Response to “Randomized controlled trial of remimazolam compared with placebo in Japanese patients undergoing upper gastrointestinal endoscopy: Phase III investigator-initiated clinical trial”

Abstract

In their multicenter randomized trial, Ichijima et al.¹ demonstrated that remimazolam achieves significantly better sedation effect during upper gastrointestinal endoscopy than a placebo. However, using a placebo control is questionable, given remimazolam's established efficacy and the typically low placebo effect (<5%). Using widely used sedatives as active comparators would have been more impactful; this limitation of study design reduces the impact of the research findings.

A recent meta-analysis reported propofol's superiority in terms of time to loss of consciousness and sedation success after the first dose, but with no differences in procedural outcomes.² Remimazolam had a better safety profile, showing lower risks of bradycardia, hypoxemia, and injection site pain. A Chinese study of 384 patients undergoing upper gastrointestinal endoscopy reported that the sedation success rate of remimazolam was noninferior to propofol (97.3% vs. 100%), with shorter time to full awakening and fewer circulatory and respiratory issues.³

Considering the potential expansion of remimazolam use over traditional sedatives like midazolam, it is encouraging that studies targeting Asian populations are increasing, as pharmacodynamics and pharmacokinetics of benzodiazepine might vary by ethnicity or genetic polymorphism.⁴ Metabolized by carboxylesterase 1, remimazolam exhibits dose-dependent sedative action and minimal tissue accumulation, largely independent of liver and kidney function. However, recent reports of re-sedation, delayed emergence, and anaphylaxis associated with remimazolam highlight the need for further research on carboxylesterase 1 polymorphism associations.⁵

In conclusion, remimazolam, a new ultra-short-acting benzodiazepine, is notable for its rapid onset, efficacy, and safety, although recent discussions on adverse effects are emerging. Further studies are required to evaluate its efficacy and safety in prolonged sedation for therapeutic endoscopy. Additionally, research on its use in higher risk patients and the benefits of drug combinations with other sedative agents will greatly aid in standardizing its use in endoscopic procedures.

Authors declare no conflict of interest for this article.