Tricyclic antidepressant toxicity

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Background

  • Abbreviation: TCA
  • Used in depression and neuropathic pain
  • Serious toxicity is almost always seen within 6hr of ingestion
  • Coingestants often increase severity of toxicity
    • Cocaine can produce the same sodium blockade effect and exacerbate a TCA overdose

Ingestion amount

  • <1mg/kg: Nontoxic
  • >10mg/kg: Life-threatening
  • >1gm: Commonly fatal

Clinical Features

  • Na Channel Blockade
    • Negative inotropy, heart block, hypotension, ectopy
  • Anti-Histamine Effects
    • Sedation, coma
  • Anti-Muscarinic Effects
    • Central
    • Peripheral
      • Mydriasis, decreased secretions, dry skin, ileus, urinary retention
      • Tachycardia, hyperthermia
  • Alpha1 Receptor Blockade
    • Sedation, orthostatic hypotension, miosis
  • Inhibition of amine reuptake
    • Sympathomimetic effects
    • Myoclonus, hyperreflexia
    • Serotonin Syndrome (only when used in combination with other serotonergic agents)

Differential Diagnosis

Anticholinergic toxicity

Sodium Channel Blockade Toxidrome

Evaluation

ECG in TCA toxicity

Management

GI Decontamination

Cardiac Toxicity[4]

Sodium Bicarbonate

  • Indications:
    • QRS >100ms, terminal RAD >120 deg, Brugada pattern, ventricular dysrhythmias
  • Initial Dosing:
    • Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.50-7.55)
    • May give as 3ampules (132 mEq) of 8.4% NaHCO3
  • Infusion Dosing[5]
    • Mix 125-150 mEq of NaHCO3 in 1L of D5W; infuse at 250 mL/hr
  • Treatment Goal:
    • QRS <100ms
    • pH 7.50-7.55
    • May continue for 12-24hrs due to the drugs redistribution from tissue
  • Treatment Monitoring
    • Monitor for volume overload, hypokalemia, hypernatremia, metabolic alkalosis

Hyperventilation

  • Consider in patients unable to tolerate NaHCO3 (renal failure, pulm/cerebral edema)
  • Hyperventilate to pH of 7.50 - 7.55 (same as bicarb administration)

Lidocaine

  • At 1.5mg/kg, consider lidocaine for ventricular dysrhythmias if NaHCO3 alone is ineffective
NOTE
avoid IA, IB, IC antiarrhythmics, Beta-Blockers, and Calcium Channel Blockers

Phenytoin

  • Consider for ventricular dysrhythmias resistant to NaHCO3 and lidocaine

Synchronized cardioversion

  • Appropriate in patients with persistent unstable tachydysrhythmias

Seizures

Hypotension

  • After repeat fluid boluses and with sodium load from NaHCO3 norepinepherine should be the first line vasopressor
  • ECMO is a successful adjunct for refractory hypotension after maximal therapy has failed

Dialysis

Not useful for enhancing elimination due to the large volume of distribution and high lipid solubility

Disposition

  • Consider discharging patients who remain asymptomatic after 6hr of observation
  • Patients with decreased level of consciousness or seizures should be admitted to ICU

See Also

Video

References

  1. Liebelt EL, Francis PD, Woolf AD. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. Ann Emerg Med. Aug 1995;26(2):195-201
  2. Goldgran-Toledano D, Sideris G, Kevorkian JP. Overdose of cyclic antidepressants and the Brugada syndrome. N Engl J Med. May 16 2002;346(20):1591-2
  3. Monteban-Kooistra WE, van den Berg MP, Tulleken JE. Brugada electrocardiographic pattern elicited by cyclic antidepressants overdose. Intensive Care Med. Feb 2006;32(2):281-5
  4. Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14
  5. Seger DL, Hantsch C, Zavoral T, Wrenn K. Variability of recommendations for serum alkalinization in tricyclic antidepressant overdose: a survey of U.S. Poison Center medical directors. J Toxicol Clin Toxicol. 2003;41(4):331-8