What causes elevated lactic acid levels in a patient?

Elevated Lactic Acid: Causes and Clinical Approach

Most Common Cause

Tissue hypoperfusion and hypoxia from inadequate oxygen delivery is the most common cause of elevated lactate, triggering anaerobic metabolism. 1

Primary Causes to Consider

Shock States and Tissue Hypoperfusion

• Sepsis and septic shock cause lactic acidosis through both impaired tissue perfusion and inflammatory mediators disrupting cellular metabolism 1
• Hemorrhagic shock from trauma produces lactate elevation that directly correlates with mortality risk 2, 1
• Cardiogenic, hypovolemic, and distributive shock all impair tissue oxygen delivery 1
• Acute mesenteric ischemia presents with elevated lactate >2 mmol/L, which indicates irreversible intestinal ischemia (Hazard Ratio: 4.1) 2

Medication-Induced Elevation

• Metformin causes lactic acidosis in patients with impaired clearance (renal failure with eGFR <30 mL/min/1.73 m²), impaired lactate clearance (liver failure), or conditions causing anaerobic metabolism (sepsis, hypoxia) 2, 3
• Epinephrine increases lactate through beta-2-adrenergic stimulation of skeletal muscle glycolysis, producing elevation independent of tissue perfusion status—this makes lactate difficult to interpret in patients receiving epinephrine infusions 4

Metabolic and Other Causes

• Thiamine deficiency causes type B lactic acidosis through impaired aerobic metabolism, particularly in malnourished patients 5
• Hematologic malignancies (acute lymphoblastic leukemia, lymphoma) produce type B lactic acidosis from tumor metabolism 6
• Liver disease impairs lactate clearance since the liver is the primary site of lactate metabolism 3
• Seizures generate lactate from intense muscle activity 7

Critical Diagnostic Thresholds

• Lactate >2 mmol/L indicates potential tissue hypoperfusion and warrants investigation 2, 1
• Lactate >5 mmol/L with anion gap acidosis defines metformin-associated lactic acidosis 3
• Serial measurements are essential: failure to normalize within 24 hours drops survival to 77.8%, and to 13.6% if elevated beyond 48 hours 2, 1

Systematic Approach to Diagnosis

Immediate Assessment

1. Check for shock states: Look for hypotension, tachycardia, altered mental status, decreased urine output, and signs of poor perfusion (cool extremities, delayed capillary refill) 1
2. Review medication list: Specifically check for metformin (especially with renal impairment) and epinephrine/vasopressor infusions 2, 4, 3
3. Assess oxygenation: Hypoxia from any cause (cardiac failure, respiratory failure, sepsis) drives anaerobic metabolism 1

Laboratory Evaluation

• Base deficit from arterial blood gas provides complementary information about global tissue acidosis—these parameters don't strictly correlate, so assess both independently 2
• Renal function (eGFR) is critical if metformin exposure exists 3
• D-dimer >0.9 mg/L has 82% specificity for intestinal ischemia if abdominal pain is present 2

Imaging When Indicated

• CT angiography should be performed urgently if mesenteric ischemia is suspected (abdominal pain with lactic acidosis, even in seemingly stable patients) 2

Critical Pitfalls to Avoid

• Don't dismiss elevated lactate in stable-appearing patients—it may indicate occult hypoperfusion requiring urgent intervention 2, 1
• Don't assume epinephrine-induced lactate elevation is benign—while it can occur without tissue hypoperfusion, you must still rule out worsening shock 4
• Don't continue metformin in at-risk patients: Stop immediately if sepsis, hypoxia, shock, acute kidney injury (eGFR <30), or before contrast imaging in patients with eGFR 30-60 mL/min/1.73 m² 2, 3
• Don't rely on single lactate measurement—serial measurements showing clearance (or lack thereof) provide prognostic information and guide resuscitation 2, 1

Management Priorities

Address Underlying Cause

• Restore tissue perfusion in shock states with fluid resuscitation and vasopressors (norepinephrine preferred over epinephrine to avoid confounding lactate interpretation) 4
• Discontinue metformin immediately if lactic acidosis suspected; consider hemodialysis for severe cases (metformin is dialyzable with clearance up to 170 mL/min) 3
• Administer thiamine (intravenous) if nutritional deficiency suspected and other causes excluded 5
• Emergency surgery may be required for mesenteric ischemia if diagnosed 2

Monitor Response to Therapy

• Repeat lactate every 2-6 hours during acute resuscitation to assess treatment effectiveness 2, 1
• Target normalization within 24 hours as this correlates with 100% survival in trauma patients 2, 1