A randomised, double-blind controlled trial of intranasal midazolam for the palliation of dyspnoea in patients with life-limiting disease.

PURPOSE: Anxiety is a major component of breathlessness and is often palliated with benzodiazepines. Midazolam is a short-acting water-soluble benzodiazepine with a rapid onset of action and short half-life. Intranasal midazolam had been shown to be of marked clinical benefit in an uncontrolled pilot study for the control of dyspnoea. A blinded randomised controlled study was therefore undertaken across four Australasian palliative care services.

METHODS: All participants received six numbered study nasal spray (SNS) bottles, three of which contained midazolam and three placebo. They were instructed to use one SNS bottle on each day they were breathless, for 6 days within 2 weeks. Dyspnoea scores were recorded before and at set time intervals following the first use of each SNS bottle.

RESULTS: Across all SNS bottles, the maximum change of 2.1 on an 11-point numerical rating scale was seen at 60 min. There was no difference in dyspnoea score between the two arms. Approximately 50 % of participants in each arm had a positive response (i.e. ≥2 point change in dyspnoea score from baseline). Anxiety scores at baseline were low. The most common adverse event was local nasal reactions.

CONCLUSION: Intranasal midazolam had no clinical benefit over intranasal placebo for the control of dyspnoea. The low level of anxiety at baseline and dose of active drug delivered may have been important factors. Many participants found the SNS bottles to be a challenging mode of drug delivery. This study confirms the importance of placebo-controlled trials for defining best clinical practise.