Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 1907-1911

The Effect of Glutathione and N-Acetylcysteine on Lipoperoxidative Damage in Patients with Early Septic Shock

ORESTE ORTOLANI, ANNA CONTI, ANGELO RAFFAELE DE GAUDIO, ELISA MORALDI, QUIRINA CANTINI, and GIANPAOLO NOVELLI

Department of Anesthesiology and Intensive Care, University of Florence; and Department of Molecular and Cellular Biology and Pathology, University of Naples Federico II, Naples, Italy

Both the hyperproduction of oxygen free radicals (OFR) and the weakening of natural scavenging mechanisms have been implicated as contributors to multiple organ failure in septic shock. This study examined whether the antioxidants glutathione (GSH) and N-acetyl-L-cysteine (NAC) play a protective role against damage by OFR in early septic shock. We randomly entered 30 patients with septic shock into one of three groups within 24 h of diagnosis. All of the patients received septic shock therapy, including parenteral nutrition, antibiotics, and volume-expanding and inotropic agents. One group (Group B) also received 70 mg/kg/d of intravenous GSH, and a second group (Group C), 70 mg/kg/d of intravenous GSH and 75 mg/kg/d of intravenous NAC. The protection against OFR damage was evaluated by measuring expired ethane, plasma malondialdehyde, erythrocyte deformability, complement activation, and clinical scores at admission and on Days 3 and 5 of treatment. A significant decrease in peroxidative indexes was observed at Day 5 in Group B as compared with both the control group and basal values. The decrease in peroxidative indexes was even more marked in Group C. Clinical scores in this group were also significantly improved. In conclusion, the administration of high doses of NAC added to GSH significantly decreased the peroxidative stress of patients with septic shock.

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