Flecainide toxicity—treatment with intravenous fat emulsion and extra corporeal life support

Keywords::

• Extracorporeal circulation
• cardiac -assist device flecainide
• intravenous fat emulsion

A 52-year-old female with history of paroxysmal atrial fibrillation, Gitelman Syndrome with hypokalemia and depression was admitted following an out-of-hospital cardiac arrest. The patient was found unresponsive after an argument with her son earlier in the day. On arrival of paramedics, a pulse was present and she was spontaneously breathing. EKG showed a wide QRS complex and profound bradycardia for which she was externally paced. Subsequently, she had pulseless electrical activity, with return of spontaneous circulation after 10 min of cardiopulmonary resuscitation. She was emergently intubated to protect her airway. She was afebrile, tachycardic, hypotensive with blood pressure of 90/55 mm Hg on vasopressors. On general examination, the patient was toxic, appearing with constricted pupils. Cardio-pulmonary examination was normal and she was noted to have intermittent seizure-like jerking movements. Laboratory work was significant for severe hypokalemia (1.7 mmol/l), bicarbonate of 16 mmol/l and lactic acid level of 10 mmol/l. Cardiac enzymes were within normal limits and flecainide level was 4.13 ug/ml (reference range: 0.2–1.0 ug/ml). Urine toxicology was negative for salicylate and acetaminophen. The patient was given bicarbonate, intravenous fat emulsion (IFE) and activated charcoal in the emergency room. After consultation with cardiac surgery and critical care medicine, a decision to proceed with extra-corporeal life support (ECLS) was taken in order to provide hemodynamic support. ECLS was initiated after femoral artery-femoral vein cut down was achieved. Patient's hemodynamics and rhythm stabilized within a few hours. ECLS was eventually weaned off over the next 24 h. The patient made a remarkable recovery and she was discharged home with cerebral performance category (CPC) scale 1 (1).

Flecainide is a Vaughan-Williams Class IC anti-arrhythmic used in the treatment of supraventricular arrhythmias (2). Intoxication with IC anti-arrhythmics has higher mortality (22.5%) compared to other drug overdoses (3). Severe flecainide overdose is associated with rapid onset of hypotension and cardiac arrhythmias and is frequently fatal (10%) (3). It acts by blocking sodium and potassium channels especially in the cardiomyocytes and the conduction system. Flecainide has high oral bioavailability, high volume of distribution, short distribution half-life (10 min) and long/variable elimination half-life (7–23 h), which makes the treatment of overdose challenging (4). Nausea and vomiting are the initial symptoms that can occur within 30 min of ingestion, with serious cardiac conduction disturbances (bradyarrhythmias, torsade de pointes, ventricular tachyarrhythmias and asystole), being manifest between 30 and 120 min (3,5) resulting in hypotension, poor organ perfusion and hemodynamic instability. Although various treatment modalities have been proposed—including gastric decontamination with activated charcoal, hemoperfusion, hemodialysis, hypertonic saline solution and sodium bicarbonate, (5–7) there are no definitive guidelines for management. IFE has been used successfully for cardiotoxicity from local anesthetics, but there is conflicting evidence for its use as primary antidote for other cardiotoxic drug poisoning (8,9). The use of IFE as an antidote for myocardium-poisoning drugs such as flecainide is based on the ‘lipid-sink theory’, i.e. adding large quantities of lipids to the blood ‘repartitions’ the drug away from the site of toxicity and into the blood (8). Cardiopulmonary bypass (CPB) has been used for treatment of other poisoning in the past (10,11) and is now being considered for the treatment of severe flecainide poisoning. ECLS provides respiratory support and crucially also maintains cardiac output, preventing end organ damage and restoring vital organ perfusion, thereby enabling renal drug elimination, hepatic drug metabolism and drug redistribution. The length of the ECLS support may be determined by serum flecainide level and cardiac stability. Over the last two decades, four cases have been reported to use ECLS with varying results (Table I). To our knowledge, we present the first case of flecainide toxicity successfully treated with both IFE and ECLS.

Table I. Characteristics of Patients with Flecainide Toxicity Treated with Extra-Corporeal Life Support.

Study (ref.)	Year	Age (years)	Sex	GCS	Initial BP	Initial HR	Flecainide level	Time to presentation	ECLS onset	ECLS duration	Complications	Outcome
Yasui et al. (12)	1997	20	F	N/A	Could not detect	40	5.45 Ug/ml	1.5 h	2 h	10 h	Persistent hemorrhage at cannulation site	Died
Corkeron et al. (13)	1999	20	F	3	60/30	N/A	I: 3000–4000 mg	15 min	5 h	30 h	Coagulopathy Femoral nerve palsy Femoral DVT	Survived
Auzinger et al. (14)	2001	30	M	3	Pulseless	20–30	I: 6000 mg 43.3 Umol/l (20 520 ng/ml)	1 h	3 h	26 h	Coagulopathy/DIC Retroperitoneal hemorrhage	Survived
Vivien et al. (15)	2010	40	F	6	70/50	30	I: 12 000 mg	10 h	N/A	48 h	N/A	Died, ECLS support for organ harvest
Sivalingam et al.	2013	52	F	N/A	80/40	30	4.13 ug/ml	3 h	3 h	24 h	None	Survived

BP, blood pressure; DIC, disseminated intravascular coagulation; DVT, deep vein thrombosis; ECLS, extra-corporeal life support; GCS, Glasgow coma scale; HR, heart rate; I, ingested quantity; N/A, not available.

In summary, our case highlights the potential use of IFE and utility of CPB/ ECLS in the treatment of severe flecainide overdose with an aim to provide hemodynamic support while redistributing the toxic agent away from the heart.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.