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Three Part Question

In [patients with acute severe asthma] does [administration of a benzodiazepine] lead to [increased morbidity and mortality]?

Clinical Scenario

A twenty year-old asthmatic lady presents to the Emergency Department with acute-onset of dyspnoea following a row with her boyfriend. She has a respiratory rate of 40/min, a pCO2 of 2.5, is tearful, extremely anxious and panicky but has an audible wheeze. You try in vain to reassure her and realise that the panic is not helping her bronchospasm. You know that benzodiazepines are to be avoided in acute severe asthma and do not prescribe them. Having stabilised her condition with nebulised salbutamol, intravenous magnesium and oral prednisolone you wonder whether there is any evidence within the literature of the harmful effect of benzodiazepines in this situation.

Search Strategy

OVID Medline 1966 - 2006 August Week 2
OVID CINAHL 1982 - August Week 2
The Cochrane Library Issue 3, 2006
OVID Medline and CINAHL:
[exp Asthma/ OR exp Bronchoconstriction/ OR exp Bronchial Constriction] AND [exp Benzodiazepines/ OR exp Diazepam/ OR exp Clonazepam/ OR exp Midazolam/ OR exp Temazepam/ OR exp Nitrazepam/ OR benzodiazepine$.mp.] limit to humans and English language
Cochrane:
[MeSH Asthma] AND [MeSH Lorazepam OR MeSH Diazepam OR MeSH Nitrazepam OR MeSH Temazepam OR MeSH Oxazepam OR MeSH Clonazepam]

Search Outcome

Altogether 99 papers were found using Medline, 6 using CINAHL and 2 using Cochrane. None of the papers were directly relevant to the three-part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses

Comment(s)

There is no published evidence of the harmful effect of benzodiazepines in acute severe asthma. The level of evidence required to make an evidence-based recommendation for their avoidance in this situation would be a case report or series. The British Thoracic Society recommends that benzodiazepines should be avoided in acute severe asthma (BTS Asthma Guideline, 2004). Benzodiazepines lead to respiratory depression, which could be potentially catastrophic in a patient with acute severe asthma who requires optimal respiratory drive. Despite a suggestion in the literature that midazolam may lead to bronchodilatation (Hirota et al, 1997), it would be unwise to recommend the use of benzodiazepines in unintubated patients with acute severe asthma. The absence of evidence does not equate to the absence of potential harm. In view of the potentially catastrophic effects of benzodiazepines in acute severe asthma, it would be unethical to perform a randomised controlled trial given the evidence currently available. Anxiety in acute severe asthma should be treated with reassurance alone.

Clinical Bottom Line

Benzodiazepines should be avoided in acute severe asthma. This recommendation is based upon expert opinion and intuition rather than evidence from within the literature.

References

1. Hirota, K. Ohtomo, N. Hashimoto, Y. Kudo, T. Ishihara, H. Matsuki, A. Midazolam reverses histamine-induced bronchoconstriction in dogs Canadian Journal of Anaesthesia 1997; 44(10):1115-9
2. British Thoracic Society; Scottish Intercollegiate Guidelines Network British Guideline on the Management of Asthma. A National Clinical Guideline Revised Edition April 2004