Postoperative delirium under general anaesthesia by remimazolam versus propofol: A systematic review and meta-analysis of randomised controlled trials

J Clin Anesth. 2025 Feb:101:111735. doi: 10.1016/j.jclinane.2024.111735. Epub 2024 Dec 30.

Abstract

Background: Remimazolam, an ultra-short-acting benzodiazepine, has similar clinical effects to propofol for sedation in general anaesthesia. However, it remains uncertain whether remimazolam could increase postoperative delirium (POD) compared with propofol.

Objectives: The purpose of our study was to compare the incidence of POD between remimazolam and propofol as sedative agents in general anaesthesia.

Study design: Systematic review and meta-analysis of randomised controlled trials (RCTs).

Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for prospective RCTs published through September 16, 2024. RCTs reporting the incidence of POD and comparing remimazolam with propofol for general anaesthesia were included. Odds ratio (ORs) were calculated using a random-effects model. The primary outcome was the incidence of POD. The secondary outcomes included time to extubation, awakening time, and adverse events such as intraoperative hypotension.

Results: A total of six RCTs involving 1107 patients were included in this meta-analysis. For the primary outcome, the incidence of POD did not differ between the remimazolam and propofol groups (OR, 0.92; 95 % confidence interval [CI], 0.58-1.44). Regarding the secondary outcomes, remimazolam was associated with a lower incidence of intraoperative hypotension compared with propofol (OR, 0.31; 95 % CI, 0.21-0.46). There were no significant differences in other secondary outcomes. In the sensitivity analysis on three RCTs including only older patients (≥60 years old), there was no significant difference in the incidence of POD (OR, 1.00; 95 % CI, 0.52-1.93).

Conclusion: Perioperative remimazolam administration did not increase POD and reduced the risk of intraoperative hypotension compared to propofol. Further large-scale RCTs are warranted to explore the association of remimazolam and POD. Systematic review protocol: PROSPERO CRD42024544122.

Keywords: General anaesthesia; Intraoperative hypotension; Postoperative delirium (POD); Postoperative delirium and cognitive dysfunction (POCD); Propofol; Remimazolam.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Comparative Study
  • Review

MeSH terms

  • Anesthesia, General* / adverse effects
  • Anesthetics, Intravenous / administration & dosage
  • Anesthetics, Intravenous / adverse effects
  • Benzodiazepines* / administration & dosage
  • Benzodiazepines* / adverse effects
  • Delirium / chemically induced
  • Delirium / epidemiology
  • Delirium / prevention & control
  • Emergence Delirium / epidemiology
  • Emergence Delirium / prevention & control
  • Humans
  • Hypnotics and Sedatives* / administration & dosage
  • Hypnotics and Sedatives* / adverse effects
  • Hypotension / chemically induced
  • Hypotension / epidemiology
  • Incidence
  • Postoperative Complications / epidemiology
  • Postoperative Complications / prevention & control
  • Propofol* / administration & dosage
  • Propofol* / adverse effects
  • Randomized Controlled Trials as Topic*

Substances

  • Propofol
  • remimazolam
  • Hypnotics and Sedatives
  • Benzodiazepines
  • Anesthetics, Intravenous