What are the causes and treatment of elevated lactic acid levels?

Lactic Acid Etiology and Treatment

Primary Etiologies of Elevated Lactate

Tissue hypoperfusion and hypoxia is the most common and most critical cause of elevated lactate, resulting from inadequate oxygen delivery to tissues that forces cells into anaerobic metabolism. 1

Type A Lactic Acidosis (Tissue Hypoperfusion)

• Sepsis and septic shock causes lactic acidosis through both impaired tissue perfusion and inflammatory mediators disrupting cellular metabolism 1
• Shock states including hypovolemic, cardiogenic, distributive, and obstructive shock all impair tissue oxygen delivery 1
• Hemorrhagic trauma produces lactate elevation that directly correlates with mortality risk 1
• Acute mesenteric ischemia from arterial embolism (often in atrial fibrillation patients) or thrombosis presents with sudden severe abdominal pain and lactate >2 mmol/L indicating irreversible intestinal ischemia (Hazard Ratio: 4.1) 1
• Cardiac arrest and acute myocardial infarction create global hypoperfusion 2

Type B Lactic Acidosis (Without Tissue Hypoperfusion)

Medication-Induced Causes

• Metformin is contraindicated when eGFR <30 mL/min/1.73 m² and should be avoided in patients with anaerobic metabolism (sepsis, hypoxia), impaired metformin clearance (renal impairment), or impaired lactate clearance (liver failure) 3, 2
• Epinephrine elevates lactate through beta-2-adrenergic receptor stimulation in skeletal muscle, activating glycogenolysis and glycolysis independent of tissue perfusion 1
• Albuterol similarly increases lactate via beta-adrenergic stimulation 4

Metabolic and Organ Dysfunction

• Liver failure impairs lactate clearance since the liver is the primary site of lactate metabolism via gluconeogenesis 3, 2
• Accelerated aerobic glycolysis from excess beta-adrenergic stimulation increases lactate production without tissue hypoxia 1
• Malignancy particularly hematological cancers can cause lactic acidosis 5

Other Causes

• Excessive alcohol intake potentiates metformin's effect on lactate metabolism and impairs hepatic lactate clearance 2
• Seizures transiently elevate lactate through intense muscle activity 6
• Diabetic ketoacidosis may have concurrent lactate elevation 6

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Diagnostic Thresholds and Prognostic Significance

Lactate >2 mmol/L indicates potential tissue hypoperfusion requiring immediate investigation, while lactate ≥4 mmol/L represents a medical emergency with 46.1% mortality comparable to overt septic shock. 1

Lactate Level Interpretation

• Normal: <2 mmol/L 3, 1
• Lactate 2-4 mmol/L: Indicates tissue hypoperfusion with 30% mortality; requires aggressive fluid resuscitation with at least 30 mL/kg IV crystalloid within first 3 hours 1
• Lactate ≥4 mmol/L: Medical emergency requiring immediate protocolized resuscitation targeting CVP 8-12 mmHg, MAP ≥65 mmHg, urine output ≥0.5 mL/kg/h, and central venous oxygen saturation ≥70% 1
• Lactate >5 mmol/L: Defines metformin-associated lactic acidosis when accompanied by anion gap acidosis and metformin plasma levels >5 mcg/mL 2

Prognostic Implications

• Normalization within 24 hours is associated with 100% survival in trauma patients 1
• Normalization within 48 hours drops survival to 77.8% 1
• Persistent elevation beyond 48 hours reduces survival to 13.6% 1
• Serial lactate measurements every 2-6 hours during acute resuscitation provide objective assessment of treatment response 1

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Treatment Approach

Immediate Management Based on Lactate Level

For lactate ≥4 mmol/L, initiate protocolized quantitative resuscitation immediately without delay for additional workup. 1

Lactate ≥4 mmol/L Protocol

• Administer at least 30 mL/kg IV crystalloid within first 3 hours 1
• Target MAP ≥65 mmHg using norepinephrine as first-line vasopressor (starting at 0.02 µg/kg/min) if hypotension persists after fluid administration 3
• Add vasopressin 0.04 units/min if MAP inadequate despite low-moderate dose norepinephrine (0.1-0.2 µg/kg/min) 3
• Monitor urine output targeting ≥0.5 mL/kg/h 1
• Repeat lactate within 6 hours and target lactate clearance of at least 10% every 2 hours during first 8 hours 1

Lactate 2-4 mmol/L Protocol

• Begin aggressive fluid resuscitation with at least 30 mL/kg IV crystalloid within first 3 hours 1
• Perform frequent reassessment with serial lactate measurements every 2-6 hours 1
• Investigate underlying cause while initiating resuscitation 1

Treating Underlying Causes

Metformin-Associated Lactic Acidosis

Immediately discontinue metformin and institute prompt hemodialysis if metformin-associated lactic acidosis is suspected (lactate >5 mmol/L with anion gap acidosis). 2

• Metformin is dialyzable with clearance up to 170 mL/min under good hemodynamic conditions 2
• Hemodialysis has often resulted in reversal of symptoms and recovery 2
• General supportive measures should be instituted promptly in hospital setting 2

When to Withhold/Discontinue Metformin

• eGFR <30 mL/min/1.73 m²: Contraindicated 3, 2
• eGFR 30-45 mL/min/1.73 m²: Dose reduction recommended; initiation not recommended 3
• Acute kidney injury, hypoxia, or shock: Discontinue immediately 3
• Before iodinated contrast imaging in patients with eGFR 30-60 mL/min/1.73 m², history of liver disease, alcoholism, acute heart failure, or intra-arterial contrast administration 2
• Sepsis or COVID-19: Metformin associated with increased lactic acidosis incidence (adjusted HR 4.46,95% CI 1.11-18.0) 3
• Surgery or procedures with restricted food/fluid intake: Temporarily discontinue 2

Sepsis and Septic Shock

• Administer broad-spectrum antibiotics within 1 hour of sepsis recognition 1
• Obtain blood cultures before antibiotics but do not delay antibiotic administration 1
• Source control through surgical or interventional means when indicated 1

Mesenteric Ischemia

Proceed urgently to CT angiography when lactate >2 mmol/L with abdominal pain, as this combination warrants immediate investigation even in hemodynamically stable patients. 1

• Immediate revascularization (endovascular preferred when available) is required 1
• Emergency surgery may be necessary if bowel infarction present 1
• Anticoagulation is essential to prevent recurrence 1

Hemorrhagic Shock/Trauma

• Achieve hemostasis through surgical or interventional means 1
• Transfuse blood products as needed to restore oxygen-carrying capacity 1
• Massive transfusion protocol when indicated 1

What NOT to Do

Do NOT administer sodium bicarbonate for pH ≥7.15, as it does not improve outcomes and may cause harm. 1

• Do not ignore elevated lactate in seemingly stable patients with normal blood pressure, as blood pressure alone is inadequate to assess tissue perfusion 1
• Do not use epinephrine as first-line vasopressor in patients requiring lactate-guided resuscitation, as it directly increases lactate production via beta-2-adrenergic effects 1
• Do not delay resuscitation to obtain imaging or additional workup when lactate ≥4 mmol/L 1
• Do not rely on plain radiography for diagnosing mesenteric ischemia 1

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Special Considerations and Clinical Pitfalls

Labor and Pregnancy

• Lactic acid should not be used to diagnose sepsis during labor per CMS guidance, as labor itself transiently elevates lactate 3
• Outside labor or immediate postpartum period, pregnant patients have lactate values similar to nonpregnant adults with expected values <2 mmol/L 3

Complementary Laboratory Testing

• Measure base deficit from arterial blood gas as it provides complementary but independent information about global tissue acidosis that doesn't strictly correlate with lactate 1
• Check anion gap (Na − [Cl+CO2] >16) to identify metabolic acidosis 1
• D-dimer >0.9 mg/L has 82% specificity for intestinal ischemia when abdominal pain present 1

Monitoring During Resuscitation

• Repeat lactate every 2-6 hours during acute resuscitation 1
• Target lactate clearance of at least 10% every 2 hours during first 8 hours 1
• Assess volume status and tissue perfusion if hypotension persists after fluid administration or initial lactate ≥4 mmol/L 3