N-Acetylcysteine treatment to prevent the progression of multisystem organfailure: A prospective, randomized, placebo-controlled study

Objectives To investigate whether prolonged infusion of N-acetylcysteine (N AG) that is commenced immediately after admission to the intensive care uni t could ameliorate the development or progression of multisystem organ fail ure and improve mortality. Design: Prospective, randomized, double-blinded clinical trial. Setting: Six-bed intensive care unit in a teaching hospital. Patients: Of the 100 patients recruited (14 withdrew), 86 patients were stu died. Interventions: After randomization, the treatment group (n = 41) received N AG (150 mg/kg bolus followed by a continuous infusion of 12 mg/kg/hr) and t he placebo group (n = 45) received 5% dextrose, from a minimum of 3 days up to a maximum of 5 days. Measurements and Main Results: There was no statistically significant diffe rence between the two groups regarding outcome as indicated by mortality an d the required days of inotropic support, mechanical ventilation, and inten sive care. The time interval between hospital and intensive care unit admis sion 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 exa mined 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 N AG. Patients admitted after 24 hrs of hospital admission had a significantl y worse mortality in the NAG-treated group (61% vs. 32% for controls; p = . 05). Conclusions: We found a nonsignificant difference in outcome between NAC an d placebo-treated patients. Our results suggest that the initiation of NAG treatment >24 hrs after hospital admission may potentially be harmful, and further studies should be undertaken to investigate the clinical use of the early application of NAG in critically ill patients.