Torsades de Pointes Following Clarithromycin Treatment
Torsades de Pointes Following Clarithromycin Treatment
A comprehensive review of current literature was performed to identify documented cases of QT interval prolongation, TdP or cardiac arrest in the presence of clarithromycin treatment. Search terms included: 'long QT', 'acquired long QT interval', 'torsades de pointes' and 'clarithromycin'. The search was limited to human subjects and case reports only. In total, 21 cases of clarithromycin induced arrhythmia were found (Table 1). Of these, five were associated with LQTS only, 11 resulted in the development of TdP and four resulted in ventricular fibrillation (VF) arrest. Two cases were omitted because they were not available in English language. Two investigators (MG, AB) reviewed the abstracts. An AC1 inter-observer analysis was performed and demonstrated an inter-observer reliability of 80.3%. Disagreement was solved by consensus.
A 75-year-old woman presented to the emergency department (ED) with pre-syncope, shortness of breath, nausea and a non-productive cough. One day prior she had been discharged from her community hospital following four days of treatment for right lower lobe community acquired pneumonia. Her treatment consisted of ceftriaxone 2 g iv. q24h plus clarithromycin 1 g iv. q24h to which she responded well within a few days. On discharge she was provided with a 1 week course of clarithromycin 500 mg twice a day (b.i.d.) and advised to follow-up with her family doctor regarding chronic renal dysfunction (eGFR = 19). No dose-adjustment for renal function was provided. That night she began to feel unwell with weakness and shaking. The next day she experienced three episodes of presyncope prompting her to visit the ED.
Her past medical history was significant for complete AV block managed with a single chamber pacemaker in VVI-R mode (EnPulse SR01, Medtronic, MN, USA), coronary artery disease with previous stenting of the right coronary artery, hypertension and dyslipidemia. The programmed parameters of the pacemaker were: lower rate at 60 bpm, upper rate at 130 bpm, amplitude at 2.0 V, pulse width at 0.40 ms and sensitivity at 4.0 mV. Other medications on admission included metoprolol 25 mg b.i.d., losartan/HCT 100 mg/25 mg daily, Crestor 40 mg daily and Plavix 75 mg daily. The patient was unaware of any drug allergies.
On examination she appeared well, was not in distress and was afebrile. Postural vitals demonstrated weakness on standing with a blood pressure of 179/107 mmHg and a heart rate of 119 beats/min. While sitting she was asymptomatic with a blood pressure of 188/71 mmHg and a heart rate 63 beats/min. Oxygen saturation was 93% on room air. Cardiac and respiratory examination was unremarkable. Crackles were most prominent in the right lower lobe corresponding to the site of the pneumonia.
Labs were drawn and a cardiac monitor was applied. Significant findings included hypomagnesemia (0.49 m mol/l) and mild hypokalemia (3.4 mmol/l). A leukocytosis of 13.8 x 10/l was also present. ECG demonstrated paced rhythm with a QTc interval of 514 ms (Figure 1). Bazett's formula was used to measure QTc.
(Enlarge Image)
Figure 1.
Paced 12-lead ECG on admission. QTc interval = 514 ms.
Approximately 1 h later the patient was found unresponsive. Cardiac monitoring demonstrated TdP deteriorating into VF (Figure 2). CPR was initiated and the patient was cardioverted three-times at 200, 300 and 360 J before resumption of paced rhythm. She was then intubated and received ketamine, levophed and midazolam. Total down time amounted to approximately 15 min before the patient was transferred to the intensive care unit (ICU) and received therapeutic hypothermia. Clarithromycin was discontinued and piperacillin/tazobactam 3.375 g iv. q6h was initiated. Additional medications in hospital included hydralazine 25 mg q6h, amlodipine 10 mg daily and heparin 5000 units b.i.d. Magnesium and potassium were supplemented as necessary.
(Enlarge Image)
Figure 2.
Cardiac monitor rhythm strip (lead II) showing non-paced beats followed by torsades de pointes degenerating into ventricular fibrillation. Note the pacemaker spikes going through the polymorphic arrhythmia. QTc intervals preceding torsades de pointes (TdP) are between 580-620 ms. A possible contributing mechanism to develop TdP is the short-long-short sequence preceding the event. Paced rates above 70 bpm have demonstrated reduced risk of developing TdP
No consideration to increasing the pacing rate was given during the acute episode.
A few days later the patient was removed from supportive ventilation and continued on antibiotic therapy including vancomycin 1g iv. q8h until her pneumonia resolved. A stress myocardial perfusion imaging study demonstrated no inducible ischemia and a normal ejection fraction of 66%. Prior to discharge the patient was upgraded to a dual chamber implantable cardioverter-defibrillator (ICD) (Fortify Assura, St. Jude Medical, MN, USA). A genetic analysis was performed to assess for congenital LQTS for which the patient is currently awaiting results. The paced QTc interval at discharge was 512 ms (Figure 3). The patient remained on Metoprolol 25 mg b.i.d. to be titrated up to its maximum tolerable dose by her family doctor. At 6 months follow-up, the patient has received no therapies from the ICD.
(Enlarge Image)
Figure 3.
12-lead ECG several days after arrest. QTc: 512 ms, with similar QTc to the ECG preceding the torsades de pointes event
Methods
A comprehensive review of current literature was performed to identify documented cases of QT interval prolongation, TdP or cardiac arrest in the presence of clarithromycin treatment. Search terms included: 'long QT', 'acquired long QT interval', 'torsades de pointes' and 'clarithromycin'. The search was limited to human subjects and case reports only. In total, 21 cases of clarithromycin induced arrhythmia were found (Table 1). Of these, five were associated with LQTS only, 11 resulted in the development of TdP and four resulted in ventricular fibrillation (VF) arrest. Two cases were omitted because they were not available in English language. Two investigators (MG, AB) reviewed the abstracts. An AC1 inter-observer analysis was performed and demonstrated an inter-observer reliability of 80.3%. Disagreement was solved by consensus.
Case Presentation
A 75-year-old woman presented to the emergency department (ED) with pre-syncope, shortness of breath, nausea and a non-productive cough. One day prior she had been discharged from her community hospital following four days of treatment for right lower lobe community acquired pneumonia. Her treatment consisted of ceftriaxone 2 g iv. q24h plus clarithromycin 1 g iv. q24h to which she responded well within a few days. On discharge she was provided with a 1 week course of clarithromycin 500 mg twice a day (b.i.d.) and advised to follow-up with her family doctor regarding chronic renal dysfunction (eGFR = 19). No dose-adjustment for renal function was provided. That night she began to feel unwell with weakness and shaking. The next day she experienced three episodes of presyncope prompting her to visit the ED.
Her past medical history was significant for complete AV block managed with a single chamber pacemaker in VVI-R mode (EnPulse SR01, Medtronic, MN, USA), coronary artery disease with previous stenting of the right coronary artery, hypertension and dyslipidemia. The programmed parameters of the pacemaker were: lower rate at 60 bpm, upper rate at 130 bpm, amplitude at 2.0 V, pulse width at 0.40 ms and sensitivity at 4.0 mV. Other medications on admission included metoprolol 25 mg b.i.d., losartan/HCT 100 mg/25 mg daily, Crestor 40 mg daily and Plavix 75 mg daily. The patient was unaware of any drug allergies.
On examination she appeared well, was not in distress and was afebrile. Postural vitals demonstrated weakness on standing with a blood pressure of 179/107 mmHg and a heart rate of 119 beats/min. While sitting she was asymptomatic with a blood pressure of 188/71 mmHg and a heart rate 63 beats/min. Oxygen saturation was 93% on room air. Cardiac and respiratory examination was unremarkable. Crackles were most prominent in the right lower lobe corresponding to the site of the pneumonia.
Labs were drawn and a cardiac monitor was applied. Significant findings included hypomagnesemia (0.49 m mol/l) and mild hypokalemia (3.4 mmol/l). A leukocytosis of 13.8 x 10/l was also present. ECG demonstrated paced rhythm with a QTc interval of 514 ms (Figure 1). Bazett's formula was used to measure QTc.
(Enlarge Image)
Figure 1.
Paced 12-lead ECG on admission. QTc interval = 514 ms.
Approximately 1 h later the patient was found unresponsive. Cardiac monitoring demonstrated TdP deteriorating into VF (Figure 2). CPR was initiated and the patient was cardioverted three-times at 200, 300 and 360 J before resumption of paced rhythm. She was then intubated and received ketamine, levophed and midazolam. Total down time amounted to approximately 15 min before the patient was transferred to the intensive care unit (ICU) and received therapeutic hypothermia. Clarithromycin was discontinued and piperacillin/tazobactam 3.375 g iv. q6h was initiated. Additional medications in hospital included hydralazine 25 mg q6h, amlodipine 10 mg daily and heparin 5000 units b.i.d. Magnesium and potassium were supplemented as necessary.
(Enlarge Image)
Figure 2.
Cardiac monitor rhythm strip (lead II) showing non-paced beats followed by torsades de pointes degenerating into ventricular fibrillation. Note the pacemaker spikes going through the polymorphic arrhythmia. QTc intervals preceding torsades de pointes (TdP) are between 580-620 ms. A possible contributing mechanism to develop TdP is the short-long-short sequence preceding the event. Paced rates above 70 bpm have demonstrated reduced risk of developing TdP
No consideration to increasing the pacing rate was given during the acute episode.
A few days later the patient was removed from supportive ventilation and continued on antibiotic therapy including vancomycin 1g iv. q8h until her pneumonia resolved. A stress myocardial perfusion imaging study demonstrated no inducible ischemia and a normal ejection fraction of 66%. Prior to discharge the patient was upgraded to a dual chamber implantable cardioverter-defibrillator (ICD) (Fortify Assura, St. Jude Medical, MN, USA). A genetic analysis was performed to assess for congenital LQTS for which the patient is currently awaiting results. The paced QTc interval at discharge was 512 ms (Figure 3). The patient remained on Metoprolol 25 mg b.i.d. to be titrated up to its maximum tolerable dose by her family doctor. At 6 months follow-up, the patient has received no therapies from the ICD.
(Enlarge Image)
Figure 3.
12-lead ECG several days after arrest. QTc: 512 ms, with similar QTc to the ECG preceding the torsades de pointes event