DOES N-ACETYL-L-CYSTEINE INFLUENCE CYTOKINE RESPONSE DURING EARLY HUMAN SEPTIC SHOCK

Study objective: To assess the effects of adjunctive treatment with N- acetyl-L-cysteine (NAC) on hemodynamics, oxygen transport variables, a nd plasma levels of cytokines in patients with septic shock. Design: P rospective, randomized, double-blind, placebo-controlled study. Settin g: A 24-bed medicosurgical ICU in a university hospital. Patients: Twe nty-two patients included within 4 h of diagnosis of septic shock. Int erventions: Patients were randomly allocated to receive either NAC (15 0 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. Measurem ents: Plasma concentrations of tumor necrosis factor-alpha (TNF), inte rleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor-alpha r eceptor-p55 (sTNFR-p55) were measured by sensitive immunoassays at 0, 2, 4, 6 and 24 h, Pulmonary artery catheter-derived hemodynamics, bloo d gases, hemoglobin, and arterial lactate were measured at baseline, a fter infusion (4 h), and at 24 h. Results: NAC improved oxygenation (P aO2/FIo(2) ratio, 214+/-97 vs 123+/-86; p<0.05) and static lung compli ance (44+/-11 vs 31+/-6 L/cm H2O; p<0.05) at 24 h. NAC had no signific ant effects on plasma TNF, IL-6, or IL-10 levels, but acutely decrease d IL-8 and sTNFR-p55 levels. The administration of NAC had no signific ant effect on systemic and pulmonary hemodynamics, oxygen delivery, an d oxygen consumption. Mortality was similar in both groups (control, 4 0%; NAC, 42%) but survivors who received NAC had shorter ventilator re quirement (7+/-2 days vs 20+/-7 days; p<0.05) and were discharged earl ier 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 i nfusion 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.