What can increase lactate levels?

What Can Increase Lactate Levels

Lactate elevation occurs primarily from tissue hypoperfusion and shock states, but also results from accelerated aerobic glycolysis driven by beta-adrenergic stimulation, medications (particularly metformin and epinephrine), liver dysfunction impairing lactate clearance, and mesenteric ischemia—all requiring different management approaches. 1

Primary Causes: Tissue Hypoperfusion and Shock

• Sepsis and septic shock represent the most common critical cause, elevating lactate through both inadequate tissue perfusion and inflammatory mediators disrupting cellular metabolism. 1

• All shock states—hypovolemic, cardiogenic, and distributive—impair tissue perfusion and drive anaerobic metabolism, with lactate levels correlating directly with mortality risk. 1

• Hemorrhagic shock and major trauma produce lactate elevation that serves as both a diagnostic and prognostic marker, with levels >2 mmol/L indicating potential tissue hypoperfusion. 1

• Mesenteric ischemia causes lactate >2 mmol/L in >88% of cases, with levels >2 mmol/L carrying a 4.1-fold increased risk of irreversible intestinal ischemia—this requires urgent CT angiography even in hemodynamically stable patients. 1, 2

Medication-Induced Lactate Elevation

• Epinephrine increases lactate through beta-2-adrenergic receptor stimulation in skeletal muscle, activating glycogenolysis and glycolysis independent of tissue perfusion status—this represents aerobic lactate production, not tissue hypoxia. 1, 3

• Metformin causes lactic acidosis when clearance is impaired (eGFR <30 mL/min/1.73 m²), when lactate clearance is impaired (liver failure), or in conditions causing anaerobic metabolism (sepsis, hypoxia). 1

• NRTIs (nucleoside reverse transcriptase inhibitors) can cause hyperlactatemia in HIV patients, requiring close monitoring for lactate levels 2-5 mmol/L and consideration of switching antiretroviral regimens if symptomatic. 1

Metabolic and Aerobic Causes

• Accelerated aerobic glycolysis from excess beta-adrenergic stimulation increases lactate production without tissue hypoxia—this mechanism explains why lactate can remain elevated despite adequate oxygen delivery and normal perfusion parameters. 1, 3, 4

• Stress states (including exercise, seizures, and catecholamine surges) increase lactate through Na+-K+-ATPase activation in skeletal muscle, driven by epinephrine stimulation rather than anaerobic metabolism. 3, 4

Impaired Lactate Clearance

• Liver dysfunction impairs lactate metabolism through the Cori cycle, causing persistent elevation despite adequate tissue perfusion—this is particularly relevant in patients with MELD scores >25 or acute-on-chronic liver failure. 1, 2

• Hepatic congestion from heart failure can produce cholestatic patterns and elevated lactate, with ischemic cholangiopathy occurring after prolonged hypotension. 1

Critical Clinical Thresholds

• Lactate ≥4 mmol/L represents a medical emergency with 46.1% mortality, requiring immediate protocolized resuscitation with fluid bolus of 30 mL/kg IV crystalloid within 3 hours and vasopressor support targeting MAP ≥65 mmHg. 1

• Lactate 2-4 mmol/L indicates moderate tissue hypoperfusion with ~30% mortality, warranting aggressive fluid resuscitation and serial monitoring every 2-6 hours. 1

• Lactate >2 mmol/L persisting >24 hours drops survival to 77.8%, and to 13.6% if elevated beyond 48 hours—making lactate clearance time a critical predictor of survival. 1

Important Diagnostic Nuances

• "Cryptic shock" occurs in up to 23% of septic patients who have lactate ≥2 mmol/L despite central venous oxygen saturation (ScvO2) >70%—normal or high ScvO2 does not rule out tissue hypoxia in sepsis due to impaired cellular oxygen utilization and mitochondrial dysfunction. 1

• Alcohol consumption confounds lactate interpretation, making base deficit from arterial blood gas a more reliable marker in alcohol-associated presentations. 1

• Labor transiently elevates lactate, so it should not be used to diagnose sepsis during active labor—outside labor, pregnant patients have lactate values similar to nonpregnant adults (<2 mmol/L). 1

Embolic Causes Requiring Immediate Recognition

• Arterial embolism to mesenteric vessels causes sudden lactate elevation and represents a medical emergency, typically manifesting as sudden intense abdominal pain with minimal physical findings in patients with atrial fibrillation or other embolic sources. 1

• Multi-organ embolic involvement can occur when emboli lodge in multiple vascular beds simultaneously, requiring CT angiography as the gold standard for diagnosis. 1

Key Management Principles

• Identify and treat the underlying cause rather than treating lactate itself—tissue hypoperfusion requires fluid resuscitation and hemodynamic support, while sodium bicarbonate should NOT be used for pH ≥7.15 as it does not improve outcomes and may cause harm. 1

• Serial lactate measurements every 2-6 hours during acute resuscitation provide objective evaluation of treatment response, targeting lactate clearance of at least 10% every 2 hours during the first 8 hours. 1, 2

• Assess multiple parameters together—lactate, base deficit, MAP ≥65 mmHg, urine output ≥0.5 mL/kg/hr, capillary refill ≤2 seconds, and mental status—as lactate alone may not reflect the complete perfusion picture. 1, 5