Is baclofen (Baclofen) safe to use in patients with Acute Kidney Injury (AKI)?

Baclofen Should Be Avoided in Patients with Acute Kidney Injury

Baclofen should be strictly avoided in patients with acute kidney injury (AKI) due to significant risk of neurotoxicity and hemodynamic instability, as it is primarily excreted unchanged through the kidneys. 1, 2

Pharmacokinetics and Risk in AKI

Baclofen is primarily eliminated via renal excretion in its unchanged form, making patients with impaired kidney function particularly vulnerable to toxicity:

• In normal kidney function, baclofen has a relatively short half-life
• In AKI, baclofen clearance is significantly reduced, leading to drug accumulation 1
• Even small doses can rapidly reach toxic levels in patients with kidney impairment 3

Clinical Manifestations of Baclofen Toxicity in AKI

Baclofen toxicity in the setting of AKI can present with:

• Altered consciousness, ranging from confusion to coma
• Respiratory depression requiring mechanical ventilation
• Seizures and status epilepticus
• Hemodynamic instability
• Abdominal pain (reported in several cases)
• Bradycardia and hypothermia 2, 3

Management Recommendations

1. Medication Selection During AKI:

   • Avoid baclofen in patients with AKI regardless of severity 2
   • Follow the KDIGO guideline recommendation to withdraw potentially nephrotoxic agents during AKI 4
   • Consider alternative muscle relaxants with less dependence on renal clearance

2. For Patients Already on Baclofen Who Develop AKI:

   • Immediately discontinue baclofen administration
   • Provide supportive care including respiratory support and seizure management
   • Consider hemodialysis for severe toxicity, especially if accompanied by coma or respiratory depression 5, 6

3. After AKI Resolution:

   • Wait until AKI has fully resolved with stable renal function for at least 24-48 hours before considering restarting baclofen 7
   • Ensure patient is euvolemic with adequate blood pressure before reintroducing any potentially nephrotoxic medications 7
   • If baclofen is absolutely necessary after AKI resolution, start with a significantly reduced dose and monitor closely

Special Considerations

• Patients with pre-existing chronic kidney disease (CKD) who develop AKI are at particularly high risk for baclofen toxicity
• The EXTRIP workgroup suggests performing extracorporeal treatment in patients with baclofen toxicity from therapeutic doses in the setting of kidney impairment, especially with coma requiring mechanical ventilation 5
• Regular monitoring of kidney function is essential in all patients receiving baclofen

Clinical Pitfalls to Avoid

• Continuing baclofen at standard doses when a patient develops AKI
• Failing to recognize baclofen toxicity symptoms, which may be mistaken for uremia or other complications of AKI
• Delaying hemodialysis in severe baclofen toxicity with kidney impairment
• Restarting baclofen too early during AKI recovery before kidney function has stabilized

Following these recommendations will help prevent potentially life-threatening baclofen toxicity in patients with AKI.