Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning.

In the present study, we aimed to compare the detoxifying effects of two fat emulsions containing either long-chain triglyceride or a mixture of medium-chain and long-chain triglycerides in the propafenone-poisoned rat model. Rats were randomly divided into 3 groups according to the fat emulsions used: long-chain triglyceride-based fat emulsion (LL) group; medium-chain and long-chain triglyceride-based fat emulsion (ML) group; normal saline (NS) group. Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was added to plasma (3.5 µg/mL) in vitro, mixed with three doses of LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of propafenone was measured. Rats treated with LL exhibited accelerated recovery, characterized by higher blood pressure and heart rate. Rats in both the LL and ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and 60 min). However, rats that received LL showed lower propafenone in myocardial tissue at the end of detoxification treatment. Rats in the ML group had the lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the in vitro experiments, propafenone decreased more dramatically in the LL group compared to the ML group. Long-chain triglyceride fat emulsion had a better effect on treating propafenone poisoning in rats.

Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning

In the present study, we aimed to compare the detoxifying effects of two fat emulsions containing either long-chain triglyceride or a mixture of medium-chain and long-chain triglycerides in the propafenone-poisoned rat model. Rats were randomly divided into 3 groups according to the fat emulsions used: long-chain triglyceride-based fat emulsion (LL) group; medium-chain and long-chain triglyceride-based fat emulsion (ML) group; normal saline (NS) group. Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was added to plasma (3.5 μg/mL) in vitro, mixed with three doses of LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of propafenone was measured. Rats treated with LL exhibited accelerated recovery, characterized by higher blood pressure and heart rate. Rats in both the LL and ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and 60 min). However, rats that received LL showed lower propafenone in myocardial tissue at the end of detoxification treatment. Rats in the ML group had the lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the in vitro experiments, propafenone decreased more dramatically in the LL group compared to the ML group. Long-chain triglyceride fat emulsion had a better effect on treating propafenone poisoning in rats.

Ventricular Tachycardia Induced by Propafenone Intoxication in a Pediatric Patient.

Unintentional poisonings are a global health problem frequently resulting in hospital admissions. Propafenone is a class 1C antiarrhythmic drug used in the second-line management of supraventricular and ventricular arrhythmias and, when unintentionally ingested, can lead to severe and life-threatening poisoning. We describe a case of a 3-year-old male patient unintentionally ingesting 300 mg (20 mg/kg) of propafenone and presenting with ventricular tachycardia with QT prolongation. Two boli of intravenous hypertonic sodium bicarbonate (total amount of 3 mEq/kg), followed by 3-hours continuous infusion of 1 mEq kg h sodium bicarbonate, were able to restore the clinical conditions of the patient. With this case report, we aim to highlight the existing challenge in the therapeutic management of propafenone intoxication that finds intravenous hypertonic bicarbonate to be a useful tool also in pediatric population.

Pediatric extracorporeal cardiopulmonary resuscitation settled in an emergency department for a propafenone intentional intoxication.

The use of drugs in suicide attempts is becoming more and more frequent among adolescents. Intentional intoxication with propafenone is very rare and mainly reported in adults associated with other drugs. The therapeutic approach is symptomatic, since there is no specific antidote for propafenone. We present a pediatric case of intentional ingestion of 1.8 g of propafenone that caused refractory cardiogenic shock. The patient was successfully rescued with extracorporeal cardiopulmonary resuscitation in the emergency department of a secondary level peripheral hospital.

Failure of Intracardiac Pacing After Fatal Propafenone Overdose: A Case Report.

BACKGROUND: Propafenone is a sodium-channel blocker, class IC antiarrhythmic drug, frequently used to manage supraventricular dysrhythmias, especially atrial fibrillation. We report a self mono-intoxication with propafenone. CASE REPORT: A 68-year-old woman presented with a decreased level of consciousness, hypotension, and electrocardiogram showing QRS widening with atrial asystole and extreme bradycardia < 20 beats/min. After initial stabilization with transcutaneous pacing, laboratory findings detected normal electrolyte ranges and metabolic acidosis, and her medical history revealed availability of propafenone due to paroxysmal atrial fibrillation and depressive syndrome, which led to the suspicion of intoxication. Despite intravenous sodium bicarbonate, calcium, norepinephrine, and aggressive fluid replacement (10% glucose with insulin), hemodynamic stability was not achieved. Temporary intracardiac pacing was implanted. However, even with multiple electrode positions, effective capture could not be achieved. At that time, transcutaneous pacing was also ineffective. Consequently, the patient died in refractory asystole due to complete myocardial nonexcitability. The concentration of 5270 ng/mL of propafenone was found in the blood at autopsy, using gas spectrometry-mass chromatography. It is the third highest reported propafenone lethal concentration and the first case in which the myocardial nonexcitability refractory to intracardiac pacing was seen despite normal electrode position in the right ventricle, with failure to achieve the patient's hemodynamic stability. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware of possible propafenone ingestion causing toxicity, which is probably more frequent than previously described, especially because propafenone is widely available due to its use in managing atrial fibrillation, the most common arrhythmia nowadays.

Lethal suicide attempt with a mixed-drug intoxication of metoprolol and propafenone - A first pediatric case report.

INTRODUCTION: The ß1 adrenergic receptor blocker metoprolol is often prescribed together with the antiarrhythmic drug propafenone. Both are metabolized by cytochrome P450 2D6 and propafenone is also an inhibitor of this enzyme. We present a pediatric case showing metoprolol and propafenone intoxication in combination. CASE: A 14-year-old girl was admitted to a local emergency department after ingestion of metoprolol (probably 1g) and propafenone (probably 1.5-3g) in a suicide attempt. She developed cardiogenic shock with cardiac arrest and was fully resuscitated. Veno-arterial femorofemoral extracorporeal membrane oxygenation was started immediately. High serum levels of both drugs were detected approximately 10h after ingestion (2630ng/mL metoprolol and 2500ng/mL propafenone). Other serial samples for the monitoring of the levels of metoprolol and its metabolite alfa-hydroxymetoprolol were obtained between days 2 and 4 after admission. The metoprolol/alfa-hydroxymetoprolol ratio on the 2nd day was 36.1, indicative of a poor metabolizer phenotype. The elimination half-life of metoprolol was prolonged to 13.2h and the clearance decreased by about 70%. The patient condition gradually worsened, brain edema and intracerebral hemorrhage occurred, and on the 6th day, the patient died. CONCLUSION: We document a pediatric case report of death due to a mixed drug overdose of metoprolol and propafenone, along with data regarding serum metoprolol, alfa-hydroxymetoprolol, and propafenone levels.

Brugada syndrome, Brugada phenocopy or none?

Brugada syndrome is a form of inherited arrhythmia syndrome characterized by a distinct ST-segment elevation in the right precordial leads. Brugada phenocopies are clinical entities that present with an electrocardiographic pattern identical to Brugada syndrome and may obey to various clinical conditions. We present a case of a suicidal attempt using a high dose of propafenone causing a Brugada-type electrocardiographic pattern. Is this a Brugada syndrome case, a Brugada phenocopy or something else?

Successful treatment of propafenone-induced cardiac arrest by calcium gluconate.

Propafenone is prescribed for the control of cardiac ventricular arrhythmias. Poisoning from propafenone intoxication is rare, but the survival rate of patients is low. We present a case of a 37-year-old man who developed cardiac arrest due to propafenone intoxication. Cardiopulmonary resuscitation, plasmapheresis, and other medical treatments had no effect on cardiac arrest. After repeated administrations of calcium gluconate, the patient achieved a full recovery. To the best of our knowledge, this is the first case report in which a full recovery from cardiac arrest was achieved by administration of calcium gluconate. We recommend that for patients poisoned by propafenone, close monitoring for decreased blood calcium is important.

Successful treatment of suicide attempt by megadose of propafenone and captopril.

Intoxication caused by propafenone is very rare, and there is no case reported before propafenone and captopril intoxication together. There are few case reports in the literature about intoxication with more than 6 g of propafenone. We present the clinical manifestation and successfully treatment of 9 g of propafenone and 1 g captopril intoxication in an 18-year-old female. An 18-year-old female was brought to the emergency department approximately half an hour after she committed suicide with 30 propafenone tablets, 300 mg each, and 20 captopril tablets, 50 mg each. Her fist electrocardiography (ECG) shows a chaotic ventricular rhythm with a prolonged QRS complex. After fluid and sodium bicarbonate infusion and permanent pacemaker implantation, sinus rhythm was achieved. This case, to our knowledge, is the first in that it describes the successful recovery of a patient who ingested extensively large doses of propafenone (9 g) and captopril (1 g), both of which are known to have severe cardiac side effects.

Overdose of propafenone surreptitiously sold as "Percocet".

BACKGROUND: Drug abuse is a common problem in the United States. Drugs can be acquired in many ways, and can be knowingly or mistakenly misrepresented when sold. Propafenone is an uncommonly encountered class IC antidysrhythmic that is a look-alike for the opioid, oxycodone/acetaminophen 5/325. OBJECTIVE: We report a case of propafenone overdose presenting with generalized tonic-clonic seizure and a widened QRS complex, occurring after the patient had reported ingesting "Percocet®" (Endo Pharmaceuticals, Chadds Ford, PA). CASE REPORT: A 17-year-old boy presented to the emergency department (ED) after a witnessed seizure lasting 2 min. The patient reported having ingested 6 "Percocet®" tablets that he purchased from a classmate. He noted feeling weak and dizzy approximately 3 h after the ingestion, just before the seizure. On arrival in the ED, the patient was awake and alert with a QRS length of 168 ms. A sodium bicarbonate bolus and infusion shortened the QRS length to 90 ms. The patient was discharged the following day with no further complications. The pills were identified as propafenone hydrochloride (HCl) 225-mg tablets. The classmate surreptitiously sold the pills as "Percocet®" due to their similar "512" imprint. CONCLUSIONS: Pharmaceutical drugs are often sold on the street, and often misrepresented. Propafenone HCl 225-mg is an uncommonly encountered pharmaceutical, but is a look-alike for oxycodone/acetaminophen 5/325. An overdose due to propafenone ingestion may present with seizures and a widened QRS complex.

Propafenone overdose: cardiac arrest and full recovery.

Intoxication caused by propafenone is very rare, and there are no known detailed epidemiological studies. We present the clinical manifestation of severe propafenone intoxication,successfully treated in a 17 year-old male. He was brought to the Intensive Care Unit after he had taken 3.0 g propafenone. The main clinical findings included: sudden cardiac arrest, coma, hypotension, left ventricular failure, bradycardia, sinoatrial block, atrioventricular junctional or/and ventricular tachycardia. During the treatment, transient heart pacing was performed and catecholamines were administered by means of continuous intravenous infusion of pressure doses as well as of infusion liquids. Cessation of toxic signs four hours after admission to hospital was observed. This relatively rare, fully symptomatic intoxication with propafenone deserved to be presented due to the drug's common usage in the treatment of dysrhythmia and life-threatening symptoms of overdosing. The course of the disease was dramatic and the patient survived only thanks to quick resuscitation, artificial ventilation, transient heart pacing, acidosis treatment and administration of pressure doses of catecholamines.

Propafenone poisoning--a case report with plasma propafenone concentrations.

Propafenone is an anti-arrhythmic drug used in the management of supraventricular and ventricular arrhythmias. It is metabolised through cytochrome P450 2D6 pathways; the major metabolites possess anti-arrhythmic activity. The cytochrome P450 CYP2D6 is coded by more than 70 alleles resulting in great genetic polymorphism of CYP2D6 isoenzymes, and up to 7% of Caucasian population are poor metabolisers. This case report describes a patient with severe overdose of propafenone who presented with coma, seizures and cardiotoxicity. The patient was managed with intravenous glucagon, hypertonic sodium bicarbonate, hypertonic saline and inotropic support. The propafenone and its 5-hydroxypropafenone (5-OHP) metabolite were measured by high-performance liquid chromatography with ultraviolet detection (no assay was available at the time to measure N-despropyl propafenone concentrations). Toxicological screen showed propafenone concentrations at a maximum of 1.26 mg/L at 9-10 h post-presentation, falling to 0.25 mg/L at 27-28 h post-presentation. No propafenone metabolite 5-OHP was detected in any sample analysed. No antidepressant or analgesic drugs were detected in toxicological screen. Propafenone overdose has been reported to be associated with features of severe cardiovascular and CNS toxicity. Aggressive treatment, meticulous monitoring and supportive care was associated with a good outcome in this case.