Prostacyclin improves glucose utilization in patients with sepsis

Abstract

Purpose: In patients with sepsis, impaired glucose metabolism and altered microcirculatory blood flow are common findings. Prostacyclin (PGI 2) improves tissue oxygenation, indicated by enhanced oxygen delivery (Do 2) and oxygen uptake (Vo2). The purpose of this study was to explore whether these effects are associated with improved glucose utilization. Methods: In 7 patients with sepsis, glucose metabolism was analyzed using dideuterated and 13C-labeled glucose and isotope dilution mass spectrometry. All patients received total parenteral nutrition with glucose covering 60% to 70% of the predicted energy expenditure and needed continuous intravenous insulin (40 μU · kg −1 · min −1) to keep blood glucose concentrations below 10 mmol · l −1. Vo2 and carbon dioxide production (Vco2) were continuously measured directly from the respiratory gases via indirect calorimetry. After equilibration of the infused labeled glucose with body glucose pool, baseline variables of glucose metabolism were assessed: glucose oxidation rate was determined from the enrichment of 13CO 2 in the expired gas during primed constant infusion of [U- 13C]glucose, glucose turnover rate (R a) from the plasma enrichment of simultaneously infused [6,6 2H 2]glucose. Endogenous glucose production rate was calculated as the difference between R a and glucose infusion rate. Then, we examined the effect of PGI 2 infusion (5 to 12.5 ng · kg −1 · min −1) on glucose metabolism and gaseous exchange. Results: The PGI 2-induced increase in DO 2 (from 15.8 to 17.7 ml · kg −1 - min −1; P < .05) resulted in an increase in directly measured Vo 2 from 5.0 to 5.3 ml · kg −1 min −1 ( P < .01) whereas Vco 2 remained unchanged. Although glucose turnover and production rates remained constant, glucose oxidation rate increased significantly from 1.21 to 1.38 mg · kg −1 · min −1 ( P < .02). Conclusions: Improving tissue perfusion and oxygenation with PGI 2 may also modify the impaired glucose metabolism by increasing glucose oxidation rate in patients with sepsis, suggesting enhanced adenosine triphosphate production.