{mosimage}BACKGROUND
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What is the diagnosis?
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HINT
Look closely at the QRS and QT intervals and at lead aVR.
Authors:
Suresh Rangarajan, MD,
Department of Internal Medicine-Pediatrics,
Univesity of California San Diego Medical Center
Wayne Whitwam, MD,
Department of Cardiology,
University of California San Diego Medical Center
eMedicine Editors:
Brady Pregerson, MD,
Depts. of Emergency Medicine
Cedars-Sinai Medical Center
Los Angeles, CA
Tri-City Medical Center
Oceanside, CA
Rick G. Kulkarni, MD,
Assistant Professor,
Yale School of Medicine,
Section of Emergency Medicine,
Department of Surgery,
Attending Physician,
Medical Director,
Department of Emergency Services,
Yale-New Haven Hospital, Conn
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Tricyclic antidepressant (TCA) overdose: This case is a classic example of a TCA overdose. In the context of the patient’s clinical presentation, known use of amitriptyline in his medication regimen, and the record of his prior presentation earlier the same day for suicidal ideation and depression, TCA overdose was strongly suspected. The ECG findings, which included a widened QRS complex to 120 msec, a prolonged QT interval at > 500 msec, and a terminal R-wave in lead aVR of > 3mm (see later in the discussion for further explanation of ECG findings), supported the clinical diagnosis. Empiric therapy with sodium bicarbonate was initiated along with intravenous fluid, and the patient’s condition stabilized. He was admitted to the Intensive Care Unit (ICU) for close observation and further management. The laboratory investigations, which included a cerebrospinal fluid analysis to rule out encephalopathy, were unremarkable. The computed tomography (CT) scan of the head was also within normal limits.
Although TCA toxicity is now rare, because of the large percentage of patients on alternative antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs), TCA toxicity should still be considered in cases of suspected medication overdose, especially for patients with a history of depression and/or tricyclic use for chronic pain. The most commonly prescribed TCA medications include amitriptyline, desipramine, imipramine, nortriptyline, doxepin, and clomipramine.
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A patient with TCA toxicity may initially present with an altered mental status ranging from confusion to coma and seizures. The primary therapeutic mechanism of action of TCAs is the inhibition of catecholamine reuptake; however, tricyclics are also potent anticholinergic agents and act to block sodium channels as well as alpha-adrenergic receptors. All of these four mechanisms of action can contribute to toxicity, with anticholinergic activity accounting for most of the effects, which manifest as dilated pupils, dry mucous membranes, altered mental status, tachycardia, pyrexia, dry skin, and decreased bowel sounds. Victims may also be hypotensive from the depletion of catecholamines and the alpha-receptor blockade. Specific mention of the effect of TCA medications on the cardiac conduction system is warranted. The changes noted on ECGs are primarily through the blockade of the fast sodium channels, resulting in a prolongation of the QRS interval (or phase 0) of the action potential to a clinically significant duration of greater than 100 ms. Phase 3 of the action potential is also slowed, resulting in a prolongation of the QT interval. Typical findings also include the development of a terminal 40ms rightward axis between 120 and 270 degrees, leading to a clinically significant terminal upward deflection in lead aVR greater than 3 mm and an associated R/S ratio in aVR greater than 0.7. Corresponding terminal deep slurred S waves in leads I and aVL may also be noted. Severe cardiac toxicity may lead to various heart blocks, asystole, ineffective myocardial contractility, and other malignant rhythms, including ventricular tachycardia and torsades de pointes.
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Treatment of TCA toxicity should focus on cardiovascular status since arrhythmia and hypotension are the leading causes of mortality in cases of TCA overdose. Sodium bicarbonate is considered the antidote of choice, as both the sodium content and the effect on serum pH are thought to play important roles. A starting dose of 2 ampules is appropriate if there is evidence of electrocardiographic toxicity; thereafter, additional boluses and a sodium bicarbonate drip should be administered, with the goal of keeping the QRS interval less than 100 ms and the serum pH between 7.45 and 7.55. If this fails to prevent arrhythmia, the additional agents of choice are lidocaine or phenytoin and magnesium. Amiodarone, procainamide, and other agents that may result in further prolongation of the QT interval should be avoided. Hypotension refractory to sodium bicarbonate and intravenous fluids may require the administration of vasopressors; norepinephrine is the preferred agent. If seizures occur, they may be treated with benzodiazepines.
In addition to specific therapy for the cardiovascular effects of TCA overdose, the basics of overdose management should be considered, including airway protection for altered mental status or seizures, gut decontamination with activated charcoal, testing for other life-threatening coingestants (such as aspirin and acetaminophen), and consultation with psychiatric services and poison control. As an aside, an important point regarding the administration of activated charcoal is that its effect diminishes with time and is likely insignificant after 4 hours post ingestion; the risk of aspiration may outweigh its benefit in a patient who is already showing signs of toxicity, especially in an individual with a depressed or worsening mental status and a potentially unprotected airway. After initial stabilization, most symptomatic tricyclic overdoses should be monitored in the ICU. It was subsequently discovered from the patient’s records that he had been dispensed 240 tablets of 25 mg amitriptyline for his back pain 6 weeks prior to the current presentation, and the patient eventually admitted to ingesting 100 of those tablets a few hours before his second visit. The changes seen on the initial electrocardiogram normalized on the follow-up ECG obtained 3 days later (see Image 2), and the patient was eventually discharged to an inpatient psychiatric facility for further therapy.
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References:
* Harrigan RA, Brady WJ. ECG abnormalities in tricyclic antidepressant ingestion. Am J Emerg Med 1999 Jul; 17(4):387-93. [MEDLINE: 10452441]
* Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev 2005; 24(4):205-14. [MEDLINE: 16390222]
* Pentel PR, Benowitz NL. Tricyclic antidepressant poisoning. Management of arrhythmias. Med Toxicol 1986 Mar-Apr; 1(2):101-21. [MEDLINE: 3784839]
