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.


METHODS
Randomized, double-blind, placebo-controlled, prospective clinical trial.


METHODS
ICUs in five clinical centers in the United States and Canada.


METHODS
Patients meeting a predetermined definition of ARDS and requiring mechanical ventilation.


METHODS
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).


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.
Bernard
G R
GR
Center for Lung Research, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tenn, USA.
Wheeler
A P
AP
Arons
M M
MM
Morris
P E
PE
Paz
H L
HL
Russell
J A
JA
Wright
P E
PE
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002302:Cardiac Output; D003545:Cysteine / Q000097:blood; D004311:Double-Blind Method; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005978:Glutathione / Q000097:blood; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011761:Pyrrolidonecarboxylic Acid; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D013844:Thiazoles / Q000627:therapeutic use*; D053778:Thiazolidines; D013997:Time Factors
D000975:Antioxidants; D016166:Free Radical Scavengers; D013844:Thiazoles; D053778:Thiazolidines; D005978:Glutathione; D003545:Cysteine; D001663:Bilirubin; D011761:Pyrrolidonecarboxylic Acid; D000111:Acetylcysteine; C029536:2-oxothiazolidine-4-carboxylic acid