Lactate as a marker of energy failure in critically ill patients: hypothesis

Abstract

Lactate measurement in the critically ill has been traditionally used to stratify patients with poor outcome. However, plasma lactate levels are the result of a finely tuned interplay of factors that affect the balance between its production and its clearance. When the oxygen supply does not match its consumption, organisms such as man who are forced to produce ATP for their integrity adapt in many different ways up to the point when energy failure occurs. Lactate, being part of the adaptive response, may then be used to assess the severity of the supply/demand imbalance. In such a scenario, the time to intervention becomes relevant: early and effective treatment may allow the cell to revert to a normal state, as long as the oxygen machinery (i.e. mitochondria) is intact. Conversely, once the mitochondria are deranged, energy failure occurs even in the presence of normoxia. The lactate increase in critically ill patients may therefore be viewed as an early marker of a potentially reversible state.

Figure 1

Quick response to lactate production following exposure of laboratory animals to hypoxia. The panel on the top represents changes in arterial oxygenation (PO₂) when inspiratory fraction of oxygen (FiO₂) is decreased to 8%. Bottom panel shows corresponding lactate changes.

Figure 2

Different responses of oxygen conformers and oxygen regulators to oxygen deprivation. Once a threshold of adaptation is reached, oxygen regulators undergo an imbalance between energy supply and energy consumption that leads to 'energy failure'.

Figure 3

ATP turnover expressed over time. The fate of a cell exposed to a decreased ATP turnover is shown. Time is essential to adaptation, the lack of which brings the cell to death.