• J Bakker, H Zhang, M Depierreux, S van Asbeck, and J L Vincent.
• Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
• J Crit Care. 1994 Dec 1; 9 (4): 236-43.

PurposeThe release of oxygen-free radicals has been implicated in both peripheral vascular and myocardial alterations of septic shock. N-Acetylcysteine (N-AC), a substrate for the production of glutathione, has potent antioxidant effects. As a nitrosothiol, it may also improve capillary blood flow. We studied the effects of N-AC in a dog model of endotoxic shock.MethodsTen pentobarbital-anesthetized, mechanically ventilated dogs were randomly assigned to receive either N-AC (150 mg/kg loading dose in 1 hour, followed by 20 mg/kg.h maintenance dose) or D5W. After the loading dose, each dog received 3 mg/kg Escherichia coli endotoxin intravenously. After 30 minutes, saline infusion was started to restore and maintain baseline filling pressures.ResultsThe loading dose of N-AC increased DO2 significantly (from 661 +/- 54 to 914 +/- 190 mL/min, P < .05), but VO2 remained stable. After the administration of endotoxin, fluid challenge restored cardiac output to baseline, in both groups. Hemoglobin and, thus, DO2 were slightly lower in the N-AC-treated dogs, but VO2 was similar in both groups. At the end of the study, O2ER was significantly higher in the N-AC-treated dogs than in the control dogs. Blood lactate levels fell more rapidly in the N-AC dogs than in the control dogs. Blood lactate levels returned to normal in the N-AC dogs but not in the control dogs. Tumor necrosis factor (TNF) also decreased significantly in the N-AC dogs but remained elevated in the control dogs.ConclusionThese data indicate that N-AC administration in endotoxic shock is well tolerated, may increase oxygen availability to the tissues, and is associated with an attenuation of TNF release.

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