Treatment with N-acetylcysteine during acute respiratory distress syndrome: A randomized, double-blind, placebo-controlled clinical study

Purpose: Intravenous N-acetylcysteine (NAC) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury. In the more serious form, namely established adult respiratory distress syndrome (ARDS) (PaO(2)/FIO(2) less than or equal to 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial. Materials and Methods: Respiratory dysfunction was graded daily according to the need for mechanical ventilation and FIO(2) and to the evolution of the lung injury score (LIS) and the PaO(2)/FIO(2) ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course. Results: NAC and placebo groups (22 and 20 patients, respectively) were comparable for demographic characteristics, ARDS categories, severity of illness (simplified acute physiology score [SAPS II]) LIS and PaO(2)/ FIO(2) ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (difference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at days 2, 3, 5, and 7 after admission, the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1. Moreover, there were no differences between the two groups at the same observation days. In both groups, the FIO(2) was significantly lower and the PaO(2)/FIO(2) ratio was significantly higher than the initial values during the evolution (FIO(2) at day 3, P <.01 for NAC and P<.05 for placebo; PaO(2)/FIO(2) at day 3: P<.01 for NAC and P<.02 for placebo), but this improvement was similar for both groups and, moreover, the between-group comparison was never significantly different at the various collection days. The LIS decreased significantly in NAC group between days 1 and 3 (2.23 +/- 0.62 v 1.76 +/- 0.17; P <.05), whereas no changes were observed in the placebo group; at day 5, there was a significant difference between the two groups (1.53 +/- 0.21 for the NAC v 2.15 +/- 0.19 for the placebo group; P<.05). In the prevalent sepsis category (10 patients in the NAC and 9 in the placebo group), the mortality rate, the need of ventilatory support, the intensive care unit stay, and the PaO(2)/FIO(2) evolution did not differ significantly in both subgroups. Conclusions: In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support. (C) 1997 by W.B. Saunders Company.