Iatrogenic Baclofen Neurotoxicity in ESRD: Recognition and Management

Abstract

Baclofen is an oral derivative of gamma-aminobutyric acid (GABA) used to treat muscular spasticity from disorders of the central nervous system. However, it is also being used for a variety of other conditions such as musculoskeletal pain, myoclonus, and alcohol withdrawal. The elimination of baclofen is heavily dependent on intact renal function, and the contraindication for use in patients with insufficient renal function is not well recognized by healthcare providers. Here, the authors report a series of mild to severe cases of baclofen intoxication in patients with end-stage renal disease. In all cases, baclofen was initiated by either inpatient or outpatient healthcare providers and the patients generally presented with altered mentation, somnolence, and/or respiratory depression. All patients were treated with aggressive hemodialysis and made a full recovery. This paper will briefly review the literature regarding baclofen intoxication, safety of baclofen use in renal disease, and efficacy of extra-corporeal therapy in the treatment of baclofen intoxication.

Baclofen-Related Neurotoxicity: Implication in a Fatality Associated With Hepatorenal Syndrome

“…Baclofen-related neurotoxicity in patients with compromised renal function has been well described 2–4. Similar to our patient, the literature includes several case reports of toxicity involving hemodialysis-dependent patients receiving baclofen treatment for hiccups 5,6.…”

Single-dose baclofen-induced neurotoxicity in a patient with end stage renal disease: case report

“…The daily therapeutic dose ranges between 5 and 60 mg [ 7 , 8 ]. Adverse effects with baclofen overdose have been noticed among people with normal kidney function such as sedation, confusion, muscle weakness and impaired consciousness [ 1 ] and these effects are attributed to its inhibitory effect on the central nervous system [ 6 ]. The reported doses of intoxication were between 80 mg and 2500 mg with the more severe among those who have ingested more than 200 mg requiring more intensive care unit admissions and for longer durations [ 9 ].…”

“…The situation becomes more complicated in those with impaired renal function as baclofen is mainly excreted by the renal system (85–90%) and the rest, 10–15%, becomes metabolized by the liver [ 6 ]. Based on this data, and knowing that the liver function is intact, or, at least, not impaired, as the liver enzymes and other related laboratory variables were within the normal range, the impaired kidney functioning capacity is the only one to be blamed as the cause of baclofen toxicity.…”

“…Baclofen acts centrally, thus it has been used to treat skeletal muscle spasms, persistent hiccups, multiple sclerosis and other spinal cord lesion-induced spasticity [ 1 , 3 , 4 , 5 ]. Baclofen is absorbed primarily by the gastrointestinal tract and more than 80% is excreted by the kidneys [ 6 ]. This explains why people with reduced kidney function are at higher risk of intoxication than those with normal kidney function.…”

“…The half-life of Baclofen ranges between 4.5–6.8 h. This half-life increases in patients with impaired renal function [ 7 ]. Baclofen can cross the Blood-Brain barrier only very slowly for central nervous system penetration but if the half-life is extended this leads to more CNS penetration and its effect in term of CNS depression can be easily pronounced [ 3 , 6 ].…”