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Fuhong Su, MD; Zhen Wang, MD; Ying Cai, MD; Myriam Remmelink, MD; Jean-Louis Vincent, MD, PhD

Arch Surg. 2007;142(2):166-171.

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.

Author Affiliations: Departments of Intensive Care (Drs Su, Wang, and Vincent) and Pathology (Dr Remmelink), and the Diabetes Center (Dr Cai), Erasme University Hospital, Free University of Brussels, Brussels, Belgium.