A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group.

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-4-carboxylate (Procysteine; Clintec Technologies Inc; Chicago [OTZ]) on these levels and on common physiologic abnormalities, 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 and requiring mechanical ventilation.

INTERVENTION

Standard care for ARDS and I.V. 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.