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

Chest. 1997 Jul;112(1):164-72. doi: 10.1378/chest.112.1.164.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Adult
  • Antioxidants / therapeutic use
  • Bilirubin / blood
  • Bronchoalveolar Lavage Fluid / cytology
  • Cardiac Output
  • Cysteine / blood
  • Double-Blind Method
  • Free Radical Scavengers / therapeutic use*
  • Glutathione / blood
  • Humans
  • Middle Aged
  • Prospective Studies
  • Pyrrolidonecarboxylic Acid
  • Respiration, Artificial
  • Respiratory Distress Syndrome, Adult / drug therapy*
  • Respiratory Distress Syndrome, Adult / physiopathology
  • Respiratory Distress Syndrome, Adult / therapy
  • Thiazoles / therapeutic use*
  • Thiazolidines
  • Time Factors

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Thiazoles
  • Thiazolidines
  • Glutathione
  • Cysteine
  • Bilirubin
  • Pyrrolidonecarboxylic Acid
  • Acetylcysteine
  • 2-oxothiazolidine-4-carboxylic acid