This statement was originally published in the SALG Patient Safety Update in June, 2026. It will be updated with any new information as this becomes available.

SALG has been made aware of a recent alert by the American Society of Anaesthesiologists that people of Venezuelan heritage may be susceptible to anaesthetic neurotoxicity due to a mutation in their mitochondrial DNA (specifically, mtND4 m.11232T>C). This mutation is rare in this population, but it has resulted in unexpected catastrophic outcomes after routine anaesthesia in adult and paediatric patients reported by South American anaesthesia societies.

Whilst mitochondrial DNA is of maternal lineage, a negative family history of anaesthetic complications does not exclude this condition. The ASA recommends screening all patients with direct maternal Venezuelan lineage. This will necessitate directly questioning patients as Venezuelan lineage cannot be deduced from names, or routine ethnicity questionnaires. The number of people of Venezuelan descent living in the UK is unknown, as this is not recorded in official data as a separate category, but estimates range between 9,000 and 25,000 depending on the source.

There is no current point of care testing available for this specific mutation, and results can take up to 6 weeks to be returned. When ordering an EDTA test, anaesthetists should specify screening for the specific ND4 mutation when completing the form along with a 10ml blood sample.

Advice on clinical management, which is broadly relevant to UK settings, is included in the alert linked above, and replicated below for ease of reference:  

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

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

1. The optimal and safest anaesthetic for patients with this ND4 mutation has not been established.

2. Given the majority of affected patients are reported to have received sevoflurane, consider avoiding the use of all volatile anaesthetics until more information is available.

3. Regional anaesthesia should be considered for appropriate patients and procedures.

4. Based on verbal reports, patients who have had complications from sevoflurane-based anaesthetics have had uneventful propofol anaesthetics. It is not yet known whether prolonged use of propofol infusions is safe in this population.

5. Midazolam, dexmedetomidine, ketamine, and short/ultra-short-acting opioids have not been implicated.   

6. Anaesthetic 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 anaesthetics. It is unknown, at this time, if this rapid change is seen in patients of Venezuelan ancestry with the mutation.

7. Patients at risk should be monitored after general anaesthesia for return to their neurocognitive baseline. Consider extended postoperative observation and monitoring of acid-base status if complications are suspected.

If similar complications to those described in the alert are observed in any patient, they should be reported through local risk management systems.