From the Guidelines
Baclofen toxicity is a life-threatening condition that requires immediate medical attention, particularly in patients who have been taking it long-term, as abrupt discontinuation can lead to severe withdrawal symptoms, including seizures, coma, and death. The management of baclofen toxicity is crucial, especially in the perioperative period, as significant withdrawal symptoms have been reported following abrupt discontinuation of baclofen in patients who take it long-term 1. Symptoms of withdrawal include:
- Visual and auditory hallucinations
- Anxiety
- Agitation
- Delirium
- Fever
- Tremors
- Tachycardia
- Seizures
Abrupt withdrawal of intrathecal baclofen is potentially life-threatening, with symptoms including high fever, altered mental status, rebound spasticity, and muscle rigidity that can lead to rhabdomyolysis, multiorgan failure, and death 1. Perioperative management of patients receiving intrathecal baclofen should be planned with input from a specialist in this area. The key to preventing baclofen toxicity is careful dosing, especially in patients with kidney disease, and patient education about medication safety. It is essential to take throughout the preoperative period and schedule surgical treatment at any time during the cycle, including on the day of injection, to minimize the risk of withdrawal symptoms 1.
From the FDA Drug Label
The precise mechanism of action of baclofen is not fully known. Baclofen is capable of inhibiting both monosynaptic and polysynaptic reflexes at the spinal level, possibly by hyperpolarization of afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect In studies with animals, baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression. ADVERSE REACTIONS The most common is transient drowsiness (10% to 63%). In one controlled study of 175 patients, transient drowsiness was observed in 63% of those receiving baclofen compared to 36% of those in the placebo group. Other common adverse reactions are dizziness (5% to 15%), weakness (5% to 15%) and fatigue (2% to 4%) Others reported: Neuropsychiatric:Confusion (1% to 11%), headache (4% to 8%), insomnia (2% to 7%); and, rarely, euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, coordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizure Cardiovascular:Hypotension (0% to 9%). Rare instances of dyspnea, palpitation, chest pain, syncope.
Baclofen toxicity may manifest as CNS depression, including symptoms such as:
- Drowsiness (10% to 63%)
- Dizziness (5% to 15%)
- Weakness (5% to 15%)
- Fatigue (2% to 4%)
- Confusion (1% to 11%)
- Ataxia
- Respiratory depression
- Cardiovascular depression Other potential symptoms of baclofen toxicity include:
- Neuropsychiatric symptoms such as hallucinations, euphoria, excitement, depression
- Cardiovascular symptoms such as hypotension, dyspnea, palpitation, chest pain, syncope
- Gastrointestinal symptoms such as nausea, constipation, abdominal pain, vomiting, diarrhea
- Genitourinary symptoms such as urinary frequency, enuresis, urinary retention, dysuria, impotence 2 2
From the Research
Baclofen Toxicity
Baclofen toxicity can occur due to intentional self-poisoning or accumulation of therapeutic doses in patients with impaired kidney function 3. The symptoms of baclofen toxicity can be severe and include:
- Coma
- Apnea
- Autonomic disturbances
- Cardiac conduction abnormalities
- Seizures
Clinical Findings
Clinical findings in patients with baclofen toxicity may include:
- Hypothermia
- Bradycardia
- Hypertension
- Hyporeflexia
- Coma
- Seizures
Management
The management of baclofen toxicity is largely supportive, and may include:
- Respiratory support
- Seizure treatment
- Administration of activated charcoal
- Use of pharmacologic adjuncts such as nifedipine, flumazenil, naloxone, lorazepam, and phosphenytion 4
- Extracorporeal treatments (ECTRs) may be considered in certain cases, particularly in patients with impaired kidney function 3
Baclofen Withdrawal
Baclofen withdrawal can also be life-threatening, with symptoms including:
- Muscle spasms
- Tremors
- Hyperpyrexia
- Delusions
- Hallucinations
- Delirium
- Severe cases can mimic meningoencephalitis, seizure disorder, or neuroleptic malignant syndrome 5
Treatment of Baclofen Withdrawal
Treatment of baclofen withdrawal includes:
- Re-administration of baclofen
- Supportive therapy
- Use of benzodiazepines, propofol, dexmedetomidine
- No specific guidelines have been established for the treatment of baclofen withdrawal 5
Key Considerations
Key considerations in the management of baclofen toxicity and withdrawal include: