What causes elevated lactic acid levels and how are they treated?

Causes of Elevated Lactic Acid and Treatment Approaches

Elevated lactic acid levels are primarily caused by tissue hypoperfusion and hypoxia, but can also result from various other pathophysiological mechanisms including medication effects, liver dysfunction, and metabolic disorders. Treatment should target the underlying cause while providing supportive care to normalize lactate levels.

Common Causes of Lactic Acidosis

Sepsis and Shock-Related Causes

• Sepsis and septic shock are medical emergencies that commonly cause lactic acidosis due to tissue hypoperfusion 1
• Elevated lactate levels (>2 mmol/L) are associated with irreversible intestinal ischemia (Hazard Ratio: 4.1) and indicate tissue hypoperfusion 1
• Non-occlusive mesenteric ischemia (NOMI) can lead to lactic acidosis due to inadequate intestinal perfusion 1

Cardiovascular Causes

• Cardiac failure and low flow states can lead to tissue hypoxia and subsequent lactate elevation 1
• Acute mesenteric arterial thrombosis or embolism causes intestinal ischemia and lactate production 1
• Abdominal compartment syndrome can impair tissue perfusion and cause lactic acidosis 1

Medication-Induced Causes

• Various medications can cause hyperlactatemia through different mechanisms, including epinephrine and albuterol as the most common agents 2
• Medication-induced lactic acidosis can occur at FDA-approved doses (86%), intentional overdoses (10.8%), or doses exceeding FDA recommendations (3.1%) 2
• Phenformin (historical example) and other medications may cause lactic acidosis by interfering with cellular metabolism 3

Other Causes

• Liver dysfunction impairs lactate clearance, as the liver is a primary site for lactate metabolism 4
• Seizures can cause transient lactic acidosis due to increased muscle activity and oxygen consumption 5
• Diabetic ketoacidosis can be associated with lactic acidosis 5
• Thiamine deficiency impairs pyruvate metabolism, leading to lactate accumulation 5
• Malignancies can cause lactic acidosis through various mechanisms including increased glycolysis 5, 4

Diagnosis and Assessment

• Elevated serum lactate levels >2 mmol/L are associated with tissue hypoperfusion and worse outcomes 1
• The presence of lactic acidosis combined with abdominal pain should prompt consideration of early computed tomography angiography (CTA) to rule out mesenteric ischemia 1
• D-dimer >0.9 mg/L has been reported as a potential marker for intestinal ischemia with specificity, sensitivity, and accuracy of 82%, 60%, and 79%, respectively 1
• No laboratory studies alone are sufficiently accurate to identify the presence or absence of ischemic or necrotic bowel, although elevated lactate and D-dimer may assist in diagnosis 1

Treatment Approaches

Addressing the Underlying Cause

• Sepsis and septic shock require immediate treatment with fluid resuscitation and antimicrobials 1
• Initial resuscitation should include at least 30 mL/kg of IV crystalloid fluid within the first 3 hours for sepsis-induced hypoperfusion 1
• Following initial fluid resuscitation, additional fluids should be guided by frequent reassessment of hemodynamic status 1

Specific Treatments for Lactic Acidosis

• Target mean arterial pressure of 65 mmHg in patients with septic shock requiring vasopressors 1
• Guiding resuscitation to normalize lactate levels is suggested in patients with elevated lactate as a marker of tissue hypoperfusion 1
• Sodium bicarbonate may be administered in severe lactic acidosis, particularly in cardiac arrest situations 6
• For cardiac arrest with severe acidosis, sodium bicarbonate injection may be given at 44.6 to 100 mEq initially and continued at 44.6 to 50 mEq every 5-10 minutes if necessary 6
• In less urgent forms of metabolic acidosis, sodium bicarbonate may be added at approximately 2-5 mEq/kg over 4-8 hours depending on severity 6

Management of Medication-Induced Lactic Acidosis

• Discontinuation of the offending medication is often necessary (34.4% of cases), though some medications may be continued without change (40.8%) or with dose reduction (11.6%) 2
• Insulin therapy has been found useful in treating phenformin-associated lactic acidosis 3
• Supportive care, bicarbonate therapy, specific antidotes, and decontamination strategies may be employed based on the specific medication involved 2

Monitoring and Prognostic Implications

• Lactate levels should be monitored during treatment as they have prognostic significance 1
• Therapy for metabolic acidosis should be monitored by measuring blood gases, plasma osmolarity, arterial blood lactate, hemodynamics, and cardiac rhythm 6
• Bicarbonate therapy should be planned in a stepwise fashion since the degree of response from a given dose is not precisely predictable 6
• It is generally unwise to attempt full correction of low total CO2 content during the first 24 hours of therapy to avoid unrecognized alkalosis 6

Cautions and Pitfalls

• Not all elevated lactate in sepsis is due to anaerobic metabolism; other mechanisms contribute to lactate production during sepsis 7
• Aggressive use of sodium bicarbonate can lead to serious complications including hypernatremia and hypervolemia 3
• Rapid infusion of large quantities of bicarbonate should be approached with caution as bicarbonate solutions are hypertonic 6
• In cardiac arrest, the risks from acidosis generally exceed those of hypernatremia 6
• Plain radiography has limited value in diagnosing conditions like mesenteric ischemia that may cause lactic acidosis 1