Effects of N-acetylcysteine in endotoxic shock.
OBJECTIVE
The release of oxygen-free radicals has been implicated in both peripheral vascular and myocardial alterations of septic shock. N-Acetylcysteine (N-AC), a substrate for the production of glutathione, has potent antioxidant effects. As a nitrosothiol, it may also improve capillary blood flow. We studied the effects of N-AC in a dog model of endotoxic shock.


METHODS
Ten pentobarbital-anesthetized, mechanically ventilated dogs were randomly assigned to receive either N-AC (150 mg/kg loading dose in 1 hour, followed by 20 mg/kg.h maintenance dose) or D5W. After the loading dose, each dog received 3 mg/kg Escherichia coli endotoxin intravenously. After 30 minutes, saline infusion was started to restore and maintain baseline filling pressures.


RESULTS
The loading dose of N-AC increased DO2 significantly (from 661 +/- 54 to 914 +/- 190 mL/min, P < .05), but VO2 remained stable. After the administration of endotoxin, fluid challenge restored cardiac output to baseline, in both groups. Hemoglobin and, thus, DO2 were slightly lower in the N-AC-treated dogs, but VO2 was similar in both groups. At the end of the study, O2ER was significantly higher in the N-AC-treated dogs than in the control dogs. Blood lactate levels fell more rapidly in the N-AC dogs than in the control dogs. Blood lactate levels returned to normal in the N-AC dogs but not in the control dogs. Tumor necrosis factor (TNF) also decreased significantly in the N-AC dogs but remained elevated in the control dogs.


CONCLUSIONS
These data indicate that N-AC administration in endotoxic shock is well tolerated, may increase oxygen availability to the tissues, and is associated with an attenuation of TNF release.
Bakker
J
J
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
Zhang
H
H
Depierreux
M
M
van Asbeck
S
S
Vincent
J L
JL
D000111:Acetylcysteine / Q000097:blood / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D007773:Lactates / Q000097:blood; D011897:Random Allocation; D012129:Respiratory Function Tests; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000097:blood / Q000627:therapeutic use*
D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D000111:Acetylcysteine