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.