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Anecdotal communications, and now published scientific reports, from South American anesthesiology societies, health agencies, and international experts on mitochondrial disorders, describe healthy adult and pediatric patients of Venezuelan lineage developing severe neurologic complications and death following routine general anesthesia. About 10 cases have now been reported in the United States. Despite incomplete and emerging clinical and scientific information, the American Society of Anesthesiologists and the Society for Pediatric Anesthesia felt the severity of the cases warranted an expert opinion communication to inform anesthesiologists and their patients.
1. Family Histories Taken on Subset of Patients
Detailed family histories were taken in a subset of affected patients. These patients were all of Venezuelan lineage, and several had family members who had adverse outcomes after an otherwise uneventful anesthetic. Almost all the affected patients are reported to have received sevoflurane, although the duration and concentrations are unknown.
2. Screening Focuses on Maternal Lineage
Genetic testing performed on a subset of patients identified multiple mitochondrial mutations. A point mutation of the NADH dehydrogenase 4 (ND4) gene (mtND4 m.11232T>C), a subunit of complex I of the mitochondrial electron transport chain was identified. Complex I is a known target of volatile anesthetics and is also known to be inhibited by propofol. Prior work has shown that impaired complex I activity correlates with hypersensitivity to volatile anesthetics in animals and humans. ND4 is inherited maternally through mitochondrial DNA. There is currently no available point-of-care screening test for the ND4 mutation.
3. Recommendations for Screening and Clinical Management to Investigate and Reduce Risk
ASA and SPA recommend that anesthesiologists consider asking patients about potential maternal Venezuelan lineage. Any patient with direct maternal Venezuelan lineage should be considered at risk. Genetic testing should be considered to confirm the presence of the mutation. The urgency of the procedure should inform the decision to proceed. Consider avoiding the use of all volatile anesthetics in patients with maternal Venezuelan lineage until more information is available. Total intravenous anesthesia with depth of anesthesia monitoring processed EEG monitoring should be considered. For those who observe a case with similar complications in any patient, anesthesiologists should report the event locally, as well as to the Anesthesia Incident Reporting System (AIRS), housed within the Anesthesia Quality Institute (AQI) at AIRS Case Entry.
This page is curated by ASA Ad Hoc Committee on Mitochondrial-Associated Sensitivity to Halogenated Agents, and was last updated April 20, 2026.
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