Does N-acetyl-L-cysteine influence cytokine response during early human septic shock?

Chest. 1998 Jun;113(6):1616-24. doi: 10.1378/chest.113.6.1616.


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-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.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis
  • Double-Blind Method
  • Female
  • Hemodynamics
  • Humans
  • Infusions, Intravenous
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Interleukins / blood*
  • Lactic Acid / blood
  • Lung Compliance
  • Male
  • Middle Aged
  • Oxygen Consumption
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor / analysis
  • Receptors, Tumor Necrosis Factor, Type I
  • Shock, Septic / blood
  • Shock, Septic / drug therapy*
  • Shock, Septic / physiopathology
  • Tumor Necrosis Factor-alpha / analysis*


  • Antigens, CD
  • Interleukin-6
  • Interleukin-8
  • Interleukins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Lactic Acid
  • Acetylcysteine