Perianesthetic Complications in Genetic Mitochondrial Disease: A Review of Case Reports.

Abstract

Background: Genetic mitochondrial diseases (GMDs) are a large group of genetically and clinically heterogeneous disorders caused by defects in genes encoding mitochondrial components. GMDs are grouped into named syndromes based on clinical presentation, for example, Leigh syndrome (LS). Surgical interventions are often required in GMDs, necessitating the use of general anesthesia (GA). Some GMD animal models show both a marked reduction in anesthetic concentrations necessary for sedation and toxic sequelae resulting from anesthetic exposures. Hypersensitivity to sedation by anesthetic agents, most notably volatile anesthetic agents (VAs), occurs in a subset of GMD patients, and some evidence suggests toxicities are also present. Reported complications of anesthesia in GMD are varied, including minor metabolic changes, acceleration of underlying disease, and death. The potential toxicity of anesthetics in the setting of GMDs has recently been underscored by deaths among pediatric and young adult patients of Venezuelan descent putatively linked to a specific mitochondrial DNA haplotype. Interpretation of clinical findings is limited by the lack of a thorough review of case reports for anesthetic exposures in GMD patients. Here, we provide a comprehensive review of published case reports for GMD patients undergoing anesthetic exposures.

Methods: Using search terms "anesthesia mitochondrial disease," "anesthesia mitochondrial disease case report," and "anesthesia Leigh syndrome" we identified case reports published up to May 2025. Non-English articles were translated and included where possible. Only reports of GMD patients undergoing GA with total intravenous anesthesia (TIVA) or VAs containing outcome information were included, totaling 148 cases from 123 reports. We examined relationships between complications and GA type, clinical diagnosis, perianesthetic drugs, procedure length and type, and general demographics. We performed a narrative review of clinical and pre-clinical literature.

Results: Overall complication rate was significantly higher in VA versus TIVA cases (42% vs. 18%, Fisher's exact p-value **p = 0.0022), as was rate of severe complications (*p = 0.01). Encephalomyelopathies, including LS, were overrepresented among cases resulting in death. Complication rate has remained relatively stable over time. Sex and age were not associated with significant differences in complication rate. Complication rate varied significantly by procedure type, and severe complications were associated with procedure length. While not statistically significant, older VAs had higher complication rates than newer VAs. Similarly, older neuromuscular blockade agents may be less safe than newer drugs. N₂O and ketamine were notably safe among drugs used in TIVA procedures.

Conclusions: Available case-report data support the notion that GMD patients are at increased risk of a variety of perianesthetic complications. Clinical symptoms and procedure length appear most strongly predictive of severe complications. Clinical and pre-clinical findings suggest more research is needed to understand the mechanisms of toxicity and more detailed reporting is needed in clinical case reports to identify potential risk factors.