Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis

Lancet. 1999 Aug 7;354(9177):505-8. doi: 10.1016/S0140-6736(98)91132-1.


High blood lactate concentration (hyperlactacidaemia) in trauma or sepsis is thought to indicate tissue hypoxia and anaerobic glycolysis even when blood pressure, cardiac output, and urine output are within clinically acceptable ranges. However, mechanisms of lactate generation by well-oxygenated tissues have received little attention. Within cells, oxidative and glycolytic energy production can proceed in separate, independent compartments. In skeletal muscle and other tissues, aerobic glycolysis is linked to ATP provision for the Na+-K+ pump, the activity of which is stimulated by epinephrine. In injured patients, hypokalaemia may reflect increased Na+,K+-ATPase activity. We propose that increased blood lactate often reflects increased aerobic glycolysis in skeletal muscle secondary to epinephrine-stimulated Na+,K+-ATPase activity and not anaerobic glycolysis due to hypoperfusion. The hypothesis explains why hyperlactacidaemia often neither correlates with traditional indicators of perfusion nor diminishes with increased oxygen delivery. When other variables have returned to normal, continued attempts at resuscitation based on elevated blood lactate may lead to unnecessary use of blood transfusion and inotropic agents in an effort to increase oxygen delivery and lactate clearance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Cell Hypoxia / physiology*
  • Humans
  • Hypoxia / blood
  • Hypoxia / diagnosis*
  • Lactic Acid / blood*
  • Resuscitation
  • Sensitivity and Specificity
  • Systemic Inflammatory Response Syndrome / blood
  • Systemic Inflammatory Response Syndrome / diagnosis*
  • Wounds and Injuries / blood
  • Wounds and Injuries / diagnosis*


  • Lactic Acid