What causes high lactic acidosis?

Causes of Elevated Lactic Acidosis

Lactic acidosis is primarily caused by tissue hypoperfusion, shock, medications, and underlying medical conditions that create an imbalance between lactate production and clearance. 1

Types of Lactic Acidosis

Type A (Hypoxic) Lactic Acidosis

• Tissue hypoperfusion and oxygen delivery issues:
  • Shock (cardiogenic, septic, hypovolemic)
  • Severe dehydration
  • Cardiac arrest
  • Acute mesenteric ischemia (AMI) 2
  • Low flow states 2
  • Multi-organ dysfunction 2

Type B (Non-Hypoxic) Lactic Acidosis

• Medication-induced:

  • Metformin (most common drug cause) 3
  • Nucleoside reverse transcriptase inhibitors (NRTIs) 2
  • Vasopressors and adrenergic drugs (epinephrine, albuterol) 4

• Underlying conditions:

  • Liver failure (impaired lactate clearance) 1, 3
  • Renal impairment 3
  • Malignancies (especially hematologic) 5, 6
  • Diabetic ketoacidosis 1

Specific Clinical Scenarios

Acute Mesenteric Ischemia

• Elevated serum lactate >2 mmol/L is associated with irreversible intestinal ischemia (HR: 4.1,95% CI: 1.4-11.5) 2
• Lactic acidosis combined with abdominal pain, even when the patient doesn't appear clinically ill, should prompt consideration for early CTA 2
• Metabolic acidosis with elevated lactate occurs in 88% of AMI cases 2

Medication-Induced Lactic Acidosis

Metformin

• Characterized by elevated blood lactate (>5 mmol/L), anion gap acidosis, and increased lactate:pyruvate ratio 3
• Risk factors include:
  • Renal impairment (primary risk factor)
  • Age >65 years
  • Hepatic impairment
  • Excessive alcohol intake
  • Hypoxic states (heart failure, MI, sepsis)
  • Use of iodinated contrast agents 3

NRTIs

• Can cause lactic acidosis with microvacuolar hepatic steatosis
• Higher risk in pregnant women, especially with d4T and ddI combination 2
• Symptoms include nausea, vomiting, abdominal pain, dyspnea, and weakness 2

Laboratory Findings

• Blood pH <7.35
• Elevated blood lactate levels (>5 mmol/L)
• Anion gap acidosis
• Increased lactate:pyruvate ratio 1
• Often accompanied by leukocytosis in infectious/inflammatory causes 2
• Elevated D-dimer (>0.9 mg/L) may be present in intestinal ischemia (sensitivity 60%, specificity 82%) 2

Clinical Presentation

• Nonspecific gastrointestinal symptoms
• Respiratory distress (Kussmaul breathing pattern in metabolic acidosis)
• Increased somnolence
• Generalized weakness 1, 3
• In malignancy-related lactic acidosis: markedly elevated LDH levels (>1785 U/L) 6

Diagnostic Pitfalls

• Lactate can be elevated due to dehydration and decreased oral intake, making it difficult to differentiate early ischemia from irreversible bowel injury based on lactate alone 2
• Malignant lactic acidosis is often misdiagnosed as sepsis 6
• Medication-induced lactic acidosis is a diagnosis of exclusion and can be overlooked 4
• Sample handling affects lactate results (requires prechilled tubes and prompt processing) 1

Management Approach

1. Identify and treat the underlying cause

   • For Type A: restore tissue perfusion and oxygen delivery
   • For Type B: discontinue offending medications, treat underlying conditions 1

2. For medication-induced lactic acidosis:

   • Immediately discontinue the offending medication
   • Consider hemodialysis for metformin-associated lactic acidosis (clearance up to 170 mL/min) 3

3. For shock-related lactic acidosis:

   • Fluid resuscitation
   • Maintain mean arterial pressure >65 mmHg using vasopressors if needed 1

4. For mesenteric ischemia:

   • Early CTA when lactic acidosis is present with abdominal pain 2

5. For malignancy-related lactic acidosis:

   • Early aggressive chemotherapy is the most effective treatment 5, 6

6. Supportive measures:

   • Regular monitoring of arterial blood gases, lactate levels, and hemodynamics
   • Bicarbonate therapy generally not recommended but may be considered when pH <7.15 with hemodynamic instability 1
   • Consider CRRT or hemodialysis for severe metabolic acidosis unresponsive to medical management 1

Remember that lactic acidosis is a medical emergency with high mortality if not promptly recognized and treated. The key to management is identifying and addressing the underlying cause rather than just treating the acidosis itself.