What causes an increase in lactate levels?

Causes of Lactate Elevation in Clinical Settings

Lactate elevation is primarily caused by tissue hypoxia and hypoperfusion, but can also result from increased production due to sepsis, medications, liver dysfunction, and other metabolic derangements even in the absence of tissue hypoxia.

Primary Mechanisms of Lactate Elevation

1. Tissue Hypoperfusion and Hypoxia

• Shock states - The most common cause of elevated lactate is tissue hypoperfusion leading to anaerobic metabolism 1
• Mesenteric ischemia - Elevated serum lactate >2 mmol/L is associated with irreversible intestinal ischemia (hazard ratio: 4.1) 2
• Cardiac failure - Reduced cardiac output leads to inadequate tissue perfusion 2

2. Sepsis-Related Mechanisms

• Increased glycolysis - Sepsis causes increased glucose turnover and lactate production even without tissue hypoxia 3
• Microcirculatory dysfunction - Sepsis impairs oxygen utilization at the cellular level despite adequate oxygen delivery 2
• Inflammatory mediators - Cytokines and endotoxins alter cellular metabolism 4

3. Medication and Toxin-Related Causes

• Vasopressors - High-dose vasoactive drugs can cause non-occlusive mesenteric ischemia (NOMI) 2
• Beta-adrenergic stimulation - Activates glycogenolysis and increases lactate production in skeletal muscles 2
• Epinephrine - Associated with transient increases in serum lactate levels compared to norepinephrine 2

4. Liver Dysfunction

• Impaired lactate clearance - The liver normally clears up to 70% of circulating lactate 5
• Hepatic ischemia - Reduced blood flow to the liver impairs lactate metabolism 5

5. Other Metabolic Causes

• Diabetic ketoacidosis - Increased lactate production due to altered metabolism 6
• Seizures - Increased muscle activity and oxygen consumption 6
• Malignancy - Tumor cells often rely on aerobic glycolysis (Warburg effect) 6

Clinical Significance and Assessment

Diagnostic Value

• Lactate >2 mmol/L is considered elevated, with severe elevation defined as >4 mmol/L 1
• Persistent elevation of lactate >2 mmol/L for >48 hours is associated with poor outcomes 1
• Elevated lactate is an independent predictor of mortality in sepsis, even without organ dysfunction or shock 7

Monitoring Recommendations

• Measure blood lactate early to establish a baseline 1
• Repeat measurements every 2-4 hours to assess clearance 1
• Target at least 10% lactate clearance within 2-4 hours 1

Special Considerations

Septic Shock

• In septic shock, hyperlactatemia is mainly related to increased production rather than decreased clearance 3
• Lactate-guided resuscitation is associated with significant mortality reduction (relative risk 0.67) 1

Hepatic Dysfunction

• Even in patients with hepatic dysfunction, initial serum lactate level remains a significant predictor of mortality in septic shock 5
• After adjusting for confounding factors, lactate level is independently associated with in-hospital mortality (odds ratio 1.281) 5

Resuscitation Targets

• Comprehensive approach using multiple parameters:
  • Mean arterial pressure ≥65 mmHg
  • Urine output ≥0.5 mL/kg/hour
  • Lactate clearance 1
• Initial fluid resuscitation with at least 30 mL/kg IV crystalloid within first 3 hours 2

Common Pitfalls

1. Assuming all lactate elevation indicates tissue hypoxia - Many cases of hyperlactatemia in sepsis occur without tissue hypoxia 4

2. Focusing solely on lactate without considering other clinical parameters - A comprehensive assessment using multiple parameters provides the most complete evaluation 1

3. Delaying treatment while awaiting lactate results - Initiate resuscitation immediately in suspected shock states 2

4. Overlooking medication effects on lactate levels - Various medications can cause lactate elevation independent of tissue perfusion 2, 6

5. Failing to trend lactate levels - Serial measurements provide more valuable information than a single value 1