Mitochondrial Disease and Anasthesia
Children with mitochondrial disorders are increasingly receiving anesthesia for a variety of diagnostic (muscle biopsy) and therapeutic/palliative procedures (fundiplication, ventriculoperitoneal shunts, gastostomy feeding catheters). Due to the primary pathologies of severe mitochondrial disorders an increased risk of perioperative complications is present. There is increasing evidence mainly from preclinical studies that almost every anesthetic and several drugs used concomitantly during anesthesia may have profound effects on mitochondrial function. The most popular intravenous anesthetic propofol causes inhibition of OXPHOS, which is a risk factor for life-threatening rhabdomyolysis, metabolic acidosis and cardiac failure during long-term infusion in adult ICU patients, and during short-term infusion in children. Peripheral nerve blocks performed with local anesthetics improve postoperative analgesia and rehabilitation in patients. However, local anesthetics can induce in-situ toxicity in both muscle and neuron. In complex I deficient (Ndufs4 knockout) mice we found a highly increased sensitivity to the volatile anesthetic isoflurane resulting in severe respiratory depression. Preclinical studies investigate the anesthetic sensitivity and differential biochemical effects of anesthetics on brain, heart and muscle mitochondria in complex I deficient (Ndufs4) mice. Clinical studies involve safety and side-effects of anesthetic techniques in children with deficiency of complex I vs other mitochondrial disorders.