Glucose metabolism during hyperdynamic septic shock: comparison between noradrenaline and vasopressin

Introduction

In septic shock, arginine–vasopressin (AVP) infusion efficiently maintains the mean arterial pressure (MAP), but may compromise hepatosplanchnic perfusion due to excessive vasoconstriction and, thus, depress whole-body and regional substrate metabolism. In this context, the underlying hemodynamic status is crucial [1]. We therefore compared the effects of noradrenaline (NA) and AVP on hepatosplanchnic blood flow, whole body glucose oxidation and hepatic gluconeogenesis during resuscitated, hyperdynamic septic shock.

Methods

After intraperitoneal faeces inoculation [2], anesthetized, mechanically ventilated and instrumented pigs were randomly assigned to NA (increments of 0.06 μg/kg/min until maximal heart rate of 160/min; n = 8) or AVP (1–5 ng/kg/min, supplemented by NA if the maximum AVP dosage alone failed to maintain MAP; n = 9) to treat sepsis-associated hypotension. During continuous infusion of stable, nonradioactively labeled 1,2,3,4,5,6-¹³C₆-glucose, blood isotope (gas chromatography–mass spectrometry) and expiratory gas ¹³CO₂ (nondispersive infrared spectrometry) enrichment was measured to derive gluconeogenesis and direct aerobic glucose oxidation [2] together with portal venous (Qpv) and hepatic arterial (Qha) blood flows (ultrasound flow probes). Data are the median (quartiles), and P < 0.05 was regarded as significant for AVP versus NA.

Results

At 24 hours of sepsis AVP resulted in significantly lower cardiac output and Qpv (20 (11–36) vs 26 (15–35) ml/kg/min), while Qha was comparable (3.0 (0.1–6.0) vs 2.1 (0.1–5.1) ml/kg/min). Despite significantly lower NA infusion rates (0.08 (0.0–0.64) vs 0.56 (0.05–4.36) μg/kg/min), AVP did not affect the parameters of energy expenditure (O₂ uptake (5.8 (3.9–8.1) vs 4.7 (4.2–6.6) ml/kg/min), CO₂ production (3.4 (2.3–4.9) vs 3.5 (2.9–4.7) ml/kg/min)), nor glucose metabolism (glucose oxidation 3.9 (0.6–4.6) vs 3.7 (0.6–4.6) mg/kg/min; gluconeogenesis 6.8 (4.6–8.5) vs 7.2 (4.9–11.0) mg/kg/min).

Conclusion

Given the markedly lower NA infusion rates, the unchanged parameters of substrate utilization suggest improved cellular energy metabolism during AVP infusion.