Malignant hyperthermia, a pharmacogenetic disorder of skeletal muscle, is a potentially fatal reaction triggered by exposure to volatile anesthetics or succinylcholine. Genetic testing of the three known involved genes (RYR1, CACNA1S, and STAC3) has become the first line of testing for malignant hyperthermia susceptibility. However, genetic testing has sensitivity of only up to 70%. Contracture testing may be used to rule out the disorder for some individuals. This study outlines a stepwise approach, using clinical history and assessment as well as interpretation of genetic variants to balance risks and benefits for individuals at risk of this disorder. This work has received an Affirmation of Value designation from the American Society of Anesthesiologists (Schaumburg, Illinois) and endorsement from the Canadian Anesthesiologists’ Society (Toronto, Canada).

Propofol emulsion, a widely used anesthetic in clinical practice, can lead to propofol infusion syndrome (PRIS) when improperly administered. PRIS is characterized by dyslipidemia and cytotoxic damage, particularly affecting peripheral neutrophils. Using an ex vivo whole blood model followed by flow cytometric analysis, this study elucidates the mechanisms underlying PRIS-induced cytotoxicity. Significant lipid droplet accumulation and increased neutrophil cell death were observed, with cell granularity correlating strongly with lipid droplet levels. Apoptosis was confirmed via cleaved caspase-3 detection and Western blot analysis, while necroptosis and pyroptosis were associated with increased pRIPK1 and cleaved caspase-1 expressions. A multicolor cytometric method identified elevated PANoptosis, characterized by the combined activation of these pathways. Inhibition of lipid lipase reduced lipolysis and lipid droplet accumulation, highlighting the role of free fatty acid in PANoptosis induction. Reactive oxygen species (ROS), particularly mitochondria-related ROS, were significantly elevated and correlated with lipid droplet levels. Mitochondrial dysfunction, indicated by a loss in mitochondrial transmembrane potential, was mitigated by ROS inhibitors, which also reduced PANoptosis. The study's findings suggest that free fatty acid and lipid droplet accumulation, in conjunction with oxidative stress, promote overdose propofol emulsion-induced PANoptosis, providing promising therapeutic targets to mitigate cytotoxic effects and offering novel insights into the early detection or therapeutic intervention of immune dysfunction associated with PRIS.

Cataract surgeries are among the most common outpatient procedures in the United States, typically accomplished with topical anesthesia and light sedation. Evidence demonstrates no benefit for comprehensive preoperative medical evaluation before low-risk procedures. In 2019, the Centers for Medicare & Medicaid Services (Baltimore, Maryland) revised regulations for hospitals and ambulatory surgery centers, eliminating the previous requirement for a history and physical examination within 30 days of ambulatory surgeries, regardless of risk. Professional guidance from the Society for Ambulatory Anesthesia (Milwaukee, Wisconsin) and the American Academy of Ophthalmology (San Francisco, California) confirms that routine, comprehensive evaluation before cataract surgeries is nonbeneficial. Despite alignment of evidence, regulatory guidance, and expert consensus, implementation has been inconsistent. Unnecessary evaluations delay care and create barriers for patients with vision impairment. This article describes efforts to streamline preoperative evaluation for low-risk eye surgeries and underscores the ethical imperative of reducing low-value practices in perioperative medicine, particularly for vulnerable patient populations.

Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort. By Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelson C, Gleich SJ, Schroeder DR, Weaver AL, and Warner DO. A nesthesiology 2009; 110:796-804. Reprinted with permission. Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities. This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with learning disabilities. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of learning disabilities, adjusting for gestational age at birth, sex, and birth weight. Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of learning disabilities (hazard ratio, 1.0; 95% CI, 0.79 to 1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for learning disabilities (hazard ratio, 1.59; 95% CI, 1.06 to 2.37; and hazard ratio, 2.60; 95% CI, 1.60 to 4.24, respectively). The risk for learning disabilities increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable; P = 0.016). Exposure to anesthesia was a significant risk factor for the later development of learning disabilities in children receiving multiple but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to learning disabilities or whether the need for anesthesia is a marker for other unidentified factors that contribute to learning disabilities.