This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Nishina, K. Articles by Minami, K. Search for Related Content PubMed PubMed Citation Articles by Nishina, K. Articles by Minami, K.

---

LETTERS TO THE EDITOR

The Efficacy of Bolus Administration of Landiolol for Attenuating Tachycardia in Pheochromocytoma

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.

View larger version (102K): [in this window] [in a new window]   Figure 1. Improvement of ST segment depression with landiolol (ECG leads II and III). (A) 1 min before landiolol, HR 100 bpm,; (B) 5 min after landiolol, HR 80 bpm.

References

1. Baraka A, Siddik SS, Jalbout M, Yaacoub C. Variable hemodynamic fluctuations during resection of multicentric extraadrenal pheochromocytomas. Can J Anaesth 2002; 49: 682–6.[Web of Science][Medline]
2. Ogata J, Yokoyama T, Okamoto T, Minami K. Managing a tachyarrhythmia with pheochromocytoma with landiolol, a novel ultrashort-acting beta-adrenergic blocker. Anesth Analg 2003; 97: 294–5.[Free Full Text]
3. Harasawa R, Hayashi Y, Iwasaki M, et al. Hemodynamic effect of bolus injection of landiolol in humans. J Anesth 2003; 17S: 232.
4. Kitamura A, Sakamoto A, Inoue T, Ogawa R. Efficacy of an ultra short-acting beta-adrenoceptor blocker (ONO-1101) in attenuating cardiovascular responses to endotracheal intubation. Eur J Clin Pharmacol 1997; 51: 467–71.[Web of Science][Medline]

Response

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 (T_max) with CI of landiolol are dose-dependent and the half-life (T_1/2) 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 K_i 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 T_max reaches the K_i 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.

References

1. Ogata J, Yokoyama T, Okamoto T, Minami K. Managing a tachyarrhythmia with pheochromocytoma with landiolol, a novel ultrashort-acting beta-adrenergic blocker. Anesth Analg 2003; 97: 294–5.
2. Motomura S, Hagihara A, Narumi Y, Hashimoto K. Time course of a new ultrashort-acting beta-adrenoceptor-blocking drug, ONO-1101: comparison with those of esmolol and propranolol by using the canine isolated, blood-perfused heart preparations. J Cardiovasc Pharmacol 1998; 31: 431–40.[Web of Science][Medline]
3. Sasao J, Tarver SD, Kindscher JD, et al. In rabbits, landiolol, a new ultra-short-acting beta-blocker, exerts a more potent negative chronotropic effect and less effect on blood pressure than esmolol. Can J Anaesth 2001; 48: 985–9.[Web of Science][Medline]
4. Muraki K, Nakagawa H, Nagano N, et al. Effects of ONO-1101, a novel beta-antagonist, on action potential and membrane currents in cardiac muscle. J Pharmacol Exp Ther 1996; 278: 555–63.[Abstract/Free Full Text]
5. Atarashi H, Kuruma A, Yashima M, et al. Pharmacokinetics of landiolol hydrochloride, a new ultra-short-acting beta-blocker, in patients with cardiac arrhythmias. Clin Pharmacol Ther 2000; 68: 143–50.[Web of Science][Medline]
6. Nicholas E, Deutschman CS, Allo M, Rock P. Use of esmolol in the intraoperative management of pheochromocytoma. Anesth Analg 1988; 67: 1114–7.[Web of Science][Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Nishina, K. Articles by Minami, K. Search for Related Content PubMed PubMed Citation Articles by Nishina, K. Articles by Minami, K.