Prophylactic scopolamine butylbromide reduces death rattle at end of life: JAMA

Health care professionals often struggle with death rattle because of the uncertainty about management.

Clinical guidelines recommend anticholinergic drugs to reduce the death rattle after non pharmacological measures fail, evidence regarding their efficacy is lacking.

A new study by Dr Harriette J. van Esch, MD and team has reported that prophylactic subcutaneous scopolamine butylbromide reduces death rattle in patients. This study is published in JAMA Network.

The objective of the study was to determine whether administration of prophylactic scopolamine butylbromide reduces the death rattle.

The study was a multicentered, randomized, double-blind, placebo-controlled trial conducted in 6 hospices in the Netherlands. Patients with a life expectancy of 3 or more days who were admitted to the participating hospices were asked to give advance informed consent from April 10, 2017, through December 31, 2019. When the dying phase was recognized, patients fulfilling the eligibility criteria were randomized. Of the 229 patients who provided advance informed consent, 162 were ultimately randomized. The date of final follow-up was January 31, 2020. Administration of subcutaneous scopolamine butylbromide, 20 mg four times a day (n = 79), or placebo (n = 78) was given. The primary outcome was the occurrence of a grade 2 or higher death rattle as defined by Back (range, 0-3; 0, no rattle; 3, rattle audible standing in the door opening) measured at 2 consecutive time points with a 4-hour interval. Secondary outcomes included the time between recognizing the dying phase and the onset of a death rattle and anticholinergic adverse events.

The results of the study were found to be

• A total of 162 patients were randomized, 157 patients (97%; median age, 76 years [IQR, 66-84 years]; 56% women) were included in the primary analyses.

• A death rattle occurred in 10 patients (13%) in the scopolamine group compared with 21 patients (27%) in the placebo group (difference, 14%; 95% CI, 2%-27%, P = .02).

• Regarding secondary outcomes, an analysis of the time to death rattle yielded a subdistribution hazard ratio (HR) of 0.44 (95% CI, 0.20-0.92; P = .03; cumulative incidence at 48 hours: 8% in the scopolamine group vs 17% in the placebo group).

• In the scopolamine vs placebo groups, restlessness occurred in 22 of 79 patients (28%) vs 18 of 78 (23%), dry mouth in 8 of 79 (10%) vs 12 of 78 (15%), and urinary retention in 6 of 26 (23%) vs 3 of 18 (17%), was found.

Dr Esch and team concluded that "Among patients near the end of life, prophylactic subcutaneous scopolamine butylbromide, compared with placebo, significantly reduced the occurrence of the death rattle."

For further information: van Esch HJ, van Zuylen L, Geijteman ECT, et al. Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of Life: The SILENCE Randomized Clinical Trial. JAMA. 2021;326(13):1268–1276. doi:10.1001/jama.2021.14785.