Effects of Anticholinergics on Death Rattle: A Systematic Review and Network Meta-Analysis

Background: Anticholinergics have been used to treat death rattle (DR) in dying patients with palliative care. However, the effect of anticholinergics is still controversial. No quantitative summary of their effects is reported. Objective: This study aimed to systematically review and quantitatively synthesize the effect of anticholinergics on DR treatment and prophylaxis. Design: A systematic search was performed in the electronic databases (PubMed, Embase^®, and Cumulative Index to Nursing and Allied Health Literature [CINAHL]) from inception to October 2021. Studies conducted to determine the effect of anticholinergics compared with other anticholinergics or placebo on noise reduction score in dying patients were included. A network meta-analysis was performed for DR treatment. The effect of anticholinergics at four hours was assessed. A pairwise meta-analysis was performed for DR prophylaxis. Results: A total of nine studies were included with 1103 patients. Six studies were randomized controlled trials, and three studies were cohort studies. Seven studies were conducted for DR treatment, while two studies were conducted for DR prophylaxis. For DR treatment, no statistically significant difference was observed between each anticholinergic (hyoscine hydrobromide, hyoscine butyl bromide, atropine, and glycopyrrolate) and placebo and among any anticholinergics. However, the surface under cumulative ranking curve indicated that hyoscine butyl bromide had the highest surface under the cumulative ranking curve (SUCRA) with 71.3%. For DR prophylaxis, the relative risk of DR occurrence for hyoscine butyl bromide was 0.23 (0.04, 1.18; I² = 84.5%) compared with no treatment. Conclusion: This study showed no strong evidence of the regular use of anticholinergics for DR treatment. In addition, hyoscine butyl bromide appears to have a high potential for DR prophylaxis.