Septic shock does not impair cardiac, renal or cerebral oxidative metabolism but may impair splanchnic metabolism in an ovine model of supported endotoxemic shock

Abstract

Introduction: Lactic acidosis is a sentinel feature of septic shock, however the source of arterial lactate remains debated. Tissue hypoperfusion with impaired oxidative metabolism and catecholamine mediated production are both proposed as causative mechanisms. Distinguishing between the two remains important as tissue hypoxia remains a potentially modifiable cause of organ dysfunction and death. Objectives: Through comparing the organ to arterial lactate gradient this study aims to establish if the heart, brain, liver and kidneys contribute to the observed arterial lactate. Utilise the lactate:pyruvate ratio to identify impaired oxidative metabolism in the above organs. Methods: Endotoxemic shock was induced in five sheep with an infusion of lipopolysaccharide. Microdialysis catheters were inserted into the heart, brain liver, kidney and femoral artery. After induction of shock animals were monitored for 12 hours during which they received protocolised haemodynamic support with noradrenaline and vasopressin. Tissue microdialysis samples were recovered hourly. Results: Univariate regression of arterial and organ lactate was performed against time. In all cases except the brain lactate rose significantly over time. 2-way comparison of mean lactate between the arterial sample and each organ was performed. The mean lactate in the brain and kidney was significantly lower than that of arterial blood. The mean lactate of the heart and liver was not significantly different from arterial blood. 2-way comparison of lactate:pyruvate (L-P) ratio was performed against a normal value of <25. On average all organs except the liver demonstrated normal L-P ratios. The mean L-P ratio of the liver was significantly higher than normal (29.7). Conclusion: These results suggest the heart, brain, liver and kidneys are not significant contributors to the increased arterial lactate in this model of experimental sepsis. Despite the observed increased lactate oxidative metabolism appears unimpaired in the heart, brain and kidneys however there is evidence impaired splanchnic oxidative metabolism.<br />