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 impro ve 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) (PaO2/FIO2 less than or equal to 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial. Materials and Methods: Respira tory dysfunction was graded daily according to the need for mechanical ventilation and FIO2 and to the evolution of the lung injury score (L IS) and the PaO2/FIO2 ratio in 42 patients with established ARDS recei ving either NAC 190 mg/kg/day or placebo as a continuous intravenous i nfusion over the first 3 days of their clinical course. Results: NAC a nd placebo groups (22 and 20 patients, respectively) were comparable f or demographic characteristics, ARDS categories, severity of illness ( simplified acute physiology score [SAPS II]) LIS and PaO2/ FIO2 ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (dif ference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at day s 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 FIO2 was significantly lower and the PaO2/FIO2 ratio was significantly higher than the initial values during the evolution (FIO2 at day 3, P <.01 fo r NAC and P<.05 for placebo; PaO2/FIO2 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 differ ent 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, th ere 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 pre valent sepsis category (10 patients in the NAC and 9 in the placebo gr oup), the mortality rate, the need of ventilatory support, the intensi ve care unit stay, and the PaO2/FIO2 evolution did not differ signific antly in both subgroups. Conclusions: In this relatively small group o f patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours nei ther improved systemic oxygenation nor reduced the need for ventilator y support. (C) 1997 by W.B. Saunders Company.