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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 3  |  Page : 595-597
Baclofen-induced neurotoxicity in a patient with end-stage renal disease


Department of Nephrology, Mahatma Gandhi Medical College and Research Institute, Puducherry, India

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Date of Web Publication13-May-2016
 

   Abstract 

Baclofen, predominantly excreted by the kidneys is accumulated in patients with renal insufficiency leading to the central nervous system toxicity. Here the author reports a patient with end-stage renal disease on maintenance hemodialysis (HD) who developed drowsiness and became unresponsive within a day after taking single 10 mg dose of baclofen. Patient improved completely after two sessions of HD.

How to cite this article:
Radhakrishnan H. Baclofen-induced neurotoxicity in a patient with end-stage renal disease. Saudi J Kidney Dis Transpl 2016;27:595-7

How to cite this URL:
Radhakrishnan H. Baclofen-induced neurotoxicity in a patient with end-stage renal disease. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Jan 16];27:595-7. Available from: https://www.sjkdt.org/text.asp?2016/27/3/595/182437

   Introduction Top


Baclofen, a centrally acting antispasmodic agent is a commonly used drug for spasticity of spinal origin and intractable hiccups of va- rious etiologies. In patients with normal renal function 69-85% of the ingested baclofen is eliminated unchanged by the kidneys and 15% is metabolized by the liver. In patients with impaired renal function half-life of the drug is prolonged[1]and accumulation of baclofen could cause the central nervous system toxicity. Hence, this drug should be used in small doses or better avoided in these patients.


   Case Report Top


A 58-year-old non-diabetic male was brought to our emergency department with the history of altered sensorium of one day duration. Patient was a known case of end-stage renal disease of unknown etiology on maintenance hemodialysis (HD) twice weekly in a peri- pheral dialysis unit for past one year. Patient had developed hiccups two days earlier for which he was prescribed tablet pantoprazole 40 mg once a day and tablet baclofen 10 mg twice a day. Patient had developed progres- sively increasing drowsiness and became un- responsive within 12 h of taking 10 mg of bac- lofen. He was referred to our center for further management.

On examination, his pulse rate was 98/min, blood pressure was 150/90 mm Hg, tempera- ture was 36.8°C, and respiratory rate was 18/min. Patient was unconscious and he was responding only to deep pain stimuli. Glasgow Coma Scale score was 8/15. Deep tendon re- flexes were sluggish. There was no focal neu- rological deficit. Retinal fundi showed Grade II hypertensive changes.

His arterial pH was 7.41, PaO298 mm Hg, and PaCO238 mm Hg. Investigations revealed blood sugar 177 mg/dL, blood urea 124 mg/dL, serum creatinine 6.1 mg/dL, sodium 140 mEq/ L, potassium 3.7 mEq/L, bicarbonate 20 mEq/ L, calcium 8.4 mg/L, phosphorus 4.0 mg/L, magnesium 1.9 mg/dL, and hemoglobin 9.7 g/ dL. His liver and thyroid function tests were normal. Plain computed tomography scan of brain was normal.

After excluding all other causes of encepha- lopathy, patient was provisionally diagnosed to have toxic encephalopathy secondary to baclofen intake. Baclofen level was not done due to lack of facility. Baclofen was discon- tinued and he was started on HD on daily basis. Patient sensorium improved significantly after two dialysis sessions. He was discharged after five days with normal sensorium.


   Discussion Top


Baclofen (4-amino-3-[-4-chlorophenyl]-buta- noic acid) is a centrally acting gamma- aminobutyric acid (GABA) agonist. It is fre- quently prescribed as an antispasmodic agent. The mechanism of action is not precisely known but it appears that in therapeutic doses, baclofen acts principally on the GABA B receptor at the spinal level. Baclofen has been widely used in multiple sclerosis and other spinal cord lesions that cause spasticity.

Eighty-five percent of an oral dose is eli- minated by the kidneys and its clearance is proportional to creatinine clearance. The elimi- nation half-life of baclofen is 2-6 h for thera- peutic oral doses in healthy volunteers and elderly patients, but half-life increases with renal insufficiency.[2]Thus, baclofen accumu- lation and neurotoxicity may occur even when normal doses are administered to patients with impaired renal function.

In therapeutic doses, spinal effects predomi- nate and neurotoxicity manifests as the dosage is increased. It is a lipophilic drug that readily penetrates the blood-brain barrier producing central nervous system manifestations.[2]Mani- festations of baclofen toxicity usually start within two to four days after starting the drug. Even a small dose as minimal as 5 mg has been documented to cause neurotoxicity. Manifestations range from altered speech, respiratory depression, akinetic mutism, and unconsciousness.

In the literature reported, patients were treated successfully by various modalities that include supportive care alone, HD and continuous ambulatory peritoneal dialysis (CAPD).[2]HD appeared to shorten the duration of toxic effects of baclofen in several patients with severely impaired renal function.[3],[4]Low pro- tein binding (31%) and low volume of distri- bution (2.4 L/kg) lead to efficient removal of baclofen by HD.[5]Though the time to recovery is long compared to HD, CAPD has been used successfully in managing baclofen toxicity in patients with renal insufficiency.[2]

Despite several case reports of baclofen toxi- city in patients with renal insufficiency, there is no clear consensus regarding the level of kidney function below which the drug should not be given. Most of the nephrologists con- sider that baclofen should better be avoided in patients with advanced renal insufficiency. If prescribed, patients should be monitored closely for toxicity.


   Conclusion Top


To the best of our knowledge, there are 43 cases of baclofen-induced neurotoxicity in pa- tients with renal failure reported in the lite- rature. The elimination of baclofen in patients with renal insufficiency is significantly de- creased which could cause rapid and severe central nervous system depression. Therefore, it is necessary to avoid or reduce baclofen dosage in patients with impaired renal func- tion. In patients who develop baclofen-induced encephalopathy, HD can rapidly revert the manifestations. Awareness of the problem and a strong index of suspicion are required to diagnose baclofen neurotoxicity.

Conflict of interest: None.

 
   References Top

1.
Mousavi SS, Mousavi MB, Motemednia F. Baclofen-induced encephalopathy in patient with end stage renal disease: Two case reports. Indian J Nephrol 2012;22:210-2.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
El-Husseini A, Sabucedo A, Lamarche J, Courville C, Peguero A. Baclofen toxicity in patients with advanced nephropathy: Proposal for new labeling. Am J Nephrol 2011;34:491- 5.  Back to cited text no. 2
    
3.
Chen KS, Bullard MJ, Chien YY, Lee SY. Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 1997;31:1315-20.   Back to cited text no. 3
    
4.
Chen YC, Chang CT, Fang JT, Huang CC. Baclofen neurotoxicity in uremic patients: Is continuous ambulatory peritoneal dialysis less effective than intermittent hemodialysis? Ren Fail 2003;25:297-305.  Back to cited text no. 4
    
5.
Dias LS, Vivek G, Manthappa M, Acharya RV. Role of hemodialysis in baclofen overdose with normal renal function. Indian J Pharmacol 2011;43:722-3.  Back to cited text no. 5
[PUBMED]  Medknow Journal  

Top
Correspondence Address:
Hemachandar Radhakrishnan
Department of Nephrology, Mahatma Gandhi Medical College and Research Institute, Puducherry - 607 402
India
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DOI: 10.4103/1319-2442.182437

PMID: 27215257

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    Abstract
   Introduction
   Case Report
   Discussion
   Conclusion
    References
 

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