Causes of Lactic Acidosis
Lactic acidosis is primarily classified into two types: Type A (hypoxic) caused by tissue hypoperfusion and Type B (non-hypoxic) caused by metabolic derangements, medications, or underlying diseases. 1, 2
Type A Lactic Acidosis (Tissue Hypoxia)
- Circulatory disorders including shock (septic, cardiogenic, hypovolemic, or obstructive) and cardiac failure lead to inadequate tissue perfusion 1, 2
- Severe infections, particularly in patients with underlying conditions like diabetes mellitus 1, 2
- Cardiovascular collapse, acute myocardial infarction, and other conditions associated with hypoxemia 3
- Hypoxic states with inadequate oxygen delivery to tissues 3
Type B Lactic Acidosis (Normal Tissue Oxygenation)
Medication-Induced
- Metformin, especially in patients with renal impairment, with an incidence of 2-9/100,000 patients/year 4, 1, 2
- Nucleoside reverse transcriptase inhibitors (NRTIs) in HIV treatment, particularly stavudine and didanosine 1, 2
- Aminoglycosides like neomycin through mitochondrial toxicity 5
Underlying Diseases and Conditions
- Hepatic impairment due to impaired lactate clearance 3
- Renal impairment, which increases risk of drug accumulation (particularly metformin) 3
- D-lactic acidosis in patients with short bowel syndrome and preserved colon 2
- Thiamine deficiency affecting pyruvate dehydrogenase function 1
Other Factors
- Excessive alcohol intake, which potentiates the effect of metformin on lactate metabolism 3
- Advanced age (>65 years), which increases risk due to higher likelihood of organ impairment 1, 3
- Radiologic procedures with iodinated contrast agents in metformin-treated patients 3
- Surgery and other procedures involving restricted food and fluid intake 3
Pathophysiological Mechanisms
- Mitochondrial dysfunction from medications like NRTIs that inhibit DNA polymerase γ 1, 2
- Anaerobic metabolism when tissues cannot receive adequate oxygen 2
- Metformin decreases liver uptake of lactate, increasing blood levels 3
Clinical Presentation and Diagnosis
- Laboratory findings include arterial pH <7.3, blood lactate >2 mmol/L, and increased anion gap (Na - [Cl+CO2] >16) 1, 2
- Clinical symptoms often include nausea, vomiting, abdominal pain, dyspnea, tachypnea, generalized weakness, and myalgias 1
- Blood lactate levels >5 mmol/L are considered abnormal, and >10 mmol/L are considered serious/life-threatening 2
Common Pitfalls to Avoid
- Failing to recognize Type B (non-hypoxic) lactic acidosis which occurs despite adequate tissue perfusion 5
- Continuing to increase fluid administration when the cause is not hypovolemia 5
- Delaying discontinuation of offending medications 5
- Not recognizing that metformin-associated lactic acidosis typically requires both elevated plasma metformin concentrations and a secondary event that disrupts lactate production or clearance 6
Management Considerations
- Treatment should focus on discontinuing offending medications and addressing the underlying cause 1, 2
- Metformin should be temporarily discontinued during surgical procedures or when patients have restricted food and fluid intake 3
- Proper lactate measurement requires prechilled fluoride-oxalate tubes, transport on ice to laboratory, and processing within 4 hours of collection 1, 2
- Hemodialysis may be necessary for severe metformin-associated lactic acidosis 3