Baclofen unerotoxicity in a chronic haemodialysis patient
Nader Bassilios,
Vincent Launay-Vacher,
Lucile Mercadal and
Gilbert Deray
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.
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Case
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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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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 4.56.8 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, 4783 Boulevard de l'Hôpital, F-75013 Paris, France. 
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References
|
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-
Davidoff RA. Anti-spasticity drugs: mechanisms of action. Ann Neurol1985; 17: 107116[ISI][Medline]
-
White WB. Aggravated CNS depression with urinary retention secondary to baclofen administration. Arch Intern Med1985; 145: 17171718[Abstract]
-
Monhart V, Balikova M. Is absorption haemoperfusion effective in the treatment of baclofen poisoning? Vnitr Lek1989; 11: 11251131
-
Parmar MS. Akinetic Mutis mafter Baclofen. Ann Intern Med1991; (115) 6: 499500
-
Himmelsbach FA, Kohler E, Zanker B et al. Baclofen intoxication in chronic haemodialysis and kidney transplantation. Dtsch Med Wochenschr1992; 19: 733737
-
Aisen ML, Dietz M, McDowell Fletcher, Kutt Henn. Baclofen toxicity in a patient with subclinical renal insufficiency. Arch Phys Med Rehabil1994; 75: 109110[ISI][Medline]
-
Peces R, Navascués RA, Baltar J, Laurès AS, Alvarez-Grande J. Baclofen neurotoxicity in chronic haemodialysis patients with hiccups. Nephrol Dial Transplant1998; 13: 18961897[Free Full Text]
-
Chen K-S, Bullard MJ, Chien Y-Y, Lee S-Y. Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacothera1997; 31: 13151320
-
Wuis EW, Dirks MJ, Termond EF, Vree TB, van der Kleijn E. Plasma and urinary excretion kinetics of oral baclofen in healthy subjects. Eur J Clin Pharmacol1989; 37: 181184[ISI][Medline]
-
Seyfert S, Kraft D, Wagner K. Baclofen toxicity during intermittent renal dialysis. Nervenarzt1981; 52: 616617[ISI][Medline]
Received for publication: 30.11.99
Revision received 12. 1.00.