THE USE OF N-ACETYLCYSTEINE AS AN ANTIOXIDANT AND MUCOLYTIC AGENT IN VENTILATED PATIENTS - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Oxygen radicals and oxygen radial mediators are thought to be important components in the development of acute lung injury: sepsis, and multiple organ failure. Injured patients, patients with pulmonary diseases, and multiple trauma patients also showed an elevated lipid peroxidation, indicating increased oxidant stress. N-Acetylcysteine (NAG) has been used as an antioxidant in a wide variety of experiments. NAC has been suggested to act by raising concentrations of cysteine, and hence glutathione, and by scavenging of oxidant species [1, 11, 17, 29]. The present study was designed to investigate whether the application of NAC in intubated patients has an effect on concentrations of reduced glutathione in plasma and bronchoalveolar lavage fluid (BAL) and on the lipid peroxidation products malondialdehyde and conjugated dienes. Because NAC has been widely used as a mucolytic drug for the treatment of lung diseases, the influence on tracheobronchial mucus was studied, too. Methods. In a randomized, double-blind, placebo-controlled study, a total of 38 long-term ventilated patients of a surgical intensive care unit were investigated. Patients were treated for 5 days with either 3 g NAC/day or placebo. The plasma concentration of reduced glutathione, malondialdehyde, and conjugated dienes were measured on admission and on the 3rd and 5th days of treatment [8, 34, 48]. Additionally, the numbers of tracheobronchial suctionings were registered and chest radiographs were evaluated. A fibre-bronchoscopy was performed on admission and on the 3rd day of treatment. The amount and viscidity of tracheobronchial secretions were examined semiquantitatively, and glutathione levels were measured in the unconcentrated BAL. The study was approved by the ethics committee of the University of Ulm. Results. The two groups were comparable with respect to age, sex, APACHE II score and diagnosis (Table 1). We found no significant differences in reduced glutathione levels in the plasma or in the BAL (Figs. 1, 2). Plasma concentrations of malondialdehyde were similar (Fig. 3). Only the levels of conjugated dienes were significantly higher on the 5th treatment day in the placebo group (Pig. 4). The organ function of the lung (FiO2, PEEP, PaO2), liver (SGOT, bilirubin), and kidney (creatinine) and coagulation parameters (PTT, prothrombin time, platelet count) were similar in the two groups during the time of investigation. We observed no clinically relevant differences in the tracheobronchial mucus (Table 2). Conclusion. The present data do not support routine use of NAC in ventilated patients, either as an antioxidant or as a mucolytic agent. Intravenous administration of 3 g NAC/day had no clinically relevant effect on glutathione levels, lipid peroxidation products, tracheobronchial mucus, and clinical condition.