CASE REPORT

 
  Erythromycin-induced Torsade De Pointes
  SPORT AND ATRIAL FIBRILLATION

Erythromycin-induced Torsade De Pointes

Amar M. Salam MB,Bs, MRCP(UK) and Ali Ashraf, MB,ChB,MS
Department of Cardiology & Cardiovascular Surgery,
Hamad Medical Corporation, Doha-Qatar

 Introduction

 Case presentation
 Discussion
 Erythromycin proarrhythmia
 Amiodarone proarrhythmia
 Case Commentary
 CONCLUSION
  REFERENCES

Introduction

   Erythromycin and amiodarone are known to cause arrhythmias individually, in particular torsade de pointes (Polymorphic ventricular tachycardia); however there is no literature describing an interaction between these two drugs when they are administered together.   We report a patient who, while on oral amiodarone, was admitted with pneumonia and developed recurrent episodes of torsade de pointes with QT interval prolongation after intravenous administration of erythromycin. The report is followed by a review of pertinent literature.

Case presentation

   A 63-year-old male presented to the Emergency Room complaining of coughing up bloodstained sputum of three days duration. This was associated with fatigability and tiredness. He gave a past medical history of paroxysmal atrial fibrillation/ flutter for which he was on amiodarone 200 mg once daily and warfarin for the last three years. He also had history of left ventricular dysfunction and was on Enalapril and lasix.
On physical examination, he was not in acute distress. Temperature was 38°C, BP 130/80, PR 88/minute, regular, and RR 22/minute. Chest examination revealed crepitations and bronchial sounds in the anterior right upper zone. Cardiac auscultation revealed normal heart sounds with a grade 1/4 pansystolic murmur at the apex. The rest of the examination was unremarkable. Chest X-ray showed consolidation of the right upper lobe. ECG showed sinus rhythm with poor r-wave progression in the chest leads. Laboratory investigations showed: Hb 9.2 gm/dl, WBC 9,900 Platelets 140,000, urea 18.9 mmol/L, creatinine 122 ummol/L, K 3.3 mmol/L, Mg 0.86 mmol/L. INR was 8.9.
The patient was admitted with diagnoses of community-acquired pneumonia and over-anticoagulation. He was given fresh frozen plasma and he was treated with intravenous erythromycin, 500 mg every 6 hours. Soon after admission he became tachypneic and hypoxic and he was intubated and put on mechanical ventilation. On the first day after admission, he was stable with reasonable blood gasses, but still febrile. Repeat WBC count was 18,000. On the third day after admission the patient went into bradycardia with a heart rate of 46-beats/ minute associated with hypotension (BP was 84/50 mmHg). The QT interval was 0.56 mm. He was given intravenous atropine and dopamine infusion after which the pulse became 70 beats/min and the BP 135/80 mmHg. His blood gasses were within normal range. On the 4th hospital day, he again developed bradycardia with a rate of 46 beats/min followed by recurrent attacks of sustained torsade de pointes (Fig.1), which required multiple D/C electrical cardioversion. In between D/C shocks, the patient's rhythm was sinus bradycardia with a QTc of 0.54 millisecond (Fig.2,3). Atropine was given as well as magnesium intravenously. Erythromycin was discontinued and a temporary pacemaker was inserted, after which the arrhythmias did not recur. The patient was given the third generation ceftriaxone intravenously. The QTc interval gradually returned to normal (became 0.36 milliseconds) (Fig.4). The temporary pacemaker was then removed and a few days later, the pneumonia resolved and patient was extubated. There was no recurrence of arrhythmia. He had an unremarkable recovery and was discharged home in good condition.

Discussion

   Dessertenne first described the term torsade de pointe in 1966 (1). It refers to a ventricular tachycardia characterized by QRS complexes of changing amplitude that appear to twist around the isoelectric line and occur at rates of 200-250/minute. It is characterized by marked QT prolongation on the electrocardiogram.
   It usually causes few hemodynamic symptoms but it is potentially lethal and carries a poor prognosis because of recurrence and sudden death in up to 31% of patients (2).

Fig.1 ECG strip showing Torsade de pointes. (See text)

Fig.2 ECG strip with long QT. (See text)

Fig.3 12 lead ECG showing long QT. (See text)

Fig.4 ECG with QT interval normalized. (See text)

   Torsade de pointes is known to be precipitated by QT prolonging drugs, mainly antiarrhythmics such as quinidine, disopyramide, procainamideand sotalol. A number of drugs which are not usually considered to have major cardiovascular effects have also been associated with torsade de pointes: these include nonsedating antihistamines, such as terfenadine, astemizole and loratadine; neuroleptics such as thioridazine and haloperidol; and antibiotics such as erythromycin. For the majority of these drugs the true incidence of torsade de pointes remains unclear.
   There are predisposing factors that are known to increase the likelihood of developing torsade de pointes. These are: electrolyte imbalance (hypokalemia, hypomagnesemia, or both), slow heart rate induced either by sinus bradycardia or heart block, and the congenital prolonged QT syndromes.
   Torsade de pointes has been shown to be related to bradycardia-dependent early after-depolarizations and/or increased dispersion of repolarization. An understanding of the basic mechanism of torsade de pointes has led to an understanding of the effective forms of therapy, which include maneuvers to increase the heart rate (pacing, isoproterenol) as well as maneuvers that may not necessarily alter the QT interval but may prevent the arrhythmia (magnesium, beta blockers) until the underlying cause has been eliminated (3-4).

Erythromycin proarrhythmia

   Erythromycin is a commonly prescribed antibiotic. It is especially effective in treating community-acquired bacterial respiratory infections. Along with its widespread use, its cardiac side effects have become more and more recognized. Administration of erythromycin has been associated with lengthening of cardiac repolarization (5) and proarrhythmia, which is (defined as the provocation of new cardiac arrhythmias or the aggravation of preexisting arrhythmias). Although uncommon, torsade de pointes with erythromycin use has been previously reported (6-8). Erythromycin has been shown to produce electrophysiologic effects similar to those of class IA and class III antiarrhythmic drugs on the cardiac muscle. The reported incidence of torsades de pointes in patients receiving erythromycin is ­ 0.4%. However, a moderate to severe delay in ventricular repolarization and prolongation of QTc interval is seen in up to 39% of these patients (9).

Amiodarone proarrhythmia

   The antiarrhythmic action of amiodarone has been attributed to homogenous prolongation of myocardial repolarization in a manner that protects against arrhythmia. However polymorphous ventricular tachycardia with typical torsade de pointes morphology has been reported with its use (10-12). The proarrhythmia generally occurs during chronic treatment in association with increase in amiodarone dosage, electrolyte disorders, or concomitant therapy with class IA antiarrhythmic drugs (13). A group of investigators reported that amiodarone-induced proarrhythmic events occurred in up to of 2% of patients, while torsade de pointes was observed in only 0.7% (14).

Case Commentary

   Our patient developed malignant torsades de pointes (fig.1) after intravenous erythromycin while he was on chronic oral amiodarone therapy. At that time the electrocardiogram showed evidence of QT interval prolongation to 0.54 millisecond (Fig.2,3). Our patient had been on chronic therapy with amiodarone without any prior episode of proarrythmic events, suggesting that the proarrhythmic effect of each drug maybe additive or that there maybe interaction between the two drugs predisposing to torsade de pointes. In addition, there was hypokalemia and hypomagnesemia, which probably were contributing factors to the development of torsade de pointes in our patient. Correction of electrolyte imbalance and discontinuation of erythromycin and amiodarone resulted in resolution of arrhythmias and the QTc interval returned within normal limits (0.40 millisecond) (Fig.4). A medline search from 1966 to the present failed to show any reported case of increased sensitivity or lowered proarrhythmic threshold with the administration of both drugs.

CONCLUSION

   Since erythromycin and amiodarone are known to cause arrhythmias individually, caution and close monitoring are necessary when the drugs are administered together and perhaps an alternative antibiotic that does not have proarrhythmic effects should be considered when treating patients at high risk of developing arrhythmias.

References

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5. Orban Z, MacDonald LL, Peters MA, et al. Erythromycin- induced cardiac toxicity. Am J Cardiol 1995;75(12):859- 61.

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8. Granberry MC, Gardner SF. Erythromycin monotherapy associated with torsade de pointes. Ann Pharmacother 1996;30(1):77-8.

9. Oberg KC, Bauman JL.QT interval prolongation and torsades de pointes due to erythromycin lactobionate. Pharmacotherapy 1995;15(6):687-92.

10. Lazzara R. Amiodarone and torsade de pointes. Ann Intern Med 1989;111(7):549-51.

11. Morgan JM, Lopes A, Rowland E. Sudden cardiac death while taking amiodarone therapy: the role of abnormal repolarization. Eur Heart J 1991;12(10):1144-7.

12. Faggiano P, Gardini A, D’Aloia A, et al. Torsade de pointes occurring early during oral amiodarone treatment. Int J Cardiol 1996;55(2):205-8.

13. Lazzara R. Antiarrhythmic drugs and torsade de pointes. Eur Heart J 1993;14 Suppl H:88-92.

14. Hohnloser SH, Klingenheben T, Singh BN. Amiodarone- associated proarrhythmic effects. A review with special reference to torsade de pointes tachycardia. Ann Intern Med 1994;121(7):529-35.