Asthma Management Handbook

Assessing response to treatment

Recommendations

Assess clinical response to each dose of bronchodilator:

  • If dyspnoea is partially relieved within first 5 minutes, reassess at 15 minutes.
  • If dyspnoea is not relieved, repeat bronchodilator dose and consider add-on options.
  • If condition deteriorates at any time, consider add-on treatment options.

Table. Add-on treatment options for acute asthma Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/61

  • Reduced wheezing alone is an unreliable indicator of improvement, as it may indicate deterioration
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Review treatment response again 10–20 minutes after third dose (approximately 1 hour after first dose). If dyspnoea persists, continue giving salbutamol every 20 minutes and consider add-on treatment options.

How this recommendation was developed

Based on selected evidence

Based on a limited structured literature review or published systematic review, which identified the following relevant evidence:

  • Camargo et al. 20031
  • Chandra et al. 20052
  • Karpel et al. 19973
  • Rodrigo and Rodrigo, 20024
  • Shrestha et al. 19965

Perform baseline spirometry and record FEV1 approximately 1 hour after giving initial bronchodilator treatment, if feasible.

Table. Tips for performing spirometry in patients with acute asthma

  • Ask the patient to sit straight upright, either in a chair or on a stretcher with their legs over the side.
  • Make sure the person forms a tight seal around the mouthpiece.
  • Tell the patient to take as deep a breath as possible, then blast out air as fast and hard as they can, then keep blowing until asked to stop. Aim for exhalation of maximal force for at least 2 seconds (6 seconds if FVC is measured).
  • You may need to give the patient lots of coaching, repeat instructions, and give immediate feedback on technique.

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  • Patients with severe acute asthma are unlikely to be able to perform spirometry
  • Do not continue attempting to obtain a spirometry reading if the patient is distressed
How this recommendation was developed

Based on selected evidence

Based on a limited structured literature review or published systematic review, which identified the following relevant evidence:

  • Arnold et al. 20126
  • Emerman and Cydulka, 19957
  • Karras et al. 20008
  • Langhan and Spiro, 20099
  • Schneider et al. 201110
  • Silverman et al. 200711
  • Wilson et al. 200312

If spirometry is not available, a peak expiratory flow meter can be used to assess initial response.

Note: PEF is not as accurate as spirometry for measuring lung function.

How this recommendation was developed

Based on selected evidence

Based on a limited structured literature review or published systematic review, which identified the following relevant evidence:

  • Abisheganaden et al. 199813
  • Geelhoed et al. 199014
  • Henderson et al. 201015
  • Ribeiro de Andrade et al. 200716

Obtain blood gas analysis in adults with features of life-threatening acute asthma (any of):

  • unable to speak due to dyspnoea
  • reduced consciousness or collapse
  • exhaustion
  • cyanosis
  • oxygen saturation <92%
  • poor respiratory effort
  • cardiac arrhythmia.
How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • British Thoracic Society and Scottish Intercollegiate Guidelines Network, 200817
  • Global Initiative for Asthma, 201218

Monitor for signs of salbutamol toxicity (e.g. tachycardia, tachypnoea, metabolic acidosis).

  • Salbutamol toxicity may occur with inhaled or IV salbutamol
How this recommendation was developed

Based on selected evidence

Based on a limited structured literature review or published systematic review, which identified the following relevant evidence:

  • Salmeron et al. 199419
  • Travers et al. 201220

Admit patient to hospital if (any of):

  • FEV1 <60% predicted at 1-hour check
  • unable to lie flat without dyspnoea
  • dyspnoea unresolved within 1–2 hours.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • Wilson et al. 200312

More information

Salbutamol in acute asthma: dosing regimens

One placebo-controlled study showed that, for patients who showed clear improvement after the first dose of salbutamol via pressurised metered-dose inhaler and spacer, there was no advantage in repeating the dose more often than every 60 minutes until full recovery (extra doses can be given as needed).3

However, in patients who did not show a clear response to the first salbutamol dose, repeating the dose at intervals of 30 minutes or less was more effective than every 60 minutes.3

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Salbutamol in acute asthma: route of administration

Inhaler plus spacer, or nebuliser

Salbutamol delivered via a pressurised metered-dose inhaler with spacer is at least as effective as salbutamol delivered via nebuliser in patients with moderate-to-severe acute asthma who do not require ventilation.212224 The use of nebulisers increases the risk of transmitting respiratory infections to staff and other patients.

Intravenous salbutamol

Overall, intravenous short-acting beta2 agonists do not appear to be superior to inhaled short-acting beta2 agonist.20

Benefits have not been demonstrated in adults.20 Very limited evidence from one study suggested that the addition of IV salbutamol to inhaled salbutamol reduced recovery time in children with severe acute asthma in the emergency department.20

However, there is a lack of consensus on the appropriate dose of IV salbutamol for children.25 Recommendations differ between guidelines in Australia26 and elsewhere.25 Doses have not been calculated based on age-specific pharmacokinetic and pharmacodynamic data. The doses recommended in guidelines are generally relatively higher than for adults on a micrograms per kilogram body weight basis.

Compared with inhaled salbutamol, intravenous salbutamol is associated with increased risk of adverse effects including tremor and hypokalaemia.2025  Concomitant use of the inhalation and IV routes may increase the risk of salbutamol toxicity.27

Note: Salbutamol concentrate for infusion is available in 5 mL ampoules containing salbutamol sulfate equivalent to 5 mg (1 mg/mL) salbutamol in a sterile isotonic solution (Ventolin obstetric injection). Salbutamol for injection is also available in ampoules of salbutamol sulphate equivalent to 500 mcg salbutamol in 1 mL sterile isotonic solution (Ventolin injection).

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Assessment of oxygen status in acute asthma

Hypoxia is the main cause of death that is due to acute asthma.28

Routine objective assessment of oxygen saturation at initial assessment of acute asthma is needed because clinical signs may not correlate with hypoxaemia.

Pulse oximetry is the internationally accepted method for routine assessment of oxygen status in patients with acute asthma.18

The risk of hypercapnoea increases when oxygen saturation falls below 92%.29

Pulse oximetry does not detect hypercapnoea, so blood gas analysis is necessary if hypercapnoea is suspected in patients with severe or life-threatening acute asthma.

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Oxygen therapy in acute asthma

Oxygen is a treatment for hypoxaemia, not breathlessness. Oxygen has not been shown to improve the sensation of breathlessness in non-hypoxaemic patients.30 When oxygen supplementation is used, pulse oximetry is necessary to monitor oxygen status and titrate to target.

The aim of titrated oxygen therapy in acute care is to achieve normal or near-normal oxygen saturation, except in patients who are at risk of hypercapnoeic respiratory failure,30 such as patients with overlapping asthma and COPD.

Adults

In adults with acute asthma, titrated oxygen therapy using pulse oximetry to maintain oxygen saturation at 93–95% while avoiding hyperoxaemia achieves better physiological outcomes than 100% oxygen at high flow rate (8 L/min).31 High-concentration and high-flow oxygen therapy cause a clinically significant increase in blood CO2 concentration in adults with acute asthma.3132

National guidelines for the management of acute exacerbations of COPD recommend that hypoxic patients should be given controlled oxygen therapy via nasal prongs at 0.5–2.0 L/minute or a venturi mask at 24% or 28%, with target oxygen saturation of over 90% (PaO2 >50 mmHg, or 6.7 kPa).33 Excessive oxygen administration should be avoided because it can worsen hypercapnoea.33

Children

Drying of the upper airway is a potential complication of oxygen therapy in children,3435 which might contribute to bronchoconstriction.35 Humidified oxygen can be considered if necessary. Humidification is usually not needed for low flow oxygen (<4 L/minute in children or 2 L/minute in infants) for short term. Humidification may be considered if the oxygen is required for longer than 48 hours or if the nasal passages are becoming uncomfortable or dry.34

Guidance on oxygen delivery techniques and practical issues is available from  Sydney Children's Hospital Network and The Royal Children's Hospital Melbourne.

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Spirometry in acute asthma

Utility

Assessment of response to treatment should include spirometry considered alongside clinical assessment. Clinical assessment alone may underestimate the severity of airflow limitation.12

On its own, FEV1 (measured by spirometry) at 1 hour after admission to the emergency department does not closely correlate with the need for hospital admission in adults with acute asthma as assessed clinically.12

Feasibility and technique

Most adults with acute asthma can perform spirometry within the first hour of admission to the emergency department.11 (Hospital staff and primary care health professionals may need specific training in spirometry technique to be able to obtain acceptable spirometry in patients with acute asthma.11)

Younger children (most children under 6 years) are unlikely to be able to perform spirometry.

It may not be feasible to apply standard spirometry technique and manoeuvre acceptability criteria in patients with acute asthma:11

  • 80% of patients older than 12 years with acute asthma can perform an FEV1 manoeuvre. A forced exhalation from total lung capacity for 2 seconds is sufficient and provides useful information about the severity of airflow obstruction11
  • two attempts may suffice if patients are unable to make three attempts11
  • variability between manoeuvres of < 10% should be considered acceptable11
  • patients may not be able to tolerate nose clips11
  • patients are unlikely to be able to exhale for long enough to demonstrate the time-volume plateau. Although patients should aim for forced exhalation of at least 6 seconds, 2 seconds is acceptable for measuring FEV1 in clinical assessment during acute asthma.11 A spirometry manoeuvre might be considered acceptable if back-extrapolated volume is either < 5% of FVC or 0.15 L (whichever is greater), or a time to peak flow < 120 ms.11

Table. Tips for performing spirometry in patients with acute asthma

  • Ask the patient to sit straight upright, either in a chair or on a stretcher with their legs over the side.
  • Make sure the person forms a tight seal around the mouthpiece.
  • Tell the patient to take as deep a breath as possible, then blast out air as fast and hard as they can, then keep blowing until asked to stop. Aim for exhalation of maximal force for at least 2 seconds (6 seconds if FVC is measured).
  • You may need to give the patient lots of coaching, repeat instructions, and give immediate feedback on technique.

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Peak expiratory flow in acute asthma

Peak expiratory flow rate obtained using a peak flow meter underestimates the severity of airflow limitation in patients with acute asthma, compared with FEV1 obtained by spirometry.36

Peak expiratory flow is not a sensitive measure of small clinical improvements as perceived by the patient.8

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Heliox in acute asthma

When giving nebulised bronchodilators in acute asthma, the use of helium-oxygen mixtures (heliox) to drive the nebuliser may be more effective than oxygen for improving lung function and reducing hospital admission rates, based on a meta-analysis of clinical trials in adults and children.37 However, the application of this finding to routine management of acute asthma is limited, because nebulisation is not routinely recommended in Australia the use of oxygen to drive nebulisers is not routinely recommended for adults who need nebulisation, and many patients do not require oxygen.

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Ipratropium in acute asthma

Ipratropium bromide alone is less effective than salbutamol alone in acute asthma.38

Early administration of ipratropium bromide in addition to beta2 agonists may reduce admission rates and improve lung function in children and adults with acute asthma, based on the findings of a systematic review of 32 randomised controlled trials.39

However, ipratropium bromide does not appear to benefit patients with less severe acute asthma (patients with acute asthma assessed as ‘mild’ in randomised controlled trials, e.g. FEV1 >70% predicted).39

Ipratropium bromide may be effective in patients with tolerance to the bronchodilator effect of short-acting beta-agonists caused by beta-receptor down-regulation.40

It is well tolerated in children with acute asthma.38

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Theophyllines in acute asthma

Aminophylline versus short-acting beta2 agonist

Intravenous aminophylline may be as effective as intravenous short-acting beta2 agonist in the management of acute asthma in adults and children, but is associated with a higher rate of adverse effects including giddiness, nausea and vomiting.41

Aminophylline plus beta2 agonist (adults)

Overall, evidence from randomised clinical trials in adults with acute asthma treated in emergency departments suggests that intravenous aminophylline given in addition to inhaled beta2 agonists does not achieve greater bronchodilation or reduce hospital admissions, compared with inhaled beta2 agonists alone.42 No sub-groups that benefit from intravenous aminophylline have been clearly identified.42 Aminophylline is associated with vomiting and cardiac arrhythmias.42

Theophylline is metabolised mainly by the liver and commonly interacts with other medicines. Its concentration in plasma should be monitored closely in older people or those with comorbid conditions.43

  • Avoid short-acting theophylline for a patient who is already using long-acting theophylline.

Aminophylline plus beta2 agonist (children)

Overall, evidence from randomised clinical trials in children with acute asthma requiring hospital admission suggests that the addition of intravenous aminophylline to beta2-agonists and corticosteroids, with or without muscarinic antagonists (anticholinergic bronchodilators), improves lung function within 6 hours of treatment, but does not appear to improve symptoms or shorten hospital stay.44 Aminophylline is associated with a significant increased risk of vomiting in children.44

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Magnesium sulfate in acute asthma

MgSO4 versus beta2 agonists

Clinical trial evidence does not support the use of magnesium sulfate as a substitute for inhaled beta2 agonists.45

Intravenous MgSO4 plus beta2 agonist

In patients with life-threatening acute asthma (FEV1 25–30% predicted) or patients with a poor response to initial bronchodilator treatment, intravenous magnesium sulfate (2 g given as single infusion over 20 minutes) can reduce hospital admission rates.18 However, it may only be effective in patients with more severe acute asthma. In a recent large, well-conducted randomised controlled trial in adults with moderate-to-severe acute asthma treated in an emergency department (excluding those with life-threatening asthma), intravenous magnesium sulfate improved dyspnoea scores but did not reduce hospital admission rates.46

In children, intravenous magnesium sulfate improves lung function and reduces the need for hospital admission.47 Fewer studies have been conducted in children under 6 years.

Intravenous magnesium sulfate is inexpensive and generally well tolerated.1846

Inhaled MgSO4 plus beta2 agonist

Overall, evidence from randomised controlled clinical trials suggests that nebulised magnesium sulfate in addition to beta2 agonist (with or without ipratropium bromide) does not reduce hospital admissions or improve lung function in adults or children, compared with beta2 agonist alone.4546  

However, the results of some clinical trials suggest that the addition of nebulised magnesium sulfate improves lung function in patients with severe acute asthma (FEV1 <50% predicted).45 In a recent large randomised controlled clinical trial in children, nebulised magnesium sulfate was associated with a small improvement in asthma symptom scores at 60 minutes. The effect was greatest in the subgroups of children with more severe acute asthma, and those with a shorter duration of symptoms.48

A recent study showed no benefit in adults for hospitalisation or dyspnoea with add-on nebulised magnesium compared with standard therapy alone, but this study excluded patients with life-threatening acute asthma as defined in this handbook.46

Fewer studies have been conducted in children than in adults.45

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Ketamine in acute asthma

There is insufficient evidence from randomised clinical trials to assess the benefits of ketamine in the management of acute asthma. Available evidence does not demonstrate benefits in non-intubated children with acute asthma.49

Ketamine has been suggested as a suitable option for pre-intubation sedation in patients with respiratory failure caused by acute asthma (where not contraindicated) because it stimulates the release of catecholamines and may contribute to bronchodilation through direct relaxation effect on bronchial smooth muscle.50 Adverse effects associated with ketamine include hypersecretion, hypotension and hypertension, arrhythmias, and hallucinations.50

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Oral montelukast in acute asthma

Evidence from randomised controlled clinical trials does not support routine use of oral leukotriene receptor agonists in acute asthma in adults or children.51

In children with acute asthma, the addition of oral montelukast to usual care does not reduce hospital admission rates, based on the findings of a systematic review and meta-analysis.51

In adults with acute asthma, the addition of oral montelukast to usual care may slightly reduce beta2 agonist requirement.51 The addition of oral zafirlukast was associated with improvement in lung function, compared with usual care.51

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Antibiotics in acute asthma

Antibiotics are not used routinely in the management of acute asthma but should be used if they would otherwise be indicated, e.g. for specific comorbidities or when there is evidence of an infective exacerbation or previous positive microbiology.

The role of atypical bacterial infections (e.g. Chlamydophyla pneumonia, Mycoplasma pneumonae) in asthma is under investigation. Atypical bacterial infections may make acute asthma more severe, especially in patients with poorly controlled asthma. Macrolide antibiotics and telithromycin (a ketolide antibiotic not registered in Australia) are active against atypical bacteria and have anti-inflammatory activity.52

Overall, evidence from randomised clinical trials does not support the routine use of antibiotics in managing acute asthma. Evidence from one clinical trial suggested that telithromycin might help improve asthma symptoms when given after acute asthma, but it was associated with nausea.5354

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The ‘lie flat’ test (adults)

In adults, at 1 hour after initial treatment, the ability to lie flat without dyspnoea is a useful indicator of adequate recovery without the need for hospital admission, particularly when combined with adequate improvement in FEV1 measured by spirometry.12

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References

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  2. Chandra A, Shim C, Cohen HW, et al. Regular vs ad-lib albuterol for patients hospitalized with acute asthma. Chest. 2005; 128: 1115-1120. Available from: http://journal.publications.chestnet.org/article.aspx?articleid=1083722
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  18. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. GINA, 2012. Available from: http://www.ginasthma.org
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  20. Travers AH, Milan SJ, Jones AP, et al. Addition of intravenous beta(2)-agonists to inhaled beta(2)-agonists for acute asthma. Cochrane Database Syst Rev. 2012; 12: CD010179. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010179/full
  21. Dhuper S, Chandra A, Ahmed A, et al. Efficacy and cost comparisons of bronchodilatator administration between metered dose inhalers with disposable spacers and nebulizers for acute asthma treatment. J Emerg Med. 2011; 40: 247-55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19081697
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  31. Perrin K, Wijesinghe M, Healy B, et al. Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma. Thorax. 2011; 66: 937-41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21597111
  32. Rodrigo GJ, Rodriquez Verde M, Peregalli V, Rodrigo C. Effects of short-term 28% and 100% oxygen on PaCO2 and peak expiratory flow rate in acute asthma: a randomized trial. Chest. 2003; 124: 1312-7. Available from: http://journal.publications.chestnet.org/article.aspx?articleid=1081910
  33. Abramson MJ, Crockett AJ, Dabscheck E, et al. The COPD-X Plan: Australian and New Zealand guidelines for the management of chronic obstructive pulmonary disease. Version 2.34. The Australian Lung Foundation and The Thoracic Society of Australia and New Zealand, 2012. Available from: http://www.copdx.org.au/
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  37. Rodrigo GJ, Castro-Rodriguez JA. Heliox-driven beta2-agonists nebulization for children and adults with acute asthma: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2014; 112: 29-34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24331390
  38. Teoh L, Cates CJ, Hurwitz M, et al. Anticholinergic therapy for acute asthma in children. Cochrane Database Syst Rev. 2012; 4: CD003797. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003797.pub2/full
  39. Rodrigo J, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005; 60: 740-746. Available from: http://thorax.bmj.com/content/60/9/740.full
  40. Haney S, Hancox RJ. Overcoming beta-agonist tolerance: high dose salbutamol and ipratropium bromide. Two randomised controlled trials. Respir Res. 2007; 8: 19. Available from: http://respiratory-research.com/content/8/1/19
  41. Travers AH, Jones AP, Camargo CA, et al. Intravenous beta(2)-agonists versus intravenous aminophylline for acute asthma. Cochrane Database Syst Rev. 2012; 12: CD010256. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010256/full
  42. Nair P, Milan SJ, Rowe BH. Addition of intravenous aminophylline to inhaled beta(2)-agonists in adults with acute asthma. Cochrane Database Syst Rev. 2012; 12: CD002742. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002742.pub2/full
  43. Gupta P, O'Mahony MS. Potential adverse effects of bronchodilators in the treatment of airways obstruction in older people: recommendations for prescribing. Drugs Aging. 2008; 25: 415-43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18447405
  44. Mitra AA, Bassler D, Watts K, et al. Intravenous aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators. Cochrane Database Syst Rev. 2005; Issue 2: CD001276. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001276.pub2/full
  45. Powell C, Dwan K, Milan SJ, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2012; 12: CD003898. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002308.pub2/full
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