We read with great interest the reports by Burow et al.  1and Salengros et al.  2of the development of metabolic acidosis during propofol infusion in the operating room and intensive care unit. It has been proposed in these articles that the patients’ symptoms were the result of excessive doses of propofol that inhibited mitochondrial respiration resulting in a metabolic acidosis. Because hundreds of thousands of adult patients have received propofol without experiencing this complication, what is different about these reported patients? We propose that these patients may have subclinical forms of mitochondrial diseases affecting either the respiratory chain complex or fatty acid oxidation,3,4which were uncovered by the infusion of propofol. The spectrum of mitochondrial disorders varies greatly and includes both primary disorders (presumably genetic) and secondary disorders that may affect mitochondrial function (such as untreated hyperthyroidism or hypothyroidism, diabetes mellitus, or drugs that would include the agents used to treat human immunodeficiency virus infections, statins, aspirin, and others).5–7The patient described by Salengros et al.  2had a history of adult-onset diabetes mellitus. Primary mitochondrial disorders can present in adults with a huge variety of signs and symptoms, including cardiac conduction defects in apparently otherwise healthy persons.8,9 

As a referral center for mitochondrial diseases, we use the muscle biopsy as one tool for assisting in the diagnosis of mitochondrial disorders. We avoid the use of propofol for anesthetizing patients undergoing this procedure. In the past, we have used short-term (15–30 min) and low-dose infusions of propofol for noninvasive diagnostic procedures in known mitochondrial patients. However, we have found in the more symptomatic patients that the use of propofol has been associated with prolonged anesthesia recovery and at times required intensive care unit admission. It seems that the duration of the infusion and the total dose of propofol may be the critical factors in these cases. In addition to propofol inhibiting mitochondrial metabolism, the lipid component of the formulation may play a role in toxicity for those patients with fatty acid oxidation disorders.

Mitochondrial diseases represent hundreds of known and theorized disorders, so there are probably some specific disorders that are more susceptible to the toxic effects of propofol and other mitochondrial poisons. The guidelines for anesthetizing these patients are to maintain normoglycemia and normothermia and to avoid any period of hypoxia so as not to stress the already diseased mitochondria.10,11Furthermore, the metabolic energy required to clear any drug must be considered before its administration. During anesthesia, the blood glucose and lactate concentrations should be carefully monitored because these patients may need glucose supplementation during these periods of stress and metabolic acidosis. This is especially important for infants because glucose is the major energy supply to the myocardium, and hypoglycemia may contribute to myocardial depression. The hypoglycemia is due to the inability of the diseased mitochondria to sustain their energy requirements from fatty acid oxidation during periods of stress, thus leading to the depletion of carbohydrate stores and the development of hypoglycemia.

We think it would be appropriate for the patients mentioned in the reports by Burow et al.  and Salengros et al.  to be evaluated a by neurologist and investigated for a mitochondrial disorder.

* The Cleveland Clinic Foundation, Cleveland, Ohio. deboerg@ccf.org

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