Anesthetic considerations in patients with mitochondrial defects

Abstract

Mitochondrial disease, once thought to be a rare clinical entity, is now recognized as an important cause of a wide range of neurological, cardiac, muscle and endocrine disorders [1–3]. The incidence of disorders of the respiratory chain alone is estimated to be about 1 per 4–5,000 live births, similar to that of more well-known neurological diseases [4, 5]. High-energy requiring tissues are uniquely dependent on the energy delivered by mitochondria, and therefore have the lowest threshold for displaying symptoms of mitochondrial disease. Thus, mitochondrial dysfunction most commonly affects function of the central nervous system, the heart and the muscular system [1, 3, 4]. Mutations in mitochondrial proteins cause striking clinical features in those tissues types, including encephalopathies, seizures, cerebellar ataxias, cardiomyopathies, myopathies, as well as gastrointestinal and hepatic disease. Our knowledge of the contribution of mitochondria in causing disease or influencing aging is expanding rapidly [4, 5]. As diagnosis and treatment improves for children with mitochondrial diseases, it has become increasingly common for them to undergo surgeries for their long-term care. In addition, often a muscle biopsy or other tests needing anesthesia are required for diagnosis. Mitochondrial disease represents probably hundreds of different defects, both genetic and environmental in origin, and is thus difficult to characterize. The specter of possible delayed complications in patients caused by inhibition of metabolism by anesthetics, by remaining in a biochemically stressed state such as fasting/catabolism, or by prolonged exposure to pain is a constant worry to physicians caring for these patients. Here, we review the considerations when caring for a patient with mitochondrial disease.

Propofol Compared with Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

“…There is currently reluctance among some anesthesiologists to use propofol on children with mitochondrial defects. 39,40 Our data may provide insights into its unique, and potentially toxic, metabolic profile in this patient population.…”

Anesthetic Management of a Patient With Carnitine-Acylcarnitine Translocase Deficiency

“…The preoperative evaluation of patients with CACT deficiency is similar to patients with other mitochondrial defects of fatty acid metabolism [5,7]. End-organ involvement related to the deficient enzyme function may include the central nervous system (developmental delay and seizures), skeletal muscle (myopathy), cardiovascular system (cardiomyopathy and arrhythmias), hepatic dysfunction, and alterations in blood glucose levels with hypoglycemia.…”

“…Through this process, fatty acids are broken down into two carbon fragments which can then enter the Kreb's cycle to generate ATP or serve as a substrate for gluconeogenesis. However, the movement of fatty acids into the mitochondria across their inner and outer membranes depends on the normal functioning of carnitine and its associated enzymes including CACT [5]. For transport through the mitochondrial membranes, the fatty acid is bound to carnitine, forming acylcarnitine which crosses the external mitochondrial membrane.…”

Propofol-related infusion syndrome heralding a mitochondrial disease: Case report

“…2,3 This is remarkable since many of the modern anesthetic agents-parenteral or inhaled-adversely affect mitochondrial function. 4 Since all cases of PRIS result from prolonged (i.e., days) use of high-dose propofol infusion, it seems unlikely that this syndrome is due to a classic drugreceptor second-messenger interaction. Something must accumulate: the parent drug, a metabolite, a component of the lipid carrier, or some combination of the above.…”