What is the cause of elevated lactic acid levels and hypoglycemia (low blood sugar)?

From the Guidelines

Elevated lactic acid and hypoglycemia require immediate medical attention to prevent progression to multi-organ failure, with initial management focusing on correcting hypoglycemia with glucose administration and addressing the underlying cause. The combination of elevated lactic acid and hypoglycemia suggests impaired cellular metabolism, where the body shifts to anaerobic glycolysis, producing lactic acid while depleting glucose stores. Common causes include sepsis, liver failure, certain medications, alcohol intoxication, and inborn errors of metabolism. According to the study published in Diabetes Care 1, hypoglycemia is defined as a blood glucose level < 70 mg/dL (3.9 mmol/L) and can be a medical emergency, especially if severe and requiring assistance from a third party. Initial management should include:

• Glucose administration, such as D50W 50mL IV for adults or D10W 2-4 mL/kg for children, to correct hypoglycemia
• Maintenance with D5W or D10W infusion
• Addressing the underlying cause, which may involve:
  • Antibiotics for infection
  • Vasopressors for shock
  • Discontinuation of offending medications
• Fluid resuscitation with normal saline or lactated Ringer's at 20-30 mL/kg is often necessary. As noted in another study published in Diabetes Care 1, hypoglycemia can usually be effectively self-treated by ingestion of glucose, but in the context of elevated lactic acid, immediate medical attention is necessary to address the underlying cause and prevent further complications.

From the Research

Elevated Lactic Acid and Hypoglycemia

• Elevated lactic acid and hypoglycemia can occur in various clinical settings, including sepsis, acute liver failure, and severe malaria 2.
• Lactic acidosis is typically due to tissue hypoxia with sepsis being the most common cause, but type B lactic acidosis should be considered in patients with persistently elevated lactate without evidence of inadequate oxygen delivery 3.
• Hyperlactatemia and hypoglycemia can coexist, and lactate can substitute for glucose as a metabolic substrate, potentially protecting against deep hypoglycemia 2.
• The combination of hypoglycemia and hyperlactatemia may be considered paradoxical, as glucose is the main precursor of lactate and lactate is reconverted into glucose by the Cori cycle 2.
• Impaired Cori cycle is a key component in metabolic states characterized by hypoglycemia and hyperlactatemia, including paracetamol-induced acute liver failure, severe malaria, lymphoma, and glucose-6-phosphatase deficiency 2.

Clinical Implications

• Lactate clearance and vasopressor use seem to be predictors for mortality in severe sepsis patients with lactic acidosis supplementing sodium bicarbonate 4.
• Initial lactate level, lactate clearance, C-reactive protein, and procalcitonin are associated with hospital mortality in critically ill patients with sepsis 4.
• Hyperlactatemia is mainly related to increased production, whereas lactate clearance is similar to healthy subjects in patients suffering from septic or cardiogenic shock 5.
• Increased lactate production is concomitant to hyperglycemia and increased glucose turnover, suggesting that glucose metabolism substantially influences lactate metabolism during critical illness 5.

Metabolic States

• Four syndromes demonstrating hypoglycemia and hyperlactatemia have been identified: paracetamol-induced acute liver failure, severe malaria, lymphoma, and glucose-6-phosphatase deficiency 2.
• Lactate-protected hypoglycemia is a viable state under experimental and clinical conditions, and patients presenting with this metabolic state should not automatically be considered to have sustained irreversible brain damage 2.
• Therapies aiming to achieve hypoglycemia might be feasible with concomitant hyperlactatemia, as lactate can substitute for glucose as a metabolic substrate 2.