European Review for Medical and Pharmacological Sciences

2006; 10: 135-151

Approach to respiratory failure in

emergency department
P. FORTE, M. MAZZONE, G. PORTALE, C. FALCONE, F. MANCINI,
N. GENTILONI SILVERI
Department of Emergency Medicine, Catholic University Rome (Italy)

Abstract. Objectives and Background:

The goal of this review is to provide update recommendations that can be used by emergency
physicians who provide primary cares to patients with Acute Respiratory Failure (ARF), from
the admission to an emergency department
through the first 24 to 48 hours of hospitalization. This work wants to address the diagnosis
and emergency medical care of ARF and the
management of medical complications.
State of the Art: A lot of statement has been
developed for the early management and treatment of ARF; moreover, over the last fifteen
years, we have assisted to the rise of a new
technique of ventilation, in the Emergency Department: Non Invasive Ventilation. This kind of
ventilation was firsthy applied in Intensive Care
and in Respiratory Care Unit. Randomized controlled clinical trials have showed its usefulness
in the early treatment of several forms of ARF,
together with medical therapy.
Key Words:
Respiratory failure, Pulmonary edema, Asthma,
Pneumoniae, Therapy in emergency department.

Introduction
Acute Respiratory Failure (ARF) was defined as the inability of the respiratory system
to exchange gases and to oxygenate the blood
adequately1-8. We can distinguish two mechanisms at the basis of ARF:
1. Failure in pulmonary ventilation (pump
failure);
2. Failure in gas exchanges (lung failure).
The first one is due to neuromuscular diseases, chest wall deformities, obstructive pulmonary diseases (Table I).

The second mechanism (mismatch in blood

gas exchanges) is due to the following different pathologies:
Adult acute respiratory distress syndrome;
Neonatal respiratory distress syndrome;
Acute cardiogenic pulmonary oedema;
Severe status asthmaticus;
Pneumonia;
Airspace collapse (atelectasis);
Pulmonary embolism.
The clinical signs and symptoms of patients
with ARF, refer to the two main manifestations of pulmonary diseases: arterial hypercapnia and hypoxemia.
The pathophysiology of hypercapnia is
based on four main mechanisms:
Increase in CO2 production (for istance,
parenteral feeding with high doses of carbohydrates; high body temperature, etc.)
Deterioration in gas exchanges as the increase in alveolar death space ventilation (for
istance in Chronic Obstructive Pulmonary
Disease COPD , because of mismatch in
ventilation/perfusion ratio, and in pulmonary
embolism);
Deterioration in respiratory mechanics
that involves a huge effort, an increase in respiratory work and the development of a rapid
shallow breathing CO2;
Alteration in the mechanism of control of
the ventilation (for istance, in chronic hypercapnia, we observe a decrease in ventilatory
drive with an increase in tolerance threshold
to CO 2; it happens in metabolic alkalosis
too).
The hypoxemia is due to different pathophysiological mechanisms:
Hypoventilation;
Alteration in gas diffusion;

Corresponding author: marinellamazzone@yahoo.it; paforte@libero.it

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P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

Table I.
Neuromuscular
diseases

Drugs abuse
Cervical tetraplegia
Curare/strychnine/
phosphate poisoning
Guillaine-Barr syndrome
Miastenia gravis; hereditary/
acquired myopathies
Botulism/Poliomyelitis
Chest wall deformities Bilateral or hypertensive
Pneumothorax
Pneumomediastinum
Post-traumatism
Obstructive diseases Severe Status Asthmaticus
Central airways obstruction

Mismatch in ventilation/perfusion ratio;

Pulmonary shunt.
Which are the clinical signs and symptoms
of hypoxemia and hypercapnia? The first one
shows with shortness of breath, tachycardia,
mental confusion, changes of personality,
restlessness, cyanosis, hyper/hypotension, arrhythmias and palpitations. Hypercapnia, instead, shows with sleepiness, mental confusion, cephalea, convulsions, arrhythmias,
miosis, papilledema, peripheral vasodilation,
hypotension and coma.
The first goal of the initial diagnostic evaluation is to understand the underling causes,
and so to do differential diagnosis among all
pathologic conditions that showed the most
important clinical symptom of this illness:
dyspnoea.

A Approach to Patients
with Dyspnoea
Clinical Evaluation
A patient with ARF usually presents with
signs of respiratory distress: dyspnoea,
cyanosis, tachypnea, accessory muscle use,
paradoxical breathing and tachycardia. Primary care physician must apply the algorithm
A-B-C-D, in order to exclude an Acute Upper Airway Obstruction (AUAO), first of all,
and then he must operate as following:
1. He has to administer high flows of oxygen, to measure blood pressure, to take
heart rate, respiratory rate, oxygen saturation, to make an electrocardiogram.
136

Moreover he has to take an arterial blood

gas sample and a peripheral venous blood
sample to evaluate CK, CKMB, T-troponine, LDH, AST, ALT and hemochrome.
2. At the same time he must evaluate the
neurological state, in order to call for the
resuscitator if Kelly score (Table II) is
more than 3.
3. If neurological state is not compromised
patient can be managed by emergency
physician, entirely. Arterial blood gas
(ABG) evaluation:
Hypoxemia with hypercapnia pump
failure due to neuromuscular disease or
chest wall deformities; Lung failure due
to COPD or acute asthmatic status.
This last situation can be treated with
pharmacological therapy and/or with
non invasive ventilation, if indicated. Patient must undergo endotracheal intubation (ETI) if his clinical conditions deteriorate.
Hypoxemia with no hypercapnia
lung failure due to ARDS or cardiogenic pulmonary oedema or pulmonary
embolism or pulmonary infection. If
oxygen saturation in more than 90%
continue to administer O 2 with face
mask and high flows. If oxygen saturation is less than 90% consider the use
of Non Invasive Ventilation (NIV), together with medical therapy.
4. Clinical evaluation must be associated
with radiological evaluation (Chest XRays) and with continuous ABG evaluations (after 1 hour and after each changing in clinical conditions). Patient must
undergo endotracheal intubation if his
clinical conditions deteriorate.
Evidence and Information Sources
A comprehensive literature search was
performed in order to select the latest recTable II. Kelly scale.
Awoke patient, he executes 3 complex orders
Awoke patient, he only executes simple orders
Sleepy patient, he can be awaken under verbal
orders
Sleepy patient, he can be awaken under physical
stimulus
Coma with no brainsteam alteration
Coma with brainsteam alteration

Approach to respiratory failure in emergency department

Table III.
Infectious

Neoplasm

Traumatic
External bodies aspiration
Anaphylaxis
Obstructive Sleep Apnea Syndrome (OSAS)
Neurogenic diseases

Viral laryngotracheitis (croup)

Bacterial epiglottiditis
Bacterial tracheitis
Subglottic hemangioma
Tracheal and endobronchial neoplasms
Thyroid and mediastinal tumors

Bilateral paralysis of recurrent nerve

Modified by G. Garetto, La Nuova Medicina dUrgenza, Ed. C.G. Torino11.

ommendations for the early diagnosis and

the therapy of the pathologies below.
In developing of the present guidelines we
considered the latest evidences in the management of dyspnoea, asthma, COPD, ARDS
and we applied the ATS Consensus Conference indications9 and the BTS guidelines10 for
the use of NIV in ARF.

B Approach to Patients with

Acute Upper Airway Obstruction
(AUAO)
Etiology
The causes of AUAO can be summarized
in Table III11.
Clinical Evaluation
We distinguish two different types of upper
airway obstruction: the extra thoracic presents inspiratory stridor, because of the collapse of upper extra thoracic airways, during
the inspiration when tracheal pressure is minor than atmospheric one. The intra thoracic
one that presents expiratory stridor, because
the extrathoracic airways collapse during the
expiration, when the intrapleural pressure is
greater than atmospheric one.
The stridor is the main symptom of
AUAO (Table IV), and its often associated
with cyanosis, loss of consciousness, napes
hyperextension (especially in the epiglottiditis), trismus (especially in the peritonsillar abscess), dysphagia (severe epiglottiditis or pha-

ryngeal obstruction). We usually observe

asymmetries in diaphragmatic ranges, in respiratory movements, in the intercostal and
supraclavicular re-entrances.
If the physician suspects an epiglottiditis, he
should be cautious in carrying out clinical examination: in fact he could provoke a complete obstruction stimulating with the tongue
depressor. Moreover, if respiratory distress
continues and the patient is stable (rapid shallow breathing, valid cough, conscious, lucid
and alert patient but with no cardiovascular alterations) physician should take blood pressure and oxygen saturation, continuously, and
often control ABG. If patient presents with
respiratory arrest he should follow the Advanced Life Support Algorithm. In a second
time physician should make differential diagnosis between epiglottiditis and viral croup.
Anaphylaxis: if patients present with glottis oedema should be immediately intubated
before developing complete obstruction of
upper airways. Then they should be submitted to infusion therapy with adrenaline (1 mg
in bolus repeatable), corticosteroids (hydrocortisol methylprednisolone) at high doses,
fluids.

Table IV. Infectious AUAO.

Supraglottic

Subglottic

Severe tonsillitis (> 10 years)

Peritonsillar abscess (> 10 years)
Retropharyngeal abscess (> 3 years)
Epiglottiditis (3-7 years)
Viral croup (3 months-3 years)
Bacterial tracheitis

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P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

Foreign bodies obstruction: do not introduce fingers into the oral cavity in order to
take it out: it could slip down. If patient can
speak the physician could remove it with a
powerful blow in the interscapular zone
(from one to four powerful blows). Moreover
he can try with Heimlichs manoeuvring. This
one can be performed with supine patient, in
case of loss of consciousness. If foreign body
cannot be still removed, patient should be
submitted to endoscopic removal, or to
cricothyroidotomy, or to tracheostomy.

C Approach to Patients with ARF

Due to Neuromuscular Diseases or
Chest Wall Deformities
Classification
See Table V for the classification
Signs and Symptoms of Hypoventilation
Rapid shallow breathing
Paradoxical breathing
Alternating breathing
Inability in carrying out a valid cough
Shortness of breathing (at the end).
In patients with chest wall diseases, ARF is
due to hypoventilation with an increase in
respiratory work and rapid shallow breathing.
Hypercapnia and hypoxemia associated with
hypoventilation due to neuromuscular diseases are due to different mechanisms:
Muscular weakness;
Decrease of pulmonary and thoracic
compliance;
Increase in respiratory work;
Decrease in central sensibility.

Table V. Infectious AUAO.

Chest wall deformities Kyphoscoliosis
Obesity-Hypoventilation
syndrome
Fibrothorax-Thoracoplastic
Ankylosing spondylitis
Bilateral diaphragmatic
paralysis
Wandering costal flap
Neuromuscular diseases

138

The clinical approach to these patients

could be differentiated on the base of their
conditions at the admission to the first aid.
Preserved and stable vital functions: if upper airways are pervious, if there are no cardio-vascular troubles and Kelly score is 1
and patient presents only dyspnoea, deliver
oxygen with facial mask and control arterial
saturation and blood pressure continuously.
If arterial blood sample shows an oxygen saturation more than 90% and a PaCO 2 less
than 45 mmHg, evaluate ABG after 1 hour
and control clinical conditions. Chest radiography should be done as soon as possible, to
help the physician in differential diagnosis
among neuromuscular diseases, chest wall deformities and brainstem pathologies.
Preserved But Instable Vital Functions
Cardio-circulatory arrest: ask for emergency team and follow the algorithm ALS for
the cardiac arrest. Patient will be admitted to
the Intensive Care Unit (ICU).

D Approach to Patients with

ARF Due to COPD
The term COPD encompasses two well defined entities: emphysema and chronic bronchitis. Emphysema is characterized by permanent and abnormal enlargement of airspace,
distal to the bronchiole, associated to a destruction of alveolar wall, without evident fibrosis, and to an obstruction of distal lower
airway. Bronchitis is defined only by a clinical
definition as presence of cough and expectoration for more than three months per year
for more than two consecutive years. The key
feature that unites these diseases (bronchitis
and emphysema) and the asthma (that were
going to treat below) under the definition of
COPD is the physiologic phenomenon of obstruction to forced expiratory airflow.
COPD is a slowly progressive disease characterized by punctuated exacerbations two or
three times a year in patients with significant
obstruction. It is identified by the presence of
airflow limitation that is not fully reversible
and does not change markedly over several
months. The disease is predominantly caused
by smoking. The exacerbation, in most cases
its due to infections, especially bacterial in-

Approach to respiratory failure in emergency department

fections (level II of evidence) 12 . The

pathogens most often involved in COPD exacerbations are Haemophilus influenzae,
Streptococcus pneumoniae, Moraxella catarrhalis13,14; less often, gram negative bacteria, Chlamydia pneumoniae and Mycoplasma
pneumoniae. Among viruses have been identified: Rhinovirus, Influenza virus, Parainfluenza virus, Coronavirus, Respiratory Syncytial Virus, Adenovirus. The cause of exacerbation may be unidentifiable up to 30% of
exacerbation15.

guiding management of patients with acute

exacerbation of COPD (level of hierarchy
IV). Spirometry, however, is fundamental to
making diagnosis of COPD because is the only accurate method of measuring the airflow
obstruction in patients. It cannot contributes
to the severity of COPD (level of hierarchy
IV) or distinguish asthma from COPD; it is a
poor predictor of disability and quality of life
in COPD (level of hierarchy IV)17; it predicts
prognosis of patients (level of hierarchy
IV)18,19.

Clinical Evaluation
The diagnosis of the exacerbations is clinical and is based on three parameters: increasing in sputum production, purulent expectoration, worsening dyspnoea. There is a severity scale for exacerbations based on these
findings16: type 1 (severe exacerbations) have
all of the above symptoms; type 2 (moderate
exacerbations) present only two of the three
symptoms; type 3 (mild exacerbations) present only one of the symptoms but associated
with one of the following at least: an upper
respiratory tract infection in the past five
days, fever, increasing in cough or wheezing,
increasing in respiratory rate or in the heart
rate by 20% above the baseline.
Each patient ranks the importance of different symptoms individually, however
breathlessness is the most significance symptom. Individual symptoms are not useful in
making or excluding the diagnosis of COPD
(level IV of hierarchy)15.

Serological Assays Are Only of

Epidemiological Value
Sputum samples for microbiological tests
(using Gram stain and culture) is indicated in
seriously ill patients, if sputum is persistently
present and purulent, or if there is a history
of prior treatment failure (level of hierarchy
IV).
Arterial blood gas sample is necessary to
assess the severity of exacerbation and for
the initial management of the patient. Moreover, patients who have low PaO 2 , high
PaCO 2, low pH are more likely to relapse
within 14 days of initial presentation.
ECG and/or Echocardiogram is useful to
assess cardiac status if there are features of
cor pulmonale (level of hierarchy IV).
CT scan of the thorax is necessary in suspect of pulmonary embolism. It is useful (level of hierarchy IV) to investigate symptoms
that seem disproportionate to the spirometric
impairment, to investigate some suspect abnormalities in chest radiograph.
Reversibility testing: there is a considerable variability in change in FEV1 in response
to the same stimulus from day to day, so it is
virtually impossible to interpret the response
to an individual reversibility test unless the
response is very large (an increase in FEV1
more than 400 ml). Reversibility testing is not
recommended in the latest guideline produced jointly by the American Thoracic Society and the European Respiratory Society.
Referral for specialist advice: these are
made when clinically indicated, at all stages
of disease, not only in the most severely disabled patients (level of hierarchy IV).

Additional Diagnostic Tests

Chest radiography: some observational
studies showed substantial rate of chest radiograph abnormalities. However, chest radiography is not routinely necessary during exacerbations, neither for the diagnosis (level of
hierarchy IV). It could be useful if there is
the suspect of pneumonia, or pneumothorax
or aspiration (such as in neuromuscolar diseases), or if patient is non-responsive to the
therapy. As chest radiography can sometime
reveal a parenchymatous pulmonary lesion
such as tuberculosis or bronchial carcinoma,
patients who have not had a radiography prior to the exacerbation should obtain one12.
Spirometry: spirometric assessment, at the
time of presentation, or during the course of
treatment, is not useful in judging severity or

Need of Hospital Management

Most patients with acute exacerbation of
COPD can be managed at home, but some of
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P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

them need hospital treatment. This may be

because of the following reasons:
Need for therapies that are not available
at home (such as non invasive ventilation);
Severe breathlessness;
Poor/deteriorating general conditions;
Cyanosis;
Worsening peripheral oedemas;
Impaired neurological conditions, mental confusion;
Acute onset;
Significant comorbility particularly for
heart diseases;
Changes in chest radiograph;
Significant alteration in arterial blood
gas analysis (PaO 2 < 60 mmHg; pH <
7.35).
Management
The following assessment about the management in acute setting of COPD are based
on the analysis of the most recent guidelines
from 2001 to 200420-23.
BRONCHODILATORS
Bronchodilators are central in management of symptoms of acute exacerbation of
COPD. However they do not modify the decline of lung function or, by inference, the
prognosis of the disease (grade B). Anticholinergic drugs inhibit vagal stimulation of
the bronchial tree and are associated with a
reduction of the smooth muscle tone and an
impairment of bronchial gland secretion. The
bronchodilating effects of short acting inhaled anticholinergics last up to 8 hours after
the administration (grade A). If administered
with metered-dose inhaler (MDI), the recommended dose of ipratropium bromide is 2-4

puff (40-80 microg) four times daily. For

more severe exacerbations, 0.5 mg each 8
hours (0.5 mg corresponds to 40 gtts of 0.25%
solution). The duration of action of short acting inhaled anticholinergic agents is greater
than that of beta 2 agonists (grade A)22. More
recently, several studies have reported
favourable effects with tiotropium a new long
acting anticholinergic bronchodilator that
must be inhaled once daily23,24.
The duration of action of short acting anticholinergic agents is greater than that of
short acting beta-agonists25 (grade of recommendation A). The combination of beta agonists and anticholinergics is more effective
and better tolerated than higher doses of either agents used alone (grade of recommendation A)26-27. The bronchodilator effects of
short acting beta agonists (i.e. salbutamol)
disappear within 4-6 hours; so for severe exacerbations is acceptable to increase the
number of administrations. Table VI (modified from COPDX plan: Australian and
New Zeland guidelines for managements of
acute exacerbation of COPD) shows the use
of bronchodilators according to the severity
of COPD.
The duration of action of short acting inhaled anticholinergic agents is greater than
that of short acting beta-agonists (salbutamol,
terbutaline) (grade of recommendation A).
The use of both of them is more effective and
better tolerated than the use of each one
alone (grade of recommendation A) 26-31 .
Long-acting beta2-agonists (salmeterol and
formoterol) provide bronchodialtion for 12
hours and are the first line treatment of acute
severe asthma. Moreover they provide sustained relief in moderate to severe exacerbation of COPD (grade of recommendation A).

Table VI.
FEV1

Suggested treatment

Mild COPD

60%-80%

Moderate COPD

40%-59%

Severe COPD

< 40%

Intermittent bronchodilators salbutamol (200 g) or ipratropium

bromide (40 g)
Intermittent or regular bronchodilators salbutamol (200-400 g
four times daily) or ipratropium bromide (40 g four times daily)
Combination bronchodilators may be considered
Regular combination bronchodilators salbutamol (200-400 g four
times daily) and ipratropium bromide (40-80 g four times daily)

Severity

Modified from GOLD85 [evidence level D]. FEV = forced expiratory volume in one second. COPD = chronic obstructive pulmonary disease.

140

Approach to respiratory failure in emergency department

At the following dosage, salmeterol (50 microg twice daily) and formoterol (12 microg
twice daily) improve the health related quality of life, lung function and symptoms.
THEOPHYLLINE
Theophylline is a non selective inhibitor of
phosphodiesterase. Besides bronchodilation
it increases central respiratory drive, respiratory muscle endurance, mucociliary clearance, cardiac output and dilation of pulmonary arteries. Theophyllines are rarely
used because of their narrow therapeutic index and the potential side effects (grade of
recommendation A).
GLUCOCORTICOIDS
Chronic treatment with oral glucocorticoids should not be used in COPD (grade of
recommendation A) 32-41. In fact their prolonged use do not modify the long term decline of FEV1. Systemic preferable oral glucocorticoids are beneficial in the management
of acute exacerbation of COPD (grade of
recommendation A). Probably they improve
the rate of lung function during the first 72
hours. Many recent COPD guidelines recommend the use of a short course (two weeks)
of oral glucocorticoids in a dosage of 0.5 mg
of prednisone or prednisolone/kg body
weight. Inhaled glucocorticoids should be
considered in patients with a documented response or those who have severe COPD with
frequent exacerbations (grade of recommendation B). Patients with clinically significant
acute bronchodilator reversibility may benefit from long term inhaled glucocorticoid
therapy42-44.
OXYGEN THERAPY AND VENTILATORY SUPPORT10
Its indicated in patients with hypoxia to increase the oxygen blood saturation up to
90%. NIV has been shown to be an effective
treatment for acute hypercapnic respiratory
failure, particularly in patients with acute exacerbation of COPD in whom a respiratory
acidosis persist despite maximum medical
treatment on controlled oxygen therapy
(grade of recommendation A). All the studies about the use of NIV in acute exacerbation of COPD have excluded patients
deemed to warrant immediate intubation.
NIV in fact should be undertaken as a therapeutic trial with a view to tracheal intubation

if it fails. A decision about tracheal intubation should be taken before initiating NIV in
each patient.
ANTIBIOTIC THERAPY
Antibiotics should be used in patients with
purulent sputum and should be administered
according to the stage of the disease (mild,
moderate or severe) and appropriate to the
bacterial agents probably involved. So in the
mild stage with a suspected infection by Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma
pneumoniae, Moraxella catarrhalis the recommended treatment is amoxicillin-clavulanic
acid (or other more inhibiting beta-lactams
available such as ampicillin-sulbactam and
amoxicillin-sulbactam), at dosage of 875/125
mg/12 h for ten days or cefuroxime (500 mg/12
h for 10 days) with azithromycin (500 mg/day
for three-five days) or clarithromicin (500 mg
twice daily for 1 week). If patients have one or
more risk factors add moxifloxacin/gatifloxacin/levofloxacin (respectively 400 mg/day,
400 mg/day and 500 mg/day for 7 days) and
telithromycin (800 mg/day for 5 days). If patients have a moderate or severe condition intravenous treatment may sometimes be necessary. The first line therapy, if enteric bacteria
or penicillin resistant streptococcus is involved
are quinolones, piperacillin-tazobactam and, if
there is a suspected infection by Pseudomonas
aeruginosa, ceftazidime, imipenem or
meropenem or cefepime.

Management of Acute Asthma

A recognized definition of acute asthma
must be still developed, despite numerous
clinical definition have been proposed in different workshops, working group, consensus
conferences and national and international
guidelines. The following table shows the major and minor criteria established by the
American Thoracic Society in 2000, to define
severe asthma45.
According to consensus guideline, a severe
episode is characterized by almost one of the
following events:
1. Accessory muscle activity;
2. Paradoxical pulse exceeding 25 mmHg;
3. Heart rate > 110 beats per minute;
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P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

4. Respiratory rate > 30 breaths per minute;

5. Arterial saturation less than 90%.
This clinical features are associated with a
forced expiratory volume or a peak expiratory flow rate less than 50%. In fact the sine
qua non of an episode of acute asthma is the
reversible, non uniform increase in airway
obstruction that induces diminished flow rate,
hyperinflation of the lung and premature airway closure. Moreover with the increase in
work of breathing and in expiratory effort the
dynamic hyperinflation rises and auto-positive end expiratory pressure (PEEP) develops.
Arterial blood gas examination: it typically
shows hypoxemia, hypocapnia, respiratory alkalosis46-50. The more severe is the attack, the
lower is the arterial oxygen saturation. However most asthmatic patients dont develop
marked hypoxemia and, also in severe attacks, its very infrequent that oxygen tension
decrease under 50 mmHg. Respiratory acidosis follows hypercapnia. With extreme flow
limitation metabolic acidosis develops. In
fact, if cardiac output is compromised develops lactic acidosis because of the hypoperfusion of peripheral tissue; in addition the increased oxygen consumption by respiratory
muscles also contributes. It may also be induced by aggressive administration of non selective sympathomimetics51.
Managements
In hospital settings for asthmatic patients
the driving gas should be oxygen for acute ill
patients. Moderately short-acting beta2adrenergic agonists such as salbutamol and
terbutaline have rapid onset of action and
provide more bronchodilation than do
methylxanthines and anticholinergics, making
them the first line treatment for acute illness.
Adult patients with acute asthma should be
given 2.5-5 mg of salbutamol or 5-10 mg of
terbutaline (Grade of recommendation B23.
There is evidence that additional benefit can
be obtained by adding anticholinergic treatment such as ipratropium bromide 500 microg (Grade of recommendation A). Treatment should be repeated if patient is non responsive to the therapy. In near fatal asthma,
the use of intravenous salbutamol (5 microg/min) and adrenaline (1 mg repeatable
for three times each 15 minutes), is effective.
142

Nebulized corticosteroids have been used

as a substitute of oral corticosteroids in moderate exacerbations of adult asthma; they
have been shown to have an oral steroid sparing effect (Grade of recommendation A)23.
Patients that are resistant or slowly responsive to beta-agonists need corticosteroids
more urgently 52-56 . Methylprednisolone
should be administered at dosage of 1 mg/kg
of body weight during the acute attack. The
US guidelines recommend 120-180 mg daily
of methylprednisolone given intravenously
(in three or four doses). It must be repeated
for 48 hours in those admitted, followed by
60-80 mg/day until the FEV1 reach the 70%
of normal. Oral prednisone (60 mg/day) can
be substituted57.
Methylxanthines, althought may have antinflammatory properties, are considerably less
effective than the sympathomimetics and
produce more significant side effects23-46.
Compared to COPD, insufficient evidence
exists to recommend the use of NIV for asthma patients; there is also insufficient evidence to recommend Continuous Positive
Airway Pressure (CPAP) in acute asthma
(Grade of recommendation C). The role of
NIV is not yet clear established57 and it could
delay the use of endotracheal intubation
when it is necessary.

E Approach to Patients with

Hypoxemic ARF
a Pulmonary Oedema
The definition of pulmonary oedema is
the overflow of fluid from the lungs capillary
to the alveolar spaces. We can distinguish two
different entities of this pathology: cardiogenic pulmonary oedema and non-cardiogenic pulmonary oedema also called ARDS
(Acute Respiratory Distress Syndrome), that
can be distinguished by clinical signs and instrumental examinations, although they present the same clinical symptoms.
The acute cardiogenic pulmonary oedema
is a hydrostatic oedema due to an impaired
function of left ventricle caused by coronary
artery disease, myocarditis, cardiomyopathy,
hypertension, congenital heart diseases. It occurs when the pulmonary capillary pressure
rises to value exceeding plasma colloid-os-

Approach to respiratory failure in emergency department

motic pressure (approximately 25 mmHg).

Clinical examination reveals a low flow state
with wet crackles, jugular venous distention,
third tone (S3 gallop), cardiomegaly. Concerning laboratory tests, ECG could shows
signs of ischemia or infarction. There could
be an increasing in cardiac enzymes and, at
the radiography, perihilar distribution of
oedema and the appearance of Kerley lines.
Pulmonary capillary wedge pressure exceeds
18 mmHg.
The treatment of acute pulmonary oedema
is based on the use of oxygen, nitrates, diuretics and, if coexists cardiogenic shock, inotropes.
Furosemide and nitrates (10 microg/min)
are the first line of medical treatment and
should be administered, together with morphine, if arterial systolic blood pressure exceed 100 mmHg. They promote diuresis
and vasodilation and so act both on the
pre-load and on the post-load of the heart,
reducing cardiac work and improving the
ejection fraction. If arterial systolic blood
pressure is between 70 and 100 mmHg
dobutamine (2-20 microg/kg/min) improves
the contractility and reduces peripheral resistances avoiding arterial vasoconstriction
(it acts only on beta receptors). If there are
signs of cardiogenic shock, dopamine (5-15
microg/kg/ min) increases the contractility
and improve the arterial blood pressure,
acting both on alpha and beta peripheral
receptors and, at low dosage, on dopaminergic receptors in the renal glomerule promoting diuresis.
Oxygen could be administered with face
masks with Venturi system or with reservoir
to reach high concentration of oxygen until
100%. During the last ten years the use of
NIV for treatment of acute pulmonary edema
is developing with modality of CPAP. CPAP
has been shown to be effective in patients
with cardiogenic pulmonary oedema who remain hypoxic despite maximal medical treatment (Grade of recommendation B) 10,59-62.
CPAP permits higher inspired oxygen content, increases mean airway pressure and improves ventilation recruiting collapsed areas
of the lung.
ARDS is defined by non cardiogenic pulmonary oedema, characterized by severe hypoxemia, new bilateral pulmonary infiltrates
at radiography, without elevated left atrial

pressure. The American - European Consensus Conference on ARDS defined the severity of the pathology by the ratio of
PaO2/FiO2: a ratio of 300 or less defines the
acute lung injury (ALI); a ratio of 200 or less
defines ARDS regardless of the amount of
PEEP needed to support oxygenation63. The
pathogenesis is due to the lung damage, that
causes an increasing in permeability of capillary endothelium and an alteration of lung
alveolar-capillary barrier with overflow of
fluid into the alveolar and interstitial space,
without increasing in pulmonary circulatory
pressure. The damage involves both the endothelial and epithelial surface; the activated
endothelium participates and partly drives
the neutrophil inflammatory response that
contributes to edema formation and fibrosis64. The most common cause of ARDS is a
severe infection and it accounts for approximately half of cases. It could present as a localized or systemic disease and the most
common agents involved are gram-negative
bacteria, that are often associated to multiple
organ failure. The last syndrome is the major
cause of death with a mortality of about
40% 65-68. Other frequent causes of ARDS
are: trauma, disseminated intravascular coagulation (DIC), acute haemorrhagic pancreatitis, aspiration of gastric contents, inhalation of foreign bodies, acute radiation pneumonitis, inhalation of toxic gases (smoke,
ozone, cadmion, chlorine, nitrogen dioxide)
or circulating foreign substances (alloxan, alpha-naphthyl thiourea). Special forms of
ARDS are showed in the table below 69
(Table VII).

Table VII. Special forms of ARDS.

Pharmaceutical
Narcotic overdose
Chemotherapy
Salicylate intoxication
Hydrochlorotiazide
Contrast fluid
Calcium antagonists overdose
High altitude
Neurogenic
Pulmonary embolism
Eclampsia
Post cardioversion
Post anesthesia
Post cardiopulmonary bypass

143

P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

Management
The main life threatening problem of
ARDS is hypoxemia, that should be alleviated by recruiting and ventilating collapsed
alveolar spaces and reducing the shunt. Hypoxemia cannot be corrected by the simple
administration of oxygen. Mechanical ventilation via endotracheal intubation should be
initiated as soon as possible. PEEP improves
oxygenation reducing the intrapulmonary
shunt. In general 5 to 20 cm H2O provides a
reasonable balance among potential effects.
In fact the heterogeneity of lung damage, due
to the different disposition of areas of consolidation and atelectasis, causes that a certain
amount of PEEP is appropriated in one region, too much in a normal region and too
low in a more damaged region. The traditional ventilation included high flow with elevated tidal volume (12 ml/kg) and high plateau
pressure (50 cm H2O), inducing ventilator-induced lung injury. A low tidal volume (6
ml/kg) and a low plateau pressure (max 30
cm H2O) decreased ARDS mortality from
40% to 31%70-73. Several studies that provide
support for the presence of endogenous glucocorticoid inadeguacy in the control of inflammation and systemic inflammation-inducted peripheral glucocorticoid resistance in
ARDS 74-78. Prolonged methylprednisolone
administration (a loading dose of 2 mg/kg,
followed by 2 mg/kg for 14 days, 1 mg/kg for
the next 1 week, 0.5 mg/kg for the next 1
week, 0.25 mg/kg for the next 1 week and
0.125 mg/kg for the latest week, for a period
of 32 days at all) may accelerate the resolution of both systemic inflammation and peripheral acquired glucocorticoid resistance in
ARDS79.
b Pneumonia
Pneumonia is defined as an inflammation
of the lung parenchyma, of the respiratory
tract distal to terminal bronchioli. The most
frequent etiology is infective (Common Acquired Pneumonia), although there are five
different kinds of pneumonia:
1. Common acquired pneumonia;
2. Nosocomial pneumonia;
3. Aspiration pneumonia;
4. Atypical pneumonia;
5. Pneumonia in elderly.
144

Clinical Manifestation
The clinical definition of common acquired
pneumonia includes such typical signs and
symptoms of lower respiratory tract infection,
shared by both pneumonia and acute exacerbation of COPD.
Pleural pain, cough with purulent expectoration, dyspnoea, tachypnoea, and other local symptoms; high fever or chills,
headache, arthritis, muscular pain.
New focal signs at the physical examination of the chest.
The chest radiography shows pleural effusion, areas of consolidations and/or atelectasis. For the diagnosis of pneumonia, the presence of an infiltrate or a consolidation in
chest radiography is necessary.
We define nosocomial pneumonia if it occurs in patients admitted since at least 48
hours or discharged no more than 8 days before the onset of symptoms, or for outpatients or visitors that attended the hospital at
least during the past 48 hours. The most frequent pathogens are aerobi bacteria Gram
negative such as Enterobacter, Acinetobacter,
Pseudomonas, Klebsiella, etc.; in the immunocompromised patients most frequently,
Staphylococcus aureus and Legionelle. Table
VIII shows the risk factors for nosocomial
pneumonia.
The aspiration pneumonia due to the entrance of fluids from stomach or upper respiratory tracts into the lower respiratory tracts,
can be classified in consideration of the three
different pulmonary damages: toxic, obstructive or infective 80 . Table IX, from IDSA
guidelines, shows in synthesis clinical manifestations and therapeutic approach to the
different forms.
Atypical pneumonia is defined for the
unusual manifestations with majority of
systemic signs and symptoms (fever,

Table VIII. Risk factors for nosocomial pneumonia.

Elderly
Severity of pathology
Admittance in ICU endotracheal intubation
Mechanical ventilation
Surgery
Previous use of antibiotics

Approach to respiratory failure in emergency department

Table IX.
Inoculum

Pulmonary

Clinical features

Therapy

Acid

Chemical
pneumonitis

Acute dyspnea, tachypnea, tachycardia with Positive-pressure

or with-out cyanosis bronchospasm, fever,
breathing IV fluids,
sputum: pink, frothy; radiograph: infiltrates
tracheal suction
in one or both lower lobes, hypoxemia

Oropharyngeal
bacterial

Bacterial infection

Usually insidious onset; cough, fever,

purulent sputum; radiograph: infiltrate
involving dependent pulmonary segment
or lobe with or without cavitation

Antibiotics

Inert fluids

Mechanical
obstruction: reflex
airway closure

Acute dyspnea; cyanosis with or without

apnea; pulmonary edema

Particulate
matter

Mechanical
obstruction

Dependent on level of obstruction,

ranging from acute apnea and rapid
death to irritating chronic cough with
or without recurrent infections

Tracheal suction:
intermittent positive
pressure breathing with
oxygen and isoproterenol
Extraction of particulate
matter, antibiotics for
superimposed infection

Modified from IDSA guidelines for CAP.

arthralgias, headache, etc.) and a poor pulmonary and chest manifestations (cough
without purulent sputum, no signs of consolidation at chest radiography). The more
frequent agents involved are Chlamydia
pneumoniae, Mycoplasma pneumoniae,
Chlamydia psittaci, Coxiella burnetii. Several studies have shown that clinical, laboratory and radiographic features cannot reliably differentiate between different
causative pathogens 81 . The diagnosis of
Chlamydia pneumoniae is made serologically or by polymerase chain reaction techniques; both Chlamydia and Mycoplasma
are relatively often detected in mixed infections with Streptococcus pneumoniae and
Haemophilus influenzae, thus making difficult to define under what circumstances
they could be considered the cause of pneumonia. Treatment is often empiric (Grade
of recommendation A II): macrolide, doxicyclin, and ciprofloxacin (Grade of recommendation B III).
The first step in a patient with a diagnosis
of pneumonia is to assess the severity of illness and the need for hospital admission that
were identified by the American Thoracic Society (ARS)82 and the British Thoracic Society (BTS) in 200183. The ATS rule is based on
the presence of at least one major criterion

(need for mechanical ventilation, an increase

in the size of infiltrates by > 50% within 48 h,
septic shock or the need of vasopressors for >
4 hours, and acute renal failure), or two minor criteria (respiratory rates > 30 breaths
per minute, PaO2/FiO2 < 250, bilateral/multilobar pneumonia, arterial blood pressure
90/60 mmHg). The BTS rule is based on the
presence of 2 main risk factors; if only one is
present clinician should evaluate pre-existent
comorbidities (age more that 50 years, congestive heart failure Ib-, ictus Ib-, coronary
artery disease III-, diabetes mellitus Ia-,
neoplasm Ib). There are 4 prognostic negative factors: mental Confusion non pre-existent, Urea > 7 mmol/l, Respiratory rate > 30
breaths/min, systolic Blood pressure < 90 (or
diastolic < 60 mmHg) (CURB).
Management
If oxygen blood parzial pressure is less
than 70 mmHg, oxygen should be administered to obtain an increasing in saturation
major that 90%. If obstructive pulmonary
diseases dont coexist, the inspiration fraction
of O2 should be greater than 0.35. In seriously ill patients, if oxygen therapy is not necessary to mantain saturation between 85 and
90%, despite maximum medical treatment,
NIV could be used to improve oxygenation,
145

P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

Table X.

Guidelines

Modifying
factors/comments

First choice

Alternatives

Outpatients
ER

LRTI#

Aminopenicillin

Canadian

No modifying factor
COPD, no recent antibiotics
or oral steroids
COPD, antibiotics or oral
steroid within 3 months

Macrolide
New macrolide

IDSA
CDC
ATS

No modifying factor
Cardiopulmonary disease
or other modifying factor

Respiratory FQ
Doxycycline/macrolide/FQ+
Macrolide/doxycycline/
cefuroxime//co-amoxiclav
New macrolide
-Lactman + macrolide
or doxycycline

Tetracyclines,
cephalosporins
respiratory quinolones,
macrolides
Doxycycline
Doxycycline
Co-amoxiclav 2nd
GEN cephalosporin +
macrolide
Respiratory FQ
Doxycycline
Respiratory FQ

Hospital treated
general ward
ERS
Canadian

-Lactman + macrolide
Respiratory FQ

IDSA
CDC
ATS

No modifying factor

-Lactman + macrolide
-Lactman + macrolide
Azithromycin i.v.

Cardiopulmonary dis or
other modifying factor

-Lactman + doxycycline
or macrolide

Canadian

P. aeruginosa not suspected

P. aeruginosa suspected

2nd-3nd GEN cephalosporin +

macrolide or FQ + rifampicin
Respiratory FQ + -lactman
Ciprofloxacin + antipseudomonas
-lactman or AG

IDSA

P. aeruginosa not suspected

2nd-4th GEN
cephalosporin +
macrolide
FQ
FQ
-Lactman + doxycycline
or FQ alone
FQ

ICU-treatment
ERS

Structural lung disease

CDC
ATS

P. aeruginosa not suspected

P. aeruginosa suspected

Extended spectrum -lactman +

FQ or macrolide
Antipseudomonas -lactman +
ciprofloxacin
-Lactman + macrolide or FQ
-Lactman + macrolide or FQ
Antipseudomonas -lactman +
ciprofloxacin

-Lactman + macrolide
Antipseudomonas
-lactman + AG +
macrolide

Respiratory FQ
Antipseudomonas
-lactman + AG +
respiratory FQ or
macrolide

ERS: European Respiratory Society; IDSA: Infection Diseases Society of America; CDC: Center for Disease
Control and Prevention; ATS: American Thoracic Society; LRTI: lower respiratory tract infection; FQ: fluoroquinolone; GEN: generation; P. aeruginosa: Pseudomonas aeruginosa; AG: aminoglycoside. #: no distinction was
made between community-acquired pneumonia and other LRTIs; +: depending on local resistance situation and
underlying factors; : risk factors for penicillin-resistant pneumococci or Gram-negative bacteria; /: risk factors
for penicillin-resistant pneumococci or Gram-negative bacteria, including nursing home patients.

146

Approach to respiratory failure in emergency department

Table XI. Suggested strategy for empirical outpatients treatment of community acquired pneumonia in the immunocompetent adult. (Modified from Eur Respir J)84.
CAP
Clinical/epidemiological data
indicating atypical pneumonia

Macrolide or doxycycline

No clinical/epidemiological data indicating

atypical pneumonia

Younger and
previously well

Older, COPD and or

other severe chronic ilness

Penicillin V or
amoxicillin

Amoxicillin
clavulanic acid

Therapy failure

Therapy failure

Macrolide or
doxycycline

Doxycycline or
respiratory fluoroquinolone

Table XII. Suggested strategy for empirical inhospital treatment of community acquired pneumonia in the immunocompetent adult. (Modified from Eur Respir J)84.
Patient to moderate
CAP

Probable pathogen
(cover required)

Mild to moderate CAP

All cases

Streptococcus pneumoniae

Chronic pulmonary disease

Haemophilus influenzae and
or post-influenza pneumonia
Moraxella catharralis
Postinfluenza pneumonia
Staphylococcus aureus
and drug addied
Epidemiological chemical
Legionella
data indicating legionella
Epidemiological clinical data
indicating other atypicals
Gram-negative cover nor
routinely necessary
(irrespective of patients
age, or whether nursing
home resident)97
Severe CAP
All cases

Mycoplasma pneumoniae and

Chamydia pneumoniae

Streptococcus pneumoniae
Haemophilus influenzae,
Moraxella catarrhalis,
Staphylococcus aureus,
atypical agents and
Gram-negative enteric bacilli

Choice of empirical therapy

Benzylpenicillin or amoxicillin clavulanic acid

Cefotaxmeceftriaxone if high rate of hyghly
penicillin-resistant pneumococci
Co-amoxiclav, or 2nd/3rd generation
cephalosporin (iv)
2nd/3rd generation cephalosporin (iv)
Respiratory FQ, or macrolide + data
benzylpenicillin/amoxixillin clavulanic
or 2nd/3rd generation cephalosporin (iv)
Macrolide or doxycycline

Cefotaxime ceftriaxone macrolide rifampicin

or benzylpenicilli respiratory FQ

Pseudomanas aeruginosa
need not be routinely
FQ: fluoroquinolone.

147

P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

reduce respiratory rate and lessen dyspnoea.

Moreover, NIV can be used as an alternative
to tracheal intubation if patient became hypercapnic (Grade of recommendation C)10.
Patients should have arterial systolic pressure > 90 mmHg and the diuresis (0.5-1
ml/kg/hour).
The empirical antibiotic treatment recommended by international guidelines is summarized in Table X (from ERJ)84.
It differs between outpatients and inhospital patients, and its based on severity of illness and the most likely pathogen involved in
various patients categories (Table XI).
Most of the outpatients should be treated
with monotherapy, most often with beta-lactam alone (amoxicillin clavulanic acid or
second and third generation intravenous
cephalosporin). If therapy fails, Mycoplasma and/or Chlamydia pneumoniae may be
involved and so treatment with doxycicline/
macrolide or fluoroquinolone should be initiated (Table XII).
The inhospital patient should be treated
within 8 hours from the admittance, with
empirical therapy (amoxicillin clavulanic
acid or second and third generation intravenous cephalosporin): it should not be delayed while waiting for the results of the
examinations (hemocultures, culture of
sputum, first of all). If patient has structural lung disease Pseudomonas should be suspected: piperacilline, piperacilline-tazobactam, cefepime, imipenem, meropenem
should be administered. If aspiration pneumonia is suspected, a therapy against
anaerobic bacteria should be initiated (beta
lactamic antibiotics plus inhibitor of beta
lactamase, clindamycin, metronidazol). If
Pneumococcus is suspected, beta lactamic
antibiotics plus inhibitor of beta lactamase
(1 g each 6 hours), cefotaxime (1 g each 8
hours), ceftriaxone (1 g each 24 hours)
should be administered, or, if patient is allergic, fluoroquinolones or quinopristin/
dalfopristin, or still linezolid or vancomycine.
In general, it is important for efficacy, as
well as to avoid development of resistance,
that high enough or frequent enough dosing
is used rather than extending therapy for >
7-10 days (except for treatment of the Legionnaires disease, where 2-3 weeks duration is recommended).
148

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