I appreciate the interest of Dr. Farag et al.  in the recent case report of asymptomatic metabolic acidosis in a patient receiving prolonged propofol infusion in the absence of any likely cause of the acidosis except propofol.1I agree that an occult mitochondrial disease is a possible etiology. The anecdotal reports of Dr. Farag et al.  on the effects of propofol in patients with mitochondrial disease are interesting, and I encourage them to publish details in a more systematized form.

However, their letter makes unsupported assumptions about propofol infusion syndrome that might adversely affect the level of vigilance for and detection of this complication. It is not true that “hundreds of thousands of adult patients have received propofol without experiencing this complication.” To the best of my knowledge, no large-scale study of acid–base balance on thousands of patients receiving high-dose, prolonged propofol infusion has been reported. The subject of the case report by me and my colleagues was completely asymptomatic and was detected only because concern about respiratory depression under deep sedation caused arterial blood gases to be checked.1It is possible that mild forms of propofol-induced acidosis are much more common than appreciated, and it is also possible that they are as rare as suggested by Farag et al.  We simply do not have the data at this time. A large-scale study is needed to answer the question.

It is also important to note that propofol infusion syndrome is so far defined only clinically, with metabolic acidosis being the invariant common factor, usually accompanied by circulatory collapse.1Although propofol can have adverse effects on mitochondria in vitro ,2there are multiple potential pathways to the clinically defined syndrome besides mitochondrial disease. Pharmacogenomic variability in propofol metabolism and nonmitochondrial sites of propofol action could cause accumulation of propofol or unusual propofol metabolites,3,4or loss of the cytoprotective effects of propofol,5–8which might otherwise mask harmful effects of propofol. The recommendations of Farag et al.  for anesthetizing patients with mitochondrial disease are reasonable and appropriate. However, anesthesiologists should still be vigilant for propofol infusion syndrome in patients without mitochondrial disease.

Mayo Clinic College of Medicine, Rochester, Minnesota. johnson.michael@mayo.edu

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