Author:
ArkadyRasin
Steven E.Aks
Description
- Class of medications sharing a similar tricyclic structure
- Mechanism of action in therapeutic dosing:
- Primarily developed as antidepressants
- Decreased use as antidepressant given alternative medications with safer profiles in overdose
- Increasingly used for chronic and neuropathic pain
- Also used for OCD, enuresis, and ADHD
Etiology
- Primary mechanism of tricyclic antidepressant (TCA) toxicity:
- Sodium channel blocking effect (quinidine-like effect)
- Inhibition of norepinephrine reuptake
- Peripheral α-blockade
- Anticholinergic effect
- TCAs:
- Newer-generation antidepressants (nontricyclic) have different toxic profile than TCAs:
- Selective serotonin reuptake inhibitors (SSRIs):
- Wider margin of safety than TCA
- Less CNS/cardiovascular toxicity
- Nonselective serotonin reuptake inhibitors:
- Serotonin and norepinephrine reuptake inhibitors TCA (SNRIs)
- Less CNS/cardiovascular toxicity
- Can cause cardiac dysrhythmias or seizures
- Venlafaxine (Effexor)
- See Antidepressants, Poisoning
Signs and Symptoms
- Rapid deterioration may occur
- Peak concentrations 2-8 hr post ingestion
- Classic TCA compounds (imipramine, amitriptyline, nortriptyline) - greatest cardiovascular toxicity
- CNS:
- Stimulation or depression
- Stimulation:
- Tremulousness
- Agitation
- Fasciculation
- Seizures (resulting acidemia may lead to worsening cardiovascular toxicity)
- Depression:
- 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
- Dry skin and mucosa
- 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
- Blood gas
- Acidosis potentiates TCA toxicity
Diagnostic Tests & Interpretation
Lab
- CBC
- Electrolytes, BUN, creatinine, glucose
- ABG
- Urine toxicology screen:
- Evaluate exposure to other toxins
- Qualitative screen, does not correlate well with degree of toxicity
- TCA levels:
- Not useful
- Do not correlate well with degree of toxicity
- Qualitative screen appropriate to confirm ingestion if necessary
Imaging
CXR 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
Prehospital
- 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
- Run ECG machine while giving bicarb to assess for response to sodium bicarbonate
- If intubated hyperventilate to maintain arterial pH of 7.45-7.5 with hyperventilation
- 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 second-line agent after sodium bicarbonate
- Hypertonic saline if life-threatening dysrhythmia and patient is alkalotic >7.55 (experimental, call Poison Center for recommendations)
- Use of class IA (procainamide) and IC agents and physostigmine contraindicated
Hypotension
- 0.9% NS fluid bolus
- Norepinephrine:
- Preferred pressor (over dopamine)
- Counters α-blockade better
- Dopamine requires higher doses
Decontamination
- Administer activated charcoal
- Ipecac contraindicated
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 mcg/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 mcg/min (peds: 0.05-0.1 mcg/kg/min) IV infusion titrated to desired effect
- Hypertonic saline: 7.5% Saline, 200-250 mL (experimental for patients with dysrhythmia refractory to bicarbonate with pH>7.55). Call Poison Control Center for guidance
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 8-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
Follow-up Recommendations
Psychiatry for suicide attempts
- BlaberMS, KhanJN, BrebnerJA, et al. “Lipid rescue” for tricyclic antidepressant cardiotoxicity . J Emerg Med. 2012;3:465-467.
- GeisGL, BondGR. Antidepressant overdose: Tricyclics, selective serotonin reuptake inhibitors, and atypical antidepressants. In: EricksonTB, AhrensW, AksSE, et al., eds. Pediatric Toxicology. New York: McGraw-Hill; 2004:297-302.
- McKinneyPE, RasmussenR. Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution . A Emerg Med. 2003;42:20-24.
- ReillyTH, KirkMA. Atypical antipsychotics and newer antidepressants . Emerg Med Clin North Am. 2007;25:477-497.
- WoolfAD, ErdmanAR, NelsonLS, 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
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