Baclofen neurotoxicity in chronic hemodialysis

Abstract

Baclofen, a GABA agonist, is frequently used to treat muscle spasticity due to spinal cord injury and multiple sclerosis. Baclofen overdose can lead to coma, respiratory depression, hyporeflexia, and flaccidity. Because baclofen is primarily excreted unchanged through the kidneys, it should be given with caution, and it may be necessary to reduce the dosage.Signs of overdose may appear suddenly or insidiously. Acute massive overdose may present as coma. Less sudden and/or less severe forms of overdose may present with signs of CNS depression, excessive salivation, dizziness, nausea and/or vomiting, somnolence, and hypotonia. Should overdose appear likely, the patient should be taken immediately to a hospital. A 46‐year‐old man, who was treated by intermittent hemodialysis (three times a week), was admitted to our unit for signs of CNS depression, dizziness, vomiting, somnolence, and hypotonia. He was treated at the relatively low dose of baclofen, 5 mg/day, because of muscle spasticity due to spinal cord injury. His temperature was 37 °C, and predialysis laboratory data were hemoglobin 11.4 g/dl, white blood cells 6550/mm3 with normal differential count, and platelets 330000/mm3. Serum sodium was 134 mmol/l, potassium 6.4 mmom/l, bicarbonate 18.3 mmol/l, urea 30 mmol/l, creatinine 998 μmol/l, glucose 5.16 mmol/l, and calcium level 2.4 mmol/l. Serum transaminases were normal. A brain computerized tomography (CT) scan showed no abnormalities. Baclofen‐associated encephalopathy was considered to be the most likely etiology for this acute neurological picture. Baclofen was then stopped. Plasma concentration of baclofen was >600 ng/ml (therapeutic range 80–400 ng/ml) after 2 hours of hemodialysis and the baclofen level rapidly fell (<200 ng/ml) at the end of the hemodialysis session. After the first 4‐h haemodialysis session, there was an incomplete recovery of the neurological status. After a renewed hemodialysis session the symptoms completely receded.The patient was discharged from the hospital 72 h later in a good condition. Patients with severely impaired renal function generally develop baclofen intoxication soon after the initiation of low‐dose therapy. Thus, the administration of baclofen, regardless of the dosage, in these patients is not appropriate.