Association of remimazolam with delirium and cognitive function: A systematic review and meta-analysis of randomised controlled trials.

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; I2  = 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; I2  = 90%) or on the third postoperative day ( n  = 163; mean difference  = 1.33, 95% CI, -0.72 to 3.38; P  = 0.2028; I2  = 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; I2  = 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.

References:

• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association Publishing; 2022.
• Hamilton GM, Wheeler K, Di Michele J, et al. A systematic review and meta-analysis examining the impact of incident postoperative delirium on mortality. Anesthesiology 2017; 127:78–88.
• Maldonado JR. Acute brain failure: pathophysiology, diagnosis, management, and sequelae of delirium. Crit Care Clin 2017; 33:461–519.
• Goldberg TE, Chen C, Wang Y, et al. Association of delirium with long-term cognitive decline: a meta-analysis. JAMA Neurol 2020; 77:1373–1381.
• Zaal IJ, Devlin JW, Hazelbag M, et al. Benzodiazepine-associated delirium in critically ill adults. Intensive Care Med 2015; 41:2130–2137.