Resistant Torsades de Pointes After Use of Slimming Pills: A Case Report

Abstract

Turkish Abstract

Introduction

Obesity is a major publıc health problem nowadays. And, it may increase the possibility of the development of numerous diseases such as cardiovascular diseases and diabetes mellitus. The identification of potential molecular targets susceptible to be manipulated from external factors, particularly food and drug agents may assist people in gaining control over appetite allowing obesity prevention ¹. So, we see that many people use herbal anti-obesity products. It may  attract users because of their health claims, assumed safety, easy availability and extensive marketing. In addition to this, these products can be very heterogeneous in nature and have unpredictable levels of active ingredients, and unpredictable and potentially harmful effects.

Here,  we report a young woman who consumed herbal product for its slimming effects and which resulted in torsades de pointes (Tdp) which was refractory to treatment. 

Case Report

A 30-years-old woman presented to the emergency department (ED) with history of sudden onset feeling unwell and syncope. Her Glasgow Coma Scale (GCS) score was 15 and her vital signs were normal at presentation. There was no special finding in physical examination and laboratory tests. She had no known prior disease, but she has been taking herbal slimming pills for 5 days. Her family said that she purchased these no-name pills over the internet. The initial electrocardiogram (ECG) showed sinus rhythm (Figure 1).

Figure 1 First ECG of patients in admission to emergency department. Normal ECG findings.

At the first hour of the presentation, she had sudden cardiopulmonary arrest due to ventricular tachycardia (Figure 2). After 10 minutes of cardiopulmonary resuscitation (CPR) according to the ACLS (Acquiered Cardiac Life Support) Pulseless Arrest Algorithm, spontaneous circulation was restored.

Figure 2 Monitor output of the patient during cardiac arrest. Ventricular tachycardia

Electrolytes were normal except potassium (3, 29 mEq/l) and it was corrected properly. Three minutes after recovery of the spontaneous circulation, she had VF again. CPR according to the ACLS started, and 300 mg amiodarone intravenously (i.v) bolus and 150 mg amiodarone infusion i.v. over ten minutes were given . After 200 joule defibrillation, the sinus rhythm was achieved. However, soon after the rhythm was TdP again (Figure 3). In the ECG monitor, when torsades rhythm seen, cardiopulmonary resuscitation started; magnesium and amiadorone treatments were given. 

Figure 3 Monitor output of the patient after cardiac arrest. Torsades de pointes as ECG finding.

All throughout the CPR, she was defibrillated approximately 80 times for vetricular fibrillation (VF) in ED. She was admitted to coronary care unit (CCU) with normal sinus rhythm at the end of nearly 220 minutes. She needed defibrillation at CCU 50 times more. Magnesium and lidocaine infusions were continued, and her supportive treatment along with close electrophysiological monitoring was carried on. The patient was discharged after 10 days without any neurological deficit and with normal ECG findings.

The final diagnosis was TdP secondary to herbal slimming pills.  Her dysrhytmia had a ?probable? association with the use the herbal slimming tablets, based on the Naranjo score of 7 points ². 

Discussion

As it is a high cost problem in developed countries, obesity is also becoming a huge problem in developing contries with increased morbidity, mortality and cost price ³.

In a study surveyed by Blanc and collegues ⁴, in USA, unprescribed weight loss product use calculated 15.2 % among adults. Women aged between 18-34 were the leading users (% 16.7) and more than one cardiotoxic agents were detected in 73.8 % of these products ⁵. Exact number, composition and theraupetic intervals of these weight loss products are unknown. In a study ⁶, possible arythmogenic effects of weigth loss products sold on the internet were investigated and in 8 out of 12 products, one or more than one compund with the possible life-threatining cardiac side effects were detected. One of these products consists of ephedra which is still illegal in the USA.

A progressively increasing number of cardiac and noncardiac drugs prolong the ventricular action potential duration (QT interval of the ECG) and causes a distinctive polymorphic ventricular tachycardia that can degenerate into VF and SCA. Medications that  cause QT interval alongation are antiarythmics, nonsedative antihistaminics (terfenadine and asetamizole), macrolides, some psychotropics and some gastric motility agents (cisapride) ⁷. In a case report, a young woman patient without any underlying cardiac disease, continuous torsade attacks, frequently recurring and in need of defibrillation were seen after cisapride use and persistant vomiting had caused electrolyte imbalance ⁸. In a 5 day interval more than 300 times of defibrillation were applied and at the end, patient survived without any sequela. Also,  electrolyte disturbances, especially hypokalemia and hypomagnesemia can predispose TdP.

Medication related torsade, without any doubt, will be seen more in women. The underlying reason may be that women are more concerned about that their appearance, or may be more prone to arrythmogenic effects of these substances. To be precise, the women buy more herbal products for different reasons to be investigated in the future.

Different polymorphic ventricular tachyarrhythmia may cause syncope or cardiac arrest in patients with no heart disease. In treatment of torsade rythm it was shown in many cases that magnesium sulphade treatment is effective ⁹. In treatment of recurring polymorphic ventricular tachycardia, during the time for total elimination of the causative agent from body, using a temporary pacemaker which supports the patient with 100-120 bpm is a reasonable treatment choice ⁹. There are good evidences that amiadorone against some disrytmias is more effective and superior to other medications ¹⁰. But in the lack of response to amiadorone as in our case, a review of the literature and the authors? experience indicate that lidocaine is a potentially useful therapy in torsade ¹¹.

Actually most of the published evidence of slimming drugs? adverse effects were found in case reports. There is no clinical study. In one case report, slimming regimen pills containing phentermine and chlorpheniramine has been associated with polymorphic ventricular tachycardia ¹². The patient has successfully been treated with magnesium sulfate infusion without recurrence of TdP and has had an uneventful recovery over a period of 36 hours. In another case, weight loss pills purchased on the internet had caused VF ¹³. Another was about an otherwise healthy woman with a history of palpitations who survived SCA from a ventricular dysrhytmia ¹⁴.

Despite magnesium and potassium therapy, dysrhythmia continued in our patient. Although, the active substance in the drug was unclear, her condition revealed an intoxication by an adrenergic drug stimulation. The apparent relationship between the initiation of treatment and the onset of electrocardiographic abnormalities, the absence of other precipitating factors, and the final normalization of QT interval after discontinuation of the drug, strongly suggest a causal relationship between herbal product and this adverse clinical event in our case.

In conclusion, everybody wants an easy way to control obesity and lose weight. Herbal anti-obesity products attract users because of their health claims, assumed safety, easy availability and extensive marketing. These products can be very heterogeneous in nature and have unpredictable levels of active ingredients. However, since most of these drugs help weight loss by adrenergic stimulation, physicians should be aware of cardiotoxic effects.

References

1. Mohamed GA, Ibrahim SRM, Elkhayat ES, El Dine RS. Natural anti-obesity agents. Bulletin of Faculty of Pharmacy, Cairo University. 2014;52:269-84.
2. Naranjo CA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239-45.
3. Arterburn DE, Crane PK, Veenstra DL. The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med.  2004;164:994-1003.
4. Blanck HM, et al. Use of nonprescription dietary supplements for weight loss is common among Americans. J Am Diet Assoc.  2007;107:441-7.
5. Pillitteri JL, et al. Use of dietary supplements for weight loss in the United States: results of a national survey. Obesity (Silver Spring). 2008;16:790-6.
6. Nazeri A, et al. Arrhythmogenicity of weight-loss supplements marketed on the Internet. Heart Rhythm. 2009;6:658-62.
7. Yang P, et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation.  2002;105:1943.
8. Akhtar H., Sami G. After more than 300 defibrillation shocks, patient still alive 12 years later refractory torsade de pointes due to polypharmacy and persistent vomiting. Journal of the Saudi Heart Association 2010;22:149-51.
9. Passman R, Kadish A. Polymorphic ventricular tachycardia, long Q-T syndrome, and Torsades de Pointes. Med Clin North Am. 2001;85:321-41.
10. Connolly SJ. Evidence-based analysis of amiodarone efficacy and safety. Circulation. 1999;100:2025-34.
11. Assimes TL, Malcolm I. Torsade de pointes with sotalol overdose treated successfully with lidocaine. Can J Cardiol.  1998;14:753-6.
12. Hung YM, Chang JC. Weight-reducing regimen associated with polymorphic ventricular tachycardia. AJEM.  2006;24:714-16.
13. Pareek M, et al. Weight loss pills purchased on the Internet as the cause of ventricular fibrillation. Ugeskr  Laeger.  2013;175:739-40.
14. Dieter RS, Vorperian VR.  Sudden cardiac death in a patient taking an over-the-counter diet pill. WMJ.   2000;99:20-2.

Information Presentation

VIIth Mediterranean Emergency Medicine Congress, Marseille, France, September 2013