Remimazolam in older surgical patients: postoperative delirium, hemodynamic stability, and mechanistic considerations

Abstract

The growing number of older adults undergoing surgery has increased interest in anesthetic strategies that preserve physiological stability without worsening postoperative neurocognitive outcomes. Remimazolam is an ultra-short-acting benzodiazepine that produces hypnosis through positive allosteric modulation of the γ -aminobutyric acid type A (GABA-A) receptor and is rapidly hydrolyzed to the low-activity metabolite CNS7054. This focused narrative review examines remimazolam in older surgical patients, with particular emphasis on postoperative delirium (POD) and hemodynamic stability. Randomized trials and meta-analyses generally report fewer hypotensive events with remimazolam than with propofol, but neurocognitive findings are heterogeneous. Earlier trials in orthopedic, hip, gastrectomy, and abdominal surgery largely reported similar POD incidence, and one trial in frail patients undergoing hip surgery reported a lower POD incidence with remimazolam. In contrast, a 2026 randomized non-inferiority trial involving 455 patients aged ≥65 years undergoing lung resection found a higher overall incidence of delirium with remimazolam (48% vs. 31%), driven predominantly by emergence delirium in the post-anesthesia care unit (46% vs. 28%), whereas delirium after post-anesthesia care unit discharge through postoperative day 3 was similar (4% vs. 5%). This temporal distinction indicates that outcome definitions and assessment windows materially influence apparent treatment effects. PACU delirium is also associated with subsequent adverse outcomes in observational studies, underscoring the clinical importance of this early phenotype. The relatively consistent hemodynamic advantage of remimazolam should therefore be regarded separately from neurocognitive benefit; reduced hypotension has not yet been shown to translate into delirium prevention. Preclinical anti-inflammatory and organ-protective pathways are biologically plausible but remain unconfirmed at clinically relevant neurocognitive endpoints. Current evidence supports individualized use rather than routine selection of remimazolam for delirium prevention.