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Tricyclic Antidepressant Toxicity in Pediatrics Medication

  • Author: Derrick Lung, MD, MPH; Chief Editor: Timothy E Corden, MD  more...
 
Updated: Apr 22, 2016
 

Medication Summary

Activated charcoal is used to prevent drug absorption. Pharmacologic therapy in patients with cyclic antidepressant (CA) toxicity is directed toward cardiac and central nervous system (CNS) effects of these drugs.

Cardiotoxicity

Sodium bicarbonate therapy is the cornerstone of treatment for cyclic antidepressant–induced conduction disturbances, ventricular dysrhythmias, and hypotension. The sodium load increases extracellular sodium concentration, improving the gradient across the sodium channel, and serum alkalinization to a pH of 7.45-7.55 appears to uncouple cyclic antidepressants from myocardial sodium channels.

Controlled studies have demonstrated that bicarbonate loading with an initial bolus of 1-2 mEq/kg of sodium bicarbonate is beneficial. Continuing a bicarbonate drip after the initial bolus, which is titrated to achieve a QRS width of 100 milliseconds, is accepted practice.

Ventricular dysrhythmias that are refractory to sodium bicarbonate may require treatment with lidocaine (class Ib), magnesium sulfate, or both. Class Ia antidysrhythmic drugs (eg, quinidine, procainamide, disopyramide) and class Ic drugs (eg, flecainide, propafenone) are contraindicated because they may worsen sodium channel inhibition.

Class III drugs (eg, amiodarone, sotalol) are contraindicated because they can further prolong the QT interval, leading to ventricular dysrhythmia. Class II beta-blockers (eg, propranolol, esmolol, metoprolol) and class IV calcium channel blockers (eg, verapamil, diltiazem, nifedipine, nicardipine) are contraindicated because they may potentiate or worsen hypotension.

Patients with hypotension refractory to fluid resuscitation and sodium bicarbonate require vasopressor support. Direct-acting alpha-agonists (eg, norepinephrine, phenylephrine) are most effective because severe hypotension is generally due to direct alpha1-blocking effects in these cases. Dopamine may not be as effective because its action is partially mediated by the release of endogenous catecholamines, and these may be depleted.

CNS toxicity

Benzodiazepines are the agents of choice for treatment of CNS toxicity from cyclic antidepressants. Phenobarbital may also be used as a long-acting anticonvulsant. Phenytoin and other electrolyte-channel modulating antiepileptics have traditionally been considered third-line for drug-induced seizures.

Physostigmine is an acetylcholinesterase inhibitor that is contraindicated in patients with cyclic antidepressant overdoses. Although physostigmine was previously advocated for relief of anticholinergic effects, it may cause bradycardia and asystole in patients with cyclic antidepressant cardiotoxicity.

Flumazenil, a benzodiazepine antagonist, is also contraindicated, even in the presence of benzodiazepine co-ingestion. Several case reports describe patients with concomitant cyclic antidepressant overdoses who had seizures after the administration of flumazenil.

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Decontaminants

Class Summary

Activated charcoal is used to prevent drug absorption. Activated charcoal is not absorbed and is excreted entirely through the GI tract. It decreases the extent of cyclic antidepressant absorption from the GI tract, thereby reducing systemic toxicity.

Activated charcoal (Actidose-Aqua, Liqui-Char)

 

Network of pores present in activated charcoal absorbs 100-1000 mg of drug per gram of charcoal. Binds TCAs present in GI tract, thereby limiting systemic absorption and hastening elimination.

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Alkalinizing agents

Class Summary

Sodium bicarbonate remains the first-line therapy for cyclic antidepressant-induced cardiotoxicity (eg dysrhythmia, conduction disturbance). Sodium bicarbonate may have beneficial effects in the treatment of cyclic antidepressant-induced seizures, although data have been far less compelling. Prophylactic use is not indicated in a patient who displays no signs of cardiotoxicity. Sodium bicarbonate provides a source of sodium and alkali, both of which are useful in cyclic antidepressant overdose.

Sodium bicarbonate

 

DOC in limiting cardiovascular morbidity in TCA overdoses.

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Vasopressors

Class Summary

These agents are indicated for persistent hypotension that is unresponsive to fluid resuscitation and sodium bicarbonate.

Norepinephrine (Levophed)

 

DOC for calcium-induced hypotension refractory to fluid or sodium bicarbonate. Stimulates beta1-adrenergic 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.

Phenylephrine (Neo-Synephrine)

 

Strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body. Increases peripheral venous return.

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Inotropic agents

Class Summary

Positive inotropic agents increase the force of contraction of the myocardium and are used to treat acute and chronic congestive heart failure. Some may also increase or decrease the heart rate (ie, positive or negative chronotropic agents), provide vasodilatation, or improve myocardial relaxation.

These agents are indicated for hypotension that is unresponsive to fluid, sodium bicarbonate, and norepinephrine therapy and is believed to be caused by myocardial depression.

Dopamine

 

Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors, which, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation are produced by higher doses.

After initiating therapy, increase dose by 1-4 mcg/kg/min q10-30min until optimal response is obtained. Satisfactory maintenance is obtained using doses of < 20 mcg/kg/min in more than 50% of patients.

In TCA cardiotoxicity, higher starting doses should be initiated to avoid unopposed beta effects.

Not usually effective in these patients because it partially depends on the release of endogenous norepinephrine for its action.

Dobutamine (Dobutrex)

 

Strong beta1-agonist producing excellent inotropy. Weak beta2-agonist that produces mild-to-moderate peripheral vasodilation.

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Antiarrhythmic agents

Class Summary

Sodium bicarbonate is the initial and most effective drug for the treatment of cyclic antidepressant-induced conduction disturbances and dysrhythmias. Lidocaine and magnesium sulfate should be reserved for dysrhythmias that are unresponsive to alkalization and sodium loading.

Lidocaine (Xylocaine)

 

Class IB antiarrhythmic that increases electrical stimulation threshold of the ventricle, suppressing automaticity of conduction through the tissue.

Second-line treatment for CA-induced arrhythmias. Alkalinization and sodium loading must be attempted before the use of any antiarrhythmic for CA-induced cardiotoxicity.

Magnesium sulfate

 

Prevents calcium influx. Also activates sodium-potassium ATPase, thus affecting sodium and potassium transport across cell membranes, which can facilitate the maintenance of the resting potential. May be of particular use in patients with torsade de pointes type of ventricular tachycardia.

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Anticonvulsant agents

Class Summary

These agents are used to prevent seizures and terminate clinical and electrical seizure activity.

Lorazepam (Ativan)

 

Sedative and anticonvulsant that may be effective in controlling CA-induced agitation or seizures. By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of the CNS, including limbic and reticular formation.

Diazepam (Valium, Diastat)

 

Depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Sedative and anticonvulsant that may be effective in controlling CA-induced agitation or seizures.

Phenobarbital (Luminal)

 

In status epilepticus, achieving therapeutic levels as quickly as possible is important. IV dose may require approximately 15 min to attain peak levels in the brain. If injected continuously until convulsions stop, brain concentrations may continue to rise and can exceed that required to control seizures. Important to use minimal amount required and to wait for anticonvulsant effect to develop before administering a second dose.

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Contributor Information and Disclosures
Author

Derrick Lung, MD, MPH Assistant Clinical Professor, Department of Emergency Medicine, San Francisco General Hospital; Assistant Medical Director, California Poison Control System, San Francisco Division

Derrick Lung, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Jeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children's Medical Center

Disclosure: Received salary from Merck for employment.

Chief Editor

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, Wisconsin Medical Society

Disclosure: Nothing to disclose.

Additional Contributors

Michael E Mullins, MD Assistant Professor, Division of Emergency Medicine, Washington University in St Louis School of Medicine; Attending Physician, Emergency Department, Barnes-Jewish Hospital

Michael E Mullins, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians

Disclosure: Received stock ownership from Johnson & Johnson for none; Received stock ownership from Savient Pharmaceuticals for none.

Acknowledgements

Heidi Connolly, MD Associate Professor of Pediatrics and Psychiatry, University of Rochester School of Medicine and Dentistry; Director, Pediatric Sleep Medicine Services, Strong Sleep Disorders Center

Heidi Connolly, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Christopher I Doty, MD, FACEP, FAAEM Assistant Professor of Emergency Medicine, Residency Program Director, Department of Emergency Medicine, Kings County Hospital Center, State University of New York Downstate Medical Center

Christopher I Doty, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Frank A Maffei, MD, FAAP Associate Professor of Pediatrics, Temple University School of Medicine; Medical Director, Pediatric Intensive Care Unit, Janet Weis Children's Hospital at Geisinger Health System

Frank A Maffei, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Samara Soghoian, MD, MA Clinical Assistant Professor of Emergency Medicine, New York University School of Medicine, Bellevue Hospital Center

Samara Soghoian, MD, MA is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Rashida Y White-McCrimmon, MD Resident Physician, Department of Emergency Medicine, Kings County Hospital Center, State University of New York Downstate Medical Center

Rashida Y White-McCrimmon, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, and Emergency Medicine Residents Association

Disclosure: Nothing to disclose.

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Toxicity, antidepressant. ECG shows the terminal R wave in aVR and the widened QRS complex associated with tricyclic antidepressant (TCA) toxicity.
 
 
 
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