title: Systemic, pulmonary, and hepatosplanchnic effects of N-acetylcysteine during long-term porcine endotoxemia.
abstract: OBJECTIVE
  Controversial data have been reported on the effects of N-acetylcysteine in patients with septic shock. We therefore investigated the systemic, pulmonary, and hepatosplanchnic hemodynamic, gas exchange, and metabolic effects of N-acetylcysteine during long-term, volume-resuscitated, hyperdynamic porcine endotoxemia, which mimics the features of hyperdynamic human sepsis.
  
  
  METHODS
  Prospective, randomized, controlled experimental study.
  
  
  METHODS
  Investigational animal laboratory.
  
  
  METHODS
  Eighteen pigs were randomized to receive endotoxin alone (controls, n = 9) or endotoxin plus N-acetylcysteine (n = 9).
  
  
  METHODS
  Anesthetized, mechanically ventilated, and instrumented animals received continuous intravenous endotoxin and were resuscitated with hydroxyethylstarch to keep mean arterial pressure >60 mm Hg. After 12 hrs of endotoxemia, they were randomized to receive either placebo or N-acetylcysteine (150 mg/kg loading dose over 1 hr followed by 20 mg.kg-1.hr-1 for 11 hrs).
  
  
  RESULTS
  Before as well as 12, 18, and 24 hrs after starting the endotoxin infusion, systemic, pulmonary, and hepatosplanchnic hemodynamics, oxygen exchange, and metabolism as well as nitric oxide, glutathione, and 8-isoprostane concentrations were assessed. N-acetylcysteine failed to improve any of the variables of the systemic, pulmonary, or hepatosplanchnic hemodynamics, gas exchange, and metabolism. Although N-acetylcysteine significantly elevated glutathione concentration, it did not influence the 8-isoprostane concentrations and even further reduced hepatic venous pH.
  
  
  CONCLUSIONS
  Despite the increased glutathione concentration, N-acetylcysteine did not improve systemic, pulmonary, and hepatosplanchnic hemodynamics, oxygen exchange, and metabolism. When compared with previous reports in the literature, a different timing of N-acetylcysteine administration and/or an ongoing or even N-acetylcysteine-induced aggravation of oxidative stress may account for this result.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
authors.forename: Damian
authors.initials: D
authors.lastname: Vassilev
authors.forename: Balázs
authors.initials: B
authors.lastname: Hauser
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bracht
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Iványi
authors.forename: Michael
authors.initials: M
authors.lastname: Schoaff
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Josef
authors.initials: J
authors.lastname: Vogt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wachter
authors.forename: Hubert
authors.initials: H
authors.lastname: Schelzig
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.forename: Uwe B
authors.initials: UB
authors.lastname: Brückner
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Gebhard
authors.initials: G
authors.lastname: Fröba
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D013154:Spleen / Q000187:drug effects; D013552:Swine; D013997:Time Factors
chemical_list: D016166:Free Radical Scavengers; D000111:Acetylcysteine