• Arnaud Vincent Vanlander, Juergen Guenther Okun, Annick de Jaeger, Joél Smet, Elien De Latter, Boel De Paepe, Georges Dacremont, Birgitte Wuyts, Bert Vanheel, Peter De Paepe, Philippe Germaine Jorens, Niels Van Regenmortel, and Rudy Van Coster.
• From the Department of Pediatrics, Division of Pediatric Neurology and Metabolism (A.V.V., J.S., E.D.L., B.D.P., R.V.C.), Department of Critical Care Medicine, Division of Pediatric Intensive Care Medicine (A.d.J.), Department of Clinical Chemistry (B.W.), Department of Emergency Medicine (P.D.P.), Ghent University Hospital, Ghent, Belgium; Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital, Heidelberg, Germany (J.G.O.); Department of Pediatrics, University of Ghent, Ghent, Belgium (G.D.); Physiology Group, Department of Basic Medical Sciences, Ghent University, Ghent, Belgium (B.V.); Department of Critical Care Medicine, Antwerp University Hospital, Antwerp University, Edegem, Belgium (P.G.J., N.V.R.); and Department of Critical Care Medicine, ZNA Antwerp, Belgium (N.V.R.).
• Anesthesiology. 2015 Feb 1;122(2):343-52.

BackgroundPropofol is a short-acting intravenous anesthetic agent. In rare conditions, a life-threatening complication known as propofol infusion syndrome can occur. The pathophysiologic mechanism is still unknown. Some studies suggested that propofol acts as uncoupling agent, others suggested that it inhibits complex I or complex IV, or causes increased oxidation of cytochrome c and cytochrome aa3, or inhibits mitochondrial fatty acid metabolism. Although the exact site of interaction is not known, most hypotheses point to the direction of the mitochondria.MethodsEight rats were ventilated and sedated with propofol up to 20 h. Sequential biopsy specimens were taken from liver and skeletal muscle and used for determination of respiratory chain activities and propofol concentration. Activities were also measured in skeletal muscle from a patient who died of propofol infusion syndrome.ResultsIn rats, authors detected a decrease in complex II+III activity starting at low tissue concentration of propofol (20 to 25 µM), further declining at higher concentrations. Before starting anesthesia, the complex II+III/citrate synthase activity ratio in liver was 0.46 (0.25) and in skeletal muscle 0.23 (0.05) (mean [SD]). After 20 h of anesthesia, the ratios declined to 0.17 (0.03) and 0.12 (0.02), respectively. When measured individually, the activities of complexes II and III remained normal. Skeletal muscle from one patient taken in the acute phase of propofol infusion syndrome also shows a selective decrease in complex II+III activity (z-score: -2.96).ConclusionPropofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.

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