Nephrol Dial Transplant (2000) 15: 715-716
© 2000 European Renal Association-European Dialysis and Transplant Association
Case Report
Baclofen unerotoxicity in a chronic haemodialysis patient
Department of Nephrology, Pitié Salpêtrière Hospital, Paris, France
Keywords: baclofen; encephalopathy; neurotoxicity
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Introduction |
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Baclofen is the ß-(
-chlorphenyl) derivative of the neurotransmitter gamma-amminobutyric acid (GABA). This centrally acting GABA agonist represents the elective pharmacotherapy for spasticity of spinal cord origin [1]. So far, few cases of baclofen-associated neurological toxicity have been reported in patients with renal insufficiency treated for severe hiccups; all had, however, received high doses of baclofen [2,3]. We report here the case of a haemodialysis patient with persistent hiccups who presented baclofen-associated encephalopathy while receiving the daily-recommended dose for patients with severe renal insufficiency. |
Case |
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TopIntroductionCaseCommentConclusionReferences |
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A 65-year-old man, who was treated by intermittent haemodialysis for 6 months, was admitted to our unit for fever and suspicion of pulmonary tuberculosis. Antituberculous therapy (isoniazide 300 mg/day, rifampicin 600 mg/day and pyrazinamide 750 mg/day) was administered orally. Two weeks later, because of hiccups resistant to metoclopramide and domperidone, baclofen was initiated at the relatively low dose of 5 mg/day. The patient responded immediately and hiccups disappeared within 48 h. Meanwhile, our patient pursued his routine haemodialysis programme (three times a week).
Four days after baclofen was initiated our patient presented acute confusion and agitation. Neurological examination revealed muscle stiffness without any signs of localization. His temperature was 37°C and predialysis laboratory data were: haemoglobin 10 g/dl, white blood cells 8100/mm3 with normal differential count, and platelets 314 000/mm3. Serum sodium was 140 mmol/l, potassium 3.9 mmom/l, bicarbonate 30 mmol/l, urea 10.6 mmol/l, creatinin 510 µmol/l, glucose 6.6 mmol/l and calcium level 2.25 mmol/l. Serum transaminases were normal. A brain computerized tomography (CT) scan showed old infarcts in nucleus caudatus. Baclofen-associated encephalopathy was considered to be the most likely aetiology for this acute neurological picture. Baclofen was then stopped. After the first 4-h haemodialysis session, there was a complete recovery of the neurological status. Antituberculous therapy was not interrupted and dosage (isoniazide, rifampicin and pyrazinamide) was not modified. The patient was discharged from hospital 48 h later in a good condition.
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Comment |
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TopIntroductionCaseCommentConclusionReferences |
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The therapeutic dosage range of baclofen is between 15 and 60 mg/day [4]. It is primarily excreted by glomerular filtration with a clearance that is proportional to creatinine clearance. After 72 h, 75% of the administered dose is recovered unchanged in the urine and 5% metabolized in healthy subjects with an elimination half-life of 4.5–6.8 h. This half-life increases in patients with ESRD and an accumulation phenomenon can occur [5].
Antituberculous therapy-associated toxicity was excluded. Plasma levels of the three antituberculous drugs were within the normal therapeutic range 2 days before the start of neurological manifestations of our patient.
Several observations of baclofen-associated encephalopathy have been reported in patients with ESRD treated with usual doses [2]. Therefore it has been suggested that baclofen dosage should be reduced to 5 mg/day in dialysis patients [5]. In our patient baclofen related encephalopathy developed after 4 days of treatment at the dose of 5 mg/day. Although serum baclofen concentrations were not assessed in our patient, the development of a baclofen-related encephalopathy was likely and further supported by the disappearance of neurological symptoms after a 4-h haemodialysis session.
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Conclusion |
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We suggest that in patients with ESRD, baclofen should be avoided. If a patient with renal failure develops severe baclofen toxicity, haemodialysis may be the appropriate treatment to alleviate clinical symptoms and shorten the recovery time.
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Notes |
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Correspondence and offprint requests to: N. Bassilios, Department of Nephrology, Pitié Salpétrière Hospital, 47–83 Boulevard de l'Hôpital, F-75013 Paris, France.
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References |
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Revision received 12. 1.00.
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