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

Lancet. 2005 Mar 5-11;365(9462):871-5. doi: 10.1016/S0140-6736(05)71045-X.


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 micromol/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.

MeSH terms

  • Aerobiosis
  • Aged
  • Enzyme Inhibitors / pharmacology
  • Glycolysis
  • Humans
  • Lactic Acid / blood
  • Lactic Acid / metabolism*
  • Microdialysis
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*
  • Ouabain / pharmacology
  • Oxygen / metabolism
  • Partial Pressure
  • Pyruvic Acid / blood
  • Shock, Septic / metabolism*
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Enzyme Inhibitors
  • Lactic Acid
  • Ouabain
  • Pyruvic Acid
  • Sodium-Potassium-Exchanging ATPase
  • Oxygen