Acute severe asthma in adults

Acute severe asthma in adults

ADULT ASTHMA Acute severe asthma in adults Key points Hannah K Bayes C Acute asthma exacerbations are potentially life threatening C Aggressive...

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ADULT ASTHMA

Acute severe asthma in adults

Key points

Hannah K Bayes

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Acute asthma exacerbations are potentially life threatening

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Aggressiveness of treatment should be guided by objective assessment of attack severity

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A lower threshold for admission should exist for patients with risk factors for fatal asthma

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Patients with life-threatening attacks or who fail to improve with initial treatment should be referred early to intensive care

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Exacerbations during pregnancy should be treated aggressively in the same manner as in non-pregnant individuals

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Agree a personalized asthma action plan before discharge

Neil C Thomson

Abstract Acute severe asthma represents a common medical emergency accounting for >65,000 UK hospital admissions each year, and asthma still accounts for approximately 1200 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 airway inflammation, resulting in periodic wheeze, cough and breathlessness. A variety of triggers can cause exacerbations, most commonly viral respiratory tract infections. 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 recorded. Patients with PEF <50% of baseline or predicted have a severe exacerbation and should be referred to hospital. Treatment aims to rapidly relieve bronchoconstriction and halt airway inflammation; oxygen, systemic corticosteroids and inhaled bronchodilators are first-line treatments. Patients with features of life-threatening asthma should be given magnesium sulphate and discussed with the intensive care team. Before discharge, medications should be reviewed, a personalized action plan agreed and early follow-up arranged.

background disease; potentially preventable factors were identified in >60% of deaths (Table 1). International1 and national3 acute asthma guidelines aim 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). Physical examination should assess exacerbation severity and identify other diagnoses or complicating illnesses, such as pneumonia, pneumothorax or pneumomediastinum. This should include ability to complete a sentence, pulse rate, respiratory rate and accessory muscle use. Asymmetrical breath sounds should prompt consideration of additional pathology, particularly 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.

Keywords Acute asthma; anticholinergics; b2-adrenoreceptor agonists; corticosteroids; exacerbation; oxygen; self-management plans

Burden of disease Acute severe asthma represents a common medical emergency, accounting for more than 65,000 UK emergency hospital admissions a year. Although mortality from asthma has steadily declined, approximately 1200 deaths are still reported yearly in the UK, and annual worldwide deaths are estimated at 250,000.1 The first UK-wide investigation into asthma deaths in 20142 highlighted that fatal exacerbations frequently occurred in the context of inappropriate medical management, adverse behavioural and social factors, and severe or poorly controlled

Functional assessments and investigations Lung function testing should be undertaken early in patients presenting with an exacerbation. Although forced expiratory volume in 1 second (FEV1) is more accurate, peak expiratory flow (PEF) is more convenient in acute settings. PEF <50% of the patient’s normal best value is the most important predictor of a severe exacerbation. If the patient’s baseline is unknown, PEF should be compared with predicted values. Oxygen saturation (SpO2) should be measured by pulse oximetry and maintained at 94e98. Arterial blood gas measurement is required with SpO2 <92% (whether breathing air or oxygen) or other features of life-threatening asthma. As most exacerbations are associated with increased respiratory drive causing hypocapnia and respiratory alkalosis, normal or raised partial pressure of carbon dioxide (PaCO2) indicates severe airway obstruction and a life-threatening attack. Chest X-ray should be performed if pneumothorax, pneumomediastinum or consolidation is suspected, there is failure to respond appropriately to treatment, or asthma is life-threatening.

Hannah K Bayes MBChB(Hon) PhD MRCP is a Respiratory Clinical Lecturer at the Institute of Immunology, Infection and Inflammation, University of Glasgow, UK. Her research interests include chronic respiratory infections and respiratory immunology. Competing interests: none declared. Neil C Thomson MBChB MD FRCP is Emeritus Professor of Respiratory Medicine at the Institute of Immunology, Infection and Inflammation, University of 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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Ó 2016 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Bayes HK, Thomson NC, Acute severe asthma in adults, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.02.012

ADULT ASTHMA

attacks or when the response to initial b2-adrenoreceptor agonist therapy is poor.

Factors associated with near-fatal or fatal asthma exacerbations2,3 C C

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Previous near-fatal asthma Previous admissions for asthma or emergency department attendances, especially in the previous 12 months Asthma requiring three or more classes of medication Heavy use of short-acting b2-adrenoreceptor agonist (‘reliever’) inhaler, e.g. >12 short-acting reliever inhalers in the previous 12 months Brittle asthma (with wide peak expiratory flow variability or severe attacks on a background of well-controlled asthma) Adverse behavioural or psychological features, including:  Non-adherence/failure to attend appointments, self-discharges or frequent home visits  Alcohol and drug misuse  Current cigarette smoking or exposure to second-hand smoke at home  Psychiatric illness  Learning difficulties  Social isolation  Financial, domestic or employment problems  Obesity

Systemic corticosteroids Systemic corticosteroids are recommended in all exacerbations and aim to suppress airway inflammation. Early use reduces mortality, hospital admissions and relapses. 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 for clinical improvement to occur. There is no additional benefit of intravenous over oral administration, but hydrocortisone intravenously (100 mg 6-hourly) can be used if reliable oral administration is not possible. Patients’ regular inhaled corticosteroids should not be discontinued during a course of systemic corticosteroids. Magnesium sulphate (MgSO4) Magnesium is thought to inhibit calcium influx into airway smooth muscle, causing bronchodilation. Studies have shown that a single dose of MgSO4 (1.2e2 g intravenously over 20 minutes) confers a modest benefit in severe asthma (PEF <50% best or predicted) not responding to initial bronchodilators, and lifethreatening attacks. The dose should not be repeated as hypermagnesaemia is associated with muscle weakness and respiratory failure. Nebulized MgSO4 is not beneficial in acute severe asthma.4

Table 1

Intravenous aminophylline and salbutamol Intravenous aminophylline and salbutamol probably confer no additional bronchodilation over inhaled bronchodilators and corticosteroids. Intravenous salbutamol, in addition to inhaled therapy, can have a role in ventilated patients and those in extremis. Intravenous aminophylline can confer benefit in a subgroup of patients with refractory exacerbations, but such patients are probably rare. As their use is also associated with adverse effects such as arrhythmias and gastrointestinal upset, they should be discussed with senior medical staff before initiating.

Differential diagnosis Given the potentially critical nature of an exacerbation, it is almost always reasonable to treat suspected acute asthma as such. Where the condition persists despite aggressive management, an awareness is needed of conditions that can be misinterpreted as acute asthma (Table 3).

Treatment After a brief initial assessment, all patients with features of a severe exacerbation should be given the following.

Other treatments Antibiotics should not be routinely prescribed in acute asthma as infective triggers are predominantly viral.

Oxygen therapy Hypoxaemia is an important cause of death in severe exacerbations. High-flow oxygen (40e60%) should be initially given to all patients with acute severe asthma and supplementary oxygen continued to maintain oxygen saturation at 94e98%.

Heliox is a mixture of helium and oxygen that produces less airway resistance than air. Based on limited small studies, there is currently insufficient evidence to support heliox as a treatment for severe exacerbations.

Nebulized b2-adrenoreceptor agonists Repeated administration of an inhaled, short-acting b2-adrenoreceptor agonist (salbutamol 5 mg or terbutaline 10 mg via oxygen-driven nebulizer) is first-line therapy to rapidly reverse bronchoconstriction. If the initial response is poor, continuous nebulization (salbutamol 5e10 mg/hour via an appropriate nebulizer) may be more effective. Administering repeated doses via a metered dose inhaler and spacer is as effective as nebulization and can be useful in the home or primary care setting.

Leukotriene antagonists block the actions of cysteinyl leukotrienes on the leukotriene receptor CysLT1 within the airways, reducing bronchoconstriction and inflammation. Their use in acute asthma has shown promise, but there is currently insufficient evidence to recommend them. Non-invasive ventilation has been used successfully in studies of hypercapnic respiratory failure in asthma, but routine use is not currently recommended. This is instead an indication for urgent anaesthetic input and endotracheal intubation.

Nebulized anticholinergics Adding anticholinergics (nebulized ipratropium bromide 0.5 mg) to nebulized b2-adrenoreceptor agonists produces greater bronchodilation. Ipratropium should be added during more severe

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Sedatives should be strictly avoided during exacerbations because of respiratory depressant effects.

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Please cite this article in press as: Bayes HK, Thomson NC, Acute severe asthma in adults, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.02.012

ADULT ASTHMA

Assessment and management of acute severe asthma Assess severity

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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 < 8 kPa – Normal PaCO2 – High H+

Near-fatal asthma • Raised PaCO2

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 5 mg + ipatropium bromide 0.5 mg 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 mins or life-threatening features: • Discuss with senior clinician • Nebulized salbutamol + ipatropium bromide repeated after 15 minutes; consider continuous salbutamol 10 mg/hour (via appropriate nebulizer) • Intravenous magnesium sulphate: single infusion of 1.2–2 g over 20 minutes • 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 < 8 kPa unless SpO2> 92%, or PaO2 normal/raised, or patient’s condition deteriorating • PEF • Chest X-ray • Electrolytes: especially K +

Discharge planning/follow-up: • Stop nebulizer therapy 24 hours before discharge • Check inhaler technique • Review asthma maintenance therapy • PEF meter and diary • Smoking cessation and allergen avoidance • Written personalized asthma action plan • GP/asthma nurse and respiratory clinic follow-up organized

GP, general practitioner; PaCO2, partial pressure of carbon dioxide in arterial blood; PaO2, partial pressure of oxygen in arterial blood; 2, oxygen saturation measured by pulse oximetry

Figure 1

measured before and 15e30 minutes after starting treatment. Throughout hospital admission, PEF should be recorded four times a day, before and after bronchodilator treatment.

Monitoring Heart rate, respiratory rate and pulse oximetry should be continuously monitored until stabilization. PEF should be

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Decision to refer to hospital or admit

Assessment of a patient with an acute exacerbation C C

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Patients with acute severe asthma should be referred to hospital and those with life-threatening or near-fatal asthma admitted. Discharge from the emergency department can be considered for patients with PEF >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 before presentation or has risk factors for fatal asthma (Table 1), there should be a lower threshold for admission.

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. NSAIDs or b-adrenoreceptor blockers) Adherence to treatment Identify any environmental triggers  Infection  Exercise  Foods  Occupational exposures  Drugs (e.g. NSAIDs)  Gastro-oesophageal reflux  Menstruation and pregnancy Smoking status, including second-hand smoke exposure

Pre-discharge planning, education and follow-up The following should be undertaken during admission:  precipitants of attack assessed  maintenance medications and inhaler technique reviewed  PEF meter and diary provided  written PEF and symptom-based personalized asthma action plan provided  smoking cessation advice given. Discharge should be planned 24 hours in advance and bronchodilators changed to a hand-held device. Criteria for discharge are subjective but usually require PEF >75% of best or predicted, with diurnal variability <25%. Written information on the admission should be faxed or emailed to the primary care practice within 24 hours of discharge. Follow-up should be arranged with the GP or asthma nurse within 2 working days and in a respiratory clinic approximately 4 weeks after discharge.

NSAID, non-steroidal anti-inflammatory drugs.

Table 2

Conditions that may mimic an acute asthma exacerbation C C C C C C C C

Acute exacerbations of chronic obstructive pulmonary disease Allergic bronchopulmonary aspergillosis Carcinoid syndrome Hyperventilation syndrome Inhaled foreign body Pulmonary oedema Upper airway obstruction (examination may identify stridor) Vocal cord dysfunction

Acute exacerbations in pregnancy Exacerbations affect 11e18% of pregnant asthmatic women. They are more common with severe, poorly controlled asthma and mostly occur in the late second trimester. As severe acute asthma poses a greater risk to the fetus than do the adverse effects of asthma therapies, exacerbations should be treated with standard management for adult asthma. Pregnant women should not be denied systemic corticosteroids. Maternal oxygen saturation should be maintained at 94e98%, and continuous fetal monitoring is recommended in severe exacerbations. A

Table 3

Arterial blood gas measurements should be repeated within 1 hour of starting treatment if initial PaO2 is <8 kPa (unless SpO2 is maintained >92%), PaCO2 is normal or raised, or the patient is deteriorating. Serum electrolytes and glucose concentrations should be monitored. Hypokalaemia and hyperglycaemia can result from b2-adrenoreceptor agonist and corticosteroid use.

KEY REFERENCES 1 Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (updated 2015). Available from: http:// www.ginasthma.com (accessed Jul 2015). 2 Royal College of Physicians report. Why asthma still kills: the national review of asthma deaths (NRAD); confidential enquiry report 2014. Available from: http://www.rcplondon.ac.uk/sites/default/ files/why-asthma-still-kills-full-report.pdf (accessed Jul 2015). 3 British Thoracic Society/Scottish Intercollegiate Guidelines Network. Guideline on the management of asthma (updated 2014). Available from: https://www.brit-thoracic.org.uk/guidelines-andquality-standards/asthma-guideline/ (accessed Jul 2015). 4 Goodacre S, Cohen J, Bradburn M, et al. Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial. Lancet Respir Med 2013; 1: 293e300.

Criteria for referral to intensive care unit/mechanical ventilation Discuss with the critical care team any patient exhibiting lifethreatening features, either present on admission and failing to improve quickly or developing despite adequate treatment. Clear indications for intubation and positive-pressure ventilation are decreased consciousness, respiratory arrest and worsening hypoxia/hypercapnia.

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Ó 2016 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Bayes HK, Thomson NC, Acute severe asthma in adults, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.02.012