Postoperative administration of landiolol hydrochloride for patients with supraventricular arrhythmia: the efficacy of sustained intravenous infusion at a low dose.

Abstract

The purpose of this study was to investigate the efficacy of landiolol hydrochloride, a short-acting beta(1) blocker, by initiating its administration at a low dose (5 microg kg(-1) min(-1)) in patients with postoperative supraventricular arrhythmia. The efficacy of landiolol was evaluated in 38 patients who, after developing postoperative atrial flutter or fibrillation, with sinus tachycardia and two patients who had a history of paroxysmal atrial fibrillation with frequent atrial extrasystole. The heart rate and blood pressure before and 2 h after the administration of landiolol were compared. A return to the sinus rhythm from supraventricular arrhythmia was noted in 89%. The heart rate was reduced from 137+/-26 bpm (before landiolol administration) to 93+/-18 bpm (2 h after the start of the medication, P<0.01). As an agent to correct an arrhythmic condition, landiolol successfully raised the systolic blood pressure from 108+/-24 mmHg (before medication) to 120+/-19 mmHg (2 h after the medication was started, P<0.05). Continuous intravenous infusion of landiolol at a low dose was found to be effective for postoperative supraventricular arrhythmia.

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Postoperative administration of landiolol hydrochloride for patients with supraventricular
arrhythmia: the efficacy of sustained intravenous infusion at a low dose

Seiichiro Wariishi, 1,2 Koichi Yamashita, 3 Hideaki Nishimori, 1
Takashi Fukutomi, 1 Masaki Yamamoto, 1 Geethalakshmi Radhakrishnan 1and Shiro Sasaguri 1

1Department of Surgery II, Faculty of Medicine, Kochi University, Kochi, Japan
2Intensive Care Unit, and 3Emergency Medicine, Kochi University Hospital, Kochi, Japan



Address reprint requests to: Seiichiro Wariishi, MD: Department of Surgery II, Faculty of
Medicine, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan
Tel: +81-88-880-2375
Fax: +81-88-880-2376
E-mail address: wari@kochi-u.ac.jp


A summary of this study was introduced at the 38th Annual Meeting of the Japanese Society for
Cardiovascular Surgery in February 2008, at Fukuoka.

The word count of this manuscript is 1986 words.

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Abstract
The purpose of this study was to investigate the efficacy of landiolol hydrochloride, a
short-acting 1 blocker, by initiating its administration at a low dose (5 g  kg-1  min-1) in
patients with postoperative supraventricular arrhythmia. The efficacy of landiolol was evaluated
in 38 patients who, after developing postoperative atrial flutter or fibrillation, with sinus
tachycardia and 2 patients who had a history of paroxysmal atrial fibrillation with frequent atrial
extrasystole. The heart rate and blood pressure before and 2 hours after the administration of
landiolol were compared. A return to the sinus rhythm from supraventricular arrhythmia was
noted in 89%. The heart rate was reduced from 137  26 bpm (before landiolol administration) to
93  18 bpm (2 hours after the start of the medication, P < 0.01). As an agent to correct an
arrhythmic condition, landiolol successfully raised the systolic blood pressure from 108  24
mmHg (before medication) to 120  19 mmHg (2 hours after the medication was started, P <
0.05). Continuous intravenous infusion of landiolol at a low dose was found to be effective for
postoperative supraventricular arrhythmia.

Keywords:  blocker, landiolol hydrochloride, postoperative care, supraventricular arrhythmia

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1. Introduction
The perioperative care is necessarily conducted under unique conditions, such as excitation of
the sympathetic nervous system, administration of agents to stimulate the circulatory system and
systemic inflammatory responses [1,2] It has been found that  blockers are not only effective in
controlling myocardial ischemia and arrhythmia but also in suppressing inflammatory cytokines
and stabilizing intravascular plaques, [3-5] thus attracting further attention to their efficacy
during perioperative care. In Japan, however, propranolol hydrochloride (hereafter abbreviated to
propranolol) is the only  blocker that is currently available for intravenous administration,
which was not always convenient for perioperative care because of its relatively long half-life [6].
Landiolol hydrochloride (hereafter abbreviated to landiolol) is a short-acting 1 blocker that has
been developed in Japan [7] Because of its extremely short half-life in blood (approximately 4
minutes), [8] it appears to be highly promising as an agent in adjusting the timing of intravenous
administration.
In view of the efficacy of  blockers in the management of postoperative supraventricular
arrhythmia, the current study was conducted employing landiolol. Based on the clinical results,
administration at a low dose was initiated.

2. Patients and Method
The subjects were 40 patients (mean age, 70  9, range, range, 41 to 84 years; 30 men and 10
women) who underwent continuous infusion of landiolol at a low dose during postoperative care
at the Kochi University Hospital that started between April 2004 and December 2007. The group
comprised those with: ischemic heart disease (12), valvular diseases (5), aortic diseases (9),
respiratory tract diseases (5), digestive system diseases (7) and others (2) (Table 1).

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Among those individuals who suffered from atrial flutter or fibrillation during the
postoperative period, the following were selected as the subjects of the present study: 38 who
failed in an attempt to correct the water-electrolyte balance and resisted the treatment of 50 mg of
pilsicainide hydrochloride (hereafter abbreviated to pilsicainide) and 2 who had a history of
paroxysmal atrial fibrillation and had began to develop frequent bouts of atrial extrasystole.
Based on the clinical experience in the use of landiolol, a continuous intravenous infusion was
started at a dose of 5 g  kg-1  min-1 for defibrillation; and depending on the heart rate and
blood pressure, it was adjusted to approximately 2 g  kg-1  min-1 every 5 to 10 minutes. These
patients suffered from the following clinical conditions: atrial fibrillation (28, with 2 maintaining
the sinus rhythm after MAZE operation), atrial flutter (5), sinus tachycardia (5) and prophylaxis
for paroxysmal atrial fibrillation (2).
The heart rate and blood pressure before and 2 hours after the administration of landiolol
were compared.
Prior to medication, the expected outcome and the need of the treatment were fully explained
to those 2 patients who were scheduled for the prevention of paroxysmal atrial fibrillation.
The age, dosages, heart rate and blood pressure of the patients were recorded as a mean 
standard deviation. For statistical analysis, the Student’s-t-test was used with the significance
level set at P < 0.05.

3. Results
For the most patients, landiolol administration was started between days 2 and 5 after
surgery (Fig. 1). Restoration of the normal sinus rhythm from supraventricular arrhythmia was
noted in 34 of the 38 patients (89%). This effect was noted in 24 of the 28 patients (86%) of

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those with atrial fibrillation and all of those with atrial flutter or sinus tachycardia. Subsequently,
the heart rate was reduced from 137  26 bpm (before the start of landiolol administration) to 93
 18 bpm (2 hours after the start of the medication, P < 0.01) (Fig. 2). As a consequence of
antiarrhythmic treatment, the systolic blood pressure rose from 108  24 mmHg (before the start
of landiolol administration) to 120  19 mmHg (2 hours after the start of the medication, P <
0.05) (Fig. 3). The maximum dosage given was 7.5  7.6 g  kg-1  min-1. Reductions in the
heart rate were noted even in the 2 patients who were treated for tachycardia associated with
chronic atrial fibrillation. In one patient who developed an electrical storm in addition to
postoperative atrial fibrillation, a complete atrioventricular block developed even at the dosage of
1 g  kg-1  min-1 but cessation of medication restored the previous state.
In both of the 2 patients who were treated to prevent paroxysmal atrial fibrillation, it was
possible to maintain the sinus rhythm when landiolol administration was started when atrial
extrasystoles repeatedly developed.

4. Discussion
Landiolol is outstanding in its immediate efficacy and adjustability [8]. Because of its high
selectivity with 1 receptors, [6] it is readily administered to patients with respiratory tract
diseases. Recently there have been occasional reports in which landiolol, with its outstanding
adjustability, was found to be effective in the treatment of not only arrhythmia due to
supraventricular tachycardia, [9] but also for correction of a left ventricular outflow tract
obstruction [10,11] and amelioration of myocardial infarction [12]. In this country, the
application of landiolol has been approved by National Health Insurance for the emergency
treatment of intraoperative and postoperative arrhythmia due to supraventricular tachycardia