Causes of Elevated Lactate Levels
The primary cause of elevated lactate levels is tissue hypoperfusion and hypoxia, resulting in anaerobic metabolism when oxygen delivery to tissues is inadequate. 1, 2
Primary Causes Related to Tissue Hypoxia
- Shock states - Hypovolemic, cardiogenic, distributive, and obstructive shock all lead to impaired tissue perfusion and subsequent lactate elevation 1, 2
- Trauma and hemorrhage - Blood loss following major trauma causes hypoperfusion, with lactate levels correlating with mortality 1, 2
- Sepsis and septic shock - Major cause of lactic acidosis due to both tissue hypoperfusion and inflammatory mediators affecting cellular metabolism 2
- Mesenteric ischemia - Intestinal hypoperfusion leads to elevated lactate, with levels >2 mmol/L indicating potential tissue hypoperfusion 1
- Cardiac failure - Low cardiac output states lead to inadequate tissue perfusion 1, 2
Medication-Induced Lactate Elevation
- Metformin - Can cause lactic acidosis, particularly in patients with impaired lactate clearance (liver failure) or metformin clearance (renal impairment with eGFR <30 mL/min/1.73m²) 1, 3
- Epinephrine - Causes elevated lactate through beta-2-adrenergic receptor stimulation in skeletal muscle, activating glycogenolysis and glycolysis, independent of tissue perfusion 2, 4
- Other medications - Various drugs can cause hyperlactatemia through different mechanisms, including albuterol and other beta-agonists 5
Metabolic Causes
- Accelerated aerobic glycolysis - Driven by excess beta-adrenergic stimulation, can increase lactate without tissue hypoxia 2, 6
- D-lactic acidosis - Occurs in patients with short bowel syndrome and preserved colon, where colonic bacteria degrade fermentable carbohydrates to form D-lactate 1
- Liver dysfunction - Impairs lactate clearance, exacerbating lactate accumulation 3
Other Important Causes
- Excessive alcohol intake - Potentiates the effect of metformin on lactate metabolism and can independently cause lactic acidosis 3
- Seizures - Increased muscle activity leads to lactate production 7
- Malignancy - Can cause lactate elevation through various mechanisms including increased glycolysis 7
Clinical Significance and Interpretation
- Elevated lactate levels (>2 mmol/L) are associated with increased mortality in various shock states 1, 2
- Serial lactate measurements provide objective evaluation of response to therapy, with normalization within 24 hours associated with improved survival 1, 2
- Lactate clearance time is a significant predictor of survival, with decreased survival if lactate levels remain elevated for >24-48 hours 2
Important Clinical Considerations
- Don't ignore elevated lactate in seemingly stable patients, as it may indicate occult tissue hypoperfusion 2
- Consider medication effects when interpreting elevated lactate levels, particularly in patients receiving epinephrine or metformin 2, 4, 3
- Base deficit values from arterial blood gas analysis can provide an indirect estimation of global tissue acidosis due to impaired perfusion when lactate measurement is unavailable 1
- The reliability of lactate determination may be lower when traumatic injury is associated with alcohol consumption 1
Diagnostic Approach
- Serial lactate measurements are more valuable than single readings for monitoring response to therapy 1, 2
- Elevated lactate with normal vital signs should still prompt consideration of early intervention, especially in conditions like mesenteric ischemia 1
- D-dimer >0.9 mg/L may assist in diagnosing intestinal ischemia when combined with elevated lactate 1