ABC | Volume 110, Nº3, March 2018

Case Report Propafenone Overdose: From Cardiogenic Shock to Brugada Pattern Julio Gil, Bruno Marmelo, Luís Abreu, Hugo Antunes, Luís Ferreira dos Santos, José Costa Cabral Serviço de Cardiologia, Centro Hospitalar Tondela, Viseu - Portugal Mailing Address: Julio Gil • Av. Rei D. Duarte, lote 12, 3ºDto. Postal Code: 3500-643, Viseu - Portugal E-mail: juliogilpereira@gmail.com ; juliogilpereira@gmail.com Manuscript received September 16, 2016; revised manuscript September 30, 2016; accepted November 03, 2016. Keywords Anti-Arrhythmia Agents; Propafenone; Arrhythmias, Cardiac; Calcium Channel Blockers; Toxicity. DOI: 10.5935/abc.20180033 Introduction Propafenone is a class IC antiarrhythmic drug used in the treatment of ventricular and supraventricular arrhythmias. 1-7 It is primarily a potent sodium channel blocker, yet also exhibits beta-blocking and calcium channel blocking activity. 4,6,7 Propafenone is able to induce important ECG changes, namely prolongation of the PR interval, bundle branch block, wide QRS and QT intervals, as well as ventricular tachycardia or bradycardia. 3,4 It may be associated with significant proarrhythmogenic effects, even at therapeutic doses. 2 A fatal overdose on propafenone is usually attributed to conduction abnormalities, leading to asystole or electromechanical dissociation. The authors describe two clinical cases of propafenone intoxication with life-threatening ECG changes, but with a favorable final outcome. Case Report Case 1 Female patient, 44 years old, with no relevant medical history. The patient was brought to the Emergency Room (ER) following voluntary ingestion of 4500mg of propafenone. While being brought to the ER, the patient had a short-lasting seizure, later regaining consciousness. Upon arrival at the ER, she had a Glasgow Coma Scale (GCS) score of 10 (Eye-3, Motor-5, Verbal-2), bradycardic (55bpm) and hypotensive (Blood Pressure [BP] 85/30mmHg). Clinical examination was unremarkable. Gastric lavage was performed, with removal of what seemed to be pill residuals. Blood work revealedmetabolic acidosis. The ECG at admission showed sinus arrhythmia, with right axis deviation, incomplete right bundle branch block (RBBB) and unspecific repolarization changes in DIII, V1 and V2. The PR, QRS and QT intervals were within normal range (Figure 1). BP did not respond to aggressive fluid therapy, thus a dopamine perfusion was started. After approximately an hour of beginning treatment, the patient suffered a tonic‑clonic seizure accompanied by extreme bradycardia and widening of the QRS. Unfortunately, due to the urgency of the situation and the critical state of the patient, these electrical changes could not be recorded through standard 12-lead ECG. She was medicated with atropine and benzodiazepine. This resulted in a comatose state (Glasgow scale of 3), worsening of metabolic acidosis and respiratory failure. The patient was intubated, placed on continuous mechanical ventilation and admitted to the Intensive Care Unit (ICU). Upon admission to the ICU, rhythm strip monitoring revealed atrial fibrillation with occasional sinus activity, along with a widening of the QRS (200 milliseconds) interval. Three hours later, sinus rhythm was restored and QRS interval returned to normal values, with an almost complete disappearance of the RBBB pattern. In the first 6 hours after admission, there was a progressive hemodynamic and clinical stabilization, allowing for a gradual weaning from aminergic and ventilator support. On day two, the patient was conscious and hemodynamically stable. She was discharged after a psychiatric consultation. Case 2 Female patient, 56 years old, with a history of Atrial Fibrillation and major depressive disorder medicated with propafenone 150 mg twice daily and duloxetine 60 mg once daily. The patient was first observed in a small community hospital after voluntarily ingesting 3000mg of propafenone. At that institution, on arrival, the patient was initially fully awake and gastric lavage was begun. However, shortly afterwards, she developed a tonic-clonic seizure, followed by two episodes of cardiac arrest due to extreme bradycardia. Resuscitation was achieved after less than 2 minutes of advanced life support and atropine administration. After ensuring hemodynamic and electrical stability, the patient was transported to a centralized hospital. Upon admission, she was bradycardic (50 bpm), normotensive (BP 139/89 mmHg), and with a GCS score of 14 (Eye 4, Motor 6, Verbal 4). ECG revealed a junctional rhythm, with a type-1 Brugada pattern in V1 to V3 leads (Figure 2). The patient was admitted to the Cardiac Intensive Care Unit for monitoring. After 24 hours of clinical, hemodynamic and electrical stability, a new ECG was performed, revealing sinus rhythm and disappearance of the Brugada pattern. Discussion Propafenone is a Vaughan Williams Class IC antiarrhythmic agent, and thus a potent sodium channel blocker. 1,3,4,6,7 It also exhibits beta-blocking and calcium channel blocking activity. 4,6,7 Nearly 100% of propafenone is absorbed. However, because of a first-pass hepatic elimination effect, its bioavailability is unpredictable. 1,4 Propafenone is metabolized into two major metabolites: 5-hydroxypropafenone and norpropafenone, a process genetically determined by the CYP2D6 enzyme system. 1,4 The propafenone elimination half-time varies depending on whether the patient is a poor or an extensive metabolizer. 1,4 There are several infrequent adverse reactions, such as hematologic (agranulocytosis), 292