Does N-Acetyl-L-Cysteine Influence Cytokine Response During Early Human Septic Shock?

¹ From the Department of Intensive Care, Erasme University Hospital, Université Libre de Rruxelles, Brussels, Belgium
² From the Academic Hospital, Vrije Universiteit, and the Department of Intensive Care, Erasme University Hospital, Université Libre de Rruxelles, Brussels, Belgium
³ From the Department of Hematology and Immunology, Erasme University Hospital, Université Libre de Rruxelles, Brussels, Belgium

Study objective: To assess the effects of adjunctive treatment with N-acetyl-L-cysteine (NAC) on hemodynamics, oxygen transport variables, and plasma levels of cytokines in patients with septic shock.

Design: Prospective, randomized, double-blind, placebo-controlled study.

Setting: A 24-bed medicosurgical ICU in a university hospital.

Patients: Twenty-two patients included within 4 h of diagnosis of septic shock.

Interventions: Patients were randomly allocated to receive either NAC (150 mg/kg bolus, followed by a continuous infusion of 50 mg/kg over 4 h; n=12) or placebo (n=10) in addition to standard therapy.

Measurements: Plasma concentrations of tumor necrosis factor- (TNF), interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor- receptor-p55 (sTNFR-p55) were measured by sensitive immunoassays at 0, 2, 4, 6 and 24 h. Pulmonary artery catheter-derived hemodynamics, blood gases, hemoglobin, and arterial lactate were measured at baseline, after infusion (4 h), and at 24 h.

Results: NAC improved oxygenation (PaO₂/FIO₂ ratio, 214±97 vs 123±86; p<0.05) and static lung compliance (44±11 vs 31±6 L/cm H₂O; p<0.05) at 24 h. NAC had no significant effects on plasma TNF, IL-6, or IL-10 levels, but acutely decreased IL-8 and sTNFR-p55 levels. The administration of NAC had no significant effect on systemic and pulmonary hemodynamics, oxygen delivery, and oxygen consumption. Mortality was similar in both groups (control, 40%; NAC, 42%) but survivors who received NAC had shorter ventilator requirement (7±2 days vs 20±7 days; p<0.05) and were discharged earlier from the ICU (13±2 days vs 32±9 days; p<0.05).

Conclusion: In this small cohort of patients with early septic shock, short-term IV infusion of NAC was well-tolerated, improved respiratory function, and shortened ICU stay in survivors. The attenuated production of IL-8, a potential mediator of septic lung injury, may have contributed to the lung-protective effects of NAC.

Key Words: antioxidants • ARDS • cytokines • glutathione • hemodynamics • lung compliance • N-acetyl-L-cysteine • oxygenation • septic shock

Submitted on May 21, 1997
Accepted on November 7, 1997

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