What are the causes of lactic acidosis?

Causes of Lactic Acidosis

Lactic acidosis can be classified into Type A (tissue hypoxia) and Type B (non-hypoxic) categories, with multiple potential causes in each category. 1, 2

Type A Lactic Acidosis (Tissue Hypoxia)

• Circulatory disorders causing inadequate tissue perfusion:

  • Shock (cardiogenic, hypovolemic, septic, or obstructive) 2
  • Cardiac failure 1
  • Severe hypotension 2

• Severe infections and sepsis, particularly in patients with underlying conditions like diabetes mellitus 1

• Hypoxic states:

  • Severe anemia
  • Carbon monoxide poisoning
  • Severe pulmonary disease 3

Type B Lactic Acidosis (Non-Hypoxic)

Medication-Induced

• Metformin: Risk increases with:

  • Renal impairment (eGFR <45 mL/min/1.73m²) 3
  • Age >65 years 3
  • Hepatic impairment 3
  • Excessive alcohol intake 3
  • Congestive heart failure 3
  • Incidence: 2-9/100,000 patients/year with 30-50% mortality 4

• Nucleoside reverse transcriptase inhibitors (NRTIs) in HIV treatment:

  • Particularly stavudine and didanosine 1, 2
  • Mechanism: inhibition of mitochondrial DNA polymerase γ 2

• Other medications:

  • Neomycin and other aminoglycosides 5
  • Propofol (with prolonged infusion) 2

Disease-Related

• Liver disease: Impairs lactate clearance 2, 6

• D-lactic acidosis:

  • Occurs in patients with short bowel syndrome and preserved colon 2
  • Caused by bacterial fermentation of carbohydrates 2

• Malignancies:

  • Particularly lymphomas and leukemias 6

• Thiamine deficiency:

  • Impairs pyruvate dehydrogenase function 6

• Rhabdomyolysis:

  • Damaged muscle tissue undergoes anaerobic metabolism 2

• Diabetic ketoacidosis:

  • Can present with concurrent lactic acidosis 1

Clinical Presentation and Diagnosis

• Laboratory findings:

  • Arterial pH <7.3 1
  • Blood lactate >2 mmol/L (elevated), >5 mmol/L (abnormal), >10 mmol/L (life-threatening) 1, 2
  • Increased anion gap (Na - [Cl+CO₂] >16) 1

• Clinical symptoms:

  • Gastrointestinal: nausea, vomiting, abdominal pain 1
  • Respiratory: tachypnea, dyspnea 1
  • Neurological: weakness, confusion 2
  • Cardiovascular: hypotension, bradyarrhythmias in severe cases 3

Management Principles

• Discontinue offending medications (metformin, NRTIs) 3

• Treat underlying causes:

  • Restore hemodynamic stability in shock 2
  • Treat infections 2
  • Correct hypoxemia 3

• Supportive measures:

  • Consider hemodialysis for severe metformin-associated lactic acidosis 3
  • Bicarbonate administration remains controversial 6
  • Consider thiamine supplementation in suspected deficiency 1

Clinical Pitfalls and Caveats

• Metformin-associated lactic acidosis has subtle onset with nonspecific symptoms; risk increases with age and renal impairment 3

• Proper lactate measurement requires prechilled fluoride-oxalate tubes, transport on ice, and processing within 4 hours 1

• Type B lactic acidosis may occur despite adequate tissue perfusion and can be missed if only focusing on circulatory causes 5

• Multiple causes of lactic acidosis often coexist in critically ill patients 7, 8

• Mortality risk increases significantly if lactic acidosis is not properly treated within the first 6 hours of hospitalization 8