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.
Design: Prospective, randomized, controlled experimental study.
Setting: Investigational animal laboratory.
Subjects: Eighteen pigs were randomized to receive endotoxin alone (controls, n = 9) or endotoxin plus N-acetylcysteine (n = 9).
Interventions: 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).
Measurements and main 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.