• Fuhong Su, Ruud Brands, Zhen Wang, Colin Verdant, Alejandro Bruhn, Ying Cai, Willem Raaben, Marty Wulferink, and Jean-Louis Vincent.
• Department of Intensive Care, Erasme Hospital, Free University of Brussels, Belgium.
• Crit. Care Med. 2006 Aug 1;34(8):2182-7.

ObjectiveAlkaline phosphatase may decrease the harmful effects of lipopolysaccharide by detoxifying lipid A. The aim of this study was to investigate whether administration of alkaline phosphatase is beneficial in a clinically relevant septic shock model.DesignInterventional laboratory study.SettingUniversity hospital animal research laboratory.SubjectsFourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (27.6 +/- 3.9 kg).InterventionsEach animal received 1.5 g/kg body weight of feces intraperitoneally to induce sepsis. Ringer's lactate and a 6% hydroxyethyl starch solution were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, animals were randomized to alkaline phosphatase (60 units/kg intravenous bolus followed by a continuous infusion of 20 units/kg/hr for a total of 15 hrs) or no alkaline phosphatase (control group).Measurements And Main ResultsAll animals were studied until their spontaneous death or for a maximum of 30 hrs. Plasma alkaline phosphatase concentrations decreased in the control group but increased in the treatment group following alkaline phosphatase administration. In the treatment group, the Pao2/Fio2 ratio was higher (p < .05), blood interleukin-6 concentrations were lower (p < .05), and the survival time was longer (median time 23.8 vs. 17 .0 hrs, p < 0.05) than in the control group. There were no significant differences in systemic hemodynamics or diuresis.ConclusionsIn this clinically relevant septic shock model, alkaline phosphatase administration improved gas exchange, decreased interleukin-6 concentrations, and prolonged survival time.

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