New and Old: Revisiting Perioperative Pharmacology

Megan Rolfzen, MD

This session, titled “Perioperative Drug Choices, What’s New?, held Saturday, May 2, at the 2026 Annual Meeting, presented by IARS and SOCCA, provided a high-level evidence review of three agents that are either being repurposed or developed as potential successors of prior anesthetics. Moderated by Igor Abramovich, MD, PhD, an assistant professor in the Department of Anesthesia and Perioperative Care at the University of California, San Francisco (UCSF), the panel topics centered on the “propofol successor,” ciprofol (also known as HSK3486), the molecularly engineered sedative remimazolam, and the surprising resurgence of the field’s oldest inhaled agent, nitrous oxide. The consensus among the speakers was that pharmacologic selection is nuanced and context dependent.

Chanhung Lee, MD, PhD, professor of anesthesia and chief of neuroanesthesia at University of California, San Francisco (UCSF), opened the session by posing a provocative question: “Nitrous oxide, is it gone yet?” Despite being synthesized in 1772 and first used in dental practice in 1844, the use of nitrous oxide remains controversial due to its environmental impact and side-effect profile. Dr. Lee referenced the landmark ENIGMA-II trial, an international, randomized, single-blind trial in 7,112 patients undergoing major noncardiac surgery, which supported the drug’s overall safety profile but highlighted its high emetogenic potential. However, the “laughing gas” of old is finding a sophisticated new life in neurosurgical mapping. Because of its minimal cortical suppression effects, nitrous oxide, as an adjunct, has shown feasibility in facilitating asleep microelectrode recording for deep brain stimulation placement and for identifying target nuclei. This approach has been documented in a 2025 retrospective single-center case series.

While nitrous oxide looks to the past, Olivier Duranteau, MD, PhD, MSc, a burn fellow at Sunnybrook Health Sciences Center in Toronto, Canada and a research fellow in the Department of Anesthesiology at Erasme Hospital in Anderlecht, Belgium, focused on the precision engineering of the present. He detailed the expanding role of remimazolam. By inserting a carboxylic ester moiety into the midazolam scaffold, researchers created a drug that undergoes rapid hydrolysis by tissues esterases (CES1) into an inactive metabolite. This organ-independent, CYP450-free metabolism results in a context-sensitive half-time of only 7-8 minutes, which is the main differentiator that allows for prolonged procedural sedation without the accumulation seen with midazolam. Dr. Duranteau noted that while remimazolam is currently FDA-approved in the US for procedural sedation lasting less than 30 minutes, it is approved for general anesthesia in other countries. Meta-analyses suggest that remimazolam-based total intravenous anesthesia may offer reduced postoperative nausea and vomiting and faster emergence compared to sevoflurane. However, there are limitations. Remimazolam precipitates in Ringer’s and Plasma-Lyte solutions, and its cost might still be prohibitive. More research is required; Phase 3 trials for use in general anesthesia have not begun.

The final presentation by Felix Borngaesser, MD, a clinician-scientist at University Clinic of AINS, Carl von Osietzky University OL in Germany, focused on ciprofol (HSK3486), an R-enantiomer that is 4-5 times more potent than propofol. The impetus behind ciprofol formulation is to maintain the rapid onset and hypnotic efficacy of propofol while mitigating its most frequent adverse effects: respiratory depression and injection pain. A multicenter, randomized (2:1), double-blind, propofol-controlled, phase 3 study evaluating HSK3486 for general anesthesia induction in 255 adults undergoing elective surgery with tracheal intubation found ciprofol to be noninferior for general anesthesia induction while causing less injection site pain. Safety outcomes for ciprofol also appear promising, with data indicating fewer hypotensive events and less respiratory depression than traditional propofol. Despite these advantages, Dr. Borngaesser acknowledged that this pharmacologic agent is still in the early stages of global adoption. With most research currently centralized in a single country and international Phase 2/3 studies still on the horizon, propofol remains the preference for cost-constrained settings and protocols relying heavily on Bispectral Index-guided titration.

By contrasting pharmacology, safety profiles, and outcomes, the speakers translated research findings into concrete bedside strategies to expand the anesthesiologist’s toolkit. The “ideal” drug choice is increasingly context dependent. While remimazolam is becoming the drug of choice for hemodynamically unstable patients or those with malignant hyperthermia susceptibility in sedation settings, propofol remains the standard for rapid onset requirements. As anesthesiology moves towards more personalized models of care, these pharmacologic innovations provide the precision needed to tailor the anesthetic to the patient’s specific neurobiological needs.