Managing cardiovascular collapse in severe flecainide overdose without recourse to extracorporeal therapy

Abstract

Flecainide overdose can rapidly result in profound cardiovascular collapse, and is associated with a relatively high mortality. A case is described where a woman with major toxicity and high serum levels was managed without recourse to invasive modalities such as cardiopulmonary bypass or extracorporeal therapies. Hypertonic sodium bicarbonate is recognized as effective therapy for hypotension and arrhythmias. More recent case reports have concentrated on the use of cardiopulmonary bypass. In this report and other reports describing successful resuscitation, the total dose of sodium bicarbonate is conspicuously higher than in reports describing extracorporeal interventions. Sodium bicarbonate should be given early in the resuscitation, and re-administered as frequently as required, targeting an alkaline pH and improved cardiac output, while accepting hypernatraemia. This case demonstrates the maxim that the correct dose of hypertonic sodium bicarbonate is 'enough'. Cardiopulmonary bypass support can be considered as a salvage therapy.

A Case of Near-fatal Flecainide Overdose in a Neonate Successfully Treated with Sodium Bicarbonate

“…A serum flecainide concentration of 3600 mcg/L (therapeutic range 200–1000 mcg/L) was reported from blood taken approximately 2.5 h post ingestion. [8]…”

Successful treatment of flecainide overdose with sustained mechanical circulatory support

“…Our patient did not receive gastric lavage because she presented to our hospital more than 1 hour after ingestion. Multiple studies support the early and ample use of hypertonic sodium bicarbonate,2, 3, 5, 7 which has been reported in doses up to 350 mEq 5 for a goal pH of 7.5–7.55 or a goal QRS width <160 ms 1 . A high sodium concentration is theorized to antagonize flecainide at sodium channels on cardiac myocytes 5 .…”

“…Flecainide causes rate-dependent slowing of the fast sodium current I Na during phase 0 of the cardiac action potential as well as inhibition of the rectifier potassium current I Kr during phase 3 2, 3, 4. Flecainide overdose is difficult to treat because of the drug’s high oral bioavailability (90%), high volume of distribution (8–9 L/kg), long half- life (up to 23 hours), poor ability to be dialyzed, lack of an antidote, and rapid onset of shock and arrhythmias (as early as 30 minutes after ingestion) 1, 5, 6…”

“…Multiple studies support the early and ample use of hypertonic sodium bicarbonate,2, 3, 5, 7 which has been reported in doses up to 350 mEq 5 for a goal pH of 7.5–7.55 or a goal QRS width <160 ms 1 . A high sodium concentration is theorized to antagonize flecainide at sodium channels on cardiac myocytes 5 . Flecainide is a weak base, and alkalization of the blood may decrease the ionized form of flecainide, which binds sodium channels 2, 7.…”

Iatrogenic Flecainide toxicity

“…There is evidence in animal models and humans that sodium bicarbonate reverses the toxic effects of flecainide 1 2. Its mechanism of action is complex and thought to be due to a combination of an increase in intracellular sodium and intracellular pH, displacing flecainide from sodium channels.…”