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.
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.
Authors: Balázs Hauser; Jochen Kick; Zsolt Iványi; Pierre Asfar; Ulrich Ehrmann; Claus-Martin Muth; Maura Albicini; Ulrich Wachter; Josef Vogt; Michael Bauer; Uwe Bernd Brückner; Peter Radermacher; Hendrik Bracht Journal: Intensive Care Med Date: 2006-03-14 Impact factor: 17.440
Authors: Jae Sung Choi; Ho Sung Lee; Ki Hyun Seo; Ju Ock Na; Yong Hoon Kim; Soo Taek Uh; Choon Sik Park; Mee Hye Oh; Sang Han Lee; Young Tong Kim Journal: Tuberc Respir Dis (Seoul) Date: 2012-07-31