What’s 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
• 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 β2-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 β2-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, 4.6–6.0 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 patient’s 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.
© 2003 The Medicine Publishing Company Ltd
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 β2-agonist can be given by repeatedly activating a metered-dose inhaler via an appropriate large-volume spacer. When the initial dose of the β2-agonist does not achieve a good result, repeat bolus nebulized doses or continuous nebulization (at a dose of 5–10 mg/hour) should be given. Intravenous administration of a β2-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 β2-agonist in patients suffering an acute severe or life-threatening event, and in those who exhibit a poor initial response to β2-agonist therapy alone. Further nebulized doses of ipratropium bromide, 0.5 mg, can be given 4–6-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, 40–50 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, 40–50 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 1.2–2 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 β2-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 60–80% helium and 20–40% 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 33–50% 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 (4.6–6.0 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, β2-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 40–60%. 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. β2-agonists are first-line agents and should be given immediately. Salbutamol, 5 mg, and terbutaline, 10 mg, are equally ef-
© 2003 The Medicine Publishing Company Ltd
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
required, because both β2-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 patient’s oxygen status, then restarting at a ventilation rate of 8–10 per minute. Discharge and follow-up – before discharge, check that the patient’s 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 45–64-year-olds to 1032/10,000 population in 75–84-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 10–20% 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): i1–94. (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.
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.
© 2003 The Medicine Publishing Company Ltd