a b s t r a c t

Propafenone is prescribed for the control of cardiac ventricular arrhythmias. Poisoning from propafenone intox- ication is rare, but the survival rate of patients is low. We present a case of a 37-year-old man who developed car- diac 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.

(C) 2017

Introduction

As a class IC antiarrhythmic drug, propafenone is commonly used for treatment of Paroxysmal supraventricular tachycardia, paroxysmal atri- al fibrillation, and ventricular arrhythmia. However, propafenone over- dose may cause adverse complications such as hypotension, prolonged QRS complex, atrioventricular block, convulsion, and cardiac arrest.

Although propafenone poisoning is rare, the survival rate of patients is low, because there is no specific treatment or antidote [1-2]. Rather, treatment for propafenone intoxication is currently limited to support based on symptoms and the patient’s condition. Here, we present a case of propafenone intoxication in which the patient achieved full re- covery with calcium gluconate treatment.

The research ethics committee of our hospital approved this case re- port, and the patient provided informed consent.

Case

A 37-year-old man with clinical depression presented with impaired consciousness and limb twitch to our hospital. When brought to the emergency department, his blood pressure was 63/43 mmHg and his electrocardiogram showed first-degree atrioventricular block. He was given 1 mEq/kg of intravenous dopamine, and intubation and propor- tional assist ventilation were performed.

Initial laboratory analyses revealed hyperkalemia (5.9 mmol/L). Other laboratory results were normal, including blood count, urea,

* Corresponding author.

E-mail address: [email protected] (Z. Yang).

creatinine, sodium, calcium, magnesium, glucose, creatine kinase, tro- ponin T, liver function, and coagulation profile. Accordingly, 125 mL of 5% sodium bicarbonate (NaHCO₃), 250 mL of glucose, and 6 units of in- sulin were administered. However, the patient did not respond to this treatment.

About 30 min later, ventricular escape rhythm appeared and heart rate was 35 bpm. Immediate and repeated medical treatment consisted of adrenaline (1 mg), isoproterenol (10 ug/kg/min), dopamine (10 ug/kg/min), dobutamine (10 ug/kg/min), 0.5 mg of atropine, and intra- venous fluids. In addition, a Temporary pacemaker was used. However, the patient exhibited no significant response to these treatments.

6 h after admission, the patient’s wife informed us that 5000 mg of propafenone was missing from their bedroom. Suspecting propafenone poisoning, we immediately performed gastric lavage, hemodialysis, and perfusion, with continuous administration of adrenaline (17 mg/h). During this process, his Blood pressure and heart rate temporarily re- covered (140/110 mmHg and 80 bpm, respectively).

Subsequently, the patient twice suffered cardiac arrest with pulseless electrical activity. Cardiopulmonary resuscitation (CPR) was immediately commenced and spontaneous circulation returned, but ventricular escape rhythm remained. After 8 h, gastric lavage, hemodial- ysis, and perfusion were stopped, while CPR was repeatedly applied. Over the next 3 h, the patient remained unstable and CPR was repeated- ly performed due to repeated cardiac arrest with pulseless electrical activity.

We thus commenced plasmapheresis. The patient did not respond to this treatment, but again suffered cardiac arrest with pulseless electrical activity. This time, CPR was conducted for 30 min and during CPR, 10 mg of adrenaline and 5 mg of atropine were also administered. However,

http://dx.doi.org/10.1016/j.ajem.2017.04.006

0735-6757/(C) 2017

return of spontaneous circulation was not achieved, and blood pressure was 50/20 mmHg.

At that time, the results of an arterial blood gas taken before this car- diac arrest revealed hypocalcemia (0.33 mmol/L of free calcium). There- fore, 20 mL of 10% calcium gluconate was administered. Autonomous cardiac rhythm occasionally returned. After 10 mL of 10% calcium gluco- nate was repeated, autonomous cardiac rhythm was sustained, and his blood pressure was 130/70 mmHg. The re-determined blood calcium was 1.89 mmol/L.

The heart rate decreased again (50 bpm) and blood pressure was 80/ 50 mmHg. The blood calcium was measured again, and the result showed 1.0 mmol/L. Therefore, 40 mL of 10% calcium gluconate was re- peated, and the heart rate and blood pressure returned to normal. Over the next 6 h, the above conditions repeated twice. Each time, calcium gluconate treatment showed a significant effect. 24 h after the patient was admitted to our hospital, normal heart rate and blood pressure were sustained without any treatment. He returned to normal life activ- ity 2 days after his admission. At that time he admitted that he had taken 5000 mg of propafenone with suicidal intent. Finally, he was discharged uneventfully after 2 days.

Discussion

Although propafenone is frequently used clinically as an antiar- rhythmic drug, there has been no detailed Epidemiological study on propafenone poisoning, perhaps because intoxication of this drug is rel- atively rare. Most early case reports indicated that propafenone over- dose has a low survival rate [1-2]. More recently, there have been reports of propafenone intoxication that was successfully reversed by treatments such as sodium bicarbonate, insulin, glucagon, and intrave- nous lipid emulsion [3-10].

Gastric lavage could be the most efficient treatment for propafenone poisoning, since there is no other way to eliminate the drug [11]. Unfor- tunately, in the present case we were not informed of possible propafenone intoxication by the patient’s family until 6 h after his hos- pital admission. Therefore, gastric lavage was of no use in this case, since the overdose of propafenone had been absorbed into the blood circulation.

Propafenone overdose can occasionally cause cardiac arrest, with a very poor prognosis [1,12]. In the present case, there were multiple car- diac arrests, and at the last cardiac arrest, CPR had no effect. Because hy- pocalcemia was observed during CPR, calcium gluconate was administered. Of particular interest, sustained calcium gluconate ad- ministration saved our patient, with full recovery from the propafenone intoxication.

Propafenone has beta-receptor and calcium channel-blocking activ- ities, which may be the mechanism underlying hypocalcemia in this case. However, since the effect of propafenone on Calcium channels is weak, continuous monitoring of blood calcium is not given adequate at- tention for patients experiencing propafenone overdose. Bayram et al.

[6] used Intravenous lipid emulsion, and not calcium gluconate, to save a patient from propafenone intoxication, although they had found hypocalcemia.

The blood calcium level of our patient was normal when his blood was first measured for electrolytes at admission. However, his blood cal- cium decreased during cardiac arrest. Surprisingly, the patient achieved a full recovery after repeated calcium gluconate administrations, even as CPR, plasmapheresis, and other medical treatments had no effect on cardiac arrest. Admittedly, since the plasma propafenone level was not measured in this patient, the extent to which plasmapheresis and other medical treatments contributed to propafenone clearance is not known. Moreover, CPR and other supportive treatments are indispens- able in the early treatment of propafenone intoxication, and at least may prevent the patient’s condition from deteriorating and leading to organ failure or brain death.

To the best of our knowledge, this is the first case report in which a full recovery from cardiac arrest was achieved by calcium gluconate ad- ministration, combined with CPR, plasmapheresis, and other medical treatments, in a patient with propafenone intoxication. Our case report suggests that in a patient poisoned by propafenone, close blood calcium monitoring is required, and it is important to attend to a decrease in blood calcium.

References

1. Clarot F, Goulle JP, Horst M, Vaz E, Lacroix C, Proust B. Case report: fatal propafenone overdoses. Case reports and a review of the literature. J Analyt Toxicol 2003;27(8): 395-9.
2. Maxeiner H, Klug E. Lethal suicidal intoxication with propafenone, after a history of self-inflicted injuries. Forensic Sci Int 1997;89(1-2):27-32.
3. Saz EU, Ucar SK, Ulger Z, Ersel M, Cevik C, Karapinar B. Successful treatment of sui-

   cidal mega dose of propafenone intoxication — a case report. Kardiol Pol 2010; 68(11):1284-5.

   Bayram B, Dedeoglu E, Hocaoglu N, Gazi E. Propafenone-induced cardiac arrest: full recovery with insulin, is it possible? Am J Emerg Med 2013;31(2) 457.e5-7.

4. Wozakowska-Kaplon B, Stepien-Walek A. Propafenone overdose: cardiac arrest and full recovery. Cardiol J 2010;17(6):619-22.
5. Bayram B, Kose I, Avci S, Arslan A, Acara C. Successful treatment of propafenone in- toxication with intravenous lipid emulsion. Pharmacotherapy 2015;35(10): e149-52.
6. Jacob J, Heard K. Second case of the use of intravenous fat emulsion therapy for propafenone toxicity. Clin Toxicol (Phila) 2011;49(10):946-7.
7. Ovaska H, Ludman A, Spencer EP, Wood DM, Jones AL, Dargan PI. Propafenone poisoning-a case report with plasma propafenone concentrations. J Med Toxicol 2010;6(1):37-40.
8. Avci A, Yilmaz A, Celik M, Demir K, Keles F. Successful treatment of suicide attempt by megadose of propafenone and captopril. Cardiovasc Toxicol 2013;13(3):230-3.
9. Unal S, Bayrakci B, Yasar U, Karagoz T. Successful treatment of propafenone, digoxin and warfarin overdosage with plasma exchange therapy and rifampicin. Clin Drug Investig 2007;27(7):505-8.
10. Benowitz N, Goldschiager N. Cardiac disturbances. In: Haddad L, Shannon M, editors. Clinical management of poisoning and Drug overdoses. 3th ed. New York: Saunders Company; 1998. p. 1181.
11. Kerns 2nd W, English B, Ford M. Propafenone overdose. Ann Emerg Med 1994; 24(1):98-103.