Role of hemodialysis in baclofen overdose with normal renal function

Abstract

The treatment of baclofen overdose is primarily supportive. There have been case reports of hemodialysis being used in patients with chronic kidney disease with baclofen overdose. A case report of hemodialysis in a baclofen-overdose patient with normal renal function is presented. Review of literature has also been provided.

Introduction

Baclofen is being used more frequently for alcohol and tobacco de-addiction.[1] Physicians and psychiatrists should be on the watch for a possible increase in number of cases of baclofen overdose. Although there have been cases where hemodialysis was used to treat baclofen overdose in patients with deranged renal functions, a case report of hemodialysis in a baclofen-overdose patient with normal renal function is presented.

Case Report

A 21-year-old male, on treatment for alcohol and tobacco dependence, presented to the emergency department within 12 hours after alleged consumption of 10 tablets of extended release baclofen (20 mg). On admission, his heart rate was 76 beats /min, blood pressure was 158/70 mm of Hg, respiratory rate was 40/min and SpO2 was less than 80% on 60% venturi mask. His Glasgow Coma Scale (GCS) was 3/15, bilateral (B/L) pupils were dilated, deep tendon reflexes were brisk and B/L plantars were extensor. Bilateral crepitations were heard on chest auscultation. He was intubated and put on mechanical ventilation. His baseline renal function tests were: S. Urea 33 mg/dl, S. Creatinine 1.3 mg/dl, S. Sodium 138 meq/l, S. Potassium 4.4 meq/l; his blood counts, liver function test and arterial blood gas analysis (on mechanical ventilation) were normal. His GCS did not show any improvement in the next 12 hours. He underwent two sessions of hemodialysis with a Fresenius hemodialysis machine on consecutive days. Following dialysis, his sensorium improved dramatically and he was successfully extubated. He underwent psychiatric evaluation and counselling prior to discharge.

Discussion

Baclofen [4-amino-3-(4-chlorophenyl)-butanoic acid) is a lipid-soluble derivative of y-aminobutyric acid (GABA). It acts as an inhibitory neurotransmitter primarily at a spinal level to reduce muscle tone, along with some supraspinal activity. It is commonly used in conditions like spasticity, dysfunctional voiding, intractable hiccups, palatal myoclonus, and trigemi-nal neuralgia.[2] It has recently been used for alcohol and tobacco de-addiction. Ingested baclofen is absorbed rapidly and completely, thereafter 69–85% is excreted without changes in urine and 15% is metabolized by the liver. The half-life is between 4.5 and 6.8 hours in healthy subjects. Baclofen is moderately lipophilic, 30% of the drug is protein bound, and can penetrate the blood–brain barrier. Common manifestations of baclofen toxicity are change in level of consciousness, hypotonia, hypotension, bradycardia, abdominal pain, nausea, and vomiting; symptoms usually resolve when baclofen is stopped. Management of baclofen overdose is primarily supportive. Several studies have noted that hemodialysis can alleviate clinical symptoms of baclofen overdose and shorten the recovery time in patients with end-stage renal disease (ESRD).[3] Low protein binding (31%) and low volume of distribution (2.4 l/kg) lead to efficient removal of baclofen by dialysis. While improvement in mental status was shown to parallel the fall in serum concentration in one study, Lipscomb et al., noted that serum elimination half-life may not reflect a slower elimination rate from the central nervous system. Delayed diffusion across the blood-brain barrier is thought to account for the lag of a few hours in clinical recovery observed in some people.[4]

All previous reports document management of baclofen overdose with supportive measures and mechanical ventilation. Hemodialysis has been tried only in patients with chronic kidney disease (CKD). This is the first reported case where hemodialysis was tried in a patient with normal renal function. Although it may be argued that this patient would have improved spontaneously over time, it is worthwhile noting that duration of mechanical ventilation is directly proportional to the serum drug level of baclofen after ingestion.[5] Hemodialysis in this case led to a dramatic improvement in patient's consciousness and he could be extubated within 48 hours of baclofen ingestion. Further, the elimination kinetics is altered in cases with chronic dosing.[6] History of the number of tablets, daily dosage and the chronicity of consumption was not reliable in this patient. Also, as tests to ascertain serum baclofen level were not available, elimination kinetics could not be calculated in this case.