Midazolam is a short-acting intravenous benzodiazepine that sees common use in the operating room (OR) due to its rapid onset of anxiolytic, sedative, and amnestic effects. Previously, it was primarily used for preoperative anxiolysis, but clinical evidence highlights its multifaceted utility in optimizing anesthetic regimens, improving the perioperative patient experience, and safely managing diverse surgical populations.
In the context of general anesthesia, midazolam exhibits a synergistic interaction when co-administered with propofol for induction and maintenance. Clinical studies measuring the endpoints of hypnosis and anesthesia have demonstrated that combining the two agents can significantly reduce propofol dosing requirements. Specifically, the addition of midazolam can reduce the dose of propofol required to achieve anesthesia by up to 52 percent.
This synergistic behavior is theoretically mediated through their concurrent activity at the central nervous system gamma-aminobutyric acid type A (GABA A) receptor complex. Research has found that utilizing midazolam as a co-induction agent with reduced-concentration propofol provides rapid and smooth loss of consciousness without exacerbating the well-documented hypotensive and cardiovascular depressant effects associated with full-dose propofol administration. Furthermore, patients receiving this combination regimen have exhibited improved perioperative amnesia without experiencing clinically prolonged postoperative recovery times.
Beyond its role in anesthetic induction, intravenous midazolam is also beneficial in preventing postoperative nausea and vomiting (PONV). A comprehensive meta-analysis of randomized controlled trials demonstrated that the preoperative or intraoperative administration of midazolam is associated with a significant reduction in overall PONV, specific rates of nausea, and the subsequent need for rescue antiemetic medications within the first 24 hours following surgery. These antiemetic benefits are observed regardless of concurrent opioid use or standard prophylactic antiemetic administration, suggesting that midazolam may exert a direct central antiemetic effect. By reducing the frequency of postoperative nausea, midazolam premedication directly contributes to improved overall patient satisfaction and can be integrated as a cost-effective component of a multimodal therapeutic approach to PONV.
Despite its clear benefits, the perioperative administration of benzodiazepines in older adult populations has historically been cautioned against due to concerns regarding the potential development of postoperative delirium. However, recent large-scale, multicenter prospective cohort studies analyzing older patients undergoing noncardiac surgery have challenged this stance.
Current evidence indicates that there is no significant association between the intraoperative use of midazolam and the incidence of postoperative delirium, a major concern for OR teams, within the first seven days after surgery in patients aged 65 years and older. The safety of midazolam in this demographic is likely attributable to its unique chemical structure, which allows for rapid oxidation and metabolism, thereby preventing prolonged accumulation. Moreover, older patients receiving midazolam have demonstrated significantly lowered postoperative anxiety scores, reinforcing its utility when carefully titrated.
The use of intravenous midazolam in the OR extends far beyond preoperative anxiolysis. Its safety profile, synergy with propofol, and capacity to reduce postoperative nausea drive its use for sedation and amnesia intraoperatively.
References
Grant, M. C., et al. “The Effect of Intravenous Midazolam on Postoperative Nausea and Vomiting: A Meta-Analysis.” Anesthesia & Analgesia, vol. 122, no. 3, 2016, pp. 656-663. Available at: https://doi.org/10.1213/ANE.0000000000000941
Short, T. G., and P. T. Chui. “Propofol and Midazolam Act Synergistically in Combination.” British Journal of Anaesthesia, vol. 67, 1991, pp. 539-545. Available at: https://bjanaesthesia.org/
Li, H., et al. “Effect of Intraoperative Midazolam on Postoperative Delirium in Older Surgical Patients: A Prospective, Multicenter Cohort Study.” Anesthesiology, vol. 142, 2025, pp. 268–277. Available at: https://doi.org/10.1097/ALN.0000000000005276
Bauer, K. P., et al. “Preoperative Intravenous Midazolam: Benefits Beyond Anxiolysis.” Journal of Clinical Anesthesia, vol. 16, 2004, pp. 177–183. Available at: https://doi.org/10.1016/j.jclinane.2003.07.003
Reinhart, D. J., et al. “Outpatient General Anesthesia: A Comparison of a Combination of Midazolam Plus Propofol and Propofol Alone.” Journal of Clinical Anesthesia, vol. 9, 1997, pp. 130–137. Available at: https://doi.org/10.1016/S0952-8180(97)00237-1