A Tissue Distribution Study of Propafenone in an Intentional Fatal Poisoning Case.

Propafenone (PPF) belongs to the class 1C antiarrhythmics and can cause electrocardiogram-associated adverse/toxic effects. Cases of PPF intoxication are rarely investigated. We developed a novel and selective GC-MS/MS method for the determination of PPF and its tissue distribution in an intentional fatal poisoning case, which is applicable to PPF quantification in the range of therapeutic to lethal concentrations in complex post-mortem samples. A simple and effective sample pretreatment was applied to all analyzed samples. PPF was determined without the need for dilution, even in highly complex samples containing a wide range of analyte concentrations. Quantification was performed using the standard addition method, developed and validated according to the ICH M10 guidelines. The obtained results indicated that the PPF concentration in the serum from blood taken while alive, before therapy, was the highest ever reported in the literature. Despite the intensive therapy after the patients' admission, the PPF concentrations in the lungs, spleen, femoral blood and cardiac blood were fatal or abnormally high. On the other hand, the concentrations in the liver and skeletal muscle were lower or approximately the same as observed in cases with therapeutic doses. To the best of our knowledge, the distribution of PPF has not been investigated in fatal intoxication cases and can be helpful in clinical or forensic toxicology.

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.

A somnolent woman in her fifties with acute circulatory failure. / En somnolent kvinne i 50-årene med akutt sirkulasjonssvikt.

BACKGROUND: A woman in her fifties was admitted to hospital with decreased awareness and circulatory failure. She had been treated with left atrial cryoablation a few weeks before admission and had been cardioverted a few days after the procedure because of relapse of atrial fibrillation. CASE PRESENTATION: On admission, the patient had systolic blood pressure of 80 mm Hg and an ECG with broad QRS-complexes at 380 ms. We suspected intoxication and she was intubated to administer activated charcoal after gastric lavage. She was cardiovascularly unstable and in need of intravenous infusion of noradrenaline and adrenaline. Further investigations at her home suggested that she had poisoned herself with 4-5 g flecainide, 0.3 g oxazepam and 0.5 g meclizine. After administration of 500 mmol sodium bicarbonate and 5 mmol calcium chloride, the QRS complexes narrowed temporarily. On day 2, due to sustained bradycardia and hypotension despite receiving adrenergic medications, a temporary pacemaker was implanted, leading to improved heart rate and blood pressure. She experienced several complications including hypertensive pulmonary oedema, atrial fibrillation, extensively prolonged QT interval because of polypharmacy and Takotsubo cardiomyopathy. She was discharged from the hospital in good health on day 17. At a follow-up visit at the outpatient clinic 12 weeks later, cardiac function had normalised. The QT interval was now normal; however, there were persistent T-wave inversions in leads I, aVL and V4-6. INTERPRETATION: Flecainide blocks sodium channels in cardiomyocytes. Intoxication with flecainide is rare, with mortality rates of about 10 %. Sodium bicarbonate in larger doses has been reported to stabilise patients with flecainide intoxication due to modification of the binding of flecainide to sodium receptors in cardiomyocytes, and due to alkalisation which makes flecainide detach from sodium receptors. Our patient had a temporary effect with narrowing of QRS complexes after receiving sodium bicarbonate. She also showed a beneficial effect from implantation of a temporary pacemaker, although earlier case reports have described problems with high thresholds and capture failure.

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.

Pilsicainide Poisoning: An Autopsy Case and Review of Literature.

We describe an autopsy case of fatal poisoning due to accidental overdose of pilsicainide, which is a Vaughan Williams class IC antiarrhythmic drug (a pure sodium channel blocker). A man in his 50s was found dead in his home at approximately noon. He had ischemic heart disease and insomnia, and had previously demonstrated improper prescription drug adherence. The autopsy revealed old coronary artery bypass grafting and mild fibrosis of myocardium, but no acute myocardial infarction was found in microscopic examination. Toxicological analysis also identified a high blood concentration of pilsicainide (femoral vein blood, 14.9 µg/mL), more than 15 times higher than reported therapeutic levels. The blood concentrations of other drugs were at therapeutic levels, and no alcohol was detected. We concluded that the cause of death was pilsicainide poisoning, based on the results of the autopsy and the toxicological examination. This is the first autopsy report of fatal poisoning due to pilsicainide as a single agent.

[Fatal flecainide intoxication in a 17-year-old girl]. / Tödliche Flecainidintoxikation eines 17-jährigen Mädchens.

A 17-year-old girl was found vomiting and somnolent at home and was taken to a hospital. The girl initially presented with ventricular tachycardia with broad QRS complexes which was very difficult to control. During the course a subsequent cardiogenic shock developed and despite exhaustion of all therapeutic options the fatal outcome could not be averted. The medicolegal autopsy revealed no evidence of any form of violence but the signs of medical treatment. Furthermore, no pathology of internal organs was detected. The toxicological analyses revealed a lethal intoxication with flecainide as the cause of death. The investigations of the police indicated that the girl took flecainide in suicidal intention.

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?

Massive diltiazem and metoprolol overdose rescued with extracorporeal life support.

The management of overdoses of cardioactive medications in the emergency department can be challenging. The reversal of severe toxicity from one or more types of cardioactive medication may fail maximal medical therapies and require extreme invasive measures such as transvenous cardiac pacing and extracorporeal life support. We present a case of massive diltiazem and metoprolol overdose refractory to maximal medical therapy, including intravenous calcium, glucagon, vasopressors, high dose insulin, and lipid emulsion. The patient experienced refractory bradydysrhythmia that responded only to transvenous pacing. Extracorporeal life support was initiated and resulted in successful organ perfusion and complete recovery of the patient. This case highlights the potential utility of extracorporeal life support in cases of severe toxicity due to multiple cardioactive medications.

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.

When potion becomes poison! A case report of flecainide toxicity.

We report a 48-day-old female infant, who developed cardiac conduction abnormalities and seizures secondary to supratherapeutic doses of oral flecainide. Flecainide was started in this infant for treatment of supraventricular tachycardia. The drug was withdrawn with successful normalization of the QRS complex and no further recurrence of seizures. The Naranjo probability score for adverse drug reaction was 8, making the causality "probable." The case restates an important message that physicians should be aware of the side effects of the drugs that they prescribe, especially of those drugs which have a narrow therapeutic window.

Unusual digoxin toxicity with myocardial injury.

A 38-year-old healthy male presented with vomiting and profuse diarrhea, associated with blurry and yellow coloration of the vision (xanthopsia). Laboratory workup was unremarkable, except for hyperkalemia (K 5.2 mEq/L) and mildly elevated troponin level 0.11 ng/mL (cut-off value 0.08). An electrocardiogram showed sinus bradycardia with deep scooping of the T waves. Although the patient denied intake of any drugs, herbs, consumption of plants, a digoxin level was drawn and was significantly elevated >5ng/mL (therapeutic range 0.8-2.0). Further questioning revealed that the patient was a pharmacist mixing raw material to fabricate medication, and that he could have incidentally ingested contaminated water. His symptoms improved with parallel improvement in the electrocardiogram T wave abnormalities. An echocardiogram was normal. The positive troponin was felt to be secondary to severe digoxin toxicity. Review of the literature however showed no report of elevated troponin in the setting of digoxin toxicity.

Lipid emulsion therapy given intraosseously in massive verapamil overdose.

Intravenous fat emulsion (IFE) therapy has been widely used in the emergency department (ED) for treating various medication overdoses. The standard recommended route to administer IFE therapy is intravenously through a peripheral or central vein. No reports of intraosseous (IO) administration in humans could be found in the literature after a brief search. We report of a patient emergently receiving IFE through the IO route. A 24-year-old woman presented to ED after a massive deliberate verapamil overdose. A decision was then made to start both vasopressors and 20% IFE therapy. Central access was established, and a norepinephrine drip was started. Intravenous fat emulsion was to be started, but peripheral access was lost at that time and not able to be reestablished. An IO line was then placed without difficulty in the left proximal tibia using an EZ-IO system. Approximately half way during the bolus administration, the intravenous pump began to alarm that the infusion was not flowing adequately. At this point, peripheral access was obtained, and IFE infusion was moved to that site. We believe that this is the first report of IFE administered via the IO route in a human. This case report illustrates a novel way of administering IFE therapy in an emergency situation where intravenous access may be difficult to obtain.

Successful treatment of flecainide-induced cardiac arrest with extracorporeal membrane oxygenation in the ED.

Flecainide is a class Ic antidysrhythmic agent used to prevent and treat tachydysrhythmias. Flecainide toxicity primarily causes cardiovascular and neurologic effects through sodium-channel blockade. There is scant evidence to support specific management, and recommended therapies have been extrapolated from management of other sodium-channel blocking drugs. Traditionally, these therapies have consisted of intravenous fluids, sodium bicarbonate, vasopressors, and cardiac pacing. Novel therapies include intravenous fat emulsion and venoarterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old woman ingested her husband's flecainide and presented to the emergency department (ED) in profound shock with a wide complex bradydysrhythmia. Despite aggressive medical therapy including sodium bicarbonate, vasopressors, cardiac pacing, and intravenous fat emulsion, her condition deteriorated and she developed pulseless electrical activity (PEA) cardiac arrest refractory to standard resuscitation. Venoarterial extracorporeal membrane oxygenation was initiated in the ED, and the patient remained comatose and critically ill in the intensive care unit. Her hemodynamics and mental status recovered, but she had compartment syndrome in her left leg requiring fasciotomy. She was discontinued from VA-ECMO on hospital day 5, extubated on hospital day 6, and discharged home with excellent neurologic recovery on hospital day 19. Intravenous fat emulsion is thought to sequester the offending agent in a plasma lipid "sink," alter ion channel permeability, and/or modify fatty acid utilization by the myocardium. The quality of evidence for intravenous fat emulsion is generally low. Venoarterial extracorporeal membrane oxygenation was used in this patient to restore organ perfusion and allow intrinsic drug metabolism and elimination. Venoarterial extracorporeal membrane oxygenation should be strongly considered for refractory shock and/or cardiac arrest secondary to flecainide toxicity.

Life-threatening flecainide overdose treated with intralipid and extracorporeal membrane oxygenation.

Flecainide is a Class Ic antiarrythmic agent associated with adverse events due to its pro-arrythmic effects. We report the case of a 33-year-old female presenting in cardiac arrest after a flecainide overdose treated with intravenous fat emulsion (IFE), sodium bicarbonate (NaHCO3), and extracorporeal membrane oxygenation (ECMO). This case reviews the pathophysiology and management of flecainide toxicity including novel strategies of IFE and ECMO.

Intravenous lipid emulsion in the emergency department: a systematic review of recent literature.

BACKGROUND: Intravenous lipid emulsion (ILE) has been broadly attempted in the resuscitation of neurologic and cardiac toxic drug overdoses, however, the role of ILE in the emergency department is poorly defined. OBJECTIVE: This review aims to identify recent literature on the use of ILE in humans as an antidote and to familiarize emergency providers with the indications, availability, dosing recommendations, and adverse reactions associated with ILE use. METHODS: A systemic literature search of MEDLINE, EMBASE, and major toxicology conference abstracts was performed for human cases using ILE as an antidote with documented clinical outcomes through January 2014. RESULTS: Ninety-four published articles and 40 conference abstracts were identified, 85% of which had positive outcomes. The most common indication for ILE was for local anesthetic systemic toxicity (LAST). The most common nonlocal anesthetic xenobiotics were tricyclic-antidepressants and verapamil. DISCUSSION: No standard of care is defined for the use of ILE, although the American Heart Association recommends use in LAST, and the American College of Medical Toxicology recommends consideration for circumstances of hemodynamic instability resultant from lipid-soluble xenobiotics. ILE should be administered per American Society of Regional Anesthesia and Pain Medicine dosing recommendations. Laboratory interference, pancreatitis, respiratory distress syndrome, and interference with vasopressors should be considered as risks but are uncommon. CONCLUSIONS: In the setting of severe hemodynamic compromise by lipid-soluble xenobiotics, ILE may be considered for resuscitation by emergency physicians. As such, ILE may be stocked in emergency departments in close proximity to resuscitation rooms and areas where local nerve blocks are performed.

[A CASE OF FLECAINIDE INTOXICATION]. / Intoxication par flécaïnide. Observation d'un cas et revue de la litérature.

Flecainide acetate is an antiarrhythmic agent commonly used in clinical practice, in particular, for the treatment of supraventricular tachycardias. We report a rare case of voluntary poisoning by flecainide. The patient was successfully resuscitated.A review of the literature related to this type of intoxication is presented.

Flecainide overdose-induced wide-complex tachyarrhythmia treated with sodium bicarbonate infusion.

Flecainide is a medication used to treat supraventricular and ventricular tachyarrhythmias. Cases of overdoses are rare, however, can lead to significant cardiac effects. In previous cases of flecainide toxicity, treatment with sodium bicarbonate, intravenous lipid emulsion and amiodarone have been reported to be effective in preventing cardiovascular collapse and reestablishing baseline rhythm. Here, we present a case of a man in his 40s presented with flecainide overdose with wide-complex tachycardia that was treated with intravenous sodium bicarbonate following failure of amiodarone to normalise QRS interval.

A life-threatening flecainide overdose treated with intravenous fat emulsion.

Flecainide is a Vaughan Williams Class Ic antidysrhythmic associated with PR, QRS, and QTc prolongation on the electrocardiogram and development of life-threatening cardiac toxicity in overdose. The cornerstone of treatment is fluid resuscitation and the administration of magnesium and sodium bicarbonate. We report a case of flecainide overdose associated with life-threatening hemodynamic compromise successfully treated with intravenous fat emulsion (IFE) therapy. IFE should be considered as a novel adjunctive therapy in patients with life-threatening toxicity following flecainide overdose.

A case of near-fatal flecainide overdose in a neonate successfully treated with sodium bicarbonate.

BACKGROUND: Flecainide is a class IC antidysrhythmic primarily indicated for ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC antidysrhythmic overdose has a reported mortality of 22%, and death results from dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide overdose in an 18-day-old treated successfully with sodium bicarbonate. CASE REPORT: An 18-day-old, 2 weeks premature, 4-kg boy developed persistently high heart rates (220-240 beats/min) and electrocardiographic changes consistent with SVT. There was minimal response to vagal maneuvers, adenosine, and esmolol, and a transthoracic echocardiogram showed no underlying structural abnormality. The patient was then started on flecainide 4 mg orally every 8 h (Q8h). After the fourth dose he developed lethargy, cold clammy skin, and a heart rate of 40 beats/min with no palpable pulse. The patient was given 0.1 mg of atropine intravenously, with an increase of the heart rate to 160 beats/min. The child's cardiac monitor revealed a wide-complex tachycardia with left bundle branch morphology, with associated pallor and poor capillary refill. Sodium bicarbonate was administered intravenously due to suspected flecainide toxicity. Approximately 5 min after intravenous administration of 10 mEq of 8.4% sodium bicarbonate twice, his rhythm converted to a narrow-complex tachycardia. A serum flecainide concentration was 1360 µg/L (therapeutic, 200-1000 µg/L) drawn 1 h before the cardiac arrest. It was later discovered that a twofold dosing error occurred: the patient received 8 mg Q8h instead of 4 mg Q8h for four doses. CONCLUSION: Flecainide toxicity in children is rare, especially in neonates. It is important for clinicians to be able to identify and treat this uncommon poisoning.