Discussion
The present case highlighted two important issues: (1) the re-recognition of the seriousness of bepridil intoxication and importance of regular plasma bepridil concentration measurement; and (2) the importance of careful arrhythmia management by the family physician and electrophysiologist at the pacemaker clinic in pacemaker patients who are taking bepridil for atrial fibrillation.
Bepridil can cause lethal ventricular arrhythmias, such as TdP with an incidence rate of 0.4%–3.4%, because of its multi-potassium-channel/calcium-channel-blocking property.3-8 Measurement of plasma bepridil concentration would be useful in preventing TdP as an adverse effect of bepridil use because a high plasma bepridil concentration of >800 ng/mL is considered a risk factor for TdP.2, 5 Plasma bepridil concentration varies greatly among individuals, even at the same dosage, because of its complex pharmacokinetics.1, 2, 5 In addition, the treatment of bepridil intoxication can be difficult once adverse effects have occurred because bepridil has a very long elimination half-life of approximately 80 h after continued intake, which can be more prolonged due to less clearance in patients with low body weight and advanced age, like the present case.1, 5 In addition, cardiac pacing may mask electrocardiographic abnormalities especially by left bundle branch block, similar to configuration due to ventricular pacing. In the case of QT prolongation, the pacing may reduce QT prolongation itself and reduce the risk of TdP.9–15 Yasuda et al. reported that triggers for TdP among patients taking bepridil were older age, bradycardia, excessive baseline QT prolongation, and hypokalemia.3 In the present case, bradycardia by reprograming to lower the heart rate during pacemaker generator exchange operation and subsequent presentation of excessive QT prolongation due to bepridil intoxication would be direct triggers for TdP. Since bepridil has very long elimination half-life, the importance of regular plasma bepridil concentration measurement or timely measurement (for instance, prior to pacemaker generator exchange operation) in pacemaker patients is emphasized.
The present case may also indicate an important pitfall in the cooperation between the pacemaker clinic and family physician. Electrophysiologists at the pacemaker clinic may tend to neglect regular measurement of plasma bepridil concentration especially when the family physician prescribes bepridil. For the family physician, arrhythmia management might be a non-expert practice, so they might neglect regular measurement of plasma bepridil concentration, especially when the patient visits a cardiologist regularly like the present case. Considering that it is unlikely for the family physician to think of the fact that 200 mg daily of bepridil is generally a risky dosage for small older patients, the electrophysiologist at the pacemaker clinic should pay attention to the arrhythmia management initiated by the family physician. The Swiss-cheese model, which is proposed as an organization’s defense against accidents by stacking a series of barriers, is often adopted when considering patient safety management. From this perspective, following aspects would help evade this type of avoidable accident: (1) awareness of this type of pitfall; (2) awareness of the importance of regular measurement of plasma bepridil concentration especially at the pacemaker clinic; (3) awareness of the danger of bepridil intoxication and importance of regular measurement of plasma bepridil concentration by family physician, if possible, and (4) awareness of the importance of close cooperation between the electrophysiologist at the pacemaker clinic and family physician in charge of the arrhythmia management of the same patient. We hope that this case alerts both electrophysiologists at the pacemaker clinic and family physicians to the avoidable occurrence of fatal arrhythmia to enhance patient safety.