Tricyclic Antidepressant, Poisoning, Emergency Medicine

Basics

Description

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

Etiology

TCAs:
- Amitriptyline
- Nortriptyline
- Imipramine
- Doxepin
Newer-generation antidepressants (nontricyclic):
- Have different toxic profile than TCAs
- See "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 depression
- Stimulation:
  - Tremulousness
  - Agitation
  - Fasciculation
  - Seizures (resulting acidemia may lead to worsening cardiovascular toxicity)
- Depression:
  - Drowsiness
  - Lethargy
  - Coma
Cardiovascular system:
- Hypotension
- Tachycardia:
  - Early; owing to blockade of norepinephrine reuptake and anticholinergic effects
- Bradycardia:
  - Late; owing to catecholamine depletion state
- ECG 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 pupils
- Decreased bowel sounds
- Urinary retention

History
Substance ingestion in patient with access to TCA
Physical Exam

CNS:
- Stimulation or depression
Cardiovascular:
- Tachycardia
- Mydriasis or midrange pupils
- Decreased bowel sounds
- Urinary 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 dysrhythmia
- QT prolongation
- PR prolongation
- Rightward shifting of terminal 40 ms QRS axis
- R-wave amplitude in aVR >3 mm
Continuous cardiac monitor

Diagnosis Tests & Interpretation

Lab

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

Imaging
Chest radiograph for aspiration pneumonia/pulmonary edema

Differential Diagnosis

Drugs that cause coma:
- Alcohols
- Alcohol withdrawal
- Anticholinergics
- Lithium
- Phencyclidine (PCP)
- Opioids
- Phenothiazines
- Sedative hypnotics
- Salicylates
Cardiotoxic drugs:
- Antidysrhythmics (category IA)
- Digoxin toxicity
- Sympathomimetics
- Anticholinergics
Drugs that cause seizures:
- Alcohol withdrawal
- Anticholinergics
- Camphor
- Isoniazid
- Lindane
- Lithium
- Phenothiazines
- Sympathomimetics
- Toxic 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 adults
- 1 " 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 width
- Maintain 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 rhythm
- Follow 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 better
- Dopamine 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.

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)

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