Beneficial Effects Of Alkaline Phosphatase In Septic Shock

Objective: Alkaline 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.Design: Interventional laboratory study.Setting. University hospital animal research laboratory.Subjects: Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (27.6 +/- 3.9 kg).Interventions. Each 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 Results., All 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/FiO(2) 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.Conclusions: In this clinically relevant septic shock model, alkaline phosphatase administration improved gas exchange, decreased interleukin-6 concentrations, and prolonged survival time.