Acute severe asthma in adults
of asthma symptoms has increased markedly over the last 30 years. The morbidity from poorly controlled disease is considerable. In the UK and Republic of Ireland, there are more than 75,000 asthma-related hospital admissions each year.1 Although mortality from asthma in the UK has been on a steady decline over the last 10 years, there are still more than 1,300 deaths reported each year. Severe disease, inappropriate medical management and adverse behavioural and psychological factors have all been implicated in fatal attacks of asthma. These are illustrated in Table 1. National2 and international3 guidelines have been developed to increase awareness of the risk factors for fatal asthma, standardize medical management and to prevent unnecessary exacerbations of asthma.
Georgina Braganza Neil C Thomson
Abstract Approximately 300 million people suffer from asthma worldwide. Asthma exacerbations account for 75,000 hospital admissions in the UK and Republic of Ireland. Asthma still accounts for in excess of 1,300 UK deaths. Risk factors for fatal asthma include poorly controlled disease, inappropriate medical management and adverse behavioural and social factors. Asthma is a chronic inflammatory condition of the airways which causes symptoms of periodic wheeze, cough and breathlessness. A variety of triggers have been identified which can cause exacerbations; these include respiratory tract infections, mainly viral, and other environmental factors. Exacerbations are identified by an increase in asthma symptoms and fall in lung function. Such features should prompt escalation of asthma treatment to prevent severe asthma attacks. All patients presenting with poorly controlled asthma symptoms should be examined and have peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) recorded. Patients with a PEF of less than 50% of baseline or predicted should be regarded as having a severe exacerbation and be referred to hospital; they require treatment with systemic corticosteroids and inhaled bronchodilators. There should be a lower threshold for admission for asthmatics who have risk factors for fatal asthma attacks. Patients who have features of a life-threatening or near-fatal attack should be discussed with a senior physician and/or intensive care immediately. Prior to discharge, patients should have a medication review and personal asthma management plan agreed. There should be early follow-up arranged and immediate written information faxed to the GP.
Pathophysiology of exacerbations Asthma is a chronic inflammatory condition affecting the airways, causing hyperresponsiveness and reversible airflow limitation, resulting in symptoms of wheeze, cough, breathlessness and chest tightness. Airway inflammation and acute bronchospasm can be induced by a variety of triggers in susceptible individuals. Respiratory tract infections, particularly viral, are the most common cause of acute attacks of asthma, but other triggers include allergens, air pollutants, exercise, foods, drugs, emotions, gastro-oesophogeal reflux, menstruation and pregnancy. When these symptoms are sustained and there is an associated fall in lung function, peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) below 20% of the baseline, this is termed an exacerbation. Such features necessitate an escalation of asthma treatment in order to prevent a severe or life-threatening attack.
Initial assessment of patients The initial assessment and management of patients with acute severe asthma is summarized in Figure 1.
Keywords acute asthma; anticholinergics; β2-agonists; corticosteroids; exacerbation; oxygen; self-management plans
Clinical features of severe asthma Severe asthma is characterized by one or more of: Previous near-fatal asthma Previous admission for asthma or A&E attendances (esp. last year) Asthma requiring three of more classes of medication Heavy use of β2-agonist Brittle asthma (either with wide PEF variability, or severe attacks on the background of well-controlled asthma) Adverse behavioural and psychological features, including: • Non-compliance/failure to attend appointments/selfdischarges • Psychiatric illnesses/learning difficulties • Alcohol and drug use • Social isolation • Obesity
Burden of disease Asthma is one of the commonest chronic conditions, with an estimated 300 million people affected worldwide. The prevalence
Georgina Braganza MBChB MRCP is a Clinical Research Fellow at the Asthma/COPD Clinical Research Centre, University of Glasgow, UK. She qualified at the University of Edinburgh. Competing interests: none declared. 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.
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Assessment and management of acute severe asthma
Acute severe asthma
• PEF: 33–50% best/predicted • Unable to complete sentences • Respirations > 25 breaths/min • Pulse > 110 beats/min
• PEF < 33% best/predicted • SpO 2 < 92% • Silent chest/cyanosis/ poor respiratory effort • Exhaustion/confusion/coma • Arterial blood gas: High H+ PaO2 < 8 Kpa Normal PaCO 2
• Raised PaCO 2
If features of life-threatening/near-fatal asthma, contact anaesthetist/refer: ITU early
Immediate treatment • Oxygen: maintain SaO 2 > 92% • Nebulized bronchodilators: salbutamol 5 mg + nebulized ipratropium bromide 0.5 mg via oxygen-driven nebulizer, routinely continued 4–6 hourly • Corticosteroids: Prednisolone 50 mg daily for at least 5 days or until recovery or i.v. hydrocortisone 100 mg 6 hourly if oral route not possible
If patient not improving within 15–30 minutes or life-threatening features: • Discuss with senior clinician • Nebulized salbutamol + ipratropium bromide every 15 min; consider continuous salbutamol: 10 mg hourly (sidestream nebulizer) • Add intravenous magnesium: 1.2–2 g infusion over 20 min • Other treatments: Consider intravenous salbutamol or aminophylline • Consider referral to ITU: for invasive monitoring ± ventilation
Monitoring/Investigations • Oximetry: maintain SpO 2 > 92% • Repeat gases if: Initial PaO 2 < 8 KPa unless SpO 2 > 92% or PCO2 normal or raised • PEF • Chest X-ray • Electrolytes – particularly K+
Discharge planning/follow-up • Check inhaler technique and assess adherence with therapy • Review asthma maintenance treatment • Smoking cessation advice if appropriate • Stop nebulized therapy 24 hours before discharge • Written asthma action plan • Respiratory clinic follow-up in 4 weeks PEF, peak expiratory flow; ITU, intensive therapy unit
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home or primary care setting, administer repeated doses via a metered-dose inhaler and spacer if a nebulizer is not available. If necessary, repeat bolus doses of β2-agonist or use a sidestream nebulizer to administer a continuous dose of salbutamol at 10 mg per hour.
History A brief history is required; it should include duration and severity of symptoms, particularly nocturnal symptoms, limitation of activities and need for bronchodilator treatment. It is also important to illicit previous asthma history, particularly hospital admissions and previous requirement for ventilation, which are important risk factors for a life-threatening attack. Patient’s current medication regime should be recorded along with an estimation of their usual bronchodilator use and the current response to this treatment. If possible, identify any environmental triggers for the attack.
Nebulized anticholinergics Nebulized ipratropium bromide (0.5 mg), when used in combination with nebulized β2-agonists, provides additional benefit in improving PEF.4 This dose can be repeated every 15 minutes. If a nebulizer is not available, administer four doses via metereddose inhaler and spacer every hour.
Examination A physical examination should be done to objectively measure severity and to identify other diagnoses and complicating illnesses, such as pneumonia, pneumothorax or pneumomediastinum. Features such as respiratory rate of more than 25 breaths per minute and heart rate of 110 beats per minute indicate a more severe attack. In later presentations or in very severe attacks the chest may be silent to auscultation, the patient may exhibit slow gasping respirations and bradycardia. The patient may become exhausted and confused.
Systemic corticosteroids Systemic corticosteroids reduce mortality and relapse rates in severe exacerbations. In patients who are able to swallow, an initial dose of 40–50 mg prednisolone should be given and should be continued for at least 5 days or until the patient has recovered. If the patient is unable to take oral treatment, substitute with hydrocortisone intravenously (100 mg) every 6 hours. There is no additional benefit of intravenous over oral treatment. Magnesium sulphate Studies have shown that a single dose of magnesium sulphate (1.2–2 g), given intravenously over twenty minutes, can be beneficial in life-threatening and near-fatal asthma when used as an adjunct to the above treatments.
Functional assessments and investigations Lung function testing should be performed in all patients presenting with an acute exacerbation. Although FEV1 may provide a more accurate assessment, a peak flow meter is often more accessible and easily administered in the accident and emergency department. A PEF less than 50% of the patient’s normal best 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 saturation and pulse oximetry should be measured and SpO2 should be maintained above 92%. In any patient with features of a severe exacerbation (PEF 50% or below) or who fail to respond to initial treatment, an arterial blood gas measurement should be performed. A partial pressure of arterial carbon dioxide (PaCO2) within the normal range or low partial pressure of arterial oxygen (PaO2) denote a life-threatening attack. A chest X-ray should be performed in any patient where there is a suspected pneumothorax, pneumomediastinum or consolidation, and in patients with life-threatening asthma.
Intravenous aminophylline/salbutamol In the past, intravenous aminophylline and salbutamol have been used to treat severe asthma exacerbations; however, there is probably no additional bronchodilational effect over inhaled β2-agonists and anticholinergics. Their use is also associated with potential adverse effects such as arrhythmias and gastrointestinal upset. In refractory exacerbations, a subgroup of patients may benefit from use of intravenous aminophylline. Current recommendations state that senior medical staff should be consulted before initiating this treatment. Other treatments Heliox is a mixture of helium and oxygen. Routine use of heliox in the treatment of patients with acute asthma is not recommended.5 However, it may be useful in a small group who have refractory asthma and severe airways obstruction. Leukotriene antagonists – pilot studies suggest some benefit from intravenous montelukast in acute asthma6 but at present there is insufficient evidence to justify their use. Antibiotics should not be prescribed unless there are radiological changes suggestive of concurrent pneumonia or confirmed bacterial infection through culture of sputum. Sedatives – there is no indication for sedative medication in acute exacerbations of asthma and their use is associated with an increase in fatality.
Treatment Following a brief initial assessment, including PEF, all patients with features of a severe attack should be given the following. Oxygen therapy Hypoxaemia is an important cause of death in severe exacerbations and therefore it is important to administer enough supplementary oxygen to maintain oxygen saturations above 92%. High-flow oxygen (40–60%) should initially be given to all patients with acute severe asthma. Nebulized β2-agonists Nebulized salbutamol (5 mg) is most commonly given, but terbutaline (10 mg) is equally efficacious. Either drug should ideally be administered via an oxygen-driven nebulizer. In the
Monitoring Patients should have continuous monitoring of heart rate, respiration rate and pulse oximetry until stabilized. PEF should be 211
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measured before commencing treatment and repeated 15–30 minutes after initiating treatment. If the patient is admitted, their PEF should be measured four times a day, before and after treatment. Arterial blood gas measurements should be repeated at two hours if initial PaO2 is less than 8 kPa, unless arterial oxygen saturation (SaO2) is maintained above 92% or PaCO2 is normal or raised, or if the patient’s condition deteriorates. Monitor serum electrolytes and glucose levels. Hypokalaemia, hypomagnesaemia and hypophosphataemia may exacerbate respiratory muscle dysfunction.
technique should be reviewed. A peak flow meter and diary should be issued with instructions and an asthma action (selfmanagement) plan should be agreed. If appropriate, give advice regarding smoking cessation and allergen avoidance. Discharge should be planned 24 hours in advance and bronchodilators changed to a hand-held device at least 24 hours prior to discharge. The timing of discharge is usually when the PEF is greater than 75% personal best or predicted and diurnal variation is less than 25%. It is vital that written information on the acute attack is faxed to the primary care practice within 24 hours of discharge. Patients should have follow-up arranged by the GP or asthma nurse within two working days and in a respiratory clinic around four weeks after discharge. ◆
Criteria for referral to intensive therapy unit/ventilation Clear indications for intubation and positive pressure ventilation are: • loss of consciousness • apnoea • cardiac arrest. Senior/specialist advice should be sought with any patients exhibiting life-threatening features, especially failure to maintain arterial PaO2 >8 kPa despite the fraction of inspired oxygen (FiO2) being 60%, rising PaCO2, exhaustion, and confusion. Although non-invasive ventilation has been used successfully in some studies of asthmatics with hypercapnic respiratory failure, its routine use is not currently recommended.
References 1 Global Initiative for Asthma (GINA). Global burden of asthma. 2004 Available at: http://www.ginasthma.com/ReportItem. asp?l1=2&l2=2&intId=94 (accessed January 2008). 2 British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on management of asthma. Revised edition, July 2007. Available at: http://www.brit-thoracic.org.uk/c2/uploads/ asthma_fullguideline2007.pdf (accessed January 2008). 3 Global Initiative for Asthma (GINA). Strategy for asthma management and prevention. 2006. Available at: http://www.ginasthma.com/ Guidelineitem.asp?l1=2&l2=1&intId=60 (accessed January 2008). 4 Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax 2005; 60: 740–46. 5 Rodrigo G, Pollack C, Rodrigo C, Rowe BH. Heliox for nonintubated acute asthma patients. Cochrane Database Syst Rev 2006; (4): CD002884. 6 Camergo CA, Howard A, Smithline H, Malice MP, Green SA, Reiss TF. A randomised controlled trial of intravenous montelukast in acute asthma. Am J Respir Crit Care Med 2003; 167: 528–33.
Decision to refer to hospital or admit Patients with acute severe asthma should be referred to hospital and those with life-threatening or near-fatal asthma should all be admitted. If the PEF is greater than 75% of personal best or predicted value following one hour of initial treatment, then discharge from A&E can be considered. However, if presentation is in the evening, the patient is pregnant or has any of the risk factors for fatal asthma (see Table 1) there should be a lower threshold for admission.
Pre-discharge planning and follow-up During the admission, patients should be assessed for any precipitants of the attack and maintenance medications and inhaler
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