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==Background==
==Background==
*Abbreviation: TCA
*[[Tricyclic antidepressants]] (TCAs) remain a '''leading cause of death from prescription drug overdose'''
*Used in depression and neuropathic pain
*Common TCAs: amitriptyline, nortriptyline, imipramine, desipramine, doxepin, clomipramine
*Serious toxicity is almost always seen within 6hr of ingestion
*Narrow therapeutic index — lethal dose is only 3-5x therapeutic dose
*Coingestants that impair metabolism through cytochrome P450 often increase severity of toxicity
*Multiple mechanisms of toxicity:
**[[Cocaine]] can produce the same sodium blockade effect and exacerbate a TCA overdose
**Sodium channel blockade → QRS widening → ventricular arrhythmias (most dangerous)
**Anticholinergic effects → tachycardia, mydriasis, urinary retention, hyperthermia, AMS
**Alpha-1 receptor blockade → hypotension
**Norepinephrine/serotonin reuptake inhibition → initial hypertension, tachycardia
**GABA-A antagonism → seizures
**Potassium channel blockade → QT prolongation
*Rapidly absorbed; toxicity can progress from alert to cardiac arrest within 1 hour


===Ingestion amount===
==Clinical Features==
*<1mg/kg: Nontoxic
===Anticholinergic Toxidrome===
*>10mg/kg: Life-threatening
*Tachycardia, mydriasis, dry skin/mouth, urinary retention
*>1gm: Commonly fatal
*Altered mental status (agitation → delirium → coma)
*Decreased bowel sounds, ileus
*Hyperthermia
 
===Cardiovascular===
*Sinus tachycardia (most common cardiac finding)
*Wide-complex tachycardia (sodium channel blockade)
*Hypotension (alpha blockade, myocardial depression)
*Right axis deviation of terminal QRS
*Brugada-like pattern
*'''Ventricular tachycardia/fibrillation''' (leading cause of death)
 
===Neurologic===
*Seizures (occur in 10-20% of significant ingestions; usually brief but may be refractory)
*Myoclonus, tremor
*Coma


==Clinical Features==
===ECG Findings (Critical)===
*Na Channel Blockade (2-6 hours post ingestion)
*QRS >100 ms: increased risk of seizures
**Negative inotropy, heart block, hypotension, ectopy
*QRS >160 ms: increased risk of ventricular arrhythmias
*Anti-Histamine Effects
*R wave >3 mm in aVR (sensitive marker of sodium channel blockade)<ref>Liebelt EL, et al. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. ''Ann Emerg Med''. 1995;26(2):195-201. PMID 7618784</ref>
**Sedation, coma
*R/S ratio >0.7 in aVR
*Anti-Muscarinic Effects (early toxicity, within 2 hours)
*Right axis deviation of terminal 40 ms QRS
**Central
*Sinus tachycardia, QT prolongation
***Agitation, delirium, confusion, [[hallucinations]]
***Slurred speech, ataxia
***Sedation, coma
***[[Seizures]]
**Peripheral
***Mydriasis, decreased secretions, dry skin, ileus, urinary retention
***Tachycardia, hyperthermia, hypertension
*α<sub>1</sub> 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==
==Differential Diagnosis==
{{Anticholinergic types}}
*Other sodium channel blocking agents: Class IA/IC antiarrhythmics, cocaine, diphenhydramine, carbamazepine
{{Sodium channel blocking toxidromes}}
*[[Anticholinergic toxicity]]
*Other causes of wide-complex tachycardia
*[[Serotonin syndrome]] (if combined with serotonergic agents)
*Mixed overdose (coingestion is common)


==Evaluation==
==Evaluation==
*Serious toxicity
*'''ECG''' ('''most important test — get immediately''')
**Conduction delays, [[SVT]], [[V-tach]], [[hypotension]]
**Repeat ECG every 15-30 minutes in first 2 hours
**Respiratory depression
*BMP: monitor for metabolic acidosis (worsens sodium channel blockade)
**[[Seizures]]
*Blood gas: pH (acidosis worsens toxicity; alkalosis is protective)
**[[Pulmonary Edema]]
*Acetaminophen and salicylate levels (coingestion screening)
*[[ECG]]
*Urine drug screen: may detect TCA, but false positives common (diphenhydramine, cyclobenzaprine, carbamazepine, phenothiazines)
**[[Sinus Tachycardia]] (most frequent dysrhythmia)
*'''TCA levels''' are NOT useful for acute management (do not correlate with toxicity)
**PR, QRS, [[QT Prolongation]]
*Lactate, glucose
***Abnormal QRS morphology (deep slurred S wave in I and AVL)
***Threshold of QRS>100 for seizures
***Threshold of QRS>160 for ventricular dysrhythmias
**[[RBBB]]
**[[Right axis deviation]] (of terminal 40ms)<ref>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</ref>
***Terminal R wave in aVR, S wave in I/aVL
***R/S > 0.7
***Otherwise, more simply put, tall R wave in aVR
**Brugada pattern (15%)<ref>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</ref><ref>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</ref>
[[File:TCA_Toxicity.jpg|thumb|ECG in TCA toxicity]]
*An urine positive test result suggests only use of a TCA or another drug that cross-reacts with the screen (antimuscarinic, antipsychotic, carbamazepine, etc.)
*Quantitative serum level does not correlate with severity of illness


==Management==
==Management==
===GI Decontamination===
===Immediate===
*[[Gastric lavage]] if <1hr after ingestion
*Continuous cardiac monitoring
*[[Activated charcoal]] 1gm/kg x1
*IV access, supplemental O2
*GI decontamination: activated charcoal 1 g/kg if presenting within 1-2 hours and patient is alert with protected airway
**Anticholinergic effects delay gastric emptying → charcoal may be beneficial even at 2+ hours
*'''Do NOT induce emesis''' (rapid deterioration risk)


===Cardiac Toxicity<ref>Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14</ref>===
===Sodium Bicarbonate (Cornerstone of Treatment)===
====[[Sodium Bicarbonate]]====
*Indicated for:
*Indications:
**QRS >100 ms
**QRS >100ms, terminal RAD >120 deg, Brugada pattern, ventricular dysrhythmias
**Ventricular arrhythmias
*Initial Dosing:
**Hypotension refractory to fluids
**Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.50-7.55)
*Bolus: 1-2 mEq/kg IV push (repeat every 3-5 minutes until QRS narrows)
**May give as 3 ampules of 8.4% NaHCO3 (150 mEq) or 7.5% NaHCO3 (134 mEq)
*Infusion: 150 mEq NaHCO3 in 1L D5W at 150-250 mL/hr after initial bolus
*Infusion Dosing<ref>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</ref>
*Goal serum pH: 7.50-7.55 (alkalosis overcomes sodium channel blockade)
**Mix 125-150 mEq of NaHCO3 in 1L of D5W; infuse at 250 mL/hr
*Mechanism: increases serum sodium (competes for channel) AND alkalosis favors protein-bound (non-toxic) TCA form
*Treatment Goal:
*Continue until QRS normalizes
**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, hypocalcemia, hypokalemia, hypernatremia, metabolic alkalosis
**Aggressively replace serum electrolytes


====Hyperventilation====
===Seizures===
*Consider in patients unable to tolerate NaHCO<sub>3</sub> (renal failure, pulm/cerebral edema)
*Benzodiazepines first-line: lorazepam 2-4 mg IV, repeat q5min
*Hyperventilate to pH of 7.50 - 7.55 (same as bicarb administration)
*'''Do NOT use phenytoin''' (also blocks sodium channels; may worsen cardiac toxicity)
 
*If refractory: propofol, phenobarbital, or intubation with neuromuscular blockade
====[[Lidocaine]]====
*Treat aggressively — prolonged seizures cause acidosis which worsens cardiac toxicity
*At 1.5 mg/kg, consider lidocaine for ventricular dysrhythmias if NaHCO<sub>3</sub> alone is ineffective
*Competitively inhibits sodium channel blockade effects of TCAs
;NOTE: Avoid IA, IC antiarrhythmics, Beta-Blockers, Calcium Channel Blockers, and amiodarone
 
====[[Phenytoin]]====
*Consider for ventricular dysrhythmias resistant to NaHCO<sub>3</sub> and lidocaine
 
====Synchronized cardioversion====
*Appropriate in patients with persistent unstable tachydysrhythmias
 
====NEVER Use [[Physostigmine]]====
*'''''NEVER''''' use [[physostigmine]] in TCA overdose as the combination leads to lethal bradyarrhythmias<ref>Schneider G. Never Use Physostigmine in a TCA Overdose. Emergency Medicine News: May 2003 - Volume 25 - Issue 5 - p 44.</ref>
**Due to dose dependent AV blockade by physostigmine
**TCA toxicity and physostigmine interact synergistically to cause AV conduction delays
 
===[[Seizures]]===
*[[Benzodiazepines]] are 1st line
*[[Barbituates]] or [[propofol]] are 2nd line
*[[Phenytoin]] ineffective as no seizure focus in brain


===Hypotension===
===Hypotension===
*After repeat fluid boluses and with sodium load from NaHCO<sub>3</sub> norepinepherine should be the first line vasopressor
*IV fluid bolus (NS 1-2L)
*ECMO is a successful adjunct for refractory hypotension after maximal therapy has failed
*Sodium bicarbonate bolus
*May also consider [[hypertonic saline|hypertonic 3% saline]] for refractory hypotension
*Norepinephrine (first-line vasopressor; alpha agonism counteracts TCA alpha blockade)
*Avoid pure beta-agonists
*Refractory: consider lipid emulsion therapy (ILE)


===Dialysis===
===Refractory Ventricular Arrhythmias===
*Not useful for enhancing elimination due to the large volume of distribution and high lipid solubility
*Sodium bicarbonate is first-line
*Lidocaine (Class IB — may be used)
*Avoid Class IA (procainamide) and Class IC (flecainide) antiarrhythmics
*Avoid amiodarone if possible (sodium channel blockade)
*Lipid emulsion therapy: 20% Intralipid 1.5 mL/kg IV bolus then 0.25 mL/kg/min for refractory arrest
*ECMO for refractory cardiac arrest


===[[Intralipid]]===
===Monitoring===
1.5 mL/kg bolus
*Serial ECGs every 15-30 min initially
*Continuous telemetry for minimum 6 hours after last ECG abnormality resolves
*ABG/VBG to guide bicarbonate therapy
*Serum pH goal 7.50-7.55


==Disposition==
==Disposition==
*Consider discharging patients who remain asymptomatic after 6hr of observation
*'''ICU admission''' for: QRS widening, arrhythmias, seizures, hypotension, altered mental status
*Patients with decreased level of consciousness or seizures should be admitted to ICU
*Monitored bed for asymptomatic patients with normal ECG × 6 hours
*Psychiatric evaluation after medical clearance for all intentional ingestions
*Consider discharge only if:
**Asymptomatic for 6 hours
**Normal ECG with QRS <100 ms
**Normal mental status
**Psychiatric clearance obtained
*Poison control: 1-800-222-1222


==See Also==
==See Also==
*[[Toxicology (Main)]]
*[[Anticholinergic toxicity]]
*[[Calcium Channel Blocker Toxicity]]
*[[Sodium channel blocker toxicity]]
*[[Beta-Blocker Toxicity]]
*[[Serotonin syndrome]]
*[[Antipsychotic Toxicity]]
*[[Toxicology]]
 
*[[Cardiac arrest]]
==Video==
{{#widget:YouTube|id=rMVw4ImwNDo}}


==References==
==References==
<references/>
<references/>
*Kerr GW, et al. Tricyclic antidepressant overdose: a review. ''Emerg Med J''. 2001;18(4):236-241. PMID 11435353
*Woolf AD, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. ''Clin Toxicol''. 2007;45(3):203-233. PMID 17453872
*Body R, et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. ''Emerg Med J''. 2011;28(4):347-368. PMID 21436332
[[Category:Toxicology]]
[[Category:Toxicology]]
[[Category:Critical Care]]

Revisión actual - 09:28 22 mar 2026

Background

  • Tricyclic antidepressants (TCAs) remain a leading cause of death from prescription drug overdose
  • Common TCAs: amitriptyline, nortriptyline, imipramine, desipramine, doxepin, clomipramine
  • Narrow therapeutic index — lethal dose is only 3-5x therapeutic dose
  • Multiple mechanisms of toxicity:
    • Sodium channel blockade → QRS widening → ventricular arrhythmias (most dangerous)
    • Anticholinergic effects → tachycardia, mydriasis, urinary retention, hyperthermia, AMS
    • Alpha-1 receptor blockade → hypotension
    • Norepinephrine/serotonin reuptake inhibition → initial hypertension, tachycardia
    • GABA-A antagonism → seizures
    • Potassium channel blockade → QT prolongation
  • Rapidly absorbed; toxicity can progress from alert to cardiac arrest within 1 hour

Clinical Features

Anticholinergic Toxidrome

  • Tachycardia, mydriasis, dry skin/mouth, urinary retention
  • Altered mental status (agitation → delirium → coma)
  • Decreased bowel sounds, ileus
  • Hyperthermia

Cardiovascular

  • Sinus tachycardia (most common cardiac finding)
  • Wide-complex tachycardia (sodium channel blockade)
  • Hypotension (alpha blockade, myocardial depression)
  • Right axis deviation of terminal QRS
  • Brugada-like pattern
  • Ventricular tachycardia/fibrillation (leading cause of death)

Neurologic

  • Seizures (occur in 10-20% of significant ingestions; usually brief but may be refractory)
  • Myoclonus, tremor
  • Coma

ECG Findings (Critical)

  • QRS >100 ms: increased risk of seizures
  • QRS >160 ms: increased risk of ventricular arrhythmias
  • R wave >3 mm in aVR (sensitive marker of sodium channel blockade)[1]
  • R/S ratio >0.7 in aVR
  • Right axis deviation of terminal 40 ms QRS
  • Sinus tachycardia, QT prolongation

Differential Diagnosis

  • Other sodium channel blocking agents: Class IA/IC antiarrhythmics, cocaine, diphenhydramine, carbamazepine
  • Anticholinergic toxicity
  • Other causes of wide-complex tachycardia
  • Serotonin syndrome (if combined with serotonergic agents)
  • Mixed overdose (coingestion is common)

Evaluation

  • ECG (most important test — get immediately)
    • Repeat ECG every 15-30 minutes in first 2 hours
  • BMP: monitor for metabolic acidosis (worsens sodium channel blockade)
  • Blood gas: pH (acidosis worsens toxicity; alkalosis is protective)
  • Acetaminophen and salicylate levels (coingestion screening)
  • Urine drug screen: may detect TCA, but false positives common (diphenhydramine, cyclobenzaprine, carbamazepine, phenothiazines)
  • TCA levels are NOT useful for acute management (do not correlate with toxicity)
  • Lactate, glucose

Management

Immediate

  • Continuous cardiac monitoring
  • IV access, supplemental O2
  • GI decontamination: activated charcoal 1 g/kg if presenting within 1-2 hours and patient is alert with protected airway
    • Anticholinergic effects delay gastric emptying → charcoal may be beneficial even at 2+ hours
  • Do NOT induce emesis (rapid deterioration risk)

Sodium Bicarbonate (Cornerstone of Treatment)

  • Indicated for:
    • QRS >100 ms
    • Ventricular arrhythmias
    • Hypotension refractory to fluids
  • Bolus: 1-2 mEq/kg IV push (repeat every 3-5 minutes until QRS narrows)
  • Infusion: 150 mEq NaHCO3 in 1L D5W at 150-250 mL/hr after initial bolus
  • Goal serum pH: 7.50-7.55 (alkalosis overcomes sodium channel blockade)
  • Mechanism: increases serum sodium (competes for channel) AND alkalosis favors protein-bound (non-toxic) TCA form
  • Continue until QRS normalizes

Seizures

  • Benzodiazepines first-line: lorazepam 2-4 mg IV, repeat q5min
  • Do NOT use phenytoin (also blocks sodium channels; may worsen cardiac toxicity)
  • If refractory: propofol, phenobarbital, or intubation with neuromuscular blockade
  • Treat aggressively — prolonged seizures cause acidosis which worsens cardiac toxicity

Hypotension

  • IV fluid bolus (NS 1-2L)
  • Sodium bicarbonate bolus
  • Norepinephrine (first-line vasopressor; alpha agonism counteracts TCA alpha blockade)
  • Avoid pure beta-agonists
  • Refractory: consider lipid emulsion therapy (ILE)

Refractory Ventricular Arrhythmias

  • Sodium bicarbonate is first-line
  • Lidocaine (Class IB — may be used)
  • Avoid Class IA (procainamide) and Class IC (flecainide) antiarrhythmics
  • Avoid amiodarone if possible (sodium channel blockade)
  • Lipid emulsion therapy: 20% Intralipid 1.5 mL/kg IV bolus then 0.25 mL/kg/min for refractory arrest
  • ECMO for refractory cardiac arrest

Monitoring

  • Serial ECGs every 15-30 min initially
  • Continuous telemetry for minimum 6 hours after last ECG abnormality resolves
  • ABG/VBG to guide bicarbonate therapy
  • Serum pH goal 7.50-7.55

Disposition

  • ICU admission for: QRS widening, arrhythmias, seizures, hypotension, altered mental status
  • Monitored bed for asymptomatic patients with normal ECG × 6 hours
  • Psychiatric evaluation after medical clearance for all intentional ingestions
  • Consider discharge only if:
    • Asymptomatic for 6 hours
    • Normal ECG with QRS <100 ms
    • Normal mental status
    • Psychiatric clearance obtained
  • Poison control: 1-800-222-1222

See Also

References

  1. ↑ Liebelt EL, et al. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. Ann Emerg Med. 1995;26(2):195-201. PMID 7618784
  • Kerr GW, et al. Tricyclic antidepressant overdose: a review. Emerg Med J. 2001;18(4):236-241. PMID 11435353
  • Woolf AD, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol. 2007;45(3):203-233. PMID 17453872
  • Body R, et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. Emerg Med J. 2011;28(4):347-368. PMID 21436332
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