weights

PHYSICAL PROPERTIES OF GASES

The gas shall occupy the available volume irrespective of the

Mass and Weight

therefore, are as follows:

THE GAS LAWS

constant. In other words the product of pressure and volume

The General Gas Law

Fig. 2.2: Velocity of a fluid increases with decrease in cross-section

GAS SOLUTION AND TENSION

temperature is increased. A state of equilibrium is reached when

EXPRESSION OF GAS VOLUMES AND PRESSURES

or STPD. STPD is used for uniformity of expression. This is done

Poiseuille equation, i.e. V = π γ4ΔP)/(8ηl). The resistance is

Flow Through Orifices

than that of air and of oxygen and depends on the fractional

Fig. 3.1: Schematic diagram to represent different

while CO2 enters the alveoli. In this manner, 250 mL of O2 enters

C = Δ VL/ Δ (PA – Ppl), where

Fig. 3.2: Diagramatic representation of pressure and volume changes during

Elastic Properties of Chest Wall and

by cuboidal epithelium and are supplied by pulmonary circulation.

Physical Principles of Gas Flow and Resistance

In a straight unbranched tube, the Hagen-Poiseuille equation allows

Total and Alveolar Ventilation

the dead space ventilation by these two mechanisms constitutes

inspiration, intrapleural pressure is less negative at the base than

each alveolus. Rough estimates put the total number of capillaries

Pulmonary Driving Pressure

Fig. 3.3: West zones of perfusion

effect on pulmonary arterial pressure, which increases the driving

a zone of reduced blood flow in that region. Zone 4 would be

Fig. 3.4: Schematic diagram representing diffusion across the alveolo-capillary

Fig. 3.5: Mismatching of ventilation and perfusion: Model A

the transfer of CO is not limited by perfusion at rest and instead is

mismatching can influence PCO2, this effect is less marked and is