Beneficial effects of ethyl pyruvate in septic shock from peritonitis

HYPOTHESIS: Infusion of ethyl pyruvate (EP) solution can improve outcome in a clinically relevant, large- animal model of septic shock resulting from fecal peritonitis. DESIGN: Prospective randomized animal study. SETTING: University hospital animal research laboratory. SUBJECTS: Fourteen female sheep. INTERVENTIONS: 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.