What to do for high lactic acid levels with glucagon infusion?

Management of High Lactic Acid Levels During Glucagon Infusion

Monitor lactate levels closely and reduce or temporarily discontinue glucagon infusion if lactic acidosis develops, while simultaneously addressing the underlying cause and providing supportive care with glucose administration and bicarbonate therapy if pH falls below 7.3.

Understanding the Mechanism

Glucagon administration can elevate lactate levels through several pathways:

• Glucagon stimulates hepatic glycogenolysis and gluconeogenesis, which increases glucose production but also generates lactate as a byproduct of anaerobic glucose metabolism 1
• The lactate-pyruvate ratio changes reflect alterations in metabolic pathways rather than necessarily indicating tissue hypoxia 1
• Plasma lactate concentration represents the balance between lactate production and removal (hepatic/renal gluconeogenesis and oxidation by muscle, liver, and kidney) 1

Immediate Assessment

When lactic acid rises during glucagon infusion, determine the type of lactic acidosis:

• Type A lactic acidosis occurs with evidence of tissue hypoxemia (shock, sepsis, poor perfusion) 1, 2
• Type B lactic acidosis occurs without tissue hypoxia and can be medication-related 1, 2
• Mixed type can occur when glucagon-induced metabolic changes combine with tissue hypoperfusion 3

Check arterial pH immediately - lactic acidosis is defined as arterial pH <7.3 with blood lactate >2 mEq/L 1

Specific Management Algorithm

Step 1: Assess Severity and Adjust Glucagon

• If lactate is mildly elevated (2-4 mmol/L) with pH >7.3: Reduce glucagon infusion rate by 50% and monitor lactate every 1-2 hours 4
• If lactate is moderately elevated (4-10 mmol/L) with pH 7.2-7.3: Temporarily discontinue glucagon and reassess the need for continued therapy 1
• If lactate is severely elevated (>10 mmol/L) or pH <7.2: Stop glucagon immediately 1, 3

Step 2: Provide Glucose Support

• Administer IV dextrose to maintain blood glucose 100-180 mg/dL, as this addresses the underlying hypoglycemia without requiring continued glucagon 4
• Use 10% dextrose in 50-mL (5-g) aliquots titrated to effect rather than bolus 50% dextrose to avoid overcorrection 4
• Monitor blood glucose every 15 minutes initially during dextrose titration 4

Step 3: Correct Acidosis if Severe

• Administer sodium bicarbonate if arterial pH <7.3 to restore acid-base balance 1, 3
• Massive bicarbonate infusions may be required (up to 45 mEq/hour) in severe cases with pH <7.0 3
• Monitor for sodium excess and consider hemodialysis if volume overload develops 1

Step 4: Address Underlying Causes

• Restore adequate tissue perfusion if shock or hypoperfusion is present 1, 2
• Treat sepsis, cardiac dysfunction, or other causes of tissue hypoxia contributing to Type A lactic acidosis 2
• Evaluate hepatic function as impaired liver metabolism reduces lactate clearance 1, 5

Alternative Hypoglycemia Management

If glucagon must be discontinued due to lactic acidosis:

• Switch to IV dextrose infusions as the primary treatment for hypoglycemia, which is preferred over glucagon in hospitalized patients with IV access 4
• Use continuous dextrose infusion (0.5 g/kg per hour) adjusted to maintain target glucose 4
• For recurrent hypoglycemia, address the root cause (insulinoma, insulin overdose, hepatic dysfunction) rather than relying on continuous glucagon 5

Monitoring Requirements

• Check lactate levels every 1-2 hours during glucagon infusion in high-risk patients 4
• Monitor arterial blood gases if lactate rises above 4 mmol/L 1
• Assess renal function and electrolytes as these affect lactate clearance 1
• Evaluate for signs of tissue hypoperfusion (altered mental status, oliguria, hypotension) that would indicate Type A lactic acidosis 3, 2

Critical Pitfalls to Avoid

• Do not continue glucagon at full dose when lactate is rising, as this can lead to severe metabolic decompensation 3
• Do not assume all lactic acidosis is Type A - glucagon can cause Type B lactic acidosis through metabolic effects alone 1, 2
• Do not use glucagon as first-line therapy in hospitalized patients with IV access, as IV dextrose is faster and avoids this complication 4
• Do not delay bicarbonate therapy if pH falls below 7.3, as severe acidosis (pH <7.0) carries high mortality 3

Special Considerations

In patients with hepatic dysfunction or liver metastases, glucagon may be less effective and more likely to cause lactic acidosis due to impaired hepatic lactate clearance and gluconeogenesis 1, 5. Consider alternative strategies for hypoglycemia management in these patients 5.