Beneficial effects of ethyl pyruvate in septic shock from peritonitis.
OBJECTIVE
Infusion of ethyl pyruvate (EP) solution can improve outcome in a clinically relevant, large- animal model of septic shock resulting from fecal peritonitis.


METHODS
Prospective randomized animal study.


METHODS
University hospital animal research laboratory.


METHODS
Fourteen female sheep.


METHODS
Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated female sheep weighing (mean +/- SD) 30.4 +/- 3.8 kg received 0.5 g/kg of feces intraperitoneally to induce peritonitis, without administration of antibiotic agents or vasoactive drugs. After surgical preparation, the ewes were randomized to receive a continuous intravenous infusion at 15 mg/kg per hour of either EP combined with Ringer lactate solution or Ringer lactate solution only. Fluid resuscitation was titrated to maintain the pulmonary artery occlusion pressure at baseline levels throughout the experiment. All animals were monitored until they died spontaneously or for a maximum of 30 hours.


RESULTS
Compared with Ringer lactate solution alone, EP administration resulted in less tachycardia, longer time to development of arterial hypotension and oliguria (median, 27 vs 15 hours and 24 vs 16 hours, respectively; both P<.01), and prolonged survival time (median, 29.5 vs 17.0 hours; P<.001). Animals who received EP also had a smaller decrease in colloid osmotic pressure (P<.05) and a tendency for lower serum interleukin 6 concentrations (P = .08).


CONCLUSIONS
In this clinically relevant model of septic shock in ewes, continuous EP infusion prolonged time to development of organ dysfunction and markedly prolonged survival. These findings suggest a potential use for EP in the treatment of severe sepsis and septic shock.
Su
Fuhong
F
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Brussels, Belgium.
Wang
Zhen
Z
Cai
Ying
Y
Remmelink
Myriam
M
Vincent
Jean-Louis
JL
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005421:Flavoring Agents; D005500:Follow-Up Studies; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D010538:Peritonitis / Q000150:complications*; D011446:Prospective Studies; D011773:Pyruvates / Q000008:administration & dosage / Q000627:therapeutic use*; D012756:Sheep; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
D005421:Flavoring Agents; D015850:Interleukin-6; D011773:Pyruvates; C046522:ethyl pyruvate