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Metabolic Acidosis due to Propofol Infusion

Farag, Ehab M.D., F.R.C.A.; DeBoer, Glenn M.D.*; Cohen, Bruce H. M.D.; Niezgoda, Julie M.D.

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To the Editor:—

We read with great interest the reports by Burow et al.1 and Salengros et al.2 of 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,3,4 which 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).5–7 The patient described by Salengros et al.2 had 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.10,11 Furthermore, 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.
Ehab Farag, M.D., F.R.C.A.
Glenn DeBoer, M.D., *
Bruce H. Cohen, M.D.
Julie Niezgoda, M.D.
* The Cleveland Clinic Foundation, Cleveland, Ohio. deboerg@ccf.org
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References

1. Burow BK, Johnson ME, Packer DL: Metabolic acidosis associated with propofol in the absence of other causative factors. Anesthesiology 2004; 101:239–41

2. Salengros J-C, Velghe-Lenelle C-E, Bollens R, Engelmen E, Barvais L: Lactic acidosis during propofol–remifentanil anesthesia in an adult. Anesthesiology 2004; 101:241–3

3. Vasile B, Rasulo F, Candiani A, Latronico N: The pathophysiology of propofol infusion syndrome: A simple name for a complex syndrome. Intensive Care Med 2003; 29:1417–25

4. Wolf A, Weir P, Segar P, Stone J, Shield J: Impaired fatty acid oxidation in propofol infusion syndrome. Lancet 2001; 357:606–7

5. Wallace DC: Mitochondrial diseases in man and mouse. Science 1999; 283:1482–8

6. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI: Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 2004; 350:664–71

7. White AJ: Mitochondrial toxicity and HIV therapy. Sex Transm Infections 2001; 77:158–73

8. Cohen BH, Gold DR: Mitochondrial cytopathy in adults: What we know so far. Cleveland Clin J Med 2001; 68:625–6, 629–42

9. Andreu AL, Hanna MG, Reichmann H, Bruno C, Penn AS, Tanji K, Pallotti F, Iwata S, Bonilla E, Lach B, Morgan-Hughes J, Dimauro S: Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA. N Engl J Med 1999; 341:1037–44

10. Farag E, Barsoum S, Spagnuolo S, Tetzlaff J: Anesthesia and muscle disease. Am J Anesthesiol 2000; 27:491–501

11. Farag E, Argalious M, Narouze S, De Boer G, Tome J: The anesthetic management of ventricular septal repair in a child with mitochondrial cytopathy. Can J Anesth 2002; 49:958–62

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