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
Prospective, randomized, double-blind, placebo-controlled study.
A 24-bed medicosurgical ICU in a university hospital.
Twenty-two patients included within 4 h of diagnosis of septic shock.
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.
Plasma concentrations of tumor necrosis factor-alpha (TNF), interleukin (IL)-6, IL-8,
IL-10, and soluble tumor necrosis factor-alpha 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.
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).
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.