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INTRODUCTION

Baclofen (Lioresal, Liofen, Gablofen) is a centrally acting muscle relaxant used therapeutically to treat muscle spasticity, often secondary to conditions such as spinal cord injury and multiple sclerosis. It has also been abused for recreational purposes.

MECHANISM OF TOXICITY

  1. As a presynaptic GABA(B) agonist, baclofen is capable of producing CNS and respiratory depression. It is also associated with paradoxical hypertonicity and seizure-like activity. In withdrawal, baclofen may cause seizures, hallucinations, and hyperthermia. Additionally, bradycardia has been reported in up to 30% of ingestions.

  2. Pharmacokinetics. Baclofen is rapidly absorbed from the GI tract with possible prolonged absorption in the setting of overdose. Peak absorption occurs within 2 hours of oral ingestion. Toxic effects may be seen within minutes of intrathecal overdose. The apparent volume of distribution is 1–2.5 L/kg. Protein binding is about 30%. Approximately 85% is excreted unchanged in urine while 15% is eliminated in the stool. The usual elimination half-life is 2.5–4 hours in therapeutic dosing, but may be prolonged in overdose (see also Table II–66).

TOXIC DOSE

Toxicity has been reported with ingestions of 200 mg in healthy adults, while intrathecal doses of 1.5 mg have been associated with severe CNS and respiratory depression. Death has occurred with ingestions of 1 g or more. A dose of 120 mg in an infant resulted in respiratory failure.

CLINICAL PRESENTATION

  1. Baclofen intoxication causes nausea, vomiting, confusion, somnolence, lethargy, and occasionally paradoxical hallucinations, agitation, and seizures. More severe toxicity is manifested by coma, respiratory failure, bradycardia, hypotension, flaccidity, mydriasis, and hypothermia. Deep coma can mimic brain death and may persist for several days postingestion. Rhabdomyolysis, status epilepticus, and first-degree AV block are rarely reported events.

  2. Baclofen withdrawal generally occurs in the setting of abrupt discontinuation of an intrathecal pump but may also occur after cessation of oral dosing. The onset is typically 24–48 hours after the dose reduction. Symptoms include agitation, seizures, tachycardia, hyperthermia, hyper- or hypotension, muscle rigidity, and hallucinations. Severe withdrawal has been reported to cause rhabdomyolysis, multi-organ system failure, and death.

DIAGNOSIS

Is usually based on a history of ingestion or known history of baclofen pump placement or manipulation as well as the clinical findings mentioned earlier. The differential diagnosis should include intoxication and/or withdrawal from other sedative-hypnotic agents, gamma hydroxybutyrate (GHB), or ethanol.

  1. Specific levels are not readily available and would not aid in the management of acute overdose, but might be necessary if the patient remains in deep coma and brain death is being considered.

  2. Other useful laboratory studies include glucose, electrolytes, BUN, creatinine, creatine kinase (CK), telemetry monitoring, and pulse oximetry.

TREATMENT

  1. Emergency and supportive measures

    1. Maintain an open airway and assist ventilation if necessary.

    2. Treat coma, seizures, arrhythmias, hypothermia, and ...

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