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Tricyclic Antidepressant, Poisoning, Emergency Medicine

Basics

Description

- Rapid deterioration may occur. - Classic TCA compounds (imipramine, amitriptyline, nortriptyline) " greatest cardiovascular toxicity - Newer agents (serotonergic agents) " less overall toxicity in overdose - CNS: - Stimulation or depression - Stimulation: - Tremulousness - Agitation - Fasciculation - Seizures (resulting acidemia may lead to worsening cardiovascular toxicity)

- Bradycardia: - Late; owing to catecholamine depletion state

- Anticholinergic effects (less common): - Dilated pupils - Decreased bowel sounds - Urinary retention

- QT prolongation - PR prolongation - Rightward shifting of terminal 40 ms QRS axis - R-wave amplitude in aVR >3 mm

- CBC - Electrolytes, BUN, creatinine, glucose - ABG - Urine toxicology screen: - TCA levels: - Not useful - Do not correlate well with degree of toxicity - Qualitative screen appropriate to confirm ingestion if necessary

- Cardiotoxic drugs: - Antidysrhythmics (category IA) - Digoxin toxicity - Sympathomimetics - Anticholinergics

- Initiate therapy for cardiac toxicity aggressively to prevent deterioration. - QRS widening (>100 " 120 ms): - Bolus with 1 amp (peds: 1 " 2 mEq/kg) of sodium bicarbonate; repeat if sudden increase in QRS width - Maintain arterial pH of 7.45 " 7.5 with hyperventilation. - Initiate sodium bicarbonate infusion if hyperventilation alone does not reach target pH.

  • Primary mechanism of tricyclic antidepressant (TCA) toxicity:Sodium channel blocking effect (quinidine-like effect)Inhibition of norepinephrine reuptakeα-blockadeAnticholinergic effect
  • Selective serotonin reuptake inhibitors (SSRIs):Wider margin of safety than TCALess CNS/cardiovascular toxicity
  • Nonselective serotonin reuptake inhibitors:Serotonin and norepinephrine reuptake inhibitors (SNRIs)Can cause cardiac dysrhythmias or seizuresVenlafaxine (Effexor)See "Antidepressants, Poisoning. "

Etiology

  • TCAs:AmitriptylineNortriptylineImipramineDoxepin
  • Newer-generation antidepressants (nontricyclic):Have different toxic profile than TCAsSee "Antidepressants, Poisoning. "
  • Rapid deterioration may occur.

Diagnosis

Signs and Symptoms

  • Rapid deterioration may occur.
  • Classic TCA compounds (imipramine, amitriptyline, nortriptyline) " greatest cardiovascular toxicity
  • Newer agents (serotonergic agents) " less overall toxicity in overdose
  • CNS:Stimulation or depressionStimulation:TremulousnessAgitationFasciculationSeizures (resulting acidemia may lead to worsening cardiovascular toxicity)Depression:
  • Cardiovascular system:HypotensionTachycardia:Early; owing to blockade of norepinephrine reuptake and anticholinergic effectsBradycardia:Late; owing to catecholamine depletion stateECG changes:QRS widening (>100 " 120 ms)Rightward shift in terminal 40 ms in frontal plane axis (R wave >3 mm in aVR)Dysrhythmias:Supraventricular tachycardia (SVT)Ventricular arrhythmias
  • Anticholinergic effects (less common):Dilated pupilsDecreased bowel soundsUrinary retention

History

Substance ingestion in patient with access to TCA

Physical Exam

  • CNS:Stimulation or depression
  • Cardiovascular:TachycardiaMydriasis or midrange pupilsDecreased bowel soundsUrinary retention (rare)

Essential Workup

  • ECG: Factors associated with TCA poisoning:Sinus tachycardia (almost always present at some time after poisoning)QRS widening:>100 ms associated with seizure>160 ms associated with ventricular dysrhythmiaQT prolongationPR prolongationRightward shifting of terminal 40 ms QRS axisR-wave amplitude in aVR >3 mm
  • Continuous cardiac monitor

Diagnosis Tests & Interpretation

Lab

  • CBC
  • Electrolytes, BUN, creatinine, glucose
  • ABG
  • Urine toxicology screen:
  • TCA levels:Not usefulDo not correlate well with degree of toxicityQualitative screen appropriate to confirm ingestion if necessary

Imaging

Chest radiograph for aspiration pneumonia/pulmonary edema

Differential Diagnosis

  • Drugs that cause coma:AlcoholsAlcohol withdrawalAnticholinergicsLithiumPhencyclidine (PCP)OpioidsPhenothiazinesSedative hypnoticsSalicylates
  • Cardiotoxic drugs:Antidysrhythmics (category IA)Digoxin toxicitySympathomimeticsAnticholinergics
  • Drugs that cause seizures:Alcohol withdrawalAnticholinergicsCamphorIsoniazidLindaneLithiumPhenothiazinesSympathomimeticsToxic alcohols

Treatment

Pre-Hospital

  • Do not be lulled into false sense of security with well-appearing patient:Rapid onset of altered mental status, seizures, and dysrhythmias occur.
  • Perform endotracheal intubation if any evidence of compromise.
  • Secure IV access.
  • Administer sodium bicarbonate if any evidence of QRS widening (>100 " 120 ms):1 ampule in adults1 " 2 mEq/kg in children
  • Ipecac contraindicated (risk for aspiration with development of depressed mental status or seizure)

Initial Stabilization/Therapy

  • ABCs:Low threshold to intubate patients with altered mental status
  • IV 0.9% normal saline (NS)
  • Oxygen
  • Cardiac monitor:For wide-complex rhythm (QRS >100 " 120 ms) bolus sodium bicarbonate
  • Naloxone, thiamine, glucose (Accu-Chek) for altered mental status
  • Flumazenil contraindicated in combined TCA/benzodiazepine overdose

Ed Treatment/Procedures

Cardiac Toxicity

  • Initiate therapy for cardiac toxicity aggressively to prevent deterioration.
  • QRS widening (>100 " 120 ms):Bolus with 1 amp (peds: 1 " 2 mEq/kg) of sodium bicarbonate; repeat if sudden increase in QRS widthMaintain arterial pH of 7.45 " 7.5 with hyperventilation.Initiate sodium bicarbonate infusion if hyperventilation alone does not reach target pH.
  • Dysrhythmia:Sinus tachycardia requires no treatment.Bolus 1 " 2 amps of sodium bicarbonate (1 " 2 mEq/kg in children) for sudden change in rhythmFollow advanced cardiac life support (ACLS) protocol with addition of sodium bicarbonate boluses:Lidocaine is 2nd-line agent after sodium bicarbonate.Use of class IA (procainamide) and IC agents and physostigmine contraindicated

Hypotension

  • 0.9% NS fluid bolus
  • Norepinephrine:Preferred pressor (over dopamine)Countersα-blockade betterDopamine requires higher doses.

Decontamination

  • Gastric lavage:For recent ingestion (<1 hr)Performed when airway has been secured in lethargic patient
  • Administer activated charcoal with sorbitol.
  • Ipecac contraindicated

Seizure

  • Diazepam 1st-line followed by phenobarbital
  • Neuromuscular paralysis with short-acting agent (rocuronium/vecuronium) for refractory seizures (monitor EEG)
  • Sodium bicarbonate bolus to prevent acidosis

Medication

First Line

  • Sodium bicarbonate: 1 " 2 amps (50 " 100 mEq) IV push (peds: 1 " 2 mEq/kg)
  • Activated charcoal slurry: 1 " 2 g/kg up to 90 g PO

Second Line

  • Dextrose: D50W, 1 amp: 50 mL or 25 g (peds: D25W, 2 " 4 mL/kg) IV
  • Diazepam (benzodiazepine): 5 " 10 mg (peds: 0.2 " 0.5 mg/kg) IV
  • Dopamine: 2 " 20 Όg/kg/min IV infusion titrated to desired effect
  • Intralipid fat emulsion 20%: 1.5 mL/kg IV followed by 0.25 mL/kg/min (experimental for patients refractory to bicarbonate). Call Poison Control Center for guidance.
  • Lorazepam (benzodiazepine): 2 " 6 mg (peds: 0.03 " 0.05 mg/kg) IV
  • Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV or IM initial dose
  • Norepinephrine: 4 " 12 Όg/min (peds: 0.05 " 0.1 Όg/kg/min) IV infusion titrated to desired effect

Follow-Up

Disposition

Admission Criteria

  • Symptomatic patients observed >6 hr
  • Altered mental status
  • Dysrhythmia or conduction delay
  • Seizure
  • Heart rate >100 beats/min 6 hr after ingestion
  • Coingestion requiring prolonged observation

Discharge Criteria

  • Asymptomatic after 6-hr observation
  • No alteration in mental status
  • Normal ECG with heart rate <100 beats/min
  • Active bowel sounds; tolerated, activated charcoal
  • Psychiatry clearance if there has been suicide attempt or gesture

Issues for Referral

Toxicology or poison center consultation for significant ingestions

Followup Recommendations

Psychiatry for suicide attempts

Pearls and Pitfalls

  • The hallmark of TCA poisoning is rapid clinical deterioration.
  • Vigilant monitoring for QRS widening beyond 120 ms is essential.
  • Achieve target pH with hyperventilation in the intubated TCA overdose patient.
  • Treat acute widening of the QRS beyond 120 ms with bolus bicarbonate.

Additional Reading

  • Blaber MS, Khan JN, Brebner JA, et al. "Lipid rescue " for tricyclic antidepressant cardiotoxicity. J Emerg Med. 2012;3:465 " 467.
  • Geis GL, Bond GR. Antidepressant overdose: Tricyclics, selective serotonin reuptake inhibitors, and atypical antidepressants. In: Erickson TB, Ahrens W, Aks SE, et al., eds. Pediatric Toxicology. New York, NY: McGraw-Hill; 2004:297 " 302.
  • Reilly TH, Kirk MA. Atypical antipsychotics and newer antidepressants. Emerg Med Clin North Am. 2007;25:477 " 497.
  • Woolf AD, Erdman AR, Nelson LS, et al. Tricyclic antidepressant poisoning: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45:203 " 233.

See Also (Topic, Algorithm, Electronic Media Element)

Antidepressant Poisoning

Codes

ICD9

969.05 Poisoning by tricyclic antidepressants

ICD10

  • T43.011A Poisoning by tricyclic antidepressants, accidental, init
  • T43.014A Poisoning by tricyclic antidepressants, undetermined, init

SNOMED

  • 69434005 Tricyclic antidepressant poisoning (disorder)
  • 290859009 Tricyclic antidepressant poisoning of undetermined intent (disorder)