Tricyclic Antidepressant Overdose

Aka: Tricyclic Antidepressant Overdose, Tricyclic Overdose, Tricyclic Antidepressant Poisoning, Tricyclic Antidepressant Toxicity, Sodium Channel Blocker Toxicity

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II. Pathophysiology: Mechanism

  1. Sodium Channel Blocker
    1. Slows Myocyte depolarization (QRS Widening, Prolonged QTc, Hypotension)
  2. Alpha Adrenergic Blocker (alpha-1 receptor blockers)
    1. Sedation, Miosis and Orthostatic Hypotension
  3. Serotonin Norepinephrine Reuptake Inhibitor
    1. Initial Tachycardia and Hypertension after acute ingestion
    2. May be followed by Hypotension with Norepinephrine depletion
  4. Antimuscarinic Anticholinergic effects
    1. Sedation

III. Pharmacokinetics: Tricyclic Antidepressant

  1. Peak concentrations 2-8 hours after ingestion
  2. Highly lipophilic
  3. High volume of distribution
  4. High Protein binding
  5. Hepatic metabolism

IV. Findings

  1. See Anticholinergic Toxicity (muscarinic Anticholinergic effects)
  2. Symptoms and Signs typically at ingestions >5 mg/kg (and typical onset within 2 hours of ingestion)
  3. Altered Level of Consciousness
    1. Confusion
    2. Agitation
    3. Delirium
    4. Lethargy
    5. Coma
  4. Hypotension
  5. Acute Respiratory Distress Syndrome
  6. Seizures (esp. when QRS Duration >100 ms)
  7. Tachycardia
  8. Urinary Incontinence

V. Diagnostics: EKG Findings

  1. R Wave in aVR (elevation of the terminal 40 msec)
    1. Tall R Wave in aVR (>3 mm, R/S ratio >0.7) suggests Right Ventricular Strain
    2. Right Axis Deviation
  2. QRS Widening >0.1 s
    1. Also seen with Cocaine and Diphenhydramine
    2. QRS >0.16 s is associated with Seizures and Dysrhythmias
    3. Mortality increases with QRS Duration
      1. Emergent management with Sodium Bicarbonate alkalinization targets the QRS width
  3. QTc Prolongation (440 to 460 msec)
  4. Sinus Tachycardia
    1. Due to Anticholinergic and Sympathomimetic effects
    2. Bradycardia may occur with severe toxicity
  5. Ventricular Dysrhythmia (e.g. Torsades de Pointes)
  6. Right Bundle Branch Block may be present

VI. Differential Diagnosis: Sodium Channel Blocker Toxicity

  1. Cardiovascular
    1. Class Ia Antiarrhythmic Drug (e.g. Procainamide)
    2. Class Ic Antiarrhythmic Drug (e.g. Flecainide)
    3. Class II Antiarrhythmic Drug (e.g. Propranolol)
  2. Gastrointestinal: Phenothiazines
    1. Prochlorperazine (Compazine)
    2. Chlorpromazine (Thorazine)
  3. Neurologic
    1. Bupivicaine (See LAST Reaction)
    2. Carbamazepine Poisoning
    3. Diphenhydramine (Anticholinergic Poisoning)
  4. Psychiatric: Antidepressants
    1. Bupropion Overdose
    2. Mirtazapine
    3. Venlafaxine
    4. Tricyclic Antidepressants (e.g. Amitriptyline, Nortriptyline)
  5. Infectious Disease: Anti-Malarials
    1. Chloroquine
    2. Hydroxychloroquine
    3. Quinine
  6. Miscellaneous
    1. Cocaine Toxicity
  7. References
    1. Berberian (2024) Crit Dec Emerg Med 38(4): 12-3

VII. Labs

  1. See Unknown Ingestion
  2. Venous Blood Gas (VBG)
    1. Obtain serial levels until stabilized
  3. Toxicology labs
    1. Comprehensive Metabolic Panel
    2. Serum Acetaminophen Level
    3. Serum Salicylate Level
    4. Urine Drug Screen
    5. Avoid Tricyclic Antidepressant levels
      1. TCA levels are send-out labs that do not assist in acute management

VIII. Precautions

  1. Tricyclic Antidepressant Overdose have a high risk of mortality
    1. Even "One Pill Can Kill" (doses >15 mg/kg)
  2. Avoid provocative agents
    1. Avoid Physostigmine
    2. Avoid Class IA Antiarrhythmics (e.g. Procainamide, Quinine)
    3. Avoid Class IC Antiarrhythmics
    4. Avoid Barbiturates and Phenytoin (see Seizures below)
  3. Avoid reducing Heart Rate
    1. Tachycardia decreases the QT Interval and is protective against Torsades de Pointes

IX. Management: General

  1. Significant risk with ingestions >10 mg/kg
  2. Intubate early in serious Tricyclic Overdose (due to rapid decompensation)
    1. Succinylcholine is preferred paralytic (unless Hyperkalemia) less Respiratory Acidosis than with longer acting agent
  3. Gastric Decontamination if early presentation
    1. Give Activated Charcoal if presenting in first 1 hour of ingestion and airway protected
  4. Disposition: Asymptomatic Ingestions <5 mg/kg
    1. Medically cleared if normal ekg and asymptomatic at 6 hours

X. Management: Neurologic

  1. Avoid Antipsychotics (may worsen cardiac conduction)
  2. Seizures
    1. Benzodiazepines: Lorazepam (Ativan)
      1. Adult: Lorazepam 2 to 4 mg IV
      2. Child: Lorazepam 0.05 to 0.1 mg/kg
    2. Avoid Barbiturates
    3. Avoid Phenytoin (Dilantin)
    4. Propofol may be used for refractory Seizures

XI. Management: Prolonged QRS interval (>0.1 s)

  1. Background
    1. Sodium Bicarbonate mechanism
      1. Alkalinize blood and increases drug binding, volume of distribution and drug urinary excretion
      2. Sodium loading helps to overcome the TCA blocking of the Sodium channels
      3. Even multiple repeat doses of Sodium Bicarbonate are safe
        1. Unlikely to causes significant Hypernatremia or Metabolic Alkalosis
    2. Monitor for Electrolyte abnormalities with high Sodium Bicarbonate dosing
      1. Hypernatremia
      2. Hypokalemia
      3. Hypocalcemia
  2. Children
    1. Sodium Bicarbonate 1-2 mEq/kg up to 50 mEq bolus, and initiate infusion
  3. Adults
    1. Sodium Bicarbonate
      1. Start: 2-4 ampules
      2. Titrate: 2 ampules every 2-5 minutes until QRS narrows (may require 15-20 ampules)
      3. May initiate Sodium Bicarbonate isotonic Sodium Bicarbonate maintenance infusion when stable
      4. Goal VBG pH 7.45 to 7.50 (no higher than 7.55)
      5. May substitute Sodium acetate if inadequate supply of Sodium Bicarbonate
    2. Other adjunctive measures
      1. Consider Intralipid
      2. Hypertonic Saline 3% 1-2 mEq/kg IV
        1. Second-line if QRS prolongation is refractory to Sodium Bicarbonate
      3. Lidocaine (Class IB Antiarrhythmic)
        1. Fast association and dissociation allows displacement of TCA from cardiac cells
        2. Results in increased repolarization time and QRS narrowing
        3. Dosing: 1.5 mg/kg per dose
      4. Ventilator
        1. Maintain standard Tidal Volumes (6-8 ml/kg) at an increased Respiratory Rate (at least 16-18 bpm)
        2. Adjust Respiratory Rate to a goal VBG pH 7.45 to 7.55
      5. Activated Charcoal
        1. Risk of aspiration even when intubated (do not give unless intubated with cuffed tube)
        2. Indicated in refractory QRS Widening to numerous bicarbonate ampules (e.g. more than 10 ampules)
          1. Suggests continued Tricyclic Antidepressant absorption (esp. if decreased GI motility)

XII. Management: Hypotension

  1. Tricyclic Antidepressants is an alpha blocker and results in Hypotension
  2. Goal: Low to normal Blood Pressure and adquate critical end-organ perfusion
  3. Intravenous Fluids
  4. Vasopressors
    1. Dopamine is NOT recommended as may exacerbate tricyclic beta mediated effects
    2. Norepinephrine 4 mg/500 cc D5W at 0.1 to 0.2 mcg/kg/min
      1. Adults: 8-12 mcg/min
      2. Children: <6 mcg/min
  5. Other measures
    1. Consider extracorporal membrane oxygenation (ECMO)
    2. Consider intra-aortic balloon pump

XIII. References

  1. (2016) CALS Manual, 14th ed, 1:132-3
  2. Masom (2017) Crit Dec Emerg Med 31(11): 24
  3. Swadron and Nordt in Herbert (2013) EM:Rap 13(3):5-7
  4. Thapar, Orantes and Miller (2022) Crit Dec Emerg Med 36(2): 19-24
  5. Henry (2006) Pediatr Clin North Am 53(2): 293-315 [PubMed]
  6. Vega (2024) Am Fam Physician 109(2): 143-53 [PubMed]

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