title: Possible pathogenic mechanism of propofol infusion syndrome involves coenzyme q.
abstract: BACKGROUND
  Propofol 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.
  
  
  METHODS
  Eight 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.
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.
authors.affiliation: 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.).
authors.forename: Arnaud Vincent
authors.initials: AV
authors.lastname: Vanlander
authors.forename: Juergen Guenther
authors.initials: JG
authors.lastname: Okun
authors.forename: Annick
authors.initials: A
authors.lastname: de Jaeger
authors.forename: Joél
authors.initials: J
authors.lastname: Smet
authors.forename: Elien
authors.initials: E
authors.lastname: De Latter
authors.forename: Boel
authors.initials: B
authors.lastname: De Paepe
authors.forename: Georges
authors.initials: G
authors.lastname: Dacremont
authors.forename: Birgitte
authors.initials: B
authors.lastname: Wuyts
authors.forename: Bert
authors.initials: B
authors.lastname: Vanheel
authors.forename: Peter
authors.initials: P
authors.lastname: De Paepe
authors.forename: Philippe Germaine
authors.initials: PG
authors.lastname: Jorens
authors.forename: Niels
authors.initials: N
authors.lastname: Van Regenmortel
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
mesh_terms: D018686:Anesthetics, Intravenous / Q000633:toxicity*; D000818:Animals; D002952:Citric Acid Cycle / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D015742:Propofol / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D013577:Syndrome; D014451:Ubiquinone / Q000378:metabolism*
chemical_list: D018686:Anesthetics, Intravenous; D014451:Ubiquinone; D015742:Propofol