Authors: Yanez Hinojosa C I et al.
Anesthesiology, February 18, 2026, 10.1097/ALN.0000000000005935
This report from the Chilean Ministry of Health describes a cluster of severe neurologic complications occurring after general anesthesia in patients with a suspected mitochondrial genetic susceptibility. The events were first recognized when the Chilean Society of Anesthesiology reported several cases of previously healthy children who developed severe neurologic injury following elective surgical procedures. Four of the affected children subsequently died.
In response to these cases, the Chilean Ministry of Health implemented a national surveillance system in July 2025 to identify additional patients who had experienced neurologic injury or death following anesthesia since 2021. Within one week of initiating surveillance, two additional cases were identified, bringing the total number of documented patients to seven.
The cohort included six children and one adult with a median age of five years. Five of the seven patients were male. All patients had mothers of Venezuelan descent, raising the possibility of a shared genetic background. The cases appeared unrelated based on national civil registry records, although distant maternal relatedness could not be completely excluded.
The procedures involved were routine and included dermoepidermal grafting, tendon repair, thoracoscopy, adenotonsillectomy, dental restoration, and inguinal hernia repair. The median duration of surgery was 47 minutes.
All seven patients received sevoflurane anesthesia, with a median exposure of approximately 0.95 minimum alveolar concentration. Six patients also received propofol, and all received fentanyl. Most patients developed neurologic symptoms shortly after anesthesia, typically immediately upon emergence, although symptom onset ranged from zero to ten days postoperatively.
Clinical manifestations included delayed emergence from anesthesia, altered consciousness ranging from drowsiness to coma, abnormal limb movements, cranial nerve dysfunction, corticospinal tract signs, and extrapyramidal symptoms. Neuroimaging frequently demonstrated bilateral basal ganglia involvement with additional abnormalities affecting deep gray matter structures such as the cerebellum and substantia nigra, findings suggestive of hypoxic–ischemic encephalopathy.
Four of the seven patients developed severe cerebral edema with intracranial hypertension and died. The median time to death was approximately nine and a half days after the initial neurologic event. The remaining three patients survived but suffered severe cognitive and motor neurologic deficits.
Initial investigations ruled out common anesthesia-related causes such as equipment malfunction, medication errors, or deviations from standard anesthetic protocols. Malignant hyperthermia was suspected in one case, but genetic testing for known malignant hyperthermia genes was negative.
Further genetic analysis identified a mitochondrial DNA variant in three patients: MT-ND4:m.11232T>C (p.Leu158Pro). This variant was present in a homoplasmic state and is currently classified as a variant of uncertain significance. The MT-ND4 gene encodes a component of mitochondrial respiratory chain complex I, which is critical for oxidative phosphorylation and cellular energy production.
Experimental evidence suggests that volatile anesthetics such as isoflurane and sevoflurane can impair mitochondrial complex I activity, leading to reduced ATP production and increased oxidative stress. In individuals with underlying mitochondrial dysfunction, anesthetic exposure may therefore exacerbate metabolic stress and contribute to neurologic injury.
Although the MT-ND4 variant has previously been associated with chronic progressive external ophthalmoplegia, it has not previously been linked to acute perioperative neurologic injury. The findings therefore raise the possibility of a previously unrecognized mitochondrial pharmacogenetic susceptibility to anesthetic agents.
However, the authors emphasize that a causal relationship between anesthesia exposure and the neurologic injuries observed has not yet been established. The available data remain limited and further investigation is required.
In response to these findings, the Chilean Ministry of Health issued recommendations emphasizing careful preoperative evaluation for potential mitochondrial disease and consideration of anesthetic strategies that may reduce mitochondrial stress when such conditions are suspected.
Ongoing national surveillance, genetic testing initiatives, and further research are being coordinated to better understand the underlying mechanisms and potential preventive strategies.
What You Should Know
A cluster of severe neurologic complications after general anesthesia was identified in Chile between 2021 and 2025.
Seven patients were identified, including six children and one adult, with four deaths.
All patients had exposure to sevoflurane during anesthesia.
Genetic testing identified a mitochondrial DNA variant affecting the ND4 component of respiratory chain complex I.
Volatile anesthetics may worsen mitochondrial dysfunction, potentially contributing to neurologic injury.
The causal relationship remains unproven, and further research is ongoing.
Key Points
Seven cases of severe neurologic injury following general anesthesia were identified through national surveillance.
Most patients developed delayed emergence followed by progressive neurologic deterioration.
Four patients died from cerebral edema and intracranial hypertension.
Genetic testing revealed the mitochondrial MT-ND4:m.11232T>C variant in several cases.
The variant may represent a pharmacogenetic susceptibility affecting mitochondrial energy metabolism.
Further epidemiologic, genetic, and mechanistic studies are needed to determine whether anesthetic exposure contributed to these outcomes.
Thank you to Anesthesiology for allowing us to summarize this article.