Rare Gene Mutation in Some with Venezuelan Ancestry Linked to Severe Neurologic Complications and Death After General Anesthesia

CHICAGO – The American Society of Anesthesiologists (ASA) and the Society for Pediatric Anesthesia (SPA) today issued an updated joint communication regarding severe neurologic complications, including stroke and death, in healthy adult and pediatric patients of Venezuelan ancestry following routine general anesthesia. There have been about 36 known or suspected cases worldwide, the majority in South American countries, with six in the United States and eight in Europe.

Detailed family histories of patients who were recently affected revealed that all were of Venezuelan heritage and several had family members who also had adverse outcomes after an otherwise uneventful anesthetic. Genetic testing on a subset of the patients found a genetic mutation in mitochondrial DNA, known as the ND4 mutation.

In July 2025, anecdotal communications from South American anesthesiology societies described cases of patients having severe complications from general anesthesia. Despite incomplete and emerging clinical and scientific information, ASA and SPA felt the severity of the cases warrant an expert opinion communication to inform anesthesiologists and their patients.

In the updated communication ASA and SPA recommend:

• Anesthesiologists consider asking their patients about potential maternal Venezuelan heritage. However, a negative family history of anesthetic complications does not rule out the risk caused by this type of genetic mutation. All mitochondrial DNA is inherited directly from the mother. Therefore, any patient with direct maternal Venezuelan lineage should be considered at risk.
• Anesthesiologists should handle questions regarding Venezuelan ancestry and associated explanations with care and sensitivity.
• Anesthesiologists should consult with genetic experts regarding testing at-risk patients and laboratories should be alerted to the specific ND4 gene mutation.

The communication also notes that even though the optimal and safest anesthetic for patients with the ND4 mutation has not yet been established, recommendations are to avoid inhaled anesthetics, consider using regional anesthesia and employ extra monitoring to note any rapid change in brain activity.

Finally, if complications occur in patients with the ND4 mutation, anesthesiologists should report the case to their institutions’ patient safety organization and the Anesthesia Incident Reporting System of the Anesthesia Quality Institute.

About the American Society of Anesthesiologists
Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific society with more than 60,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during, and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/madeforthismoment. Follow ASA on Facebook, X, Instagram, Bluesky, and LinkedIn.

About the Society for Pediatric Anesthesia
The mission of the Society for Pediatric Anesthesia, a non-profit medical society, is to advance the health and well-being of children through perioperative care, research, advocacy, and collaboration among members, patients, families and professional organizations worldwide. The Society serves nearly 5,000 members through continuing medical education activities, research opportunities, and networking. For more information visit www.pedsanesthesia.org.

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