title: Sedation using propofol induces similar diaphragm dysfunction and atrophy during spontaneous breathing and mechanical ventilation in rats.
abstract: BACKGROUND
  Mechanical ventilation is crucial for patients with respiratory failure. The mechanical takeover of diaphragm function leads to diaphragm dysfunction and atrophy (ventilator-induced diaphragmatic dysfunction), with an increase in oxidative stress as a major contributor. In most patients, a sedative regimen has to be initiated to allow tube tolerance and ventilator synchrony. Clinical data imply a correlation between cumulative propofol dosage and diaphragm dysfunction, whereas laboratory investigations have revealed that propofol has some antioxidant properties. The authors hypothesized that propofol reduces markers of oxidative stress, atrophy, and contractile dysfunction in the diaphragm.
  
  
  METHODS
  Male Wistar rats (n = 8 per group) were subjected to either 24 h of mechanical ventilation or were undergone breathing spontaneously for 24 h under propofol sedation to test for drug effects. Another acutely sacrificed group served as controls. After sacrifice, diaphragm tissue was removed, and contractile properties, cross-sectional areas, oxidative stress, and proteolysis were examined. The gastrocnemius served as internal control.
  
  
  RESULTS
  Propofol did not protect against diaphragm atrophy, oxidative stress, and protease activation. The decrease in tetanic force compared with controls was similar in the spontaneous breathing group (31%) and in the ventilated group (34%), and both groups showed the same amount of muscle atrophy. The gastrocnemius muscle fibers did not show atrophy.
  
  
  CONCLUSIONS
  Propofol does not protect against ventilator-induced diaphragmatic dysfunction or oxidative injury. Notably, spontaneous breathing under propofol sedation resulted in the same amount of diaphragm atrophy and dysfunction although diaphragm activation per se protects against ventilator-induced diaphragmatic dysfunction. This makes a drug effect of propofol likely.
authors.affiliation: From the Department of Surgical Intensive and Intermediate Care, and Department of Anesthesiology, University Hospital of the RWTH Aachen, University of Excellence, Aachen, Germany (C.S.B.); Fonds voor Wetenschappelijk Onderzoek-Flanders, Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium (K.M.); Department of Anesthesiology, University Hospital of the RWTH Aachen, University of Excellence, Aachen, Germany (R.R., I.B., and C.B.); Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium (D.T., N.C., and G.G.-R.); and Institute of Neuropathology and JARA, Translational Brain Medicine, Aachen; University Hospital of the RWTH Aachen, University of Excellence, Aachen, Germany (J.W.).
authors.forename: Christian S
authors.initials: CS
authors.lastname: Bruells
authors.forename: Karen
authors.initials: K
authors.lastname: Maes
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Debby
authors.initials: D
authors.lastname: Thomas
authors.forename: Nele
authors.initials: N
authors.lastname: Cielen
authors.forename: Ingmar
authors.initials: I
authors.lastname: Bergs
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Gayan-Ramirez
mesh_terms: D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D003964:Diaphragm / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D009133:Muscular Atrophy / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration; D012121:Respiration, Artificial / Q000379:methods*; D055397:Ventilator-Induced Lung Injury / Q000503:physiopathology
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol