Baclofen Potentiates Neurological Impairment in Dialysis Disequilibrium Syndrome

Dialysis disequilibrium syndrome (DDS) is a complication of hemodialysis (HD) that manifests as neurologic symptoms and signs related to osmotic fluid shifts. The drug baclofen is a centrally acting gamma aminobutyric acid (GABA) analog and muscle relaxant that is often used as a treatment for spasticity and as a first-line therapy for hiccups. Baclofen neurotoxicity produces symptoms of generalized CNS depression that can be more prominent in patients with end-stage renal disease (ESRD). We present a case of encephalopathy observed in a 68-year-old male following a first-time dialysis for a patient with ESRD who was initially treated for persistent hiccups with baclofen, in order to examine a possible and previously unreported neurotoxicologic interaction between baclofen and dialysis. Following successful treatment of hiccups due to uremia with baclofen, the drug was discontinued and the patient was administered two sessions of HD for two hours with low blood flow rate. After HD, the patient's blood urea nitrogen (BUN) declined to 50 mg/dL and the patient became profoundly lethargic with accompanying confusion and episodes of agitation, prompting a diagnosis of DDS. After further HD therapy was withheld, the patient's BUN increased to 87 mg/dL and his mental status returned to baseline within 72 hours. Notably, the reduction in BUN produced by HD was below the suggested threshold level that is likely to cause cerebral edema and also lower than that reported in several case studies of DDS. These findings suggest that in the setting of poor renal excretion in ESRD, a residual level of baclofen remained after HD that was sufficient to lower the magnitude of BUN reduction necessary to elicit the patient's symptoms of DDS. Therefore, it is recommended that when baclofen and dialysis are co-administered to first-time HD patients, dialysis length and flow rate should not be arbitrarily set or modified but instead titrated to BUN levels so that each daily clearance of BUN is ≤20 mg/dL.