Incidence and predictors of postoperative delirium following remimazolam administration: a systematic review and meta-analysis of 29 randomized trials

Postoperative delirium is a significant and common complication in surgical patients, particularly in vulnerable populations such as the elderly. Remimazolam, a novel benzodiazepine, has been introduced as an anesthetic agent with a favorable pharmacokinetic profile. However, its potential association with postoperative delirium remains unclear. This study aims to systematically synthesize available evidence on the incidence of delirium following remimazolam administration in surgical patients. We sought to identify significant moderators of delirium incidence and to explore predictors of delirium through meta-regression analysis. A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar, up to May 20, 2024. The search was updated on Feb 2nd, 2025. Randomized trials were selected based on predefined criteria, and data on patient characteristics, surgical details, and delirium incidence were extracted. A meta-analysis was performed to calculate the pooled incidence rate of delirium, and subgroup and meta-regression analyses were conducted to identify incidence rate moderators. A total of 29 RCTs, including 2,435 patients, were analyzed. The pooled incidence of postoperative delirium following remimazolam administration was 5% (95%CI: 3-7%). ASA III-IV patients had a delirium rate of 19% (95%CI: 15-23%) compared to 1% (95%CI: 0-1%) for ASA I-II. Age was a key factor, with children showing the highest rate (11%, 95%CI: 3-19%), followed by elderly patients (8%, 95%CI: 4-13%), while adults had the lowest (1%, 95%CI: 0-2%). Delirium incidence was highest in oncologic (16%, 95%CI: 0-34%) and orthopedic surgeries (12%, 95%CI: 9-14%), and lowest in gastrointestinal and endoscopic procedures (0%, 95%CI: 0-1%). High-dose remimazolam was linked to the lowest delirium incidence, while moderate doses had higher rates. Meta-regression identified surgery type as the primary predictor, with orthopedic surgery having the highest risk compared to laparoscopic and abdominal procedures (coefficient = 0.081, p = 0.03). Postoperative delirium occurs in 5% of surgical patients following remimazolam administration. Key moderators include ASA classification, age, surgery type, and anesthetic dosing. Remimazolam may be safely used in surgical patients, particularly when higher doses are administered, but caution is warranted in high-risk populations such as elderly patients and those undergoing complex surgical procedures.