A trial of antioxidants N-acetylcysteine and procysteine in ARDS

Objective: To determine the levels of glutathione and cysteine in patients with ARDS and examine the effect of treatment with N-acetylcysteine (NAC) and L-2-oxothiazolidine-1-carboxylate (Procysteine; Clintec Technologies Inc; Chicago [OTZ]) on these levels and on common physiologic abnomalities, and organ dysfunction associated with ARDS. Design: Randomized, double-blind, placebo-controlled, prospective clinical trial. Setting: ICUs in five clinical centers in the United States and Canada. Patients: Patients meeting a predetermined definition of ARDS anti requiring mechanical ventilation. Intervention: Standard care for ARDS and IV infusion, every 8 h for 10 days, of one of the following: NAC (70 mg/kg, n = 14), OTZ (63 mg/kg, n = 17), or placebo (n = 15). Main results: Both antioxidants effectively repleted RBC glutathione gradually over the 10-day treatment period (47% and 49% increases from baseline values for NAC and OTZ, respectively). There was no difference in mortality among groups (placebo, 40%: NAC, 36%; OTZ, 35%). However, the number of days of acute lung injury was decreased and there was also a significant increase in cardiac index in both treatment groups (NAC/OTZ[+]14%; placebo[-]6%). Conclusions: Our findings suggest that repletion of glutathione may safely be accomplished with NAC or OTZ in patients with acute lung injury/ARDS. Such treatment may shorten the duration of acute lung injury, but larger studies are needed to confirm this.