[Flecainid intoxication: Evolution, complications and care of]. / Intoxication volontaire à la flecaïnide : évolution, complications et prise en charge.

This report presents the case of a young man of 24 years old with Asperger syndrome who ingest quantities of medication whose flecainide. Resume of his stay in intensive care unit, notably serious adverse effect which ventricular tachycardia with membrane stabilizing effect and lengthening of stay in intensive care unit. Study of literature of different take care already published, with notion of mid-term leaching of flecainide which were ingest days before, at different levels all over the world.

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.

[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.

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.

Brugada Pattern Caused by a Flecainide Overdose.

BACKGROUND: Brugada pattern can be found on the electrocardiogram (ECG) of patients with altered mental status, usually with fever or drug intoxication. Diagnosis remains challenging, because the ECG changes are dynamic and variable. In addition, triggers are not always clearly identified. In patients with atrial fibrillation (AF), the use of class IC antidysrhythmic drugs can unmask a Brugada pattern on the ECG, especially if combined with other medications acting on sodium channels. CASE REPORT: A 62-year-old man with a medical history of AF was admitted to our emergency department for altered mental status. The ECG at the time of admission showed a Brugada pattern, triggered by a flecainide overdose (about 1 g), in association with an unknown dose of lamotrigine and quetiapine. After discontinuation of all medications, the Brugada pattern disappeared and his ECG showed no abnormalities. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients with AF, the use of class IC antidysrhythmic drugs, if overdosed, can trigger a Brugada ECG pattern, and therefore it can increase the risk for malignant dysrhythmias. It is important to provide, to all patients with a Brugada ECG pattern, a list of drugs to avoid, and to underline the synergistic interplay between drugs, taking into consideration all patients' comorbidities.

Attempted suicide by Flécainide overdose: A case report.

Class Ic antiarrythmic overdose is associated with a relatively high mortality. We presenta case report regarding a suicidal intoxication of an 18-year old female with a medical history of Wolff-Parkinson-White syndrome. The preliminary examination highlighted a profound cardiovascular collapse. The electrocardiogram showed a PR interval extended to 360 ms. The QRS complexes were enlarged to 360 ms with a right bundle brunch block appearance associated with left posterior hemibloc. There were repolarization abnormalities such as elevation of the J-point, convex ST segment and biphasic T wave in the right precordial leads ("Brugada-Like ECG pattern"). Sodium bicarbonate was administered. A rapid decrease in the duration of the QRS complexes was noted as well as a slowing of the heart rate. The electrocardiogram aspect on the 4th day showed the reappearance of the ventricular pre-excitation. The severity and lethal potential of Flecainide poisoning are linked to the cardiotoxic effects of these molecules. The prognosis remains poor despite progress in intensive care procedures.

[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.

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.

Lesson of the month 1: Acute flecainide overdose and the potential utility of lipid emulsion therapy.

Lipid-emulsion therapy (Intralipid®) has been advocated as a potential treatment for the management of cardio-toxicity arising from lipid-soluble drugs, particularly those acting upon sodium channels. This, on the basis of a number of ex vivo studies and animal models, suggests that partitioning a drug into lipid could alter its pharmacokinetics and result in significant clinical improvements. Its subsequent use in clinical case series has been seen as confirmation of this mechanism of action. While there are undoubtedly instances where lipid emulsion therapy has been associated with a desirable outcome in humans, as described in this case report, clinicians are reminded that they should not attribute causality, on this basis alone.

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.

Regulation of SCN5A by microRNAs: miR-219 modulates SCN5A transcript expression and the effects of flecainide intoxication in mice.

BACKGROUND: The human cardiac action potential in atrial and ventricular cells is initiated by a fast-activating, fast-inactivating sodium current generated by the SCN5A/Nav1.5 channel in association with its ß1/SCN1B subunit. The role of Nav1.5 in the etiology of many cardiac diseases strongly suggests that proper regulation of cell biology and function of the channel is critical for normal cardiac function. Hence, numerous recent studies have focused on the regulatory mechanisms of Nav1.5 biosynthetic and degradation processes as well as its subcellular localization. OBJECTIVE: The purpose of this study was to investigate the role of microRNAs in the Scn5a/Nav1.5 posttranscriptional regulation. METHODS: Quantitative polymerase chain reaction, immunohistochemical and electrophysiological measurements of distinct microRNA gain-of-function experiments in cardiomyocytes for the assessment of Scn5a expression. RESULTS: Functional studies of HL-1 cardiomyocytes and luciferase assays in fibroblasts demonstrate that Scn5a is directly (miR-98, miR-106, miR-200, and miR-219) and indirectly (miR-125 and miR-153) regulated by multiple microRNAs displaying distinct time-dependent profiles. Cotransfection experiments demonstrated that miR-219 and miR-200 have independent opposite effects on Scn5a expression modulation. Of all the microRNAs studied, only miR-219 increases Scn5a expression levels, leading to altered contraction rhythm of HL-1 cardiomyocytes. Electrophysiological analyses in HL-1 cells revealed that miR-219 increases the sodium current. In vivo administration of miR-219 does not alter normal cardiac rhythm, but abolishes some of the effects of flecainide intoxication in mice, particularly QRS prolongation. CONCLUSION: This study demonstrates the involvement of multiple microRNAs in the regulation of Scn5a. Particularly, miR-219 increases Scn5a/Nav1.5 transcript and protein expression. Our data suggest that microRNAs, such as miR-219, constitute a promising therapeutical tool to treat sodium cardiac arrhythmias.

Irreversible third-degree heart block and pacemaker implant in a case of flecainide toxicity.

An 82-year-old white woman was seen in the emergency department (ED) after ingesting 400 mg of flecainide in an attempt to treat an episode of dizziness and palpitations that occurred while she was gardening. Consequently, she developed bradycardia, hypotension, and complete heart block. In addition to supportive care, she also received sodium bicarbonate, atropine, calcium gluconate, and dopamine in an effort to reverse the heart block. The patient continued to remain in heart block and was sent to the cardiac catheterization laboratory for placement of an external pacing wire, which stabilized the patient. After further evaluation, a permanent pacemaker was implanted during her admission. External pacing wires may be useful in the treatment of complete heart block in cases of flecainide poisoning when a patient is unresponsive to drug therapy provided in the ED.

Arrhythmogenic effect of flecainide toxicity.

Flecainide is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia. In overdose cases, flecainide can induce life treating ventricular arrhythmias and cardiogenic shock. We report the case of a 72-year-old woman admitted to our intensive care unit for a regular monomorphic wide complex tachycardia (QRS duration 240 ms, right bundle branch block and superior axis morphology) without apparent P waves. Clinical examination showed slight left congestive heart failure signs without cardiogenic shock. An intravenous bolus of 10 mg adenosine 5'-triphosphate (ATP) was ineffective to stop the tachycardia. The diagnosis of ventricular tachycardia induced by flecainide overdose was considered. 500 mL of intravenous 84‰ sodium bicarbonate was administrated. The patient's QRS narrowed immediately and 12-lead ECG showed sinus rhythm. Blood samples confirmed the flecainide overdose and the clinical status progressively improved.