Lactate and pyruvate concentrations and their ratios as a marker for local or systemic hypoxic-ischaemic injury

Abstract

Lactate and pyruvate play a crucial role in assessing the metabolic status of critically ill patients. Under normal conditions, lactate is produced by anaerobic glycolysis and is excreted by the liver and kidneys. Elevated lactate levels, referred to as hyperlactatemia, can be caused by various conditions, including tissue hypoxia, impaired oxygen utilisation, and metabolic disorders. Hyperlactatemia is often associated with adverse outcomes, particularly in critical illnesses such as sepsis and shock. Lactic acidosis, characterised by both elevated lactate levels and decreased blood pH, further exacerbates metabolic acidosis and leads to multi-organ failure if left untreated. The lactate-to-pyruvate ratio (L/P) is a potential biomarker to differentiate between hypoxic and non-hypoxic hyperlactatemia. A high L/P ratio indicates significant mitochondrial dysfunction and impaired oxidative metabolism, which often means a poorer prognosis. Conversely, a lower L/P ratio tends to indicate a more favourable outcome. However, the clinical utility of the L/P ratio is limited by the difficulty of measuring pyruvate and its dependence on factors such as pH and redox potential. Although lactate measurements are routinely performed in the emergency department and intensive care unit, there is little data on the prognostic value of the L/P ratio. Recent studies have shown that persistent hyperlactatemia with an elevated L/P ratio during the first 24 hours of septic shock correlates with increased mortality and organ failure. In addition, research on critical conditions such as the coronavirus 2019 disease (COVID-19) suggests that circulating pyruvate levels may also predict disease severity. Overall, the L/P ratio has the potential to be a valuable tool for monitoring critically ill patients, but further research is needed to confirm its broader clinical applicability.