ADULT ASTHMA

Whats new ?

Acute severe asthma

in adults

Patients with severe asthma and adverse behavioural

and psychological factors are at particular risk of
fatal/near-fatal episodes

Colin Robertson

Intravenous magnesium sulphate has replaced

aminophylline as second-line therapy
Patient education and follow-up are essential to reduce
the frequency and severity of further episodes
Despite major improvements in the recognition of patients with
asthma and their treatment, both chronically and for acute episodes, acute severe asthma remains a life-threatening condition.
Most patients who die from asthma have a history of chronic, often
severe disease, but fatal or near-fatal events can occur in patients
who have previously exhibited only mild or moderate symptoms.
A background of poor behavioural and psychosocial features is
well recognized in these patients (Figure 1). Medical factors in
at-risk patients include:
prior severe episodes
admission to or attendance at an A&E department with asthma
during the last year
heavy use of 2-agonists
those taking three or more classes of asthma medication
those with brittle asthma.
Peaks of asthma deaths occur in the summer in younger patients
and the winter in older patients, possibly reflecting triggers of the
event. Most asthma deaths occur in the community, and in most
patients symptoms develop over hours or days rather than minutes.
The importance of patient education about asthma in general,
how to recognize the severity of symptoms and the institution of
preventive therapy cannot be over-emphasized.

Who needs referral to hospital?

Any patient with acute severe or life-threatening features should
be referred to hospital. Treatment should begin (see below) and
continue in transit to hospital. In the UK, ambulance crews can
administer oxygen and nebulized 2-agonists and institute ECG and
arterial oxygen saturation (SaO2) monitoring (pulse oximetry).

Investigations
Assessment of oxygenation and ventilation pulse oximetry is
commonly available in and out of hospital and provides a simple,
non-invasive estimate of tissue oxygen saturation. An SaO2 of 92%
or less indicates a life-threatening attack. Arterial blood analysis
is required in all patients with any life-threatening feature (Figure
2) and in any patient with SaO2 less than 92%. Normal arterial
partial pressure of carbon dioxide (PaCO2, 4.66.0 kPa) implies a
life-threatening episode. Raised PaCO2 or respiratory acidaemia is
particularly ominous.
Other investigations no individual laboratory marker at a
single point in time is useful for prognosis. A full blood count
is commonly performed, but a raised WBC count is common in
acute asthma even in the absence of infection. Urea and electrolyte

How to recognize a severe attack

Increasing symptoms of wheeze, dyspnoea, chest tightness or
coughing are common. Figure 2 lists the features of acute severe,
life-threatening and near-fatal attacks. It should be noted that
the absence of any of these features does not preclude a severe
attack. No clinical feature, individually or combined with others,
is specific for a severe event.
Measurement of peak expiratory flow (PEF) is the single most
important objective clinical measurement in the community, in
the A&E department and in hospital. PEF is best expressed as a
percentage of the patients previous best value. If this is not known,
a percentage of the predicted value is a rough guide. A PEF of less
than 50% indicates acute severe asthma; less than 33% indicates
a life-threatening situation.

Factors associated with fatal/near-fatal asthma attacks

Behavioural
Poor compliance/non-compliance with
therapy/GP or hospital reviews/hospital admission
Denial
Psychiatric
Psychosis
Depression
Major tranquillizer use
Alcohol/drug misuse
Social
Learning, work or income problems
Social isolation
Childhood abuse
Severe family or other stress
Obesity

Colin Robertson is Consultant in Emergency Medicine at the Royal

Infirmary, Edinburgh, UK. His research interests include cardiorespiratory
resuscitation, multiple trauma and pre-hospital care.

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ADULT ASTHMA

fective. The drug should preferably be given in a wet nebulizer

driven by oxygen. If an oxygen source is not available, an airdriven nebulizer should be used. If a nebulizer is not available,
the 2-agonist can be given by repeatedly activating a metered-dose
inhaler via an appropriate large-volume spacer.
When the initial dose of the 2-agonist does not achieve a good
result, repeat bolus nebulized doses or continuous nebulization (at
a dose of 510 mg/hour) should be given. Intravenous administration of a 2-agonist is indicated only in patients in whom nebulized
therapy cannot be used.
Ipratropium bromide nebulized ipratropium bromide, 0.5 mg,
should be added to the nebulized 2-agonist in patients suffering an
acute severe or life-threatening event, and in those who exhibit a
poor initial response to 2-agonist therapy alone. Further nebulized
doses of ipratropium bromide, 0.5 mg, can be given 46-hourly.
Corticosteroids reduce mortality and relapse rates and should
be given at the earliest possible opportunity. If the patient can
swallow, oral therapy is as effective as parenteral administration.
An initial dose of prednisolone, 4050 mg p.o., should be given.
An initial dose of hydrocortisone, 100 mg i.v., can be given to
patients who are unable to take oral treatment. Subsequently,
prednisolone, 4050 mg/day p.o., is given for at least 5 days.
(When hydrocortisone is used, the dose is 100 mg 6-hourly i.v.)
Magnesium sulphate is an adjunctive therapy in acute severe
asthma. It appears to act by blocking bronchial smooth muscle
calcium channels, inhibiting cholinergic neuromuscular transmission and stabilizing lymphocytes and mast cells. A single dose
of 1.22 g i.v. infused over 20 minutes should be considered in
life-threatening or near-fatal cases, or when a patient with acute
severe asthma has not responded well to inhaled bronchodilator
and corticosteroid therapy, after senior review. Repeated doses are
not indicated. Adverse effects of magnesium infusion, including
flushing, sweating, nausea, hypotension and muscle weakness,
are usually related to too rapid a rate of infusion.
Aminophylline intravenous aminophylline was commonly
used in the past, but does not produce additional benefit in patients
who have already received 2-agonists and corticosteroids. Adverse
affects including cardiac arrhythmias, nausea and vomiting are
more likely. As a consequence, intravenous aminophylline should
be used only under the direction of a senior, experienced clinician.
No loading dose should be used in patients who have been taking
aminophylline or theophylline orally; it is vital to measure blood
levels of aminophylline.
Other treatments bacterial infection is an uncommon precipitant of acute severe asthma, and routine or blind antibiotic
therapy is not indicated. Antibiotics may be required for patients
with pyrexia, purulent sputum or clinical/radiological evidence of
pneumonia.
Heliox (a mixture of 6080% helium and 2040% oxygen)
reduces airflow resistance because its density is lower than that
of air. It has been suggested that it may be of value in acute severe
asthma by reducing the work of breathing for sufficiently long to
allow other therapeutic modalities to take effect. This concept
is theoretically attractive but has not yet been shown to be of
unequivocal benefit.
Rehydration (oral and/or intravenous) may be required in some
patients, particularly when symptoms have been present for days
before admission. Regular estimations of plasma potassium, magnesium and phosphate (and correction when necessary) may be

Features of acute severe, life-threatening and

near-fatal asthma attacks
Acute severe asthma
Any one of the following
Peak expiratory flow 3350% best or predicted
Respiratory rate 25 per minute
Heart rate 110 per minute
Unable to complete sentences in one breath
Life-threatening asthma
Any one of the following in a patient with severe asthma
Peak expiratory flow < 33% best or predicted
SaO2 < 92%
Silent chest
Cyanosis
Poor respiratory effort
Bradycardia or other arrhythmia
Hypotension
Exhaustion
Confusion, altered consciousness or coma
PaO2 < 8 kPa
Normal PaCO2 (4.66.0 kPa)
Near-fatal asthma
Raised PaCO2 ( > 6.0 kPa) and/or patient requires mechanical
ventilation with raised inflation pressures

measurements may be useful, particularly in patients who are

already taking corticosteroids, 2-agonists or diuretics, because
hypokalaemia, hypomagnesaemia and hypophosphataemia may
be present and aggravate respiratory muscle function. Elevated
lactate levels are common, but reflect general tissue hypoxia and
are unhelpful prognostically. Chest radiography is not routinely
required, but should be undertaken in patients with suspected
pneumothorax, pneumomediastinum or pulmonary consolidation
or collapse, in life-threatening presentations, and in those who fail
to respond to treatment appropriately or require ventilation.

Management
Patients should be seen and treated immediately in a highdependency or resuscitation area of the A&E department or receiving unit. ECG, SaO2 and non-invasive blood pressure recordings are the minimum monitoring requirements.
Oxygen therapy hypoxaemia is almost invariably present in
patients with acute severe asthma. All patients should be given
oxygen at a high inspired concentration, using a mask that can
deliver an FiO2 of 4060%. The aim is to maintain SaO2 above 92%.
Nebulizers should be oxygen-driven whenever possible. Concerns
that hypercapnoea may be induced by high-flow oxygen, as may
occur in some patients with chronic obstructive pulmonary disease
(COPD), are unfounded. Hypercapnoea in the context of acute
severe asthma indicates a near-fatal event and mandates immediate involvement of senior specialist/anaesthetic staff.
2-agonists are first-line agents and should be given immediately. Salbutamol, 5 mg, and terbutaline, 10 mg, are equally ef-

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CHRONIC OBSTRUCTIVE PULMONARY DISEASE

required, because both 2-agonists and corticosteroid therapy can

cause or exacerbate hypokalaemia.
Senior/ICU assistance should be sought immediately in every
patient with features of life-threatening asthma (Figure 2). Tracheal
intubation is clearly required in patients with cardiac arrest, apnoea
or loss of consciousness. Otherwise, the decision to intubate and
institute positive-pressure ventilation in an asthmatic patient
requires senior specialist expertise.
While preparations are being made for emergency intubation,
the patient should be given 100% oxygen by an anaesthetic mask.
Data on the optimal induction agent are limited, but ketamine (a
parenteral anaesthetic agent) and inhalational anaesthetics (e.g.
isoflurane, halothane, ether) have been used and have bronchodilating properties. Their use requires specialist expertise, because
they have vasodilating and myocardial depressant actions and
may sensitize the myocardium to catecholamines. The potential
for induction of life-threatening arrhythmias and/or hypotension
is high.
Following intubation, use of a benzodiazapine is indicated to
ensure sedation, with neuromuscular blockade to improve pulmonary compliance and aid ventilation. A ventilation strategy of
controlled hypoventilation (permissive hypercapnoea) with high
FiO2 is commonly used. Often, only a short period of ventilation and ICU care is required, because most patients respond
rapidly to these and previously started treatments. However,
positive-pressure ventilation in patients with asthma has specific
problems including hypotension, barotrauma (pneumothorax
and pneumomediastinum) and nosocomial infection. The most
common cause of severe hypotension in a ventilated asthmatic
patient is auto-positive end-expiratory pressure secondary to air
trapping. This can be corrected by stopping ventilation for a brief
period (< 60 seconds) while observing the patients oxygen
status, then restarting at a ventilation rate of 810 per minute.
Discharge and follow-up before discharge, check that the
patients inhaler technique is adequate, that all medications (inhalers, corticosteroid, antibiotics) have been altered appropriately,
and that he or she has and understands a PEF record chart and
symptom-based asthma plan. The GP must be informed directly
whenever a patient with asthma has needed A&E or hospital treatment following an exacerbation. The patient should be reviewed
by an asthma liaison nurse or GP within 48 hours of discharge,
and in a specialist hospital clinic after about 1 month.

COPD: causes and pathology

William MacNee

Chronic obstructive pulmonary disease (COPD) is a general term

encompassing several previously used clinical labels such as
chronic bronchitis and emphysema, chronic obstructive airways
disease and chronic obstructive lung disease. COPD is defined
by the Global Initiative for Obstructive Lung Disease (GOLD) as
a disease state characterised by airflow limitation that is not fully
reversible. The airflow limitation is usually both progressive and
associated with an abnormal inflammatory response of the lungs
to noxious particles or gases.
Few population-based prevalence surveys of COPD have
been published. Data based on physician diagnosis from the UK
General Practice Research Database indicate a prevalence in 1997
of 1.7% in men and 1.4% in women. The prevalence of COPD in
men reached a plateau in the mid-1990s, but continues to increase
in women. In the UK, about 30,000 deaths/year are caused by
COPD; this accounts for about 6% of all male and 4% of all
female deaths. The annual NHS workload for COPD exceeds that
of asthma. About 25% of all medical admissions are as a result
of respiratory diseases, and more than 50% of these are cases of
COPD. In general practice, annual consultation rates for COPD
increase with age from 417/10,000 population in 4564-year-olds
to 1032/10,000 population in 7584-year-olds.

Risk factors
Exposure to tobacco smoke cigarette smoking is the most
important risk factor for COPD. In general, the greater the exposure
to tobacco, the greater the risk, though there is wide variation in
susceptibility (Figure 1). The commonly cited statement that only
1020% of smokers appear to be susceptible and develop clinically
significant COPD is probably an underestimate, because COPD is
under-diagnosed.
Passive exposure to cigarette smoke may also contribute to
respiratory symptoms and to COPD. Smoking during pregnancy
may increase the risk of COPD by affecting fetal lung growth.
Recurrent bronchopulmonary infections the British hypothesis suggests that persistent airflow obstruction may be the end
result of damage caused by repeated bronchopulmonary infections.
A history of severe childhood infections has been associated with
reduced lung function and increased respiratory symptoms in

FURTHER READING
British Thoracic Society, Scottish Intercollegiate Guidelines Network.
British guideline on asthma management: a national clinical
guideline. Thorax 2003; 58: (Suppl. 1): i194.
(Essential reading for all clinicians involved in the care of asthma
patients.)
Cates C J, Rowe B H, Bara A. Holding chambers vs nebulisers for
beta-agonist treatment of acute severe asthma. The Cochrane Library
2001; 3.
Parameswaran K, Belda J, Rowe B H. Addition of intravenous
aminophylline to beta2 agonists in adults with acute asthma.
The Cochrane Library 2001; 3.
Rowe B H, Bretzlaff J A, Bourdon C et al. Magnesium sulphate for treating
exacerbations of acute asthma in the emergency department.
The Cochrane Library 2001; 2.

MEDICINE

William MacNee is Professor of Respiratory and Environmental Medicine

at the University of Edinburgh Medical School, Edinburgh, UK,
Consultant Physician and Patient Services Director in Lothian University
NHS Trust, an MRC Research Fellow in Edinburgh, and MRC Travelling
Fellow to the University of British Columbia, Vancouver, Canada.

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