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
    • Cocainecan 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
  • May also consider hypertonic 3% saline for refractory hypotension

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
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