Association of remimazolam with delirium and cognitive function

BACKGROUND AND STUDY OBJECTIVE Delirium is an organic mental syndrome significantly associated with long-term cognitive decline, increased hospital stays and higher mortality. This systematic review of randomised controlled trials (RCTs) with meta-analysis assesses the association of remimazolam with postoperative cognitive function and delirium compared with non-benzodiazepine hypnotics. DESIGN Systematic review of RCTs with meta-analysis. DATA SOURCES PubMed, Embase, Cochrane Library and Web of Science databases up to 27 April 2024. ELIGIBILITY CRITERIA Adult patients undergoing general anaesthesia or sedation procedures; use of remimazolam as the primary hypnotic or as an adjunct, administered via intermittent bolus or continuous infusion; comparison with other hypnotics or sedatives; evaluation of cognitive function or delirium. MAIN RESULTS Twenty-three RCTs with 3598 patients were included. The incidence of delirium was not significantly different between remimazolam and other sedatives in general anaesthesia and sedation procedures [ n = 3261; odds ratio (OR) = 1.2, 95% confidence interval (CI), 0.76 to 1.91; P = 0.378843; I 2 = 17%]. Regarding cognitive function evaluation, remimazolam showed no difference compared with the control group in Mini-Mental State Examination (MMSE) scores on the first postoperative day ( n = 263; mean difference = 0.60, 95% CI, −1.46 to 2.66; P = 0.5684; I 2 = 90%) or on the third postoperative day ( n = 163; mean difference = 1.33, 95% CI, −0.72 to 3.38; P = 0.2028; I 2 = 93%). Remimazolam exhibited superiority over the control group in MMSE scores on the seventh postoperative day ( n = 247; mean difference = 0.53, 95% CI, 0.30 to 0.75; P < 0.0001; I 2 = 28%). CONCLUSION Remimazolam does not increase the incidence of delirium or cognitive impairments compared with non-benzodiazepine hypnotics. However, the analysis showed that the type of surgery significantly influenced the incidence of delirium. Additionally, remimazolam was associated with better short-term postoperative cognitive function. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42024532751.