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


METHODS
Prospective, randomized, double-blind, placebo-controlled study.


METHODS
A 24-bed medicosurgical ICU in a university hospital.


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


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Spapen
H
H
Department of Intensive Care, Academic Hospital, Vrije Universiteit, Brussels, Belgium.
Zhang
H
H
Demanet
C
C
Vleminckx
W
W
Vincent
J L
JL
Huyghens
L
L
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D019344:Lactic Acid / Q000097:blood; D008170:Lung Compliance; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015703:Antigens, CD; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019344:Lactic Acid; D000111:Acetylcysteine