Systemic, pulmonary, and hepatosplanchnic effects of N-acetylcysteine during long-term porcine endotoxemia.
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.
Vassilev
Damian
D
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
Hauser
Balázs
B
Bracht
Hendrik
H
Iványi
Zsolt
Z
Schoaff
Michael
M
Asfar
Pierre
P
Vogt
Josef
J
Wachter
Ulrich
U
Schelzig
Hubert
H
Georgieff
Michael
M
Brückner
Uwe B
UB
Radermacher
Peter
P
Fröba
Gebhard
G
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
D016166:Free Radical Scavengers; D000111:Acetylcysteine