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/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.

CONCLUSIONS

In this clinically relevant septic shock model, alkaline phosphatase administration improved gas exchange, decreased interleukin-6 concentrations, and prolonged survival time.