Lactate Measurement and Management

Introduction to Lactate Measurement

• Lactate measurement is a standard clinical test performed in laboratories and point-of-care devices, according to the American College of Critical Care Medicine 1
• Blood lactate serves as both a diagnostic parameter and prognostic marker of hemorrhagic shock, as recommended by the American College of Critical Care Medicine 1, 2

Clinical Significance of Lactate

• Lactate threshold in exercise testing is defined as the oxygen uptake (VO₂) at which blood lactate level increases, as defined by the American Thoracic Society 3
• Elevated serum lactate levels >2 mmol/L are associated with irreversible intestinal ischemia (Hazard Ratio: 4.1, 95% CI: 1.4-11.5; p<0.01) and are considered an indicator of tissue hypoperfusion or other pathological processes, with normal blood lactic acid levels being ≤2 mmol/L in most clinical settings 4, 2, 5

Prognostic Value of Lactate

• In patients with hemorrhagic shock, lactate normalization within 24 hours is associated with improved survival, with a survival rate of 100%, whereas survival decreases to 77.8% if normalization occurs within 48 hours, as reported by the American College of Critical Care Medicine 2
• In CHF patients, lactate threshold <11 mL·min⁻¹·kg⁻¹ is associated with a mortality risk ratio of 2.7 at 6 months, according to the European Respiratory Society 6
• Serial lactate measurements provide valuable prognostic information in circulatory shock, with lactate clearance (decrease by at least 10-20%) used as a resuscitation target in sepsis, and lactate normalization strategies associated with reduced mortality in septic patients, with serial lactate measurements every 4-6 hours essential to assess lactate clearance and treatment efficacy 2, 7, 8

Alternative Predictors and Causes of Lactic Acidosis

• Base deficit may be a better predictor than lactate in alcohol-associated trauma, as suggested by the American College of Critical Care Medicine 1
• Lactic acidosis can be caused by various factors, including metformin toxicity, liver dysfunction, alcoholism, and NRTI medications, as stated by the American College of Physicians 8
• Other causes of lactic acidosis include alcoholic ketoacidosis, salicylates, methanol, paraldehyde, and diabetic ketoacidosis, which can present with a mixed picture of ketoacidosis and lactic acidosis, as reported by the Diabetes Care society 9
• Anion gap >27 mmol/L strongly suggests ethylene glycol poisoning, and immediate treatment is necessary, as recommended by the Critical Care society 10
• Calculate osmolar gap - elevated gap (>10) with high anion gap suggests toxic alcohol ingestion, according to the Critical Care society 10

Diagnosis and Measurement of Lactate

• Lactate levels must be measured correctly using prechilled fluoride-oxalate tubes, transported on ice, processed within 4 hours, and collected without tourniquet or fist-clenching to ensure accurate results, as recommended by the American College of Physicians 8
• Direct lactate measurement is essential, and treatment should not be delayed while waiting for a definitive diagnosis in severely acidotic patients, with consideration of ethylene glycol poisoning with very high anion gaps 10

Management of Lactic Acidosis

• Initial management includes administering crystalloid fluids (30 mL/kg IV) if signs of hypoperfusion are present, with reassessment of hemodynamic status frequently after initial fluid resuscitation, targeting mean arterial pressure of 65 mmHg if shock is present, as recommended by the Intensive Care Medicine society 11
• Further resuscitation should be guided to normalize lactate levels, with fluid resuscitation with 20-40 ml/kg of either 0.9% saline or 4.5% human albumin solution recommended to correct hypovolemic shock, and avoidance of excessive fluid administration, especially in patients at risk for fluid overload 11, 12, 13, 14, 3
• The primary treatment is to identify and address the underlying cause, with specific interventions determined by the type of lactic acidosis (Type A or Type B), as recommended by the Surviving Sepsis Campaign guidelines and the American College of Physicians 11, 15, 16
• Vasopressor support with norepinephrine as the first-line agent and adrenaline as the second-line agent should be considered if hypotension persists despite adequate fluid resuscitation, with regular monitoring of arterial blood gases, plasma osmolarity, hemodynamics, cardiac rhythm, and renal function crucial in managing lactic acidosis 17, 12
• Ventilatory support should be considered for patients with respiratory failure, with caution to avoid rapid rise of PCO2 even to normal levels before acidosis is partly corrected, and monitoring for signs of fluid overload and reducing infusion rates if present, as recommended by the American Academy of Pediatrics and the American Thoracic Society 12, 14, 3

Special Considerations

• In obstetric patients, lactate >2 mmol/L in the absence of labor is considered an indicator of end-organ injury, but during labor and immediately postpartum, lactic acid levels may be physiologically elevated and should not be used for diagnosis 18
• Patients with liver dysfunction may require more aggressive intervention due to impaired lactate metabolism, and D-lactic acidosis can occur in patients with short bowel syndrome or intestinal bacterial overgrowth, requiring different management, according to the European Society of Gastrointestinal Endoscopy 19, 8
• The National Kidney Foundation recommends discontinuing metformin when eGFR falls below 30 mL/min/1.73 m², and dose reduction to 1000 mg daily is recommended when eGFR is 30-44 mL/min/1.73 m², with a strength of evidence based on clinical guidelines 20
• In COVID-19 patients with diabetes, metformin use was associated with increased lactic acidosis (adjusted HR 4.46) 21