Occasional essay Varying clinical significance of hyperlactataemia

Lactate levels are frequently cited as an indicator of inadequate tissue perfusion or oxygenation. However, due to the variety of mechanisms by which an elevated plasma lactate level can occur, the diagnostic and prognostic implications of hyperlactataemia are not always straightforward. Although extensively described and differentiated from type A lactic acidosis, the clinical and prognostic significance of hyperlactataemia in the absence of impaired oxygen delivery (DO2) has not been well defined. Hyperlactataemia is defined by a measured blood lactate level above the normal range (> 2mmol/L), while lactic acidosis is defined by the presence of a blood lactate concentration > 5 mmol/L concurrent with a metabolic acidaemia (pH < 7.35). Lactic acidosis has been divided into “type A”, associated with impaired delivery of oxygen to tissues (DO2), and “type B”, where lactic acidosis occurs in the presence of normal DO2. Lactic acidosis occurring in the setting of normal DO2 may represent increased cellular production of lactate, reduced tissue uptake or utilisation of oxygen, or reduced lactate clearance. There is increasing recognition that hyperlactataemia and lactic acidosis may occur in the absence of tissue hypoxia. However, interpretation of hyperlactataemia as an indication of inadequate tissue perfusion or oxygenation continues, resulting in interventions aimed at increasing tissue oxygen delivery (DO2). Glucose (85%) and amino acids (15%) are metabolised to pyruvate in all cells, generating ATP and NADH. The Krebs cycle and oxidative phosphorylation within the mitochondria generates ATP via metabolism of pyruvate to CO2 and water. This process is dependent on the maintenance of a minimum local concentration of oxygen. Normal aerobic metabolism generates 36 mol of ATP for every 1 mol of glucose. Any process impairing metabolism of pyruvate, particularly tissue hypoxia, leads to accumulation of pyruvate and its alternative metabolite, lactate. This process provides a mechanism where ATP production can continue in states of tissue hypoxia, but is far less efficient than aerobic metabolism. Anaerobic metabolism produces 2 mol of ATP for every 1 mol of glucose utilised. The lactate produced in erythrocytes (which lack mitochondria) and by anaerobic metabolism is metabolised mainly in the liver. Each molecule of lactate metabolised also regenerates a molecule of bicarbonate, replacing that used in initially buffering lactic acidosis. Lactate accumulates in the presence of tissue hypoxia, but may also increase in aerobic conditions where increased glycolysis occurs, as with stimulation by endogenous or exogenous catecholamines. Measurement of the ratio between lactate and pyruvate concentrations may distinguish between situations of increased cellular metabolism (ratio normal 10:1) and tissue hypoxia (ratio elevated > 10:1). Clinically, moderate hyperlactataemia may also occur in the absence of acidosis as in patients receiving renal replacement therapy (RRT) with lactatecontaining dialysate. However, increasing hyperlactataemia will inevitably result in metabolic acidosis, by virtue of the increased presence of the strong ion lactate. Hyperlactataemia in the critically ill may then take one of three forms: 1. Moderate hyperlactataemia without acidosis. 2. Lactic acidosis associated with impaired DO2 (Type A). 3. Lactic acidosis associated with preserved DO2 (Type B).