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1 From the Center for Lung Research, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
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 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.
Key Words: antioxidants • ARDS • cysteine • glutathione • lung injury • N-acetylcysteine • oxothiazolidine-carboxylate • procysteine
Submitted on July 29, 1996
Accepted on March 20, 1997
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