Mitochondrial disorders are a heterogeneous group of genetic diseases resulting from mutations in either nuclear or mitochondrial DNA². These mutations can lead to impaired oxidative phosphorylation, the process by which cells generate energy². Mitochondrial disorders can affect any tissue, but especially tissue with high energy demands such as the brain, heart, muscles, and liver². These disorders require tailored and complex anesthetic approaches based on each patient’s specific mitochondrial defect and clinical presentation, as the stress of surgery and anesthesia can further challenge their already compromised metabolic state^2,3.

Anesthetic agents pose a challenge in patients with mitochondrial disorders because they act on the central nervous system, a system very dependent on mitochondrial function³. Volatile anesthetics in particular have an increased depressive effect on mitochondrial function that exacerbates any underlying dysfunction³. When possible, regional anesthesia techniques or short-acting agents may be preferable to general anesthesia³. Fortunately, however, if general anesthesia cannot be avoided, most of these agents have been shown to be used in patients with mitochondrial disorders without complication when appropriately monitored¹.

Proper preoperative preparation and intraoperative monitoring are critical to safe patient care³. Thorough preoperative evaluation should include a detailed history of the patient’s mitochondrial disorder, previous anesthetic experiences, and any associated comorbidities³. Consultation with a mitochondrial disease specialist or geneticist can provide valuable insights into the specific needs of the patient³. Intraoperatively, continuous monitoring of vital signs, temperature, and end-tidal CO2 is crucial in detecting early signs of metabolic decompensation³. Invasive monitoring, such as arterial lines and central venous catheters, may be necessary in complex cases³. It is also essential to minimize situations that increase metabolic demand, such as hypothermia, hypovolemia, and hypoglycemia³.

One difficulty in proper anesthesia planning is the frequent delay in diagnosis of mitochondrial disorders due to the variability in clinical presentations¹. Often, patients, and particularly pediatric patients, come to the operating room carrying a diagnosis of unspecified myopathy, and while these patients typically do well, there are always risks when administering volatile and intravenous agents, including the risk of malignant hyperthermia which is a life-threatening condition³. Genetic studies can determine whether a patient carries the defect that increases susceptibility to MH; however, they are not always possible, as they require a geneticist’s input³. In the more likely situation, the anesthesiologist must suspect mitochondrial dysfunction in patients with unspecified myopathy and look for metabolic derangements that would occur with disruption to the oxidative phosphorylation process consistent with mitochondrial disease³. This includes increases in pyruvate, lactate, systemic acylcarnitine, and altered amino acids³. These abnormalities, as well as symptoms of encephalopathy and end-organ dysfunction, should prompt further investigation³.

Anesthesia management in patients with mitochondrial disorders requires meticulous and individualized approaches. Understanding the underlying pathophysiology of these conditions, choosing anesthetic agents with minimal mitochondrial toxicity, and maintaining perioperative metabolic stability are paramount. Collaboration between anesthesiologists, mitochondrial disease specialists, and other healthcare providers is essential to optimize outcomes and minimize complications in this vulnerable patient population.

References

1. Driessen J, Willems S, Dercksen S, Giele J, van der Staak F, Smeitink J. Anesthesia-related morbidity and mortality after surgery for muscle biopsy in children with mitochondrial defects. Paediatr Anaesth. 2007 Jan;17(1):16-21. doi: 10.1111/j.1460-9592.2006.02043.x. PMID: 17184426.

2. Gorman GS, Chinnery PF, DiMauro S, et al. Mitochondrial diseases. Nat Rev Dis Primers. 2016;2:16080.

3. Niezgoda J, Morgan PG. Anesthetic considerations in patients with mitochondrial defects. Paediatr Anaesth. 2013 Sep;23(9):785-93. doi: 10.1111/pan.12158. Epub 2013 Mar 28. PMID: 23534340; PMCID: PMC3711963.