Acute severe asthma in adults
What’s new? C
Hannah K Bayes C
Neil C Thomson C
Acute severe asthma represents a common medical emergency accounting for over 75,000 UK hospital admissions each year and asthma still accounts for approximately 1500 UK deaths annually. Risk factors for fatal asthma include poorly controlled disease, inappropriate medical management, and adverse behavioural and social factors. Asthma is characterized by chronic airways inflammation, resulting in periodic wheeze, cough and breathlessness. A variety of triggers can precipitate an exacerbation; viral respiratory tract infections are the most common. Exacerbations are identified by an increase in asthma symptoms and fall in lung function. National and international acute asthma management guidelines highlight best practice. All patients presenting with poorly controlled asthma symptoms should be examined and peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) recorded. Patients with a PEF less than 50% of baseline/predicted have a severe exacerbation and should be referred to hospital. Treatment aims to rapidly relieve bronchoconstriction and halt airways inflammation; oxygen, systemic corticosteroids and inhaled bronchodilators represent first-line treatments. Patients with features of life-threatening asthma should receive magnesium sulphate and be discussed with intensive care. Prior to discharge, patients’ medications should be reviewed, asthma self-management plan agreed and early follow-up should be arranged.
worldwide deaths are estimated at 250,000.1 Fatal exacerbations occur more commonly in the context of adverse behavioural and social factors, inappropriate medical management and severe background disease (Table 1). International1 and national2 acute asthma guidelines have been developed, aiming to translate research advances into clinical practice, standardize acute asthma care and improve asthma morbidity and mortality.
Initial assessment of patients The assessment and management of patients with acute severe asthma is summarized in Figure 1. Treatment intensity is tailored to exacerbation severity and objective assessment is paramount. History and examination A brief history is required (Table 2). The physical examination should assess exacerbation severity and identify other diagnoses or complicating illnesses, such as pneumonia, pneumothorax or pneumomediastinum. This will include the patient’s ability to complete a sentence, pulse rate, respiratory rate and accessory
Keywords Acute asthma; anti-cholinergics; b2-agonists; corticosteroids; exacerbation; oxygen; self-management plans
Factors associated with near-fatal or fatal asthma exacerbations
Burden of disease Acute severe asthma represents a common medical emergency, accounting for over 75,000 emergency hospital admissions each year in the UK. Although mortality from asthma has been steadily declining over the last decade, there are still approximately 1500 deaths reported each year in the UK and annual
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Hannah K Bayes MBChB BMedSci MRCP is a Respiratory Clinical Research Fellow at the Institute of Immunology, Infection and Inflammation, University of Glasgow, UK. Competing interests: none declared.
Previous near-fatal asthma Previous admission for asthma or emergency department attendances, especially in the previous 12 months Asthma requiring three or more classes of medication Heavy use of b2-agonist Brittle asthma (either with wide peak expiratory flow variability, or severe attacks on the background of well-controlled asthma)
Adverse behavioural or psychological features, including: Non-adherence/failure to attend appointments/self-discharges/ frequent home visits C Alcohol and drug misuse C Psychiatric illness/learning difficulties C Social isolation C Financial, domestic or employment problems C Obesity C
Neil C Thomson MBChB MD FRCP is Professor of Respiratory Medicine at the University of Glasgow and Honorary Consultant, Gartnavel General Hospital, Glasgow, UK. He qualified from the University of Glasgow and trained in Glasgow and McMaster University, Canada. His research interests include the study of mechanisms and treatment of asthma. Competing interests: none declared.
Supplementary oxygen should maintain oxygen saturations at 94e98%, in line with recent emergency oxygen guidelines3 Arterial blood gas measurement is required in any patient with an SpO2 less than 92% (whether breathing air or oxygen) or with other features of life-threatening asthma In hospital, ambulance and primary care, nebulized b2-agonist bronchodilators should preferably be driven by oxygen Leukotriene antagonists represent a promising treatment for which further research is required
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Assessment and management of acute severe asthma Assess severity
Acute severe asthma •PEF 33–50% best/predicted •respiratory rate > 25/min •pulse > 110 beats/min •Unable to complete sentences
Life-threatening asthma • PEF < 33% predicted/best • SpO2 < 92% • Silent chest/cyanosis/ poor respiratory effort • Exhaustion/altered conscious level • Hypotension/arrhythmia • Arterial blood gases: •PaO2 < 8kPa •Normal PaCO2 • High H+
Near-fatal asthma •Raised PaO2
Consider if additional risk factors for fatal asthma
If features of life-threatening/near-fatal asthma, contact intensive care early
Immediate treatment: • Oxygen: maintain SpO2 at 94–98% • Nebulized bronchodilators: salbutamol 5mg + ipatropium bromide 0.5mg via oxygen-driven nebulizer, routinely continued 4 6 hourly •Corticosteroids: Prednisolone 40 50 mg once daily for at least 5 days or until recovery. If oral route not possible, hydrocortisone 100 mg 6-hourly. If patient not improving within 15–30 minutes or life-threatening features: • Discuss with senior clinician • Nebulized salbutamol+ ipatropium bromide repeated after 15 mins; consider continuous salbutamol 10mg/hour (via appropriate nebulizer) • Intravenous magnesium sulphate: single infusion of 1.2–2g over 20 min • Other treatments: Consider intravenous salbutamol or aminophylline • Consider referral to intensive care: for invasive monitoring +/- ventilation
Monitoring/investigations: • Oximetry: maintain SpO2 at 94–98% • Repeat blood gases (within 1-hour) if: initial PaO2 < 8kPa unless SpO2 > 92%, or PaO2 normal/raised, or patient’s condition deteriorating •PEF • Chest X-ray • Electrolytes: especially K+
Discharge planning/follow-up: •Check inhaler technique •Review asthma maintenance therapy •PEF meter and diary •Smoking cessation and allergen avoidance • Stop nebulizer therapy 24-hours before discharge • Written asthma action plan • GP/asthma nurse and Respiratory clinic follow-up organized PEF: peak expiratory flow; SpO2: oxygen saturation measured by pulse oximetry; PaO2: partial pressure of oxygen in arterial blood; PaCO2: partial pressure of carbon dioxide in arterial blood
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awareness of conditions that may be misinterpreted as acute asthma (Table 3).
Assessment of a patient with an acute asthma exacerbation
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Duration and severity of symptoms Previous asthma history, particularly previous hospital admissions and requirements for ventilation which are important risk factors for a life-threatening attack Whether regular asthma control is adequate, including nocturnal wakening, limitations of activities and use of bronchodilators Current medication regimen Any new medications (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) or b-blockers) Concordance with treatment Identify any environmental triggers
Following a brief initial assessment, all patients with features of a severe exacerbation should be given the following. Oxygen therapy Hypoxaemia is an important cause of death in severe exacerbations. High-flow oxygen (40e60%) should be given initially to all patients with acute severe asthma and supplementary oxygen continued to maintain oxygen saturations at 94e98%.3 Nebulized b2-agonists Repeated administration of an inhaled, short-acting b2-agonist (salbutamol 5 mg or terbutaline 10 mg via oxygen-driven nebulizer) is the first-line therapy used to rapidly reverse bronchoconstriction. If initial response is poor, continuous nebulization (5e10 mg/hour via an appropriate nebulizer) may be more effective.4 Administering repeated doses via a metered-dose inhaler and spacer is equally effective as nebulization and can be useful in the home or primary care setting.5
Infection Exercise Foods Occupational exposures Drugs (e.g. NSAIDs) Gastrooesophageal reflux Menstruation and pregnancy Smoking status
Nebulized anticholinergics Anticholinergics (nebulized ipratropium bromide 0.5 mg), in combination with b2-agonists, produce greater improvements in PEF.6 Ipratropium should be added during more severe attacks or when response to initial b2-agonist therapy is poor.
muscle use. Asymmetric breath sounds should prompt consideration of additional pathology, particularly a pneumothorax. In delayed presentations or life-threatening attacks, the patient can become exhausted and confused, with poor respiratory effort and bradycardia, and the chest becomes silent to auscultation.
Systemic corticosteroids Systemic corticosteroids are recommended in all asthma exacerbations with the aim of suppressing airways inflammation. Early use reduces mortality, requirement for hospital admission and relapses.7,8 An initial dose of prednisolone (40e50 mg) should be given and continued for at least 5 days or until recovery. It can take up to 4 hours after administration before clinical improvements are observed and there is no additional benefit of intravenous over oral administration. If the patient is unable to take oral treatment, hydrocortisone intravenously (100 mg 6-hourly) can be used. Patients’ regular inhaled corticosteroids should not be discontinued during a course of systemic corticosteroids.
Functional assessments and investigations Lung function testing should be undertaken early in all patients presenting with an exacerbation. Although forced expiratory volume in 1 second (FEV1) is more accurate, peak expiratory flow (PEF) is more convenient in the acute setting. A PEF less than 50% of the patient’s normal best value is the most important predictor of a severe exacerbation. If the patient’s baseline is not known, PEF should be compared with predicted values. Oxygen saturations (SpO2) should be measured via pulse oximetry and maintained at 94e98%.3 Arterial blood gas measurement is required in any patient who has an SpO2 less than 92% (whether breathing air or oxygen) or other features of life-threatening asthma. As most asthma exacerbations are associated with an increased respiratory drive causing hypocapnia and respiratory alkalosis, the finding of a normal or raised partial pressure of carbon dioxide (PaCO2) indicates severe airway obstruction and a life-threatening attack. A chest X-ray should be performed if pneumothorax, pneumomediastinum or consolidation is suspected, and in lifethreatening asthma.
Conditions that may mimic an acute asthma exacerbation C
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Differential diagnosis Given the potentially critical nature of an asthma exacerbation, it is almost always reasonable to treat suspected acute asthma as such. However, appropriate management of patients whose distress persists despite aggressive management also requires an
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Acute exacerbation of chronic obstructive pulmonary disease (COPD) Allergic bronchopulmonary aspergillosis (ABPA) Carcinoid syndrome Hyperventilation syndrome Inhaled foreign body Pulmonary oedema Upper airway obstruction (examination may identify stridor) Vocal cord dysfunction
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Criteria for referral to intensive care unit/mechanical ventilation
Magnesium sulphate Magnesium is thought to inhibit calcium influx into airway smooth muscle, thereby causing bronchodilation. Studies have shown that a single dose of magnesium sulphate (1.2e2 g intravenously over 20 minutes) confers a modest benefit in severe asthma not responding to initial bronchodilators and lifethreatening attacks.9 Repeated doses should not be administered, as hypermagnesaemia is associated with muscle weakness and respiratory failure.
Any patient exhibiting life-threatening features, whether present on admission and failing to improve quickly or developing despite adequate treatment, should be discussed with the critical care team. Clear indications for intubation and positive pressure ventilation are decreased consciousness, respiratory arrest, or worsening hypoxia/hypercapnia.
Decision to refer to hospital or admit Intravenous aminophylline/salbutamol Intravenous aminophylline and salbutamol probably confer no additional bronchodilation over inhaled bronchodilators and corticosteroids. There use is also associated with adverse effects such as arrhythmias and gastrointestinal upset. In refractory exacerbations, a subgroup of patients may benefit from intravenous aminophylline. Such patients are probably rare and treatment should be discussed with senior medical staff before initiating.
Patients with acute severe asthma should be referred to hospital and those with life-threatening or near-fatal asthma should all be admitted. Discharge from the emergency department can be considered in patients with a PEF greater than 75% best or predicted 1 hour after initial treatment. However, if the patient presents at night, lives alone, is pregnant, was taking an adequate dose of oral corticosteroids pre-presentation or has any risk factors for fatal asthma (Table 1), there should be a lower threshold for admission.
Pre-discharge planning, education and follow-up
Other treatments Antibiotics should not be routinely prescribed in acute asthma as infective triggers are predominantly viral in aetiology.
The following measures should be undertaken during admission: assessment for precipitants of attack maintenance medications and inhaler technique reviewed PEF meter and diary provided asthma action (self-management) plan agreed smoking cessation and allergen avoidance advice given. Discharge should be planned 24 hours in advance and bronchodilators changed to a hand-held device. Criteria for hospital discharge are subjective, but usually require that PEF is greater than 75% of best or predicted and diurnal variability is less than 25%. Written information on the patient’s admission should be faxed to the primary care practice within 24 hours of discharge. Follow-up should be arranged with the GP or asthma nurse within two working days and in a respiratory clinic approximately 4 weeks after discharge.
Heliox is a mixture of helium and oxygen, which produces less airway resistance than air. Based on limited small studies, there is currently insufficient evidence to support heliox as a treatment for severe asthma exacerbations.10 Leukotriene antagonists block the actions of cysteinyl leukotrienes on the leukotriene receptor CysLT1 within the airways, reducing bronchoconstriction and inflammation. Studies of intravenous11 and oral montelukast12 in acute asthma have shown promise, but there is currently insufficient evidence to recommend their use. Non-invasive ventilation has been used successfully in studies of asthmatics with hypercapnic respiratory failure,13 but its routine use is not presently recommended and it should be considered only in an intensive care setting.
Acute exacerbations in pregnancy Exacerbations affect 11e18% of pregnant asthmatics and are more common in women with severe, poorly controlled asthma, occurring most frequently in the late second trimester. As severe acute asthma in pregnancy poses a greater risk to the fetus than do the adverse effects of asthma therapies, the exacerbation should be treated as per standard management for adult asthmatics. Pregnant women should not be denied systemic corticosteroids. Maternal oxygen saturations should be maintained at 94e98% and continuous fetal monitoring is recommended in severe exacerbations. A
Sedatives should be strictly avoided during exacerbations due to respiratory depressant effects.
Monitoring Patients should have continuous monitoring of heart rate, respiratory rate and pulse oximetry until stabilized. Before commencing treatment PEF should be measured and repeated 15e30 minutes after initiating treatment. Throughout the hospital admission PEF should be recorded four times a day, before and after bronchodilator treatment. Arterial blood gas measurements should be repeated within 1 hour of commencing treatment if initial PaO2 is less than 8 kPa unless SpO2 is maintained above 92%, PaCO2 is normal or raised, or the patient’s condition is deteriorating. Serum electrolytes and glucose concentrations should be monitored. Hypokalaemia and hyperglycaemia can result from use of b2-agonists and corticosteroids.
REFERENCES 1 Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (updated 2010). Available from: http:// www.ginasthma.com (accessed August 2011). 2 British Thoracic Society/Scottish Intercollegiate Guidelines Network. Guideline on the management of asthma (updated 2011). Available from: http://www.brit-thoracic.org.uk/guidelines/asthma-guidelines. aspx (accessed August 2011).
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3 O’Driscoll BR, Howard LS, Davison AG, Soc BT. BTS guideline for emergency oxygen use in adult patients. Thorax 2009 Jan; 64 (vol. 63, suppl 6, pg vi1, 2008). 4 Camargo Jr CA, Spooner CH, Rowe BH. Continuous versus intermittent beta-agonists in the treatment of acute asthma. Cochrane Database Syst Rev 2003. Issue 4 Art. No.: CD001115. 5 Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev 2006. Issue 2 Art. No.: CD000052. 6 Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax 2005 Sep; 60: 740e6. 7 Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev 2001. Issue 1 Art. No.: CD002178. 8 Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev 2007. Issue 3 Art. No.: CD000195. 9 Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo Jr CA. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev 2000. Issue 2 Art. No.: CD001490. 10 Rodrigo G, Pollack C, Rodrigo C, Rowe BH. Heliox for nonintubated acute asthma patients. Cochrane Database Syst Rev 2006. Issue 4 Art. No.: CD002884.
11 Camargo Jr CA, Gurner DM, Smithline HA, et al. A randomized placebocontrolled study of intravenous montelukast for the treatment of acute asthma. J Allergy Clin Immunol 2010 Feb; 125: 374e80. 12 Ramsay CF, Pearson D, Mildenhall S, Wilson AM. Oral montelukast in acute asthma exacerbations: a randomised, double-blind, placebocontrolled trial. Thorax 2011 Jan; 66: 7e11. 13 Soroksky A, Stav D, Shpirer I. A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway pressure in acute asthmatic attack. Chest 2003 Apr; 123: 1018e25.
Practice points C C
Acute asthma exacerbations are potentially life threatening Aggressiveness of treatment should be guided by objective assessment of the attack severity A lower threshold for admission should exist for asthmatics with risk factors for fatal asthma Patients with life-threatening attacks or who fail to improve with initial treatment should be referred early to intensive care Exacerbations during pregnancy should be treated aggressively in the same manner as non-pregnant individuals Agree an asthma action plan before discharge
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