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Department of Anesthesia and Perioperative Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
To the Editor:
Beta-adrenoceptor antagonists including esmolol are employed in the management of intraoperative tachyarrhythmia (1). We read with great interest the report by Ogata et al. (2) of a patient with pheochromocytoma given infusion of landiolol, a new ß-antagonist, during surgery. In this letter, we would like to share our experience with a case of epinephrine-dominant pheochromocytoma (86-yr-old male) that we previously treated with landiolol. The patient also had right coronary artery stenosis, and his preoperative hemodynamics were well controlled with oral nilvadipine and doxazosin. He underwent laparoscopic adrenalectomy under general anesthesia, which was induced with propofol and fentanyl, and maintained with sevoflurane. Blood pressure (BP) and heart rate (HR) were stable during induction of anesthesia and tracheal intubation. Intraoperative BP was controlled by continuous infusion of nitroprusside and intermittent doses of phentolamine. After pneumoperitoneum was started, HR increased to over 100 beats per minute (bpm) along with the ST segment depression. Bolus administration of 5 mg of landiolol (approximately 0.1 mg/kg) suppressed the pneumoperitoneum-induced tachycardia (maximum HR: 109 bpm) Electrocardiography indicated that landiolol had improved the ST segment depression associated with tachycardia (Fig. 1). The dose of 5 mg was recommended for the treatment of intraoperative tachyarrhythmia (3). However, HR increased again to over 110 bpm during manipulation of the adrenal tumor. Two successive doses of landiolol (5 mg each) were then given, leading to a slight decrease of 10 bpm in HR, but it remained at more than 100 bpm for 10 min. An additional dose (5 mg) of landiolol successfully reduced HR from 107 to 93 bpm. The drainage vein of the tumor was ligated 9 min after the last dose of landiolol, after which HR remained stable around at 70 bpm.
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References
Department of Anesthesiology, University of Occupational and Environmental Health School of Medicine, Fukuoka, Japan
In Response:
We appreciate Nishina et al.’s interest in our single report on managing pheochromocytoma-induced tachyarrhythmia with landiolol (1) and their insightful discussion. They speculated that a bolus injection (BI) of landiolol (approximately 0.1 mg/kg) would be useful, since this could effectively attenuate epinephrine-induced tachycardia and myocardial ischemia. Although we agree to some extent, several issues remain.
They favored a BI of landiolol instead of a continuous infusion (CI). The heart rate (HR) decreases more rapidly with a BI of landiolol than it does with esmolol (2,3), whereas, in papillary muscle, the time required for 50% removal of the ß-antagonism of landiolol is shorter than that of esmolol with CI (4). In patients with arrhythmias, the maximum blood concentrations (Tmax) with CI of landiolol are dose-dependent and the half-life (T1/2) is as short as 4 min (5). Therefore, BI would reveal the negative chronotropic action of landiolol, since the blood concentration of landiolol would rise excessively (over 2 µM) and drop rapidly within 4 min. Additionally, in humans, the Ki of the ß1 and ß2 adrenoceptors with landiolol are 62.1 and 1890 nM, respectively (unpublished data from Ono Pharmaceutical CO Ltd., Osaka, Japan). These findings point to two major problems. First, the BI of landiolol potentially affects ß2 adrenoceptors, since the Tmax reaches the Ki of the ß2 adrenoceptor, which could result in unexpected adverse reactions, including bronchoconstriction. Second, with a single 5-mg dose, the landiolol concentration would not remain at its pharmacologically relevant concentration for more than 5 min. Therefore, CI of landiolol is necessary to maintain an adequate blood concentration. Their case required three additional boluses of landiolol, due to its rapid disappearance. Although BI of esmolol has been established, there are few reports on BI of landiolol. In our case, the HR was easily managed by titrating the landiolol dose during the manipulation, since we could predict the HR from the pharmacological and clinical findings (1).
Since the hemodynamic features of BI of esmolol have been well demonstrated, theoretically this protocol could be used in pheochromocytoma patients (6). However, there are no reports on the BI of landiolol. Although we may well become more skilled at giving landiolol by BI, more study is necessary to clarify the pharmacodynamics and clinical characteristics of bolus landiolol. Without fur-ther evidence, BI of landiolol remains contraindicated in severe cases.
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