Mechanism of Cholestyramine-Induced Metabolic Acidosis
Cholestyramine causes hyperchloremic metabolic acidosis primarily through its anion exchange properties, where chloride ions are released in exchange for bile acids, leading to excessive chloride absorption and subsequent acidosis. 1
Pathophysiological Mechanism
- Cholestyramine is a chloride-containing anion exchange resin that binds bile acids in the intestine, releasing chloride ions in the process 1
- This exchange leads to increased chloride absorption from the intestinal lumen into the bloodstream, resulting in hyperchloremia 2
- The excess chloride reduces the strong ion difference (SID), calculated as the difference between strong cations (primarily Na+) and strong anions (primarily Cl-), which directly lowers blood pH according to Stewart's approach 3
- Prolonged use of cholestyramine can produce hyperchloremic acidosis, especially in younger and smaller patients where the relative dosage may be higher 1
Risk Factors for Developing Acidosis
- Renal insufficiency - impairs the kidney's ability to compensate for acid-base disturbances 1
- Volume depletion - exacerbates the acidosis by limiting renal compensation 1
- Concomitant spironolactone use - may worsen electrolyte imbalances 1
- Pediatric patients - more susceptible due to higher relative dosing and immature renal function 1, 4
- Inadequate hydration - proper hydration is essential when using cholestyramine 1
Clinical Presentation and Diagnosis
- Patients may present with lethargy, confusion, and drowsiness 2
- Laboratory findings typically show:
- Diagnosis is supported by exclusion of other causes of hyperchloremic metabolic acidosis and temporal relationship with cholestyramine use 2
Management Considerations
- Intravenous sodium bicarbonate can rapidly correct the acidosis in severe cases 2
- Discontinuation of cholestyramine may be necessary in patients with significant acidosis 5
- Careful monitoring of electrolytes and acid-base status is recommended during cholestyramine therapy, particularly in high-risk patients 1
- Ensuring adequate hydration is important to minimize risk 1
- Consider dose reduction in patients with renal insufficiency or those at higher risk 1
Prevention Strategies
- Start with lower doses in high-risk patients and gradually increase as tolerated 1
- Monitor serum electrolytes regularly, especially in patients on long-term therapy 1
- Ensure adequate fluid intake during cholestyramine treatment 1
- Consider alternative bile acid sequestrants in patients with pre-existing acid-base disorders 6
- Avoid concomitant use with medications that might worsen acidosis 1
Understanding this mechanism is crucial for clinicians prescribing cholestyramine, particularly for patients with risk factors that may predispose them to developing metabolic acidosis.