ObjectivesTo investigate whether prolonged infusion of N-acetylcysteine (NAC) that is commenced immediately after admission to the intensive care unit could ameliorate the development or progression of multisystem organ failure and improve mortality.DesignProspective, randomized, double-blinded clinical trial.SettingSix-bed intensive care unit in a teaching hospital.PatientsOf the 100 patients recruited (14 withdrew), 86 patients were studied.InterventionsAfter randomization, the treatment group (n = 41) received NAC (150 mg/kg bolus followed by a continuous infusion of 12 mg/kg/hr) and the placebo group (n = 45) received 5% dextrose, from a minimum of 3 days up to a maximum of 5 days.Measurements and Main ResultsThere was no statistically significant difference between the two groups regarding outcome as indicated by mortality and the required days of inotropic support, mechanical ventilation, and intensive care. The time interval between hospital and intensive care unit admission showed great variability, with a median of 24 hrs for the whole sample. By splitting the groups with this median value, the effect of NAC was examined on patients admitted within 24 hrs and after 24 hrs of arrival to the hospital. There was a nonsignificant difference in mortality in favor of NAC. Patients admitted after 24 hrs of hospital admission had a significantly worse mortality in the NAC-treated group (61% vs. 32% for controls; p = .05).Conclusions24 hrs after hospital admission may potentially be harmful, and further studies should be undertaken to investigate the clinical use of the early application of NAC in critically ill patients. (Crit Care Med 1999; 27:1100-1104)