Hardy, J., Randall, C., Pinkerton, E., Flatley, C., Gibbons, K., & Allan, S. (2016). A randomised, double-blind controlled trial of intranasal midazolam for the palliation of dyspnoea in patients with life-limiting disease. Supportive Care in Cancer, 24, 3069–3076.
To investigate the effect of a short-acting intranasal benzodiazepine on dyspnea, which is extremely common in those with life-limiting disease and negatively impacts quality of life (QOL)
Participants were given six identical bottles of nasal spray, three of which contained a placebo and three of which contained midazolam (benzodiazepine being studied) with the concentration of 0.5 mg per spray. The bottles were numbered one through six in random sequence. Patients were instructed to inhale a total of three times on each occasion of use with the total dose of active drug delivered being 1.5 mg. The participants were asked to use bottle number 1 on the first day, number 2 on the second day, and so on, using no single nasal spray for more than 24 hours. The dosages were not to be delivered more frequently than every four hours, and if participants did not experience dyspnea on a certain day, they were not required to use a nasal spray that day. The participants were formally assessed by investigators at baseline, day 7, and day 14. The participants were also contacted by phone throughout the study on specific days to ensure compliance. The participants formally scored the first dose administered each day, and at the end of each study day, participants documented how many times they used the nasal spray and if there was any benefit using a variety of tools and surveys.
The Covi Anxiety Scale (CAS) and the Cancer Dyspnea Scale (CDS) were completed by clinicians and examined verbal reports, patient behaviors, and somatic symptoms of anxiety. Participants documented how many times they had used the nasal spray in 24 hours and if they found any benefit in a daily log. Participants rated dyspnea, anxiety, and drowsiness on an 11-point numerical rating scale (NRS).
No significant benefit of the intranasal midazolam on anxiety scores was noted. No difference at any time point of investigation existed between the midazolam and the control group, and no difference in the dyspnea scores or positive change in dyspnea existed between the control bottles of nasal spray and the midazolam when looking closer into age, gender, baseline anxiety, depression, and disease. The greatest benefit was seen at 30 minutes after the use of both the control spray and the midazolam, with no difference between the two groups. When questioned about adverse events, participants revealed that side effects worse than they were at baseline were low grade and most likely from the use of the nasal spray, with the most common being nasal cavity irritation and sinus reactions.
The study failed to demonstrate a meaningful benefit of intranasal midazolam on dyspnea or anxiety. Though the nasal cavity is thought to be a good way to deliver the effects of medications quickly, intranasal midazolam did not effectively relieve the participants’ dyspnea.
The study findings demonstrated that intranasal midazolam was not effective in relieving dyspnea. This study magnified the importance of finding ways to better control dyspnea in terminally ill patients and the impact on quality of life if not done. The effectiveness of benzodiazepines on dyspnea needs further investigation, and nurses should continue with the administration of low-dose opioids to treat patient dyspnea, as this remains the evidence-based medication of choice.