Intravenous fat emulsion therapy for intentional propafenone intoxication

To the Editor:

Clinical Toxicology recently published a systematic review on lipid emulsions in the treatment of acute poisoning.¹ Intravenous fat emulsion (IFE) therapy in oral intoxications is only recommended after failure of general supportive therapy for hemodynamically significant intoxications with fat soluble agents. But this raises the question: besides optimal type, dose, and duration of IFE therapy, what would be an acceptable delay?

We treated a previously healthy 21-year-old woman, with no psychiatric history, for intentional ingestion of approximately 30 tablets of propafenone (150 mg). Propafenone is a lipophilic class 1C antidysrhythmic agent used for the treatment of life-threatening supraventricular and ventricular dysrhythmias. Intoxications with propafenone are rare and can potentially be fatal.²

On arrival of the ambulance, the patient was still conscious, but vomiting. She finally collapsed and suffered from tonic clonic insults for which she received diazepam rectally and midazolam intravenously. Subsequently, asystole was recorded and cardiopulmonary resuscitation (CPR) was initiated; she was intubated and ventilated. The first documented rhythm was sinus bradycardia with first grade AV block and a wide QRS-complex of 320 msec without cardiac output. After 30 min of CPR, output was documented and she was transported to the emergency department. During transportation, the patient was hemodynamically unstable with severe shock. CPR was restarted because of asystole that converted to wide-complex tachycardia. Treatment of a propafenone intoxication is supportive and no specific antidote is available.³ Maximal supportive therapy included high-dose epinephrine and norepinephrine infusion, and sodium bicarbonate because of metabolic acidosis and in view of the sodium channel effects of propafenone. However, QRS width remained around 300 msec. To counteract possible calcium channel and beta-receptor blocking effects of propafenone, calcium chloride and glucagon were administered. Gut decontamination was performed with laxatives and active charcoal. Because of persistent hemodynamic shock, IFE was initiated (dosage: bolus 100 ml 20%, followed by continuous infusion of 100 ml/h with a total amount of 1000 ml). Within 1 h, epinephrine and norepinephrine requirement decreased by 40% and QRS duration improved to 200 msec. Despite hemodynamical stabilization, the patient died on day 3 after withdrawal of life-prolonging supportive therapy because of irreversible neurological damage sustained during the prolonged shock state.

There is convincing evidence that IFE is effective in treating toxicity caused by parenteral administration of local anesthetics.^4–6 Several case reports describe the use of IFE in intoxications other than with local anesthetic agents.^7,8 It appears that a favorable response to IFE therapy is correlated with the lipophilicity (logP) of the drug, e.g. in case reports of oral intoxication with verapamil (logP = 3.8) and propranolol (logP = 3.6), IFE therapy seemed to have a positive effect on hemodynamic.^8,9 Since propafenone is a lipophilic drug (logP = 4.7), the use of IFE seemed legitimate in our case. We started IFE therapy in agreement with current recommendations after failure of standard therapy, but irreversible neurological damage was already sustained.^1,10,11 In a case of acute poisoning with refractory shock or cardiac arrest, despite general supportive measures and without an available antidote, we argue to not postpone IFE therapy. Although further evidence is needed, prompt IFE therapy could possibly prevent the adverse outcome in these “nothing to lose cases.”

Declaration of interest

All authors have read and approved the paper and have met the criteria for authorship as established by the International Committee of Medical Journal Editors. All authors declare that they do not have any conflict of interest.