Lactate in Shock: Pathophysiology, Prognostic Value, and Resuscitation Strategy for the Cardiologist

Lactate is a biochemical marker of shock and now occupies a central position in the diagnostic definitions, severity classifications, and prognostic risk stratification systems used in every form of circulatory failure encountered by the cardiologist. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) incorporated lactate greater than 2 mmol/L into the definition of septic shock, and the Society for Cardiovascular Angiography and Interventions shock classification uses lactate to anchor its hypoperfusion criteria across stages B through E. Landmark cardiogenic-shock trials—IABP-SHOCK II, ECLS-SHOCK, and DanGer Shock—all required hyperlactatemia in their inclusion criteria, and lactate measured early after presentation predicts mortality independent of treatment assignment. Despite this central role, the biology of lactate generation in shock has been substantially revised. Aerobic glycolysis driven by catecholamine-stimulated Na + /K + -ATPase activity, microcirculatory shunting, mitochondrial dysfunction, and impaired hepatic clearance contribute alongside (and often more than) anaerobic glycolysis from frank tissue hypoxia. The shift in pathophysiologic understanding has translated into a more nuanced view of lactate-guided resuscitation: lactate kinetics correlate with outcome, but trials targeting lactate normalization have produced mixed results, and the ANDROMEDA-SHOCK and ANDROMEDA-SHOCK-2 studies suggest that peripheral perfusion-targeted strategies may match or surpass lactate-targeted protocols in septic shock.