Episode #306 Venezuelan Ancestry Anesthesia Alert

Opening Clip: There are reports of healthy adults and pediatric patients of Venezuelan ancestry under going routine general anesthetic who have suffered unexpected catastrophic outcomes including severe neurologic damage and death. Keep your practice up to date and your patients safe with these new recommendations for patients of Venezuelan ancestry from the ASA and SPA.

• “Anesthesia professionals should consider asking patients about maternal Venezuelan heritage. A negative family history of anesthetic complications does not eliminate risk. Any patient with direct maternal Venezuelan lineage should be considered at risk.
• Anesthesia professionals should handle questions regarding Venezuelan ancestry and associated explanations with care and sensitivity.
• Anesthesia professionals should consult with genetic experts regarding testing at-risk patients and laboratories should be alerted to the specific ND4 gene mutation.”

Hello and welcome back to the Anesthesia Patient Safety Podcast. I’m your host, Alli Bechtel.

Before we dive further into the episode today, we’d like to recognize Medtronic corporate supporter of APSF. Medtronic has generously provided unrestricted support to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Medtronic – we wouldn’t be able to do all that we do without you!”

Our featured article is “Perioperative Practices for Patients of Venezuelan Ancestry” by Megha Karkera Kanjia and colleagues. This article is an APSF Article Between Issues published online March 13, 2026. To follow along with us, head over to APSF.org and click on the Newsletter Heading. The second one down is APSF Articles Between Issues. Then, you can scroll down until you get to our featured article, and I will include a link in the show notes as well.

Concerns were first raised by anaesthesiology societies in South American of sporadic anecdotal reports of otherwise healthy patients of Venezuelan descent who developed significant neurologic injury following uneventful anaesthetics. This has led to the American Society of Anesthesiologists and the Society for Pediatric Anesthesia and Wake Up Safe groups issuing a joint statement warning about these safety concerns in July 2025. This warning was then updated in January 2026 with additional details including the following:

• The high risk patients have maternal Venezuelan ancestry
• There may be a specific genetic mitochondrial mutation combined with sevoflurane and the combination may lead to a catastrophic outcome.

We are still learning more about this, and it has been difficult to figure out what is going on. Family histories have been inconsistent with some patients reporting family members with adverse events related to anesthesia and others reporting no family history of problems with anesthesia in the past. We have seen that all of the events occurred following an anaesthetic with Sevoflurane. Genetic testing has found that the implication most implicated is the NADH dehydrogenase 4 gene located in Complex 1 of the Electron Transport Chain. Volatile anesthetics and propofol both interact with Complex 1 and may increase the risk, but it is more complicated than that. Additional mitochondrial genomic variants have been found in affected patients so there may be genetic heterogenicity. Let’s look at this a little closer. Mitochondrial mutations may be homoplasmic or heteroplasmic and this depends on the number of mitochondria carrying the mutation. The severity of the reaction to the anesthetic likely depends on the amount of affected mitochondria. The cases that have been studied so far have been shown that the patients were homoplasmic, meaning 100% of the mitochondria carried the mutation. Mitochondrial DNA is maternally inherited so the mutation would likely be present in all offspring of an affected mother. So, if this is confirmed, the other and all siblings of an affected child would carry the same mutation.

Patients with this specific mitochondrial gene mutation have a significant hypersensitivity to inhaled anesthetics which looks like patients with severe mitochondrial complex 1 disease. We still don’t know if propofol can cause the same adverse reaction since long-term outcome data are limited. This is an important area for careful consideration and research especially for patient receiving propofol infusions. At this time, all of the reported adverse events have followed exposure to Sevoflurane.

Let’s review the current recommendations for patients of Venezuelan ancestry from the ASA and SPA. I will include the links to these updates in the show notes as well.

Here are the recommendations for screening patients:

1. Anesthesiologists should 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.

Next up, here are the recommendations for genetic testing:

1. Mitochondrial DNA sequencing of patients and/or their maternal relatives may be available to confirm the presence of the mutation. Additionally, it is important to alert testing laboratories of the specific mutation of interest, which you can find in the show notes. 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.
3. Informed consent should be obtained from the patient or authorized caregiver for any genetic testing.

And now we come to the recommendations for clinical management based on the current evidence:

1. The urgency of the procedure should inform the decision to proceed with the anesthetic.
2. 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.”

We hope that you will check out the ASA and SPA Updates as well.

Further research will help to answer important questions including the following:

• What is the prevalence and penetrance of this mutation in the population?
• Are there specific levels of anesthetic or a type of anesthetic that causes the most significant reactions?
• Is this mitochondrial mutation the only mutation that can cause this reaction or are there other mutations or nucleotide interactions that can cause this reaction as well?

Research is needed in this area to help keep patients safe during anesthesia care. In addition, SPA and ASA will continue to monitor for cases and update recommendations as needed. If you observe similar complications to those described on the podcast today, we hope that you will consider reporting the event locally and consider reporting cases to a patient safety organization and the Anesthesia Incident Reporting System that is housed within the Anesthesia Quality Institute. I will include the link in the show notes. These reports are confidential and protected as a federally designated patient safety organization. Submitting a report to the Anesthesia Incident Reporting System is the best way to bring together known or suspected cases in a central protected registry.

Another way to help keep your patients safe is to use appropriate screening questions to identify high-risk patients. These questions can be sensitive so it is important to provide a short explanation for why the questions is being asked. It is also important to highlight that these questions are not related to immigration status. Some pediatric hospitals use a scripted approach to this topic along with informational handouts available in the preoperative area for patients and families. Here is an example that you may be able to use for screening pediatric patients:

“All children respond to anesthesia medications differently. We are currently learning that some children respond differently to specific medications which we commonly use, and recently a link has been reported around children of a specific background. Our goal is to provide the best anesthetic and select the best medications for your child, so we are asking families about their ancestry. In some case reports, children born to mothers of Venezuelan ethnicity, have had challenges in metabolizing medications that we commonly use. We are avoiding specific medications which may be more difficult for them to break down if we have this information about the maternal ancestry.”

Anesthesia professionals should highlight that there are safe anesthetic options for patients who may have mitochondrial defects and the best medications will be selected based on the patient’s history and other comorbidities. Going forward, it will be important to stay up to date with any new evidence or new approaches as we learn more about this mutation and the interactions with anesthetic medications.

If you have any questions or comments from today’s show, please email us at [email protected]. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today.

We are excited to announce the 2026 APSF Trainee Quality Improvement Patient Safety Recognition Program. This program hosts tracks for physician anesthesiology residents nurse anesthesia students, and student anesthesiology assistants. Eligible participants include current trainees and those who graduated in the immediately prior academic year. This is your chance to demonstrate your program’s work in patient safety and QI initiatives. The winner in each track will be notified around August 1, 2026 and the APSF will sponsor the winners to attend the 2026 Stoelting Conference in National Harbor Maryland to share your work and network with attendees. Here’s how to submit your work. You may independently determine he best media for submitting your project summary. Acceptable formats include a document or an audio or video recording. The submission deadline is June 1, 2026 so you have some time to get organized and excited to submit your best work and support he APSF vision. Check out the show notes for more information about the submission process. You can also email [email protected] with any questions.

Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

© 2026, The Anesthesia Patient Safety Foundation