What are the types, diagnosis, and treatment of lactic acidosis?

Lactic Acidosis: Types, Diagnosis, and Treatment

Classification of Lactic Acidosis

Lactic acidosis is classified into two fundamental types based on the presence or absence of tissue hypoxia: Type A results from inadequate tissue perfusion and oxygen delivery, while Type B occurs without hypoxia due to metabolic disturbances, drug toxicity, or impaired lactate clearance. 1, 2

Type A Lactic Acidosis (Tissue Hypoxia)

• Circulatory shock (septic, cardiogenic, hypovolemic) causing inadequate tissue perfusion 1, 2
• Severe cardiac failure with reduced cardiac output 1
• Acute mesenteric ischemia - particularly critical as 88% of patients present with metabolic acidosis and lactate >2 mmol/L carries a hazard ratio of 4.1 for irreversible intestinal ischemia 1
• Severe anemia limiting oxygen-carrying capacity 2
• Respiratory failure with hypoxemia 2

Type B Lactic Acidosis (Without Tissue Hypoxia)

• Metformin-associated lactic acidosis - incidence 2-9 per 100,000 patients/year, dramatically increased with renal impairment 1, 3
• Nucleoside reverse transcriptase inhibitors (NRTIs) - particularly stavudine and didanosine, with incidence of 1.3 cases per 1,000 person-years of exposure 1, 4
• Liver disease - impairs lactate clearance since the liver is the major site of lactate removal 1
• D-lactic acidosis - occurs in patients with short bowel syndrome and preserved colon due to bacterial fermentation 1, 2
• Thiamine deficiency - affects pyruvate dehydrogenase function 2
• Malignancy and inborn errors of metabolism 1

Diagnostic Approach

Laboratory Criteria

Blood lactate >2 mmol/L indicates elevation, >5 mmol/L is abnormal, and >10 mmol/L represents a serious, life-threatening condition requiring immediate intervention. 1, 2

• Arterial pH <7.35 (acidosis) 1, 2
• Increased anion gap (Na - [Cl + HCO3] >16) 1, 2
• Lactate:pyruvate ratio elevated 3
• Metformin plasma levels >5 mcg/mL in metformin-associated cases 3

Critical Specimen Collection Requirements

Proper lactate measurement requires prechilled fluoride-oxalate tubes, transport on ice, processing within 4 hours, and collection without tourniquet or fist-clenching to avoid falsely elevated results. 1

Clinical Presentation

• Gastrointestinal symptoms: nausea, vomiting, abdominal pain 1, 2, 4
• Respiratory symptoms: tachypnea, dyspnea (compensatory hyperventilation) 1, 2
• Neurological symptoms: weakness, confusion, altered mental status 1, 2
• Cardiovascular: hypotension and resistant bradyarrhythmias in severe cases 3

Identifying the Underlying Cause

• Assess hemodynamic status for shock states and tissue perfusion 1
• Review medication history - metformin, NRTIs, linezolid 1
• Evaluate liver and kidney function - both organs critical for lactate clearance 1
• Consider mesenteric ischemia if abdominal pain with elevated urea and lactate >2 mmol/L - obtain CT angiography immediately as diagnostic delay is the dominant mortality factor (30-70%) 1
• Check for sepsis using appropriate screening protocols 5

Special Diagnostic Considerations

In laboring patients, lactic acid should not be used to diagnose sepsis during labor per CMS guidance, as labor itself elevates lactate levels. 5

Treatment Algorithm

Immediate Management Priorities

The cornerstone of treatment is identifying and aggressively treating the underlying cause - there is no specific therapy for lactic acidosis itself that improves mortality. 1, 6, 7

Step 1: Discontinue Offending Agents Immediately

• Stop metformin immediately if suspected - contraindicated with eGFR <30 mL/min/1.73 m² 3
• Discontinue NRTIs (stavudine, didanosine) in HIV patients - high mortality without intervention 1
• Hold metformin before contrast procedures in patients with eGFR 30-60 mL/min/1.73 m², hepatic impairment, alcoholism, or heart failure 3

Step 2: Restore Tissue Perfusion (Type A)

• Fluid resuscitation: 15-20 mL/kg/hour isotonic saline initially if shock present 1
• Treat sepsis aggressively: source control, antibiotics within 3 hours, hemodynamic support per SEP-1 protocol 5, 1
• Ensure adequate oxygenation and ventilation 1

Step 3: Address Specific Causes

• For D-lactic acidosis: restrict mono/oligosaccharides, encourage polysaccharides (starch), provide thiamine supplements, administer broad-spectrum antibiotics 1
• For mesenteric ischemia: emergent CT angiography, consider urgent laparotomy if perforation suspected 1
• For metformin-associated lactic acidosis: prompt hemodialysis is recommended (metformin clearance up to 170 mL/min) and often reverses symptoms 1, 3

The Sodium Bicarbonate Controversy

Sodium bicarbonate is NOT recommended for lactic acidosis and should be avoided. The Surviving Sepsis Campaign explicitly recommends against using sodium bicarbonate to improve hemodynamics or reduce vasopressor requirements in hypoperfusion-induced lactic acidemia with pH ≥7.15. 1

Why Bicarbonate Should Be Avoided:

• Does not improve hemodynamics or cardiovascular function 1, 8
• May increase lactate production 1
• Causes hypernatremia and volume overload 1
• Generates CO₂ which can worsen intracellular acidosis 1
• Has never been shown to improve survival in any study 1, 8

The oft-cited rationale that bicarbonate might ameliorate hemodynamic depression has been convincingly disproved. 8

Supportive Care Measures

• Thiamine supplementation to address potential pyruvate dehydrogenase dysfunction 1
• Monitor and correct electrolyte abnormalities, particularly hyperkalemia in rhabdomyolysis-associated cases 1
• Serial lactate monitoring within 6 hours to assess response to treatment 1

High-Risk Populations Requiring Vigilance

Metformin Users

• Elderly patients (>65 years) have higher risk due to greater likelihood of hepatic, renal, or cardiac impairment 1, 3
• Renal impairment - check eGFR before initiating metformin and at least annually; more frequently in elderly 3
• Acute illness - discontinue metformin immediately in sepsis, acute kidney injury, or hypoxic states 1, 3
• Surgical procedures - temporarily discontinue when NPO due to risk of volume depletion and hypotension 3

HIV Patients on NRTIs

• Risk factors: obesity, female sex, prolonged use (>6 months), pregnancy 1
• Subtle early symptoms (nonspecific GI symptoms, dyspnea, weakness, myalgias) should not be ignored as they often precede severe acidosis 1

Critical Pitfalls to Avoid

• Do NOT ignore mesenteric ischemia when lactate is elevated with abdominal pain and elevated urea - obtain emergent CT angiography 1
• Do NOT use bicarbonate - it does not improve outcomes and may cause harm 1, 8
• Do NOT ignore persistent hyperlactatemia even without hypotension - it may indicate occult tissue hypoperfusion or organ dysfunction 1
• Do NOT rely on single hematocrit measurements to assess severity, as initial values don't accurately reflect blood loss 1
• Do NOT use lactate to diagnose sepsis during labor per CMS guidance 5