Question
A 36-year-old woman is brought to the emergency department 2 hours after taking an unknown quantity of her antidepressant medication. She is drowsy and confused. Examination shows dilated pupils, dry mucous membranes, a heart rate of 128 beats/min and blood pressure of 88/54 mmHg. She subsequently develops a generalized tonic-clonic seizure.
Her ECG shows sinus tachycardia with a QRS duration of 132 ms and prolonged QT interval.
What is the most appropriate immediate specific treatment?
A. Intravenous amiodarone
B. Intravenous sodium bicarbonate
C. Intravenous flumazenil
D. Intravenous metoprolol
E. Intravenous verapamil
Answer
B. Intravenous sodium bicarbonate
Explanation
This is a classic presentation of tricyclic antidepressant (TCA) toxicity. Common implicated drugs include amitriptyline, dosulepin/dothiepin and imipramine.
TCA overdose produces toxicity through several mechanisms, but the most dangerous is blockade of fast myocardial sodium channels. This slows ventricular depolarisation and produces QRS widening, hypotension and potentially life-threatening ventricular arrhythmias.
The combination of reduced consciousness, seizures, anticholinergic features and a broad QRS complex is particularly characteristic.
The ECG is the critical investigation. A QRS duration >100 ms indicates significant sodium-channel blockade and is an important indication for intravenous sodium bicarbonate. A QRS >100 ms is associated with an increased risk of seizures, while marked widening, particularly >160 ms, is associated with a high risk of ventricular arrhythmias.
Intravenous sodium bicarbonate is therefore the treatment of choice in a patient with TCA poisoning and QRS prolongation, ventricular arrhythmia, significant hypotension or metabolic acidosis. It works both by increasing serum pH and by increasing extracellular sodium concentration, thereby reducing TCA binding to cardiac sodium channels.
Treatment is usually given as repeated IV boluses of sodium bicarbonate with close ECG, blood gas and electrolyte monitoring. Therapy is generally titrated to clinical improvement and narrowing of the QRS, while avoiding excessive alkalosis.
Seizures should be treated with benzodiazepines. Hypotension initially requires IV crystalloid and sodium bicarbonate; persistent hypotension may require a vasopressor such as noradrenaline.
Class IA and IC antiarrhythmics should be avoided because they also block sodium channels and can worsen cardiotoxicity. Flumazenil should not be used in suspected TCA or mixed-drug overdose because it can precipitate seizures. Intravenous lipid emulsion may occasionally be considered as rescue therapy in severe refractory cardiovascular toxicity or cardiac arrest after specialist toxicology advice.
Summary for quick exam revision
Tricyclic antidepressant overdose is a potentially fatal poisoning in which neurological and cardiovascular toxicity dominate the clinical picture. Important TCAs include amitriptyline, dosulepin/dothiepin and imipramine. Anticholinergic manifestations include dilated pupils, dry mouth, urinary retention, reduced bowel sounds and tachycardia. CNS toxicity causes agitation, confusion, reduced consciousness and generalized seizures. The most dangerous mechanism is fast sodium-channel blockade in the myocardium, producing delayed ventricular depolarisation, QRS widening, hypotension and ventricular arrhythmias. A 12-lead ECG is therefore one of the most important investigations in suspected TCA overdose. A QRS duration greater than 100 ms indicates significant toxicity and is associated with an increased risk of seizures, while a QRS greater than about 160 ms indicates a particularly high risk of ventricular arrhythmias. Metabolic acidosis increases the amount of free active TCA and aggravates cardiotoxicity, so an arterial or venous blood gas is useful. Intravenous sodium bicarbonate is the key specific treatment when there is QRS widening, ventricular dysrhythmia, significant hypotension or acidosis. Sodium bicarbonate increases serum pH and extracellular sodium concentration, thereby reducing sodium-channel blockade and often narrowing the QRS. Seizures are treated with benzodiazepines. Hypotension is treated with fluids, sodium bicarbonate and, if necessary, a vasopressor such as noradrenaline. Class IA and IC antiarrhythmics should be avoided because additional sodium-channel blockade can worsen the poisoning. Flumazenil should also be avoided because it may precipitate seizures, particularly in mixed overdose. Severe refractory cardiovascular collapse may occasionally require intravenous lipid emulsion with specialist toxicology input. The key exam association is therefore anticholinergic features + seizures + broad QRS after antidepressant overdose → think severe TCA toxicity and give IV sodium bicarbonate.