Joint Communication from the American Society of Anesthesiologists and the Society for Pediatric Anesthesia

Update regarding severe neurological complications and death after general anesthesia in adult and pediatric patients of Venezuelan ancestry (January 27, 2026)

The latest guidance and updates can be found at asahq.org/raregenemutation (April 2026)

Recent communications from South American anesthesia societies describe healthy adult and pediatric patients of Venezuelan ancestry who have had unexpected catastrophic outcomes, including severe neurologic damage with basal ganglia infarcts and death, after routine anesthetic exposures. Since word of these cases has spread, additional cases in Europe and the United States have been identified.

Most of what is known about the clinical cases has been shared only through personal communication or non-peer-reviewed publications. Although complete anesthetic and medical records are protected health information and, therefore, not accessible in most cases, the Society for Pediatric Anesthesia (SPA) and the American Society of Anesthesiologists (ASA) believe the severity of these cases warrants developing and sharing expert opinion despite incomplete and emerging clinical and scientific information.

Detailed family histories were taken in a subset of affected patients. These patients were all of Venezuelan heritage, 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. A few of the patients reportedly received propofol infusions without incident. Critically, we do not know the granular details of each anesthetic. Thus, it is impossible to know all the drugs administered to each patient, their doses, concentrations, and/or durations. There is also limited information on the use of depth-of-anesthesia monitoring in these cohorts.

Genetic testing performed on a subset of these patients identified multiple mitochondrial mutations. The best described, at this time, is 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. 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.  There is currently no available point-of-care screening test for the ND4 mutation.

ND4 is a protein subunit of complex I that is maternally inherited through mitochondrial DNA. In this population, patients expressing the mutant gene do not appear to exhibit significant signs of mitochondrial dysfunction until anesthetic exposure. Inhibition of complex I by volatile anesthetics can decrease ATP production, thereby suppressing central nervous system activity. Propofol may also inhibit mitochondrial function at multiple sites, including complex I. However, the relative risks between sevoflurane and propofol in these patients are unknown at this time.

These recommendations are provided in a situation where much more is unknown than known. As a consequence, these recommendations are broad and somewhat imprecise. Anesthesiologists must use their own knowledge and judgment on how to approach this issue with their patients. ASA and SPA will update these recommendations as more information becomes available.

Screening for Risk

1. At this time, we 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.
2. Anesthesiologists should be prepared to respond to concerns from patients about questions regarding Venezuelan ancestry and should approach these questions and associated explanations with care and sensitivity.

Genetic Testing

1. Mitochondrial DNA sequencing of patients and/or their maternal relatives is available to confirm the presence of the mutation. Additionally, it is important to alert testing laboratories of the specific mutation of interest (mtND4 m.11232T>C). Historically, laboratories have interpreted this mutation as a normal variant. The genetic laboratory should be asked to report whether this mutation is present or absent.
2. Anesthesiologists should consider consulting their local genetics experts to identify laboratories that can perform genetic testing in patients at risk and to assist in the management of any patients or families found to have the mutation of concern (mtND4 m.11232T>C).
3. Informed consent should be obtained from the patient or authorized caregiver for any genetic testing. 

Clinical Management

The urgency of the procedure should inform the decision to proceed with the anesthetic.

In the absence of definitive genetic testing, if the decision is made to proceed with anesthesia and the patient is considered to be at risk, the anesthetic plan should be developed considering the following:

1. The optimal and safest anesthetic for patients with this ND4 mutation has not been established.
1. Given the majority of affected patients are reported to have received sevoflurane, consider avoiding the use of all volatile anesthetics until more information is available.
2. Regional anesthesia should be considered for appropriate patients and procedures.
3. Based on verbal reports, patients who have had complications from sevoflurane-based anesthetics have had uneventful propofol anesthetics. It is not yet known whether prolonged use of propofol infusions is safe in this population.
4. Midazolam, dexmedetomidine, ketamine, and short/ultra-short-acting opioids have not been implicated.   
2. Anesthetic depth monitoring with processed EEG to avoid burst suppression may be advisable. Some patients with complex I gene mutations show a rapid change (decrease) in EEG activity with exposure to volatile anesthetics. It is unknown, at this time, if this rapid change is seen in patients of Venezuelan ancestry with the mutation.
3. Patients at risk should be monitored after general anesthesia for return to their neurocognitive baseline. Consider extended postoperative observation and monitoring of acid-base status if complications are suspected.

SPA and ASA will continue to monitor cases and publish more detailed recommendations as supported by the latest evidence.

Should similar complications to those described above be observed in any patient, anesthesiologists should report the event locally, as well as consider reporting cases to their facility patient safety organization (PSO) and the Anesthesia Incident Reporting System (AIRS), housed within the Anesthesia Quality Institute (AQI) at AIRS Case Entry. AIRS reports are confidential and protected by AQI's status as a federally designated PSO. Submission to AIRS will provide the best ability to collate and analyze known or suspected cases in a central protected registry.

Useful resources, including the prior ASA and SPA communication on this subject, are being compiled and will be periodically updated.

Anesthesiologists may submit questions on this issue and this joint communication to ASA Quality and Regulatory Affairs at [email protected].

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