[+]Updated 2017 Mar 31 10:29 AM (ET)

 midazolam may reduce tachycardia in first hour of admission in patients with

tricyclic antidepressant poisoning (ARYA Atheroscler 2016 Jul) view update
 tricyclic antidepressants, especially amitriptyline, associated with more overdose
fatalities than any other drug used to treat depression in the United States from
2000-2014 (Am J Psychiatry 2017 May 1) view update

Overview and Recommendations

Background
 Tricyclic antidepressant (TCA) poisoning results from intentional or accidental
ingestion of TCAs at or above the recommended therapeutic dose, resulting in
anticholinergic effects and potentially cardiac arrhythmia, seizure, and coma.
 Antidepressants are a common cause of prescription drug-related self-poisonings in
the developed world.
 TCAs that have been associated with toxic exposures reported to poison control
centers in the United States include:
 amitriptyline
 clomipramine
 desipramine
 doxepin
 imipramine
 nortriptyline
 protriptyline
 trimipramine
 Dosages associated with TCA toxicity:
 Acute ingestions of 10-20 mg/kg of most TCAs can cause severe
cardiovascular and central nervous system complications.
 In adults, > 1 g can be associated with life-threatening complications.
 In children < 6 years old, clinical toxicity is reported with ingestions > 5
mg/kg.
 Severe complications can also occur at lower doses, especially with patient
comorbidities, coingestants, and specific TCAs (desipramine, nortriptyline,
trimipramine, and protriptyline).
 Risk factors in adults include depression or chronic pain, female gender, or dose ≥
150 mg.
Evaluation
 If overdose with an unknown substance is suspected, consider assessment of serum
electrolytes, osmolality, quantitative concentrations of tricyclic antidepressants
(TCAs), and levels for acetaminophen, salicylates, and ethanol.
 The diagnosis is usually based on a combination of:
 history of TCA ingestion or high risk of intentional overdose (such as
suicidal intent)
 clinical findings consistent with TCA toxicity, including tachycardia, central
nervous system effects, or anticholinergic symptoms
 electrocardiogram (ECG) findings
 The most specific ECG sign of TCA toxicity is right axis deviation of
the terminal 40-millisecond vector of the QRS complex in the frontal
plane (terminal 40 [T 40]-millisecond axis).
 An R wave in aVR with an S wave in lead I is an indicator of a
rightward T 40-millisecond axis.
 The T 40-millisecond axis is usually at maximum deviation
(rightward rotation) at time of presentation or within 5 hours.
 Obtain an ECG on presentation to the emergency department to assist in risk
stratification and management of patients with TCA overdose (Strong
recommendation).
 Obtain serial ECGs to monitor for findings associated with increased risk for
developing complications (Strong recommendation), including:
 QRS prolongation > 100 milliseconds (reported to be the strongest
predictor of complications, with progressively wider QRS complex
associated with increasing risk for seizures and arrhythmias)
 QTc prolongation > 430 milliseconds
 R/S ratio > 0.7 in lead aVR
 Electrocardiography is preferable to serum toxicology analysis for predicting
complications of TCA poisoning.
 Obtain blood gas analysis on initial assessment to assess for acidosis, and repeat as
needed for monitoring during treatment (Strong recommendation).
 Venous sampling is an acceptable alternative to arterial sampling unless
hypoxia or hypoventilation is suspected.

Management
 Initial management
 Consider giving IV bolus fluids as first-line therapy to treat hypotension
induced by tricyclic antidepressant (TCA) overdose (Weak
recommendation).
 Airway management
 Assess neurological status and if the Glasgow Coma Scale score is ≤
8, intubate at the earliest opportunity (Strong recommendation).
  Consider intubation in patients with a Glasgow Coma Scale score
that is > 8 if accompanied by airway compromise, hypoventilation, or
refractory seizures (Weak recommendation).
 See Anticholinergic poisoning for additional information on the general
approach to acute poisoning.
 Consider gastric decontamination only if within 1 hour of ingestion and if the
airway is protected (Weak recommendation).
 Activated charcoal single dose
 25-100 g for adolescents and adults
 10-25 g or 0.5-1 g/kg for children ≤ 1 year old
 25-50 g or 0.3-1 g/kg for children aged 1-12 years
 Consider a gastric lavage only for a potentially life-threatening overdose.
 Management of hemodynamic instability
 Plasma alkalinization to serum pH 7.45-7.55 using sodium bicarbonate is
recommended for dysrhythmias or hypotension (Strong recommendation),
even in the absence of acidosis.
 Consider this for treatment of QRS prolongation that is > 100
milliseconds (Weak recommendation).
 Suggested dosing:
 for life-threatening toxicity, 50-100 mL 8.4% sodium
bicarbonate IV (50 mmol), may repeat dose with blood gas
monitoring to achieve pH 7.45-7.55
 for more stable patients, 500 mL of 1.26% sodium bicarbonate
(75 mmol) has less risk of skin necrosis if extravasation
occurs
 in children, 1-2 mEq/kg bolus if QRS interval > 120
milliseconds
 Addition of sodium bicarbonate might reduce mortality and time in
the intensive care unit in patients with severe tricyclic antidepressant
toxicity.
 Use vasopressors for hypotension that does not respond to initial treatment
with IV fluids and sodium bicarbonate (Strong recommendation).
 Examples of dosing in adults:
 norepinephrine 0.5-20 mcg/minute IV (adjust to maintain low
normal blood pressure)
 Examples of dosing in children:
 dopamine - start at 5 mcg/kg/minute, increase by increments
of 5 mcg/kg/minute
 norepinephrine
 0.1 mcg/kg/minute
 adjust to maintain low normal blood pressure,
maximum 6 mcg/minute
 Epinephrine may be better than norepinephrine for refractory
hypotension and preventing arrhythmias.
 Consider magnesium sulfate for dysrhythmias that do not respond to other
treatments (Weak recommendation).
 Consider glucagon 10 mg IV for life-threatening hypotension or arrhythmias
 refractory to other treatment (Weak recommendation).
 Consider IV lipid emulsion therapy (or intralipid emulsion therapy) for life-
threatening tricyclic antidepressant cardiotoxicity that is unresponsive to
other treatments (Weak recommendation).
 Seizure control
 Benzodiazepines are recommended to control seizures (Strong
recommendation).
 The suggested dosing of lorazepam for seizures:
 in adults is 2-4 mg IV
 in children is 0.05-0.1 mg/kg IV
 Do not use phenytoin (Strong recommendation).
 Follow-up
 In patients with severe toxicity (such as heart rate > 120 beats/minute and
QT interval > 480 milliseconds), consider inpatient cardiac monitoring.
 Discharge from the emergency department is suggested for patients who are
stable with no signs of toxicity and no electrocardiogram abnormalities
(including QRS < 100 milliseconds) after 6 hours of observation (Strong
recommendation).
 Determining cause of overdose may help identify patients who should be referred
for psychiatric or drug treatment.
 Refer patients who have attempted suicide for psychiatric evaluation (and
likely psychiatric admission).
 Refer patients with substance abuse issues for counseling and treatment.