Chapter 7. Toxidromes
A 36-year-old woman presents to emergency department (ED). Her vitals on arrival are heart rate of 135 bpm, blood pressure of 108/60 mm Hg, respiratory rate of 10 breaths/min, and oxygen saturation of 88%. She is drowsy and oriented to self only, with pupillary dilation, marked dysarthria, myoclonus, 4+ reflexes throughout, and ataxia on neurologic exam. She has dry mucous membranes and axillae and diminished bowel sounds and a full bladder on general exam. She was last seen normal 3 hours prior. During her initial evaluation in the ED, she has a generalized tonic-clonic seizure that lasts 45 seconds. The patient is intubated in the ED; blood is sent for toxicology, and an electrocardiogram (ECG) is obtained. This reveals a heart rate of 135 bpm, right axis deviation (125°) as evidenced by terminal R wave in lead aVR, PR prolongation, and widened QRS interval (>100 milliseconds) with premature ventricular beats. What is the next best step in treatment?
D. Physostigmine salicylate
C. This patient’s presentation is consistent with tricyclic antidepressant (TCA) toxicity. TCA-induced cardiotoxicity is the most important factor contributing to patient mortality. TCAs cause inhibition of sodium influx through voltage-gated sodium channels. Inhibition of fast sodium channels in His-Purkinje cells leads to delayed depolarization and conduction abnormalities. This impaired sodium entry induces decreased contractility. Sodium blockade results in prolongation of phase 0 of the action potential, and the effects become more pronounced with rapid heart rate, hyponatremia, and acidosis. ECG changes caused by sodium channel blockade include PR and QRS interval prolongation, and right axis deviation may identify patients at high risk for severe toxicity. A terminal right axis deviation >120° and widened QRS interval >100 milliseconds are indications to pursue either sodium bicarbonate therapy or mechanical ventilation–induced respiratory alkalosis. Sodium channel blockade can be overcome by serum alkalization and/or increased serum sodium concentrations via infusion of intravenous (IV) sodium bicarbonate. The rapid influx of sodium promotes release of intracellular calcium stores and improves myocardial contractility.
TCAs have a large volume of distribution and are highly lipophilic. Half-life ranges from 24 to 48 hours, and elimination occurs by hepatic metabolism. Only 1% to 2% of the total body burden of TCAs is found in the blood. Thus, hemodialysis or forced diuresis is unlikely to work.
TCAs are competitive inhibitors of acetylcholine at both central and peripheral muscarinic receptors. Physostigmine is an acetylcholinesterase inhibitor and can reverse antimuscarinic effects and thus has historically been used to reverse TCA effects. The antimuscarinic clinical manifestations are not directly responsible for TCA-related major toxicity or deaths and do not require specific therapy other ...