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Toxicity, Cyclic Antidepressants: Treatment & Medication
Updated: Nov 3, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Endotracheal intubation is necessary in a patient who is obtunded and unable to protect the airway. Intravenous access should be established as soon as possible. Administer intravenous fluid if the patient is hypotensive. Prompt transport of the patient to the nearest emergency department is implicit.
Evidence-based management guidelines for tricyclic antidepressant poisoning are available from the American Association of Poison Control Centers.9
Emergency Department Care
The greatest risk of seizures and arrhythmias occurs within the first 6-8 hours of cyclic antidepressant (CA) ingestion. The treatment of an asymptomatic patient with a history of CA ingestion is mainly supportive therapy. For all patients with possible CA toxicity, airway protection, ventilation and oxygenation, intravenous fluids, cardiac monitoring, and performing ECG are all essential measures.
Consider early gastric decontamination using charcoal if the patient presents within 2 hours of ingestion.
Once suicidal ideation is ruled out and the patient remains asymptomatic for 6-8 hours postingestion without any ECG changes, the patient may be discharged home. If suicidal ideation is present, evaluation for admission to a psychiatric facility is mandatory.
- Airway: Endotracheal intubation may be necessary in patients who present with seizures or who are in a comatose state for airway protection.
- Hyperventilation: The use of hyperventilation is controversial. It has been recommended traditionally for the resultant alkaline state hyperventilation achieves. Alkalinization is thought to increase protein binding of CA and promote CA excretion, thereby decreasing cardiotoxicity. However, a randomized controlled animal study shows that hyperventilation has little effect on reversing CA toxicity.10
- Hypotension
- Normal saline intravenous fluids are indicated for CA-induced hypotension.
- For hypotension refractory to intravenous saline, vasopressors with alpha-agonist effect (eg, Neo-Synephrine, norepinephrine) may be used.
- GI decontamination: Once the patient is stabilized, activated charcoal can be considered.
- Intravenous sodium bicarbonate
- Serum alkalinization with intravenous sodium bicarbonate has been the mainstay of therapy in CA-induced cardiovascular toxicity. Prolonged QRS is most often the indication for serum alkalinization in CA toxicity. Not all physicians agree on what the duration of QRS should be in order for them to institute intravenous sodium bicarbonate therapy. However, about 88% of the poison control directors in the United States use a QRS of 100 milliseconds or greater as the cut off for intravenous sodium bicarbonate. Evidence suggests the reversal of toxic effects of CA (eg, QRS prolongation, myocardial depression) following serum alkalization and sodium loading with sodium bicarbonate.
- Animal studies have shown hypertonic saline to be effective in reversing CA toxicity.10 However, no study adequately compared the efficacy of hypertonic saline versus sodium bicarbonate. Sodium loading may be the most important factor in the reversal of the symptoms of cyclic antidepressant toxicity.
- Hypertonic saline: The use of hypertonic saline in CA toxicity remains controversial. Though 7.5% hypertonic saline has been shown to correct hypotension and QRS widening in severe CA overdose in a swine model,10 limited evidence supports the use of hypertonic saline in CA toxicity in humans.
- Benzodiazepines: The seizures in CA toxicity are usually self-limited. The treatment of choice for prolonged or recurrent seizures in CA toxicity is a benzodiazepine. Most CA-induced seizures are usually brief and resolve prior to the administration of anticonvulsants. General anesthesia should be reserved for patients with status epilepticus who are unresponsive to the standard treatment regimen (eg, benzodiazepines, barbiturates, propofol). This may prevent hyperthermia and rhabdomyolysis.
- Hemodialysis or hemoperfusion: Because of the large volume of distribution and high protein-binding characteristics of CAs, hemodialysis has not been shown to be effective in the treatment of CA overdose.
- Physostigmine: This is a short-acting cholinesterase inhibitor used for the reversal of anticholinergic symptoms. It should not be used in treating CA toxicity because of the reported cases of physostigmine-induced seizures and asystole.
Consultations
- Poison control center
- Toxicologist
- Cardiologist for pacemaker placement and arrhythmia management, when indicated
- ICU admission for patients with cardiovascular and/or neurologic manifestations of CA toxicity
Medication
Treatment of cyclic antidepressant (CA) toxicity focuses on airway management, dysrhythmias, seizures, and hypotension. Sodium bicarbonate, benzodiazepines, and norepinephrine are the DOCs for these complications.
GI decontaminant
This agent prevents further absorption of drug and other co-ingestants from the GI tract.
Activated charcoal (Liqui-Char)
Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. May be administered with or without cathartic (eg, Sorbitol 70%), except in young pediatric patients, where electrolyte imbalance may be of concern. Does not dissolve in water.
For maximum effect, administer within 30 min of ingesting poison.
Adult
1 g/kg PO initial (if the ingestion occurred 1-2 h before presentation)
Pediatric
1-2 g/kg PO; not to exceed 15-30 g
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases adsorptive properties)
Documented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway with absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Check for presence of bowel sounds before repeat administration to minimize risk of charcoal ileus; not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administering; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black
Cardiovascular agents
Sodium bicarbonate is indicated for QRS intervals greater than 100 milliseconds, seizures, acidosis (pH level <7), hypotension, cardiac arrest, or dysrhythmia. Antidysrhythmic agents may be helpful. However, avoid certain drugs that exacerbate the cardiac effects of CAs, such as quinidine and procainamide (class IA), flecainide (class IC), and bretylium and amiodarone (class III). Vasopressors are used for the treatment of hypotension not corrected by intravenous fluids.
Sodium bicarbonate (Neut)
First-line therapy for QRS interval >100 milliseconds or if dysrhythmias are present. Correction of acidosis promotes protein binding of CA and improves myocardial contractility. Doses or IV drip may be administered with a pH goal of 7.5-7.55. Monitor and replace potassium as needed to prevent hypokalemia.
Adult
1-2 mEq/kg bolus IV; IV drip of 3 amps of sodium bicarbonate in 1 L of D5W to maintain a pH of 7.45-7.55
Pediatric
Administer as in adults
Urinary alkalinization, induced by increased sodium bicarbonate concentrations, may cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; increases levels of amphetamines, pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine
Alkalosis; hypernatremia; hypocalcemia; severe pulmonary edema; unknown abdominal pain
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Should only be used to treat documented metabolic acidosis and hyperkalemia-induced cardiac arrest; can cause alkalosis, decreased plasma potassium, hypocalcemia, and hypernatremia; may cause sodium retention if renal function is impaired; caution in conditions with electrolyte imbalances, such as CHF, cirrhosis, edema, corticosteroid use, or renal failure; when administering, avoid extravasation because can cause tissue necrosis
Lidocaine (Xylocaine)
Class IB antiarrhythmic that increases electrical stimulation threshold of ventricle, suppressing automaticity of conduction through tissue. Second DOC for CA dysrhythmias.
Adult
1-1.5 mg/kg IV bolus, may repeat up to total of 3 mg/kg; maintenance drip of 1-4 mg/min by mixing 2 g in 250 mL of D5W
Pediatric
20-50 mcg/kg IV bolus; 1 mcg/kg/min
Coadministration with cimetidine or beta-blockers, increases toxicity; coadministration with procainamide and tocainide may result in additive cardiodepressant action; may increase effects of succinylcholine
Documented hypersensitivity; Adams-Stokes syndrome, Wolff-Parkinson-White syndrome; severe SA, AV, or IV block if artificial pacemaker not in place
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Use a solution without preservatives; caution in heart failure, hepatic disease, hypoxia, hypovolemia or shock, respiratory-depression, and bradycardia; reduce dose by 50% in acute hepatic failure patients; may increase risk of CNS and cardiac adverse effects in elderly patients; high plasma concentrations can cause seizures, heart block, and AV conduction abnormalities
Norepinephrine (Levophed)
Stimulates beta1- and alpha-adrenergic receptors, which, in turn, increases cardiac muscle contractility, heart rate, and vasoconstriction. As a result, systemic blood pressure and coronary blood-flow increases. DOC to treat hypotension refractory to fluid resuscitation in CA toxicity. Dopamine is second-line and less effective.
Adult
2-4 mcg/min IV; titrate to desired response; 8-30 mcg/min usual range
Pediatric
0.05-0.1 mcg/kg/min IV; not to exceed 2 mcg/kg/min
Enhances pressor response of norepinephrine by blocking the reflex bradycardia caused by norepinephrine
Documented hypersensitivity; peripheral or mesenteric vascular thrombosis because ischemia may be increased and area of infarct extended
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Correct blood-volume depletion, if possible, before therapy; extravasation may cause severe tissue necrosis and, thus, should be administered into a large vein; caution in occlusive vascular disease
Anticonvulsants
Benzodiazepines are preferred for treatment of seizures. Do not use barbiturates in patients with hypotension. Do not use phenytoin in patients with dysrhythmias.
Lorazepam (Ativan)
Sedative hypnotic with short onset of effects and relatively long half-life (longer than diazepam).
By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.
Monitoring patient's blood pressure after administering dose is important. Adjust prn.
Adult
2-4 mg/dose IV over 2-5 min; may repeat in 10-15 min, usual maximal dose 8 mg
Pediatric
0.05-0.1 mg/kg/dose IV over 2-5 min; not to exceed 4 mg/dose; may repeat dose of 0.05 mg/kg in 10-15 min prn
Toxicity in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs
Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma; pregnancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease; may cause respiratory depression
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Shorter acting than lorazepam.
Adult
0.02-0.05 mg/kg IV at 2 mg/min; not to exceed 5-10 mg
Pediatric
0.05-0.1 mg/kg IV at 1 mg/min
Toxicity in CNS increases with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity); may cause respiratory depression
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose.
Adult
Loading dose: 0.2 mg/kg IV
Continuous infusion: 0.1-0.4 mg/kg/h IV
Intubation and pressor support will be necessary
Alternatively: 10-15 mg IM; when other access impossible
Pediatric
Loading dose: 0.15 mg/kg IV
Maintenance dose: Infuse 1 mcg/kg/min
Titrate dose upward q5min until clinical seizure activity is controlled
Sedative effects may be antagonized by theophyllines; narcotics and erythromycin may accentuate sedative effects because of decreased clearance
Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, and hepatic failure; may cause respiratory depression
Phenobarbital (Barbita, Luminal)
Used for seizures not responding to benzodiazepines. Significant respiratory depression; patient may require endotracheal intubation.
Adult
Load 15-20 mg/kg IV at 25-30 mg/min; not to exceed 300-800 mg
Pediatric
Administer as in adults
May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and fatality; chloramphenicol, valproic acid, and MAOIs may increase phenobarbital toxicity; rifampin may decrease phenobarbital effects; induction of microsomal enzymes may result in decreased effects of PO contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy); menstrual irregularities may also occur
Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritic patients
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause respiratory depression; in prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema
Miscellaneous
Magnesium sulfate has been successfully used in an overdose with refractory ventricular fibrillation.12 Animal studies have shown that magnesium sulphate converted ventricular tachycardia to sinus rhythm in 9 of 10 rats.13
Magnesium sulfate
Given parenterally, magnesium decreases acetylcholine in motor nerve terminals and acts on myocardium by slowing rate of S-A node impulse formation and prolonging conduction time. May be helpful in treating ventricular fibrillation in TCA toxicity, but further study is needed.
Adult
For life-threatening arrhythmia, 1-2 g IV (8-16 mEq) in 100 mL D5W, administered over 5-60 min followed by an infusion of 0.5-1 g/h
Pediatric
20-100 mg/kg/dose IV q4-6h prn; in severe cases, doses as high as 200 mg/kg/dose have been used
Aminoglycosides increase magnesium sulfate's neuromuscular blockade; CNS depressants increased CNS depression; neuromuscular antagonists, betamethasone (pulmonary edema), ritodrine increased cardiotoxicity
Heart block; serious renal impairment; myocardial damage; hepatitis; Addison disease
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Use with caution in patients with impaired renal function; use with caution in digitalized patients (may lead to heart block); monitor serum magnesium level, respiratory rate, deep tendon reflex, renal function when magnesium sulfate is administered parenterally; use with extreme caution in patients with myasthenia gravis or other neuromuscular disease
More on Toxicity, Cyclic Antidepressants |
| Overview: Toxicity, Cyclic Antidepressants |
| Differential Diagnoses & Workup: Toxicity, Cyclic Antidepressants |
 Treatment & Medication: Toxicity, Cyclic Antidepressants |
| Follow-up: Toxicity, Cyclic Antidepressants |
| References |
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References
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Further Reading
Keywords
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