Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study

Summary Background Hyperlactataemia during septic shock is often viewed as evidence of tissue hypoxia. However, this blood disorder is not usually correlated with indicators of perfusion or diminished with increased oxygen delivery. Muscles can generate lactate under aerobic conditions in a process linking glycolytic ATP supply to stimulation of Na + K + ATPase. Using in-vivo microdialysis, we tested whether inhibition of Na + K + ATPase can reduce muscle lactate. Methods In 14 patients with septic shock, two microdialysis probes were inserted into the quadriceps muscles and infused with lactate-free Ringer's solution in the absence or presence of 10 −7 mol/L ouabain, a specific inhibitor of Na + K + ATPase. We measured lactate and pyruvate concentrations in both the dialysate fluid and arterial blood samples. Findings All patients had increased blood lactate concentrations (mean 4·0 mmol/L; SD 2·1). Lactate and pyruvate concentrations were consistently higher in muscle than in arteries during the study period, with a mean positive gradient of 1·98 mmol/L (SD 0·2; p=0·001) and 230 μmol/L (30; p=0·01), respectively. Ouabain infusion stopped over production of muscle lactate and pyruvate (p=0·0001). Muscle lactate to pyruvate ratios remained unchanged during ouabain infusion with no differences between blood and muscle. Interpretation Skeletal muscle could be a leading source of lactate formation as a result of exaggerated aerobic glycolysis through Na + K + ATPase stimulation during septic shock. Lactate clearance as an end-point of resuscitation could therefore prove useful. Relevance to clinical practice In patients with septic shock, a high lactate concentration should be interpreted as a marker of disease, portending a bad outcome. The presence of hyperlactataemia in resuscitated septic patients should not be taken as proof of oxygen debt needing increases in systemic or regional oxygen transport to supranormal values. Lactate, instead of being regarded only as a marker of hypoxia, might be an important metabolic signal.