Asthma Management Handbook

Continuing treatment and considering additional treatment

Recommendations

Consider add-on treatments based on response to initial doses of salbutamol.

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

How this recommendation was developed

Consensus

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

If response to initial inhaled salbutamol is incomplete or poor, add inhaled ipratropium bromide and continue salbutamol as needed.

Adults: Give ipratropium bromide 8 puffs (21 mcg/actuation) via pressurised metered-dose inhaler and spacer every 20 minutes for first hour. Repeat 4–6 hourly for 24 hours.

If a nebuliser is being used to deliver salbutamol, 500 mcg ipratropium bromide can be added to the nebulised solution every 20 minutes for first hour. Repeat 4–6 hourly.

Children 6–12 years: Give ipratropium bromide 8 puffs (21 mcg/actuation) via pressurised metered-dose inhaler and spacer every 20 minutes for first hour. Repeat 4–6 hourly for 24 hours.

If a nebuliser is being used to deliver salbutamol, 500 mcg ipratropium bromide can be added to the nebulised solution every 20 minutes for first hour. Repeat 4–6 hourly.

Children 0–5 years: Give ipratropium bromide 4 puffs (21 mcg/actuation) via pressurised metered-dose inhaler and spacer (+ mask if needed) every 20 minutes for first hour. Repeat 4–6 hourly for 24 hours.

If a nebuliser is being used to deliver salbutamol, 250 mcg ipratropium bromide can be added to the nebulised solution every 20 minutes for first hour. Repeat 4–6 hourly.

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:

  • Iramain et al. 20111
  • Rodrigo and Castro-Rodriguez, 20052
  • Teoh et al. 20123

Montelukast is not recommended for the management of acute asthma in adults or children in acute care settings.

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:

  • Adachi et al. 20124
  • Watts and Chavasse, 20125

For adults with severe or life-threatening acute asthma, or with poor response to repeated maximal doses of other bronchodilators, consider intravenous magnesium sulfate.

Give magnesium sulfate 10 mmol diluted in a compatible solution as a single infusion over 20 minutes.

  • Intravenous magnesium sulfate may be associated with hypotension 

Table. How to administer intravenous magnesium sulfate Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/95

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:

  • Global Initiative for Asthma, 20126
  • Mohammed and Goodacre, 20077
  • Powell et al. 20128
  • Song and Chang, 20129

For children 2 years and older with poor response to initial bronchodilator therapy, consider intravenous magnesium sulfate.

Give magnesium sulfate 0.1–0.2 mmol/kg (maximum 10 mmol) diluted in a compatible solution as a single infusion over 20 minutes.

Do not use intravenous magnesium sulfate in children younger than 2 years.

  • Intravenous magnesium sulfate may be associated with hypotension 

Table. How to administer intravenous magnesium sulfate Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/95

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:

  • Global Initiative for Asthma, 20126
  • Mohammed and Goodacre, 20077
  • Powell et al. 20128

In critical care units (e.g. emergency department, intensive care unit, high-dependency unit), IV salbutamol can be considered for patients with life-threatening acute asthma that has not responded to continuous nebulised salbutamol, after considering other add-on treatment options.

  • Salbutamol toxicity may occur with either the inhaled or IV route of administration. Risk may be increased when the inhaled and IV routes are used concomitantly.

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

 
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:

  • Travers et al. 201210
  • Travers et al. 201211
  • Abramson et al. 200112

If using IV salbutamol to manage acute asthma, follow your hospital/organisation’s protocol for dosage and delivery.

If no local protocol is available, use the following as a guide:
Using a 1 mg/mL (1000 mcg/mL) salbutamol concentrate for infusion, prepare a solution of 5 mg in 50 mL normal saline. Deliver by continuous infusion or bolus.

Children 2–12 years:
Loading dose of 5 mcg/kg/minute (maximum 200 mcg/minute) for 1 hour and then infusion of 1–2 mcg/kg/minute (maximum 80 mcg/minute).

Adults and children older than 12 years:
As continuous infusion: initial loading dose of 200 mcg over 1 minute and then start infusion at 5 mcg/minute (can increase to 10 mcg/minute, then up to 20 mcg/minute every 15–30 minutes according to response)
As bolus: 250 mcg over 5 minutes.

  • The initial dose should be reduced for older adults. Dose reduction may be needed for people with impaired renal function. Impaired liver function may result in accumulation of unmetabolised salbutamol. Refer to TGA-approved product information.

Monitor blood electrolytes, heart rate and acid/base balance (blood lactate).

  • Salbutamol toxicity can occur with either the inhaled or IV route of administration. Risk may be increased when the inhaled and IV routes are used concomitantly.
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):

  • GlaxoSmithKline Australia Pty Ltd 200813

If the patient is starting to tire, or shows signs of respiratory failure, consider noninvasive positive pressure ventilation.

For patients with respiratory arrest, acute respiratory failure that does not respond to treatment, severe exhaustion suggesting impending respiratory arrest, or failure of noninvasive positive pressure ventilation, start mechanical ventilation.

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:

  • Brandao et al. 200914
  • Gupta et al. 201015
  • Lim et al. 201216
  • Soroksky et al. 201017
  • Soma et al. 200818
  • Williams et al. 201119

If intubation is needed, ketamine can be considered.

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:

  • Jat and Chawla, 201220

If dyspnoea does not respond to treatment, consider transfer to an intensive care unit.

How this recommendation was developed

Consensus

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

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. 200321

More information

Ipratropium in acute asthma

Ipratropium bromide alone is less effective than salbutamol alone in acute asthma.3

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.2

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).2

Ipratropium bromide may be effective in patients with tolerance to the bronchodilator effect of short-acting beta-agonists caused by beta-receptor down-regulation.22

It is well tolerated in children with acute asthma.3

Close
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.8

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.6 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.23

In children, intravenous magnesium sulfate improves lung function and reduces the need for hospital admission.7 Fewer studies have been conducted in children under 6 years.

Intravenous magnesium sulfate is inexpensive and generally well tolerated.623

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.823  

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).8 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.24

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.23

Fewer studies have been conducted in children than in adults.8

Close
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.252628 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.10

Benefits have not been demonstrated in adults.10 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.10

However, there is a lack of consensus on the appropriate dose of IV salbutamol for children.29 Recommendations differ between guidelines in Australia30 and elsewhere.29 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.1029  Concomitant use of the inhalation and IV routes may increase the risk of salbutamol toxicity.12

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).

Close
Adrenaline in acute asthma

Systemic adrenaline (intravenous in clinical settings with appropriately trained staff, or intramuscular) is indicated for patients with anaphylaxis and angioedema,631 but current evidence does not support its routine use in the management of acute asthma in the absence of anaphylaxis.6

Nebulised adrenaline does not have a significant benefit over salbutamol or terbutaline in the management of moderate-to-severe acute asthma in adults and children.32

Close
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.11

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.33 No sub-groups that benefit from intravenous aminophylline have been clearly identified.33 Aminophylline is associated with vomiting and cardiac arrhythmias.33

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.34

  • 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.35 Aminophylline is associated with a significant increased risk of vomiting in children.35

Close
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.36 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.

Close
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.20

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.37 Adverse effects associated with ketamine include hypersecretion, hypotension and hypertension, arrhythmias, and hallucinations.37

Close
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.5

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.5

In adults with acute asthma, the addition of oral montelukast to usual care may slightly reduce beta2 agonist requirement.5 The addition of oral zafirlukast was associated with improvement in lung function, compared with usual care.5

Close
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.38

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.3940

Close
Non-invasive positive pressure ventilation in acute asthma

Efficacy

Few randomised clinical trials have evaluated non-invasive positive pressure ventilation (biphasic positive airway pressure or continuous positive airway pressure) for adults with severe acute asthma.16 This technique has not been shown to reduce risk of death or the need for intubation, but may reduce hospital admissions, length of hospital stay and length of ICU stay.16 It may also improve lung function, but evidence is inconsistent.16

Delivering bronchodilators in patients undergoing noninvasive positive-pressure ventilation

When delivering nebulised salbutamol while using noninvasive positive-pressure ventilation set at pressures commonly used in clinical practice, the amount of salbutamol inhaled is likely to be significantly higher than with a nebuliser alone (based on a bench model of a spontaneously breathing adult). This increase may be because the ventilator tubing acts as a spacer.41

The position of the nebuliser in the ventilator circuit significantly affects the total dose of salbutamol inhaled. Salbutamol is delivered most effectively when the nebuliser is positioned immediately after the expiration port (i.e. starting from the facemask, the expiration port is positioned before the nebuliser).41

Close
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.21

Close

References

  1. Iramain R, Lopez-Herce J, Coronel J, et al. Inhaled salbutamol plus ipratropium in moderate and severe asthma crises in children. J Asthma. 2011; 48: 298-303. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21332430
  2. 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
  3. 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
  4. Adachi M, Taniguchi H, Tohda Y, et al. The efficacy and tolerability of intravenous montelukast in acute asthma exacerbations in Japanese patients. J Asthma. 2012; 49: 649-656. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22742205
  5. Watts K, Chavasse RJ. Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children. Cochrane Database Syst Rev. 2012; Issue 5: CD006100. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22592708
  6. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. GINA, 2012. Available from: http://www.ginasthma.org
  7. Mohammed S, Goodacre S. Intravenous and nebulised magnesium sulphate for acute asthma: systematic review and meta-analysis. Emerg Med J. 2007; 24: 823-830. Available from: http://emj.bmj.com/content/24/12/823.long
  8. 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
  9. Song WJ, Chang YS. Magnesium sulfate for acute asthma in adults: a systematic literature review. Asia Pac Allergy. 2012; 2: 76-85. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269605/
  10. 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
  11. 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
  12. Abramson MJ, Bailey MJ, Couper FJ, et al. Are asthma medications and management related to deaths from asthma?. Am J Respir Crit Care Med. 2001; 163: 12-18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11208619
  13. GlaxoSmithKline Australia Pty Ltd. Product information: Ventolin Sugar Free Syrup and Injection (salbutamol). Therapeutic Goods Administration, Canberra, 2008. Available from: https://www.ebs.tga.gov.au
  14. Brandao DC, Lima VM, Filho VG, et al. Reversal of bronchial obstruction with bi-level positive airway pressure and nebulization in patients with acute asthma. J Asthma. 2009; 46: 356-61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19484669
  15. Gupta D, Nath A, Agarwal R, Behera, D.. A prospective randomized controlled trial on the efficacy of noninvasive ventilation in severe acute asthma. Respir Care. 2010; 55: 536-43. Available from: http://rc.rcjournal.com/content/55/5/536.short
  16. Lim WJ, Mohammed Akram R, Carson KV, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst Rev. 2012; 12: CD004360. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004360.pub4/full
  17. Soroksky A, Klinowski E, Ilgyev E, et al. Noninvasive positive pressure ventilation in acute asthmatic attack. Eur Respir Rev. 2010; 19: 39-45. Available from: http://err.ersjournals.com/content/19/115/39.long
  18. Soma T, Hino M, Kida K, Kudoh, S.. A prospective and randomized study for improvement of acute asthma by non-invasive positive pressure ventilation (NPPV). Intern Med. 2008; 47: 493-501. Available from: https://www.jstage.jst.go.jp/article/internalmedicine/47/6/476493/_article
  19. Williams AM, Abramo TJ, Shah MV, et al. Safety and clinical findings of BiPAP utilization in children 20 kg or less for asthma exacerbations. Intensive Care Med. 2011; 37: 1338-43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21567114
  20. Jat KR, Chawla D. Ketamine for management of acute exacerbations of asthma in children. Cochrane Database Syst Rev. 2012; 11: CD009293. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009293.pub2/full
  21. Wilson MM, Irwin RS, Connolly AE, et al. A prospective evaluation of the 1-hour decision point for admission versus discharge in acute asthma. J Intensive Care Med. 2003; 18: 275-285. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15035763
  22. 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
  23. 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: 293-300. Available from: http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70070-5/fulltext
  24. Powell C, Kolamunnage-Dona R, Lowe J, et al. MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial and economic evaluation of nebulised magnesium sulphate in acute severe asthma in children. Health Technol Assess. 2013; 17: 1-216. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24144222
  25. 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
  26. Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013; 9: Cd000052. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24037768
  27. Cates CJ, Bestall J, Adams N. Holding chambers versus nebulisers for inhaled steroids in chronic asthma. Cochrane Database Syst Rev. 2006; Issue 1: CD001491. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001491.pub2/full
  28. Ferguson C, Gidwani S. Delivery of bronchodilators in acute asthma in children. Emerg Med J. 2006; 23: 471-472. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564350/
  29. Starkey ES, Mulla H, Sammons HM, Pandya HC. Intravenous salbutamol for childhood asthma: evidence-based medicine?. Arch Dis Child. 2014; 99: 873-877. Available from: http://adc.bmj.com/content/99/9/873.abstract
  30. Babl FE, Sheriff N, Borland M, et al. Paediatric acute asthma management in Australia and New Zealand: practice patterns in the context of clinical practice guidelines. Arch Dis Child. 2008; 93: 307-312. Available from: http://adc.bmj.com/content/93/4/307.abstract
  31. Australasian Society of Clinical Immunology and Allergy (ASCIA). Acute management of anaphylaxis guidelines. ASCIA, Sydney, 2013. Available from: http://www.allergy.org.au/health-professionals/papers/acute-management-of-anaphylaxis-guidelines
  32. Rodrigo GJ, Nannini LJ. Comparison between nebulized adrenaline and beta2 agonists for the treatment of acute asthma. A meta-analysis of randomized trials. Am J Emerg Med. 2006; 24: 217-22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16490653
  33. 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
  34. 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
  35. 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
  36. 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
  37. Brenner B, Corbridge T, Kazzi A. Intubation and mechanical ventilation of the asthmatic patient in respiratory failure. Proc Am Thorac Soc. 2009; 6: 371-379. Available from: http://www.atsjournals.org/doi/full/10.1513/pats.P09ST4
  38. Johnston SL. Macrolide antibiotics and asthma treatment. J Allergy Clin Immunol. 2006; 117: 1233-1236. Available from: http://www.jacionline.org/article/S0091-6749(06)00741-X/fulltext
  39. Black PN. Antibiotics for the treatment of asthma. Curr Opin Pharmacol. 2007; 7: 266-71. Available from: http://www.sciencedirect.com/science/article/pii/S1471489207000616
  40. Johnston SL, Blasi F, Black PN, et al. The Effect of Telithromycin in Acute Exacerbations of Asthma. N Engl J Med. 2006; 354: 1589-1600. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa044080#t=article
  41. Calvert LD, Jackson JM, White JA, et al. Enhanced delivery of nebulised salbutamol during non-invasive ventilation. J Pharm Pharmacol. 2006; 58: 1553-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17132219