Chronic Obstructive Pulmonary Disease, Carbon Dioxide

retention and high Oxygen flows: A literature review.

Philip Shields RN Ba Nursing (Hons)

Introduction
This literature review was born from the author’s curiosity. The graduate nurse often encounters
empirical and anecdotal accounts regarding the delivery of high flow Oxygen and its ability to “wipe
out” the “hypoxic drive” in Carbon Dioxide (CO2) retaining Chronic Obstructive Pulmonary Disease
(COPD) patients.
This review will attempt to determine if this belief has an empirical grounding. The purpose of this
literature review is to provide an understanding of current clinical modalities regarding Oxygen therapy
for non-exacerbated and exacerbated COPD CO2 retaining patients with an emphasis on effective
oxygen application grounded in literature. The review has a general medical/surgical ward nurse focus.

Although it is not the purpose of this literature review to detail anatomy and physiology, the review
will briefly define COPD to aid understanding, particularly focusing upon the condition’s cause and
resultant systemic affects. An outline of “normal’ Partial Pressures of Oxygen (PaO2) and Carbon
dioxide (PaCO2) will be provided with reference to basic chemoreceptor operation.
Various non-invasive oxygen delivery devices encountered in a ward will be examined and their basic
functionality explained.
Endeavouring to understand the evolution of treatment for non-exacerbated CO2 retaining patients
suffering from COPD, the review will explore a selection of the literature from the 1960’s to the
present day in chronological order.
The review will conclude with a summary of findings.

Method
The researcher used “Lib Explore’ which is a multi faceted database search engine available through
La Trobe University’s library. A sub-set of relevant health databases nested into the user interface
allowed a systematic and focussed crawl by Lib Explore with every Boolean expression. A broad
search was commenced using pulmonary keywords such as “COPD”, “CO2 retention” and “hypoxic
drive”. During the broader search, keywords were also entered into the public search engine “Google”
to provide leads to articles that could be followed up later in Lib Explore. Examining the hundreds of
responses it was realised that the search could be narrowed using keywords such as “Fraction of
inspired” and “non-exacerbation” and COPD. The final narrowed searches used Boolean expressions
such as “non exacerbation” and “copd” and “passive” not “ventilation”.
The selected literature was recorded in “end note” and tagged in a collection folder for sorting and later
scrutiny. To enable multiplatform editing, the document was placed on "Google docs" and scrutinized
by the Medical ward Nurse Unit manager and a masters in Nursing.

What is COPD?
Martini, (2005) states that COPD is an “umbrella” term that embraces three overlapping pulmonary
disorders, namely, Asthma, Bronchitis and Emphysema. Being progressive in aetiology, restricting
airflow to the lungs and reducing alveolar expansion characterize this group.
Asthma
This disorder restricts airflow across the bronchial tree by constricting the smooth muscle and
producing oedema and swelling of the mucosa (Martini & Welch, 2005).
Current research suggests production of mucus is accelerated in response to an auto-immune reaction to
an allergen. Asthmatics may have an accelerated growth, differentiation and recruitment of mast cells,
basophils, eosinophils and B-cells, all of which are involved in humoral immunity, inflammation, and
the allergic response. In asthma, this arm of the immune response is possibly overactive (De Paz,
Esteban, Garcia, & Martinez, 2004).

Bronchitis
Is an inflammation and swelling of the bronchial lining and is characterised by overproduction of
mucous secretions. In time, these secretions will block the minor airways and decrease respiratory
efficiency. A great deal of research has been conducted exploring the role bacterial infections play in
the exacerbations of Bronchitis, including the role Enterobacteriaceae and Pseudomonas play in acute
exacerbations (Eller, Ede, Schaberg, & Niederman, 1998) . Patients with chronic bronchitis may have
heart failure resulting in systemic oedema and low oxygenation manifesting as cyanosis.

Emphysema
Is characterised by the irreversible destruction of lung gas exchange surfaces within the alveoli. It is
caused by the inhalation of toxic gases and particles particularly from smoking. Individuals with
chronic emphysema tend to exert large amounts of energy compensating for the loss of functioning
tissue to maintain a relatively normal arterial Oxygen partial pressure (Martini & Welch, 2005).

Non-invasive oxygenation
It is not the intention of this literature review to describe physiology and chemoreceptor theory in
detail. That having been stated, to understand the effect of non-invasive oxygen delivery in the chronic
COPD patient it is essential that “normal” operational parameters be outlined. Porth, (2005) states that
the normal carotid arterial PaO2 lies between 80 and 100 mm Hg and the arterial PaCO2 is 35 to 45 mm
Hg in healthy individuals.

Three current theories

There is confusion in the literature regarding the breathing mechanism in COPD patients. In an article
published in the “Medical Surgical nursing journal” Simmons and Simmons (2004) outline three
predominant theories regarding breathing control in these individuals.

The authors explain the hypoxic drive as a process whereby the patient is triggered to breathe by virtue
of increased acidity in Ph sensing peripheral chemoreceptors. They cite Whitnack (2001) who states in
the Adult acute care bulletin that this theory is all but disproven. Their description of the hypoxic drive
has elements of the Haldane effect whereby CO2 replaces O2 in haemoglobin. The Haldane effect is the
second most popular theory in the literature.

The Ventilation/Perfusion (V/Q) mismatch theory is cited in the majority of the literature as the most
plausible mechanism. V/Q matching is said to occur in alveoli when the capillary flow matches
ventilation ensuring a 1:1 exchange of gases across the surface. A high mismatch is termed “dead
space” and is present when more ventilation occurs than perfusion. The theory states that as COPD
patients are given high flow oxygen the V/Q match changes due to long term vasoconstricted
capillaries dilating causing an increase in PaO2 and PaCO2 (Epstein & Singh, 2001). There is much
debate and confusion in the literature regarding the actual cause.

Interestingly, Martini, (2005) observes that although Ph receptors react quickly to an initial change, if
CO2 levels are maintained over hours the receptors accept the level as “normal”. As a result, over time,
the effect of the CO2 receptors on the regulation of the breathing centre declines and these receptors
cease to be a reliable regulator. Fortunately, the action of Oxygen receptors remains intact, correctly
responding to changes in O2 levels.
Martini (2005), notes that chronic COPD patients may be operating with an arterial Carbon Dioxide
level between 50 and 55 MM Hg, their CO2 receptors regarding this elevated range as “normal
operation” and thus providing regulation within this boundary.
Martini (2005), observes that O2 receptors are the only reliable breathing centre regulator in these
patients.

Oxygen delivery devices

Strachan and Knoble, (2001) state that masks can be divided into two categories, fixed and variable.
Both types of mask entrain (bring in) air from outside mixing with Oxygen. The Hudson mask and
nasal cannula are examples of variable delivery devices as the resultant percentage of Oxygen (and air
mixture) to the patient is dependent on variable parameters including the rate of breathing, position of
the device and Oxygen flow rate.
It can be seen that entrained air is not regulated in a variable device simply by looking at the holes in a
Hudson mask, thus, an accurate percentage of Oxygen can never be delivered.
Strachan and Knoble (2001), observe that the percentage of entrained air can be minimised (and
Oxygen increased) by utilising a rebreather bag attachment to the Hudson mask.

Fixed devices primarily used with COPD patients regulate entrained air via a rotating fenestrated
adaptor and deliver a known percentage of Oxygen. The researchers state these devices are also useful
as a fixed reference prior to an accurate arterial blood gas measurement. These masks are supplied
with a table showing the O2 flow rate against entrained air setting with the resultant percentage of
delivered Oxygen (Strachan & Noble, 2001).

Oxygen therapy in COPD patients

Medical and nursing anecdotal lore states that administering high flows of Oxygen to a COPD CO2
retainer will reduce hypoxic drive thus eventually resulting in apnoea, the purpose of this review is to
ascertain if this belief has an empirical basis grounded in literature.

The literature review commenced with the reviewer attempting to track the earliest mentioning of the
hypoxic drive theory. What primarily emerged in the early literature was the fact that subjects were a
mixture of non-ventilated individuals who where exacerbated, non exacerbated, CO2 and non CO2
retainers.

The earliest literature consistently named an increase of pulmonary dead space and an increase of
arterial Carbon Dioxide as a problem when Oxygen low is increased.

An example is the Lee and Read (1967), study. The researchers hypothesized that an increase in
Oxygen delivery to COPD patients may increase pulmonary dead space by reversing alveoli pulmonary
vasoconstriction. Such a reversal would increase perfusion through previously poorly ventilated alveoli
thus diverting blood flow from well ventilated areas resulting in an increase in dead space and PaCO . 2

This effect would be more pronounced in COPD patients. The authors studied 58 COPD non-
exacerbated outpatients, unfortunately none of which were CO2 retainers. They found that 37 patients
had an increase of 4% dead space after 100% Oxygen was administered. Oddly, PaCO2 was not
recorded.

Rudolph, Banks & Semple (1977), conducted a literature review and proposed an alteration to the
(then) current hypothesis in the British Lancet. They outlined the current thinking as: patients with
chronic respiratory failure have a lower than normal respiratory sensitivity to Carbon Dioxide and
instead rely on a strong “hypoxic drive” from the peripheral chemoreceptors. This drive is removed by
administering Oxygen. Hypoventilation occurs which results in hypercapnia.
Unfortunately, the term “hypoxic drive” is not further explained and the authors mention “Oxygen” not
“high flow Oxygen”.
As an amendment to the hypothesis the authors argue that the studies of the day were confusing and
contradictory and proposed that this was the result of the “hypoxic drive” occurring only in patients
displaying chronic exacerbation, they reasoned it was not a mechanism in remission. They theorized
that the “hypoxic drive” was a consequence of cerebral metabolic changes, in particular, an increase of
lactic acid in cerebrospinal fluid and not the action of peripheral chemoreceptors as was the current
thinking.
This is a very interesting study as it outlines the 1977 description of “hypoxic drive” theory, which is
difficult to locate in current literature. On the other hand, their amendment to hypothesis regarding the
action of lactic acid on central chemoreceptors can be found in today’s textbooks.

Aubier, Murciano, & Fournier (1980), Studied 20 non intubated patients in acute respiratory failure.
The researchers concluded that an increase in pulmonary dead space accounted for elevated carbon
Dioxide levels shortly after inspired Oxygen levels had been increased.

In the same journal volume, Aubier, Murciano, & Milic-Emili (1980), studied the effects of 100%
oxygen on pulmonary minute volume and arterial blood gases in COPD patients during acute
respiratory failure. They observed that initially the minute volume decreased by 18% from the baseline
when oxygen was administered. After 15 mins, minute volume had increased to 93% of baseline.
Despite this negative and then positive excursion, Carbon Dioxide levels had increased markedly.
Aubier et al. concluded that the initial lowering of minute volume was caused by the removal of the
hypoxic stimulus and the subsequent increase of Carbon Dioxide levels stimulated thoracic muscles to
responded bringing the minute volume positive to compensate. The researchers concluded that the
ratio between ventilation and perfusion increased caused an increase in dead space.

Sassoon, Hassell and Manutte (1987), studied 17 COPD patients not all of whom were CO2 retainers
and were in optimum condition. Using a transcutaneous CO2 detector they concluded that an increase
of Fraction of Inspired oxygen (FIO2) caused an increase in Carbon Dioxide due to a 4% increase in
pulmonary dead space.

A study that is frequently mentioned in the literature post 1990’s is the Crossley, McGuire, Barrow &
Houston (1997), single blinded prospective study conducted in a tertiary Canadian teaching hospital’s
intensive care unit.
Twelve intubated COPD patients weaned from mechanical ventilation were studied both at their
baseline Fraction of inspired Oxygen (FIO2) (0.3 to 0.4), and following a 20-min period of exposure to
an FIO2 of 0.7.
Using the paired Student's t-test the researchers concluded that CO2-retaining COPD patients following
a period of mechanical ventilation with PaO in the normal range can safely receive oxygen
2

supplementation without retaining CO or a depression of respiratory drive occurring. A new

2

ventilation/perfusion relationship is established during ventilation to normoxia and this relationship is

not altered by further increasing the FIO2.

Many commentaries regarding the Crossley et al study appear in critical care literature. Hoyt (1997) is
one such, the author states that the basic issue for the exacerbated CO2 retaining COPD patient is
delivery of sufficient oxygen to vital organs. Thus, clinical decision making based on the mythology
that increased oxygen delivery causes apnoea and cardiorespiratory arrest in patients with COPD by
turning off the “hypoxic drive” might be tantamount to withholding or delivering inadequate doses of
oxygen to meet metabolic needs.
The author provides a summation when he states that care is based on the nurse’s knowledge that an
increase in dead space and difficulty eliminating CO2 are the critical issues with COPD CO2 retaining
patients.
He states that pathways should be constructed to help the patient eliminate CO with mechanical
2

ventilation, or possibly non invasive ventilation while meeting the patient's needs for oxygen. Simmons
& Simmons (2004), add that although the arterial blood gas measurement is the “gold standard’ for
determining base line PaO2 and PaCO2, the nurse must closely monitor the patient using bedside
oximetry machines. The authors warn that these machines do not measure a rise in CO2.

Until 2009 there is very little information in the literature regarding optimum flow rates and oximetry
for resting, sleeping and exercising non exacerbated COPD patients. The literature does seem to concur
that an optimum resting arterial Oxygen partial pressure is approximately 60 to 80 mm Hg. Findlay
(1982), states that the optimum nasal cannula flow rate to achieve this pressure would be approximately
2 litre per minute. It could be argued however that this fixed rate is subject to many variables as
discussed earlier in this literature review regarding oxygen delivery devices and physiological
constraints.

The Australian Lung Foundation produced the “Australian and New Zealand Guidelines for the
management of Chronic Obstructive Pulmonary Disease” (COPDX, 2009). This document provides
guidelines describing the administration of controlled oxygen delivery to non-exacerbation COPD
patients, it appears on page 52, section X3.1 and states:

“Controlled oxygen delivery (28%, or 0.5–2.0 L/min) is indicated for hypoxaemia”.

This lead statement is alluding to 28% for a fixed venturi device and 0.5-2.0 L/min for variable devices,
this is made clearer later in the text.
“Correction of hypoxaemia to achieve a PaO2 of at least 55 mmHg (7.3 kPa) and an oxygen saturation
of 88%–92% is the immediate priority. Where there is evidence of acute respiratory acidosis (or a rise
in PaO2), together with signs of increasing respiratory fatigue and/or obtunded conscious state, assisted
ventilation should be considered. Early non- invasive positive pressure ventilation (NIPPV) may reduce
the need for endotracheal intubation.
Administering oxygen at an inspired oxygen concentration (fraction of inspired oxygen; FiO2) of 24%–
28% by means of a venturi mask is usually sufficient to improve oxygenation in most patients. Nasal
cannulas, although more comfortable, deliver a variable concentration of oxygen, but a flow of 0.5–2.0
L per minute is usually sufficient. Gas flow provided through Hudson-type masks is inadequate when
patients are tachypnoeic, so these should not be used. Careful monitoring with oximetry and, where
hypercapnia is a potential concern, arterial blood gas measurement is required. There is no benefit in
trying to obtain SpO2 levels over 92%”.
“High flow Oxygen should be avoided, as it is rarely necessary and may lead to hypoventilation and
worsening respiratory acidosis. Patients should be weaned off supplementary oxygen as soon as
possible, with none for 24–48 hours before discharge, unless home oxygen is prescribed.”

Although it not the intention of this literature review to research ventilation techniques in COPD
patients, the interested reader is directed to sections X 3.2 and X3.3 in the document (COPDX, 2009).

Similarly, the British National Institute for Clinical Excellence in their management of chronic
obstructive pulmonary disease in adults in primary and secondary care guidelines state that oxygen
therapy is indicated in stable COPD patients when their partial arterial pressure of oxygen is between
54.75 and 60 mm Hg and or a saturation of less that 90%, 30% of the time occurs (NICE, 2004).

What is the upper limit O2 flow for COPD patients? Findlay et al. (1982), state that 4 litres/minute
should not be exceeded with nasal prongs due to drying out of the nasal mucosa. The literature
routinely refers to .5 to 2 Litre/Min for resting COPD patients using variable devices. Commentary
such as Findley (1982) and Simmonds (2004) state that Oxygen flow for variable and fixed devices
should achieve a resting saturation of 88 to 92%.

Conclusion
This literature review’s aim was to determine if high flow Oxygen causes apnoea in COPD CO2
retaining patients.

It was found that COPD is an “umbrella” term for three overlapping pulmonary disorders, namely:
asthma, bronchitis and emphysema. The disorders are similar as all three are progressive in aetiology,
restrict airflow to the lungs and reduce alveolar expansion.

Is the hypoxic drive phenomena grounded in empirical observation? The “hypoxic drive” was
mentioned in literature circa 1970 and as late as 2001. It was believed COPD patients had a lower
respiratory sensitivity to Carbon Dioxide and their breathing reflex relied on the hypoxic drive,
therefore, high flows of Oxygen would eradicate this drive. It was reasoned that hypoventilation caused
the elevation in CO2 levels. There is no evidence in the literature to support empirical existance of
hypoxic drive phenomena.

The literature suggests hypoventilation in COPD patients due to high flows of Oxygen is a case of
correct observation but wrong interpretation of events. Very early in the literature it was observed an
increase in Oxygen flow for non exacerbated COPD CO2 retaining patients elevated pulmonary dead
space and caused a rapid increase of CO2 with pulmonary acidosis resulting. The V/Q mismatch is a
popular theory throughout the years, it states that Oxygen causes a vascular activation around hitherto
dormant alveoli causing the rapid release of CO2 and an increase of pulmonary dead space, this is the
most popular theory but the cause is unknown.

Prior to the 1990’s only convenience study non intubated patients could be found in the literature. A
study in 1997 found that intubated patients did not have an increase in CO2 levels and dead space when
their fraction of inspired Oxygen was increased. It found that mechanical and non invasive ventilation
appeared capable of “breathing off” CO2 in COPD individuals incapable of achieving this themselves.
What are the recommended flow rates, masks and oxygen saturations for resting COPD CO2 retainers
in a ward situation?
Fixed Oxygen masks, also known as venturi masks entrain (bring in) a fixed percentage of air that
enables a fixed percentage of Oxygen to be delivered to the patient. It was found that venturi masks
regulating 28% Oxygen are recommended for non exacerbated resting COPD patients.

Both Australian and British COPD authorities agree Oxygen delivery to the resting non exacerbated
COPD patient should maintain saturation levels of 88-92% with 92% being optimum, they state that
greater than 92% Oxygen saturation is not beneficial.

Variable devices such as nasal prongs and Hudson masks cannot by design deliver an accurate
percentage of Oxygen but nasal prongs are frequently used for patient comfort. The Australian COPD
authority state variable delivery devices are generally operated between .5 and 2 Litre/minute to
maintain optimum saturation. The nurse can conclude that by their very nature these devices are
variable and the literature states that it is not recommended to exceed 4 Litre/min with nasal prongs.
Although an arterial blood gas is the ‘gold standard” measurement, vigilant transcutaneous oximetry is
recommended to monitor and maintain an optimum resting saturation.

The review found that Oxygen flows above the recommended rate to maintain an optimum O2
saturation in CO2 retaining COPD patients have the ability to cause hypoventilation due to an increase
in CO2 and respiratory tract dead space, therefore, pulmonary acidosis may result. It found that nurses
should not halt Oxygen to exacerbating COPD patients. Modern literature reinforces the fact that
human metabolism requires oxygen. Withholding Oxygen resulting in hypoxemia to vital organs is
clearly detrimental to healthy people and COPD sufferers alike. The literature suggests clinical
pathways should ensure adequate oxygenation while reducing CO2 in exacerbated patients using non
invasive and invasive ventilation.
References

Aubier, M., Murciano, D., & Fournier, M. (1980). Central respiratory drive in acute respiratory
failure of patients with chronic obstructive pulmonary disease. The American review of
respiratory disease, 122, pp 191-199.
Aubier, M., Murciano, D., & Milic-Emili, J. (1980). Effects of administration of O sub 2 on
ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute
respiratory failure. The American review of respiratory disease, 122, pp 747-754.
COPDX. (2009). The COPDX Plan: Australian and New Zealand Guidelines for the
management of Chronic Obstructive Pulmonary Disease. Retrieved 14th March, 2009, from
http://www.copdx.org.au/guidelines/documents/COPDX_v2_18.pdf
Crossley, D. J., McGuire, G. P., Barrow, P. M., & Houston, P. L. (1997). Influence of inspired
oxygen concentration on deadspace, respiratory drive, and PaCO sub 2 in intubated patients
with chronic obstructive pulmonary disease. Critical Care Medicine, 25(9), pp 1522-1526.
De Paz, B., Esteban, R., Garcia, P., & Martinez, G. (2004). Pathophysiology, etiology and
additional treatment of asthma. Acta Pediatrica Espanola, 62(9), 385-400.
Eller, J., Ede, A., Schaberg, T., & Niederman, M. S. (1998). Infective exacerbations of chronic
bronchitis: Relation between bacteriologic etiology and lung function Chest, 113(6), 1542-
1548.
Epstein, S., & Singh, N. (2001). respiratory acidosis. respiratory care(46), pp 366-383.
Findley, L. J., Whelan, D. M., & Moser, K. (1982). Long-term oxygen therapy in COPD. Chest,
83, pp 671-674.
Hoyt, J. (1997). Debunking myths of chronic obstructive lung disease. Critical Care Medicine,
25(9), pp 1450-1451.
Lee, J., & Read, J. (1967). Effect of oxygen breathing on distribution of pulmonary blood flow
in chronic obstructive lung disease. The American review of respiratory disease, 96, pp 1173-
1180.
Martini, F. H., & Welch, K. (2005). Anatomy & Physiology Applications Manual. Sydney:
Pearson.
NICE. (2004). Management of chronic obstructive pulmonary disease in adults in primary and
secondary care. London: National Institute for Clinical Excellence
Porth, C. M. (2005). Pathophysiology Concept of altered health states. (7th ed.). Philadelphia:
Lippincott and Williams.
Rudolph, M., Banks, R. A., & Semple, S. J. G. (1977). Hypercapnia during oxygen therapy in
acute exacerbations of chronic respiratory failure. The Lancet(September 3rd), 483-486.
Sassoon, C. S. H., Hassell, K. T., & Manutte, C. K. (1987). Hyperoxic-induced hypercapnia in
stable chronic obstructive pulmonary disease. The American review of respiratory disease, 135,
pp 907-911.
Simmons, P., & Simmons, M. (2004). Informed Nursing Practice: The Administration of
Oxygen To Patients with COPD. Medsurg Nursing, 13(2), 82.
Strachan, L., & Noble, D. W. (2001). Hypoxia and surgical patients - prevention and treatment
of an unnecessary cause of morbidity and mortality. J.R.College of Surgery, Edinborough, 46,
297-302.
Whitnack, J. (2001). Notes from the editor: The death of the hypoxic drive theory. Adult acute
care (September/October), pp 1-2.