What are the causes and base rate of lactic acidosis?

Causes and Base Rate of Lactic Acidosis

Lactic acidosis is primarily classified into Type A (inadequate tissue perfusion/oxygenation) and Type B (other causes), with metformin-associated lactic acidosis being rare at 2-9 cases per 100,000 patients per year. 1

Classification of Lactic Acidosis

Type A Lactic Acidosis (Tissue Hypoxia)

• Circulatory disorders including shock and cardiac failure leading to inadequate tissue perfusion 1, 2
• Severe infections and sepsis causing systemic hypoperfusion 1
• Pulmonary disorders resulting in hypoxemia 2
• Hemoglobin transfer disorders affecting oxygen delivery to tissues 2

Type B Lactic Acidosis (Non-Hypoxic)

• Medication-induced, particularly metformin in patients with renal impairment 1, 3
• Nucleoside reverse transcriptase inhibitors (NRTIs) in HIV treatment, especially stavudine and didanosine 4, 1
• Liver disease impairing lactate metabolism 2
• D-lactic acidosis in patients with short bowel syndrome and preserved colon 1
• Malignancies causing increased glycolysis 2
• Thiamine deficiency affecting pyruvate dehydrogenase function 2
• Uncoupling of oxidative phosphorylation 2

Base Rate and Epidemiology

• Lactic acidosis is the most common form of metabolic acidosis 5
• Metformin-associated lactic acidosis occurs at a rate of 2-9 cases per 100,000 patients per year 1
• Incidence is higher in patients with renal impairment, with eGFR <30 mL/min/1.73m² 4, 3
• Lactic acidosis from metformin is exceedingly rare even in patients with GFR 30-60 mL/min/1.73m² 4
• In a study of patients with type 2 diabetes and COVID-19, metformin use was associated with increased incidence of lactic acidosis (adjusted hazard ratio 4.46) 4

Diagnostic Criteria

• Blood lactate levels >2 mmol/L are considered elevated 1
• Levels >5 mmol/L are considered abnormal 1, 3
• Levels >10 mmol/L are considered serious/life-threatening 1
• Arterial pH <7.3 with increased anion gap (>16) 1
• Metformin-associated lactic acidosis is characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis, and increased lactate:pyruvate ratio 3

Risk Factors

• Renal impairment (eGFR <45 mL/min/1.73m²) 4, 3
• Advanced age (>65 years) 1, 3
• Liver disease 4, 2
• Cardiac disease, including congestive heart failure 4, 3
• Hypoxic conditions 2
• Sepsis and severe infections 1, 6
• Concurrent use of medications that impair renal function or increase metformin accumulation 3
• Radiologic procedures with iodinated contrast in patients on metformin 3
• Alcohol abuse 4

Clinical Presentation

• Often presents with nonspecific symptoms including:
  • Gastrointestinal symptoms (nausea, vomiting, abdominal pain) 1, 3
  • Respiratory symptoms (tachypnea, dyspnea) 1
  • Neurological symptoms (weakness, confusion, somnolence) 1, 3
• Severe cases may present with hypotension and resistant bradyarrhythmias 3
• In metformin overdose, can present with euglycemic diabetic ketoacidosis 7

Management Principles

• Discontinuation of offending medications (metformin, NRTIs) 1, 3
• Treatment of underlying causes (infection, shock, hypoxia) 1, 2
• Supportive care in a hospital setting 3
• Hemodialysis for severe metformin-associated lactic acidosis (metformin is dialyzable with clearance up to 170 mL/min) 3
• Sodium bicarbonate administration is controversial and may increase lactate production 2
• Early identification and intervention is crucial for improving outcomes 6

Special Considerations

• Metformin should be discontinued at the time of or prior to iodinated contrast imaging procedures in patients with eGFR between 30-60 mL/min/1.73m² 3
• The incidence of lactic acidosis in HIV patients has decreased as newer antiretrovirals have replaced older NRTIs like didanosine, stavudine, and zidovudine 4
• Multiple causes of lactic acidosis may coexist in critically ill patients 8