The American Society of Anesthesiologists (ASA) and the Society of Pediatric Anesthesia (SPA) are alerting anesthesia providers of reported rare but severe neurologic injury and death following routine anesthesia in adult and pediatric patients of Venezuelan ancestry. Reports initially came from South American anesthesia societies last summer, but additional cases in the United States and Europe have since been identified.

Affected patients were previously healthy and most reportedly received sevoflurane, although all the drugs administered and their doses, concentrations and durations are unknown. Although available data are incomplete and largely derived from case reports and expert communication, the severity and consistency of these events prompted issuance of interim clinical guidance.

Genetic testing has revealed that a subset of patients carried a mitochondrial ND4 mutation, affecting complex I of the electron transport chain, a known target of volatile anesthetics. There is no point-of-care screening test, and patients may be asymptomatic until anesthetic exposure. All affected patients were of Venezuelan heritage. Several also had family members who had experienced adverse outcomes after the use of anesthesia.

The ASA and SPA have compiled an initial set of recommendations for doctors providing anesthesia, acknowledging they “are broad and somewhat imprecise” because “much more is unknown than known.” These include:

1. Screening for risk – It is recommended to ask patients about potential maternal Venezuelan heritage as this population may be considered at risk. Be prepared to respond to concerns from patients about these questions with care and sensitivity.
2. Genetic testing – Mitochondrial DNA sequencing of patients and/or relatives can confirm the presence of the mutation. Testing laboratories should be alerted of the specific mutation (mtNDF m.11232T>C) as many have historically interpreted it as a normal variant. Informed consent should be obtained from patients or caregivers.
3. Clinical management – The decision to proceed should be informed by the urgency of the procedure. If proceeding with a patient considered to be at risk, consider avoiding sevoflurane, utilizing regional anesthesia and/or implementing non-implicated drugs such as midazolam, dexmedetomidine, ketamine and short/ultra-short-acting opioids. Anesthetic depth monitoring with processed EEG may be advisable, though it is still unknown if a rapid change in EEG activity is seen in this patient population. Patients should be monitored after general anesthesia for return to baseline.

Both the SPA and ASA will continue to monitor cases and will periodically update their resources and recommendations on this matter at ASAhq.org/advocating-for-you/guidance/asa-and-spa.