Authors: Megan Rolfzen, MD
IARS Daily Dose, May 3, 2026. “New and Old: Revisiting Perioperative Pharmacology.”
This article reviewed several emerging and re-emerging pharmacologic agents discussed during the 2026 IARS and SOCCA Annual Meeting session titled “Perioperative Drug Choices, What’s New?” The focus centered on how modern anesthetic management is becoming increasingly individualized, with anesthesiologists selecting agents based not only on efficacy, but also on hemodynamic profile, metabolism, recovery characteristics, environmental impact, and patient-specific risks.
One major topic was the continued evolution of nitrous oxide. Although nitrous oxide has historically been criticized for postoperative nausea and vomiting as well as environmental concerns, presenters emphasized that the drug may still have niche applications in modern anesthesia practice. Dr. Chanhung Lee discussed findings from the ENIGMA-II trial, which demonstrated an acceptable overall safety profile in major noncardiac surgery despite the known emetogenic effects of nitrous oxide. More importantly, nitrous oxide is now being explored in neurosurgical applications because of its minimal cortical suppression properties. Recent reports suggest it may facilitate asleep microelectrode recordings during deep brain stimulation procedures by preserving neurophysiologic signaling and helping identify target nuclei more accurately.
The session also examined remimazolam, a newer benzodiazepine-based sedative engineered from the midazolam scaffold. By incorporating a carboxylic ester moiety into the molecular structure, remimazolam undergoes rapid hydrolysis by tissue esterases rather than relying on hepatic CYP450 metabolism. This produces a short context-sensitive half-time of approximately 7–8 minutes and allows prolonged sedation with less accumulation than traditional midazolam. Presenters noted that remimazolam is currently FDA-approved in the United States for procedural sedation lasting less than 30 minutes, although some countries have already approved it for general anesthesia. Meta-analyses suggest remimazolam-based TIVA may reduce postoperative nausea and vomiting and permit faster emergence compared with sevoflurane anesthesia. Limitations include incompatibility with certain IV solutions such as Ringer’s and Plasma-Lyte, as well as ongoing cost concerns. Large Phase 3 studies evaluating use for general anesthesia are still pending.
The final section focused on ciprofol (HSK3486), an R-enantiomer structurally related to propofol but significantly more potent. Ciprofol was designed to preserve the desirable hypnotic profile and rapid onset of propofol while reducing common adverse effects such as injection pain, hypotension, and respiratory depression. A multicenter randomized double-blind Phase 3 trial involving 255 adults undergoing elective surgery demonstrated that ciprofol was noninferior to propofol for induction of general anesthesia and produced less injection pain. Early safety data also suggest lower rates of hypotension and respiratory depression. Despite these promising findings, ciprofol remains in the early stages of international adoption, with most studies originating from a single country and limited global Phase 2 and Phase 3 data currently available. Propofol therefore remains the dominant agent in many settings because of familiarity, lower cost, and compatibility with BIS-guided protocols.
The presenters concluded that anesthetic drug selection is increasingly context dependent and moving toward a personalized medicine model. Remimazolam may become especially valuable for hemodynamically unstable patients or patients susceptible to malignant hyperthermia requiring sedation, while propofol continues to dominate rapid induction settings. Nitrous oxide, despite its age, may retain important specialized applications in neuromonitoring and functional neurosurgery. Overall, the session highlighted how future anesthetic care may rely less on one “best” drug and more on matching pharmacologic properties to specific physiologic and surgical needs.
Key Points
• Nitrous oxide may still have valuable neurosurgical applications despite historical concerns regarding PONV and environmental impact.
• Remimazolam offers rapid organ-independent metabolism with reduced accumulation compared with midazolam.
• Remimazolam-based anesthesia may reduce PONV and speed emergence compared with sevoflurane.
• Ciprofol appears noninferior to propofol for induction while potentially reducing hypotension, respiratory depression, and injection pain.
• Future perioperative pharmacology is increasingly focused on individualized anesthetic selection tailored to patient physiology and procedural goals.
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