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Carbamazepine Poisoning, Emergency Medicine

Basics

Description

- Therapeutic uses of carbamazepine: - Anticonvulsant - Treatment of chronic pain - Migraine prophylaxis - Mood stabilizer

- Mechanism: - Anticholinergic - Similarities to phenytoin and tricyclic antidepressants (TCAs) - Sodium channel blocker - Decreases synaptic transmission

- Cardiovascular system: - Hypotension - Conduction disturbances (mostly in elderly) - Supraventricular tachycardia - Sinus tachycardia or bradycardia - ECG changes: - Prolongation of PR, QRS, and QTc intervals - T-wave changes

- May present with seizures or altered mental status - May be combative or drowsy - Sinus tachycardia (massive carbamazepine overdose) - Bradydysrhythmia (often seen in elderly with mild increase in carbamazepine level) - Anticholinergic manifestations: - Decreased bowel sounds - Mydriasis - Flushing - Urinary retention

- Neuromuscular changes: - Tremor - Slurred speech - Myoclonus - Choreiform and choreoathetoid movements

- ECG: - Conduction delays: - Increased QRS interval - Increased PR interval - QTc prolongation

- Electrolytes, BUN/creatinine, glucose: - Hyperglycemia - Hypokalemia - Hyponatremia

- Multidose activated charcoal: - Decreases mean half-life of carbamazepine - Binds unabsorbed drug in GI tract - Interrupts enterohepatic circulation - Do not give additional sorbitol

- Charcoal hemoperfusion/hemodialysis: - Removes small to moderate amount of ingested dose - Patients usually do well with supportive care without hemoperfusion or dialysis - Indicated in cases of clinical deterioration or lack of improvement with good supportive care

- Respiratory depression: - Intubation - Ventilatory support

  • Therapeutic uses of carbamazepine:AnticonvulsantTreatment of chronic painMigraine prophylaxisMood stabilizer
  • Mechanism:AnticholinergicSimilarities to phenytoin and tricyclic antidepressants (TCAs)Sodium channel blockerDecreases synaptic transmission

Etiology

Toxicity may occur from:

  • Suicide attempt
  • Accidental ingestion
  • Supratherapeutic dosing
  • Drug-drug interaction

Diagnosis

Signs and Symptoms

  • Neurologic manifestations common
  • Cardiotoxicity rare, except in massive overdose
  • CNS:AtaxiaDizzinessDrowsinessNystagmusHallucinationsCombativenessComaSeizures
  • Respiratory system:Respiratory depressionAspiration pneumonia
  • Cardiovascular system:HypotensionConduction disturbances (mostly in elderly)Supraventricular tachycardiaSinus tachycardia or bradycardiaECG changes:Prolongation of PR, QRS, and QTc intervalsT-wave changes

Higher incidence of neurologic manifestations

History

  • Overdose of carbamazepine or extended-release versions
  • Time of ingestion
  • Is the bottle available
  • Accidental or intentional ingestion
  • Coingestions

Physical Exam

  • May present with seizures or altered mental status
  • May be combative or drowsy
  • Sinus tachycardia (massive carbamazepine overdose)
  • Bradydysrhythmia (often seen in elderly with mild increase in carbamazepine level)
  • Anticholinergic manifestations:Decreased bowel soundsMydriasisFlushingUrinary retention
  • Neuromuscular changes:TremorSlurred speechMyoclonusChoreiform and choreoathetoid movements

Essential Workup

  • Continuous cardiac monitor
  • Serum carbamazepine level:Therapeutic, 6-12 μg/LLevels >25-40 μg/mL associated with serious toxicity:ComaSeizuresRespiratory failureConduction defectsSerum levels do not clearly predict clinical toxicity:Active metabolite carbamazepine 10, 11 epoxide not measuredNeurologic manifestations depend on CNS (not serum) levelSerial levels may be needed owing to erratic absorption of carbamazepine.
  • ECG:Conduction delays:Increased QRS intervalIncreased PR intervalQTc prolongationDysrhythmias
  • Serum acetaminophen level (to evaluate for coingestion in a suicide attempt)

Diagnosis Tests & Interpretation

Lab

  • CBC:Leukopenia or leukocytosis
  • Electrolytes, BUN/creatinine, glucose:HyperglycemiaHypokalemiaHyponatremia
  • Arterial blood gases (ABGs)
  • Urinalysis:
  • Pregnancy test
  • ALT, AST, bilirubin, alkaline phosphatase:May be mildly elevatedUsually not clinically significant

Imaging

CXR:

  • Aspiration pneumonia
  • Pulmonary edema

Differential Diagnosis

  • Drugs that cause decreased mental status:AlcoholAnticholinergicsBarbituratesBenzodiazepinesLithiumOpiatesPhenothiazines
  • Drugs that cause seizures:Alcohol withdrawalAnticholinergicsCamphorIsoniazidLithiumPhenothiazinesSympathomimetics:TCAs
  • Drugs that cause abnormal movement:AntihistaminesButyrophenonesCaffeineCocaineLevodopaMeperidinePhencyclidinePhenothiazinesPhenytoinTCAs

Treatment

Pre-Hospital

  • Do not administer ipecac.
  • Intubate if significant respiratory depression or airway compromise.
  • Secure IV access.
  • Get complete information about all products potentially ingested.

Initial Stabilization/Therapy

  • ABCs
  • IV access and fluid resuscitation if hypotensive
  • Oxygen
  • Cardiac monitor
  • Naloxone, thiamine, D50W (or Accu-Chek) if altered mental status

Ed Treatment/Procedures

  • General management:Activated charcoal:Administer sorbitol with 1st dose (only) of activated charcoal.Administer with caution if GI activity is decreased.Contraindicated if bowel sounds are absentMultidose activated charcoal:Decreases mean half-life of carbamazepineBinds unabsorbed drug in GI tractInterrupts enterohepatic circulationDo not give additional sorbitolCharcoal hemoperfusion/hemodialysis:Removes small to moderate amount of ingested dosePatients usually do well with supportive care without hemoperfusion or dialysisIndicated in cases of clinical deterioration or lack of improvement with good supportive care
  • Respiratory depression:IntubationVentilatory support
  • Hypotension:Bolus with IV isotonic crystalloid solutionNorepinephrine if unresponsive to IV fluids
  • Seizures:Diazepam (drug of choice)Phenobarbital (if diazepam ineffective)Phenytoin not effective in most toxic seizures
  • Cardiac conduction delay:QRS widening (>100 msec):Sodium bicarbonate (to overcome sodium channel blockade)
  • Psychiatric consultation if suicide attempt

Medication

First Line

  • Activated charcoal (initial bolus): Slurry 1-2 g/kg up to 100 g PO
  • Multidose activated charcoal: 25 g (peds: 0.25 g/kg) q2h PO after bolus dose (above); can also use 50 g q6h PO/NG

Second Line

  • Dextrose: D50W 1 ampule: 50 mL or 25 g (peds: D25W 2-4 mL/kg) IV
  • Diazepam: 5-10 mg (peds: 0.2-0.5 mg/kg) IV
  • Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV/IM initial dose
  • Norepinephrine: 2-4 μg/min (peds: 0.05-0.1 μg/kg/min) IV titrated to effect
  • Sodium bicarbonate: 1 or 2 amps IV push (peds: 1-2 mEq/kg)

Follow-Up

Disposition

Admission Criteria

  • Decreased mental status at any time, even if resolving (tends to recur with fluctuating drug levels):Observe at least 24 hr for late relapse.
  • Seizures
  • Cardiac dysrhythmias
  • Lack of psychiatric clearance after suicidal ingestion

Discharge Criteria

  • Asymptomatic after 6 hr of observation
  • Normal mental status
  • Normal or baseline ECG
  • GI motility present
  • Psychiatric clearance (after suicidal ingestion)

Issues for Referral

Suicidal patients need psychiatric evaluation referral.

Followup Recommendations

Supratherapeutic dosing will need ongoing monitoring by physician treating underlying disorder.

Pearls and Pitfalls

  • Carbamazepine levels commonly rebound to higher levels during treatment. Obtain serial measurements for severe ingestions.
  • Monitor closely for arrhythmias.
  • Multidose charcoal may be needed for more serious ingestions.
  • Paradoxical seizures may occur, use benzodiazepines to treat initially (diazepam is the drug of choice).

Additional Reading

  • Brahmi N, Kouraichi N, Thabet H, et al. Influence of activated charcoal on the pharmacokinetics and the clinical features of carbamazepine poisoning. Am J Emerg Med. 2006;24:440-443.
  • Perez A, Wiley JF. Pediatric carbamazepine suspension overdose-Clinical manifestations and toxicokinetics. Pediatr Emerg Care. 2005;21(4):252-254.
  • Pilapil M, Peterson J. Efficacy of hemodialysis and charcoal hemoperfusion in carbamazepine overdose. Clin Toxicol (Phila). 2008;46(4):342-343.
  • Schmidt S, Schmitz-Buhl M. Signs and symptoms of carbamazepine overdose. J Neurol. 1995;242:169-173.

Codes

ICD9

966.3 Poisoning by other and unspecified anticonvulsants

ICD10

  • T42.1X1A Poisoning by iminostilbenes, accidental, init
  • T42.1X2A Poisoning by iminostilbenes, intentional self-harm, init
  • T42.1X4A Poisoning by iminostilbenes, undetermined, initial encounter

SNOMED

  • 241753006 Poisoning by carbamazepine (disorder)
  • 290962008 Intentional poisoning by carbamazepine (disorder)
  • 290961001 Accidental poisoning by carbamazepine (disorder)
  • 290963003 Poisoning by carbamazepine of undetermined intent (disorder)