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Shimizu T, Takekita Y, Aoki N, Suwa T, Yasuda K, Uchinuma N, Tominaga H, Kojima Y, Kawashima H, Kato M, Tajika A. Beta-blockers for electroconvulsive therapy: A systematic review and meta-analysis. J Psychiatr Res 2025; 183:269-281. [PMID: 40015235 DOI: 10.1016/j.jpsychires.2025.01.059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 01/24/2025] [Accepted: 01/31/2025] [Indexed: 03/01/2025]
Abstract
Electroconvulsive therapy (ECT) is an established treatment for various mental disorders. However, ECT can induce significant haemodynamic fluctuations, raising safety concerns. This systematic review and meta-analysis aimed to evaluate the effects of adding beta-blockers to ECT on maximum heart rate after stimulation and the occurrence of adverse events. Only randomised controlled trials (RCTs) that compared the addition of beta-blockers to ECT with treatment as usual (TAU), such as placebo added to ECT or ECT without antihypertensive or antiarrhythmic medications, were included. The primary outcomes were maximum heart rate and the percentage of patients who experienced adverse events after stimulation. A total of 31 publications (33 studies, 42 comparisons, 1476 participants) were included. The beta-blocker group showed a significant reduction in maximum heart rate after stimulation compared to TAU group (28 publications, 29 studies, 38 comparisons, n = 1,375, mean difference (MD) = 21.98, 95% CI 17.94-26.02, p < 0.01). Significant differences were maintained in subgroup and sensitivity analyses. Furthermore, there was no significant increase in the risk of adverse events after stimulation compared to TAU group (20 publications, 21 studies, 27 comparisons, n = 1,014, RR = 1.44, 95% CI 0.93-2.25, p = 0.11). This is the first meta-analysis to assess the cardiovascular effects of beta-blockers during ECT. It demonstrated that the addition of beta-blockers to ECT may stabilise heart rate after stimulation without increasing adverse events. These results suggest that the addition of beta blockers may benefit high-risk patients who experience difficulty continuing ECT due to adverse events such as arrhythmias or tachycardia after stimulation.
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Affiliation(s)
- Toshiyuki Shimizu
- Department of Neuropsychiatry, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
| | - Yoshiteru Takekita
- Department of Neuropsychiatry, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
| | - Nobuatsu Aoki
- Department of Neuropsychiatry, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
| | - Taro Suwa
- Department of Neuropsychiatry, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Kazuyuki Yasuda
- Department of Neuropsychiatry, University of Yamanashi Faculty of Medicine, Yamanashi, Japan.
| | - Nina Uchinuma
- Department of Neuropsychiatry, University of Yamanashi Faculty of Medicine, Yamanashi, Japan.
| | | | - Yuki Kojima
- Department of Neuropsychiatry, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
| | - Hirotsugu Kawashima
- Department of Neuropsychiatry, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Masaki Kato
- Department of Neuropsychiatry, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
| | - Aran Tajika
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/ School of Public Health, Kyoto, Japan.
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Eibensteiner F, Mosor E, Tihanyi D, Anders S, Kornfehl A, Neymayer M, Oppenauer J, Veigl C, Al Jalali V, Domanovits H, Sulzgruber P, Schnaubelt S. The Impact of Chronic Oral Beta-Blocker Intake on Intravenous Bolus Landiolol Response in Hospitalized Intensive Care Patients with Sudden-Onset Supraventricular Tachycardia-A Post Hoc Analysis of a Cross-Sectional Trial. Pharmaceutics 2024; 16:839. [PMID: 38931959 PMCID: PMC11207374 DOI: 10.3390/pharmaceutics16060839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 06/28/2024] Open
Abstract
Background: Landiolol, a highly cardioselective agent with a short half-life (2.4-4 min), is commonly used as a perfusor or bolus application to treat tachycardic arrhythmia. Some small studies suggest that prior oral β-blocker use results in a less effective response to intravenous β-blockers. Methods: This study investigated whether prior chronic oral β-blocker (Lβ) or no prior chronic oral β-blocker (L-) intake influences the response to intravenous push-dose Landiolol in intensive care patients with acute tachycardic arrhythmia. Results: The effects in 30 patients (67 [55-72] years) were analyzed, 10 (33.3%) with and 20 (66.7%) without prior oral β-blocker therapy. Arrhythmias were diagnosed as tachycardic atrial fibrillation in 14 patients and regular, non-fluid-dependent, supraventricular tachycardia in 16 cases. Successful heart rate control (Lβ 4 vs. L- 7, p = 1.00) and rhythm control (Lβ 3 vs. L- 6, p = 1.00) did not significantly differ between the two groups. Both groups showed a significant decrease in heart rate when comparing before and after the bolus administration, without significant differences between the two groups (Lβ -26/min vs. L- -33/min, p = 0.528). Oral β-blocker therapy also did not influence the change in mean arterial blood pressure after Landiolol bolus administration (Lβ -5 mmHg vs. L- -4 mmHg, p = 0.761). Conclusions: A prior chronic intake of β-blockers neither affected the effectiveness of push-dose Landiolol in heart rate or rhythm control nor impacted the difference in heart rate or mean arterial blood pressure before and after the Landiolol boli.
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Affiliation(s)
- Felix Eibensteiner
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria; (F.E.)
| | - Emmilie Mosor
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria; (F.E.)
| | - Daniel Tihanyi
- Department of Pulmonology, Clinic Ottakring, Vienna Healthcare Group, 1160 Vienna, Austria
| | - Sonja Anders
- Department of Pulmonology, Clinic Penzing, Vienna Healthcare Group, 1140 Vienna, Austria
| | - Andrea Kornfehl
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria; (F.E.)
| | - Marco Neymayer
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria; (F.E.)
| | - Julia Oppenauer
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria; (F.E.)
| | - Christoph Veigl
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria; (F.E.)
| | - Valentin Al Jalali
- Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
| | - Hans Domanovits
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria; (F.E.)
| | - Patrick Sulzgruber
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria
| | - Sebastian Schnaubelt
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria; (F.E.)
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Floria M, Oancea AF, Morariu PC, Burlacu A, Iov DE, Chiriac CP, Baroi GL, Stafie CS, Cuciureanu M, Scripcariu V, Tanase DM. An Overview of the Pharmacokinetics and Pharmacodynamics of Landiolol (an Ultra-Short Acting β1 Selective Antagonist) in Atrial Fibrillation. Pharmaceutics 2024; 16:517. [PMID: 38675178 PMCID: PMC11054558 DOI: 10.3390/pharmaceutics16040517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 03/30/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024] Open
Abstract
Landiolol is an ultra-short-acting, selective β1-adrenergic receptor blocker that was originally approved in Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1-selectivity, potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half-life (around 4 min); moreover, it may have a potential therapeutic effects for sepsis and pediatric patients. Landiolol seems to be superior to other short-acting and selective beta-blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting β1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.
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Affiliation(s)
- Mariana Floria
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.F.); (A.B.); (D.E.I.); (D.M.T.)
- Saint Spiridon Emergency Hospital, 700115 Iasi, Romania; (C.P.C.); (G.L.B.)
| | - Alexandru Florinel Oancea
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.F.); (A.B.); (D.E.I.); (D.M.T.)
- Saint Spiridon Emergency Hospital, 700115 Iasi, Romania; (C.P.C.); (G.L.B.)
| | - Paula Cristina Morariu
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.F.); (A.B.); (D.E.I.); (D.M.T.)
- Saint Spiridon Emergency Hospital, 700115 Iasi, Romania; (C.P.C.); (G.L.B.)
| | - Alexandru Burlacu
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.F.); (A.B.); (D.E.I.); (D.M.T.)
- Cardiovascular Disease Institute, 700503 Iasi, Romania
| | - Diana Elena Iov
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.F.); (A.B.); (D.E.I.); (D.M.T.)
- Saint Spiridon Emergency Hospital, 700115 Iasi, Romania; (C.P.C.); (G.L.B.)
| | | | - Genoveva Livia Baroi
- Saint Spiridon Emergency Hospital, 700115 Iasi, Romania; (C.P.C.); (G.L.B.)
- Department of Surgery, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Celina Silvia Stafie
- Department of Preventive Medicine and Interdisciplinarity, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Magdalena Cuciureanu
- Department of Pharmacology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Viorel Scripcariu
- Department of Surgery, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
- Regional Institute of Oncology, 700483 Iasi, Romania
| | - Daniela Maria Tanase
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.F.); (A.B.); (D.E.I.); (D.M.T.)
- Saint Spiridon Emergency Hospital, 700115 Iasi, Romania; (C.P.C.); (G.L.B.)
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Bezati S, Boultadakis A, Ventoulis I, Polyzogopoulou E, Parissis JT. Optimal use of intravenous landiolol in acute cardiac care. Expert Rev Cardiovasc Ther 2023; 21:855-866. [PMID: 37902562 DOI: 10.1080/14779072.2023.2277354] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 10/26/2023] [Indexed: 10/31/2023]
Abstract
INTRODUCTION B-blockers are regarded as beneficial pharmacologic agents in cardiac care, but their role in the acute setting remains ambiguous. Increasing evidence supports the important role of landiolol in critical care, a highly cardioselective intravenous b-blocker with rapid onset of action and short elimination time. Among its most valuable properties, which may aid to overcome special reservations related to b-blocker therapy in the acute setting, landiolol has a potent negative chronotropic effect while at the same time it exhibits a mild negative inotropic effect. AREAS COVERED This expert opinion review aims to present basic pharmacologic aspects of landiolol and provide current clinical research focused on its efficacy and safety. EXPERT OPINION Landiolol is a valuable and safe pharmacologic agent in acute cardiac care. Japanese and European guidelines have incorporated its use for the management of atrial tachyarrhythmia in patients with cardiac dysfunction. Although emerging clinical trials have experimented its use in patients with sustained ventricular tachycardia/fibrillation, acute myocardial infarction undergoing primary percutaneous intervention and in patients with septic cardiomyopathy, more studies are needed in order to establish its value in such cardiac conditions.
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Affiliation(s)
- Sofia Bezati
- Emergency Medicine Department, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Antonios Boultadakis
- Emergency Medicine Department, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, Kozani, Greece
| | - Eftihia Polyzogopoulou
- Emergency Medicine Department, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - John T Parissis
- Emergency Medicine Department, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
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Schnaubelt S, Eibensteiner F, Oppenauer J, Tihanyi D, Neymayer M, Brock R, Kornfehl A, Veigl C, Al Jalali V, Anders S, Steinlechner B, Domanovits H, Sulzgruber P. Hemodynamic and Rhythmologic Effects of Push-Dose Landiolol in Critical Care-A Retrospective Cross-Sectional Study. Pharmaceuticals (Basel) 2023; 16:134. [PMID: 37259286 PMCID: PMC9967759 DOI: 10.3390/ph16020134] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 01/06/2023] [Accepted: 01/10/2023] [Indexed: 08/30/2023] Open
Abstract
BACKGROUND The highly β1-selective beta-blocker Landiolol is known to facilitate efficient and safe rate control in non-compensatory tachycardia or dysrhythmia when administered continuously. However, efficacy and safety data of the also-available bolus formulation in critically ill patients are scarce. METHODS We conducted a retrospective cross-sectional study on a real-life cohort of critical care patients, who had been treated with push-dose Landiolol due to sudden-onset non-compensatory supraventricular tachycardia. Continuous hemodynamic data had been acquired via invasive blood pressure monitoring. RESULTS Thirty patients and 49 bolus applications were analyzed. Successful heart rate control was accomplished in 20 (41%) cases, rhythm control was achieved in 13 (27%) episodes, and 16 (33%) applications showed no effect. Overall, the heart rate was significantly lower (145 (130-150) vs. 105 (100-125) bpm, p < 0.001) in a 90 min post-application observational period in all subgroups. The median changes in blood pressure after the bolus application did not reach clinical significance. Compared with the ventilation settings before the bolus application, the respiratory settings including the required FiO2 after the bolus application did not differ significantly. No serious adverse events were seen. CONCLUSIONS Push-dose Landiolol was safe and effective in critically ill ICU patients. No clinically relevant impact on blood pressure was noted.
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Affiliation(s)
- Sebastian Schnaubelt
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Felix Eibensteiner
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Julia Oppenauer
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Daniel Tihanyi
- Department of Pulmonology, Clinic Penzing, Vienna Healthcare Group, 1140 Vienna, Austria
| | - Marco Neymayer
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Roman Brock
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Andrea Kornfehl
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Christoph Veigl
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Valentin Al Jalali
- Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
| | - Sonja Anders
- Department of Pulmonology, Clinic Penzing, Vienna Healthcare Group, 1140 Vienna, Austria
| | - Barbara Steinlechner
- Department of Anaesthesia, Intensive Cate Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Hans Domanovits
- Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Patrick Sulzgruber
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria
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Ferraris A, Jacquet-Lagrèze M, Cazenave L, Fornier W, Jalalzai W, Rousseau-Saine N, Pozzi M, Fellahi JL. Effects of landiolol on macrocirculatory parameters and left and right ventricular performances following cardiac surgery: A randomized controlled trial. J Cardiothorac Vasc Anesth 2022; 36:2864-2869. [DOI: 10.1053/j.jvca.2022.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 11/11/2022]
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Abstract
Atrial tachyarrhythmias often occur in patients with worsening heart failure (HF), and the development of atrial tachyarrhythmias in acute decompensated HF (ADHF) causes an uncontrolled heart rate (HR) and leads to further exacerbation of HF and persistence of a decompensated HF state. Landiolol, a short-acting intravenous beta-1 blocker, shows very high cardiac beta-1 selectivity and has a very short elimination half-life of approximately 4 min. As shown in several reports, the benefit of intravenous landiolol is that it lowers the ventricular rate early after the start of use without markedly deteriorating haemodynamics. After the cardiac status is stabilized by rapid control of HR, subsequent basic HF pharmacotherapy and rhythm control therapies will be effective for improving outcomes. Because of the pharmacokinetic properties of landiolol, if the patient suffers an adverse reaction such as hypotension or bradycardia, such effects can be quickly reversed by tapering the dose or discontinuing use altogether. Based on several clinical studies, this review discusses the efficacy, safety and role of intravenous landiolol in acute HR control in patients with atrial tachyarrhythmias and ADHF.
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Affiliation(s)
- Tsuyoshi Shiga
- Corresponding author. Tel: +81 3 3433 1111, Fax: +81 3 5472 6466,
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Lall R, Mistry D, Skilton E, Boota N, Regan S, Bion J, Gates S, Gordon AC, Lord J, McAuley DF, Perkins G, Singer M, Young D, Whitehouse T. Study into the reversal of septic shock with landiolol (beta blockade): STRESS-L Study protocol for a randomised trial. BMJ Open 2021; 11:e043194. [PMID: 33593781 PMCID: PMC7888319 DOI: 10.1136/bmjopen-2020-043194] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
INTRODUCTION In 2013, a single-centre study reported the safe use of esmolol in patients with septic shock and tachycardia who required vasopressor therapy for more than 24 hours. Although not powered to detect a change in mortality, marked improvements were seen in survival (adjusted HR, 0.39; 95% CI, 0.26 to 0.59; p<0.001). Beta blockers are one of the most studied groups of drugs but their effect in septic shock is poorly understood; proposed mechanisms include not only the modulation of cardiac function but also immunomodulation. METHODS AND ANALYSIS STRESS-L is a randomised, open-label, non-blinded clinical trial which is enrolling a total of 340 patients with septic shock as defined by Sepsis-3 consensus definition and a tachycardia (heart rate ≥95 beats per minute (bpm)) after vasopressor treatment of at least 24 hours. Standard randomisation (1:1 ratio) allocates patients to receive usual care (according to international standards) versus usual care and a continuous landiolol infusion to reduce the heart rate between 80 and 94 bpm. The primary endpoint is the mean Sequential Organ Failure Assessment score over 14 days from entry into the trial and while in intensive care unit. Results will inform current clinical practice guidelines. ETHICS AND DISSEMINATION This trial has clinical trial authorisation from the UK competent authority, the Medicines and Healthcare products Regulatory Agency, and has been approved by the East of England-Essex Research Ethics Committee (reference: 17/EE/0368).The results of the trial will be reported first to trial collaborators. The main report will be drafted by the trial coordinating team, and the final version will be agreed by the Trial Steering Committee before submission for publication, on behalf of the collaboration. REGISTRATION The trial is funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) (Project Number: EME-14/150/85) and registered ISRCTN12600919 and EudraCT: 2017-001785-14.
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Affiliation(s)
- Ranjit Lall
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
| | - Dipesh Mistry
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
| | - Emma Skilton
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
| | | | - Scott Regan
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
| | - Julian Bion
- Intensive Care Medicine, University of Birmingham, Birmingham, UK
| | - Simon Gates
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Anthony C Gordon
- Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK
| | - Janet Lord
- NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UK
| | | | - Gavin Perkins
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Mervyn Singer
- Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK
| | - Duncan Young
- Kadoorie Centre for Critical Care Research, Nuffield Division of Anaesthesia, University of Oxford, Oxford, UK
| | - Tony Whitehouse
- Department of Critical Care and Anaesthesia, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Institute of Inflammation and Aging, University of Birmingham, Birmingham, UK
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Stix G, Wolzt M, Domanovits H, Kadlecová P, Husch B, Trebs M, Hodisch J, Unger M, Krumpl G. Open-Label Two-Dose Pilot Study of Landiolol for the Treatment of Atrial Fibrillation/Atrial Flutter in Caucasian Patients. Circ J 2019; 84:33-42. [PMID: 31813897 DOI: 10.1253/circj.cj-19-0661] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND We investigated for the first time the suitability of landiolol, an ultra-short-acting β1-specific β-blocker, for the treatment of atrial fibrillation/atrial flutter (AF/AFL) in Caucasian patients. METHODS AND RESULTS The 20 study patients received landiolol as a continuous infusion (starting dose 40 µg/kg/min) with (B+CI) or without (CI) a preceding bolus dose (100 µg/kg/min administered over 1 min) in a prospective open-label study. The primary endpoint was the proportion of patients with sustained heart rate (HR) reduction ≥20% or to <90 beats/min within 16 min of starting the CI. Secondary endpoints were the pharmacodynamics, pharmacokinetics, AF/AFL symptoms, safety and tolerability of landiolol. At 16 min, HR was reduced in all patients treated with landiolol. The primary endpoint was met by 60% of patients in the CI group and 40% in the B+CI group without a significant group difference. Overall reduction of AF/AFL symptoms at 16 min was 72%. Safety and local tolerability of landiolol were excellent, and no serious adverse events occurred. CONCLUSIONS Continuous infusion of landiolol with a starting dose of 40 µg/kg/min is suitable for the acute treatment of tachycardic AF/AFL in Caucasian patients. Administration of a preceding bolus seems unnecessary.
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Affiliation(s)
- Guenter Stix
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna
| | - Michael Wolzt
- Department of Clinical Pharmacology, Medical University of Vienna
| | - Hans Domanovits
- Department of Emergency Medicine, Medical University of Vienna
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Walter E, Heringlake M. Cost-Effectiveness Analysis of Landiolol, an Ultrashort-Acting Beta-Blocker, for Prevention of Postoperative Atrial Fibrillation for the Germany Health Care System. J Cardiothorac Vasc Anesth 2019; 34:888-897. [PMID: 31837963 DOI: 10.1053/j.jvca.2019.11.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 10/28/2019] [Accepted: 11/04/2019] [Indexed: 11/11/2022]
Abstract
OBJECTIVES Landiolol is an ultrashort-acting beta-blocker with high beta-1 receptor affinity and less blood pressure-lowering properties than other beta-blockers available for intravenous use in Germany. The present analysis aimed to determine whether perioperative treatment with landiolol in cardiac surgical patients is cost-effective under the conditions of the German Diagnosis-Related Groups health cost reimbursement system. DESIGN On the basis of clinical outcome data from a meta-analysis that included 622 patients from 7 randomized controlled trials, a decision-model was developed to determine the cost-effectiveness of landiolol versus standard-of-care (SoC). SETTING Hospital setting. PARTICIPANTS Hospital patients undergoing a representative mix of cardiac surgical procedures (MIX-CS) and isolated coronary artery bypass grafting (CABG). INTERVENTIONS Landiolol versus SoC in prevention of atrial fibrillation immediately after cardiac surgery. MEASUREMENTS AND MAIN RESULTS The model benefit was expressed in a reduction of postoperative atrial fibrillation (POAF) episodes and reduced complications. The model calculated total inpatient costs over the hospital length of stay. Costs from published sources were used for the German hospital perspective. SoC was associated with POAF rates of 36.0% to 39.2% and 24.4% to 30.1% in the MIX-CS and CABG populations, respectively. Patients with POAF had a higher morbidity and mortality. Estimated total costs for SoC patients in the MIX-CS and CABG groups were 28.792 € and 25.630 €, respectively. Landiolol reduced the incidence of POAF to 12.6% in the MIX-CS and 12.1% in the CABG groups. This was associated with a cost reduction of 2.209 € and 1.470 €. CONCLUSIONS This analysis suggests that preventing POAF with landiolol is highly cost-effective. Additional studies are needed to assess whether a comparable reduction in POAF and associated cost savings may be achieved using conventional intravenous beta-blockers or amiodarone.
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Affiliation(s)
- Evelyn Walter
- IPF Institute for Pharmaeconomic Research, Vienna, Austria.
| | - Matthias Heringlake
- Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany
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Sanad MH, Farag AB, Motaleb MA. Radioiodination and biological evaluation of landiolol as a tracer for myocardial perfusion imaging: preclinical evaluation and diagnostic nuclear imaging. RADIOCHIM ACTA 2018. [DOI: 10.1515/ract-2018-2980] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Abstract
The present work has assessed the ability and competency of radioiodinated landiolol that is considered a potential cardio selective imaging agent. Landiolol was radiosynthesized with [131I] using chloramine-T (Ch-T) as an oxidizing agent. To give high radiochemical yield of the [131I]landiolol reaching values of 98% with high stability up to 48 h. The labeled compound was separated and purified using thin layer chromatography (TLC), paper electrophoresis and high performance liquid chromatography (HPLC). Biodistribution studies indicated that [131I]landiolol gave high heart uptake ratio of [45.0±0.19% ID/g at 2 min post injection (p.i.)]. Therefore, [131I]landiolol could be considered as a novel tracer to image heart with high heart/blood ratio within 60 min.
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Affiliation(s)
- M. H. Sanad
- Labeled Compounds Department , Hot Labs Center, Atomic Energy Authority , P.O. Box 13759 , Cairo , Egypt , Tel.: 00201006131628, Fax: 0020225180527, E-mail:
| | - A. B. Farag
- Pharmaceutical Chemistry Department, Faculty of Pharmacy , Ahram Canadian University , Giza , Egypt
| | - M. A. Motaleb
- Labeled Compounds Department , Hot Labs Center, Atomic Energy Authority , P.O. Box 13759 , Cairo , Egypt
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Annane D, Ouanes-Besbes L, de Backer D, DU B, Gordon AC, Hernández G, Olsen KM, Osborn TM, Peake S, Russell JA, Cavazzoni SZ. A global perspective on vasoactive agents in shock. Intensive Care Med 2018; 44:833-846. [PMID: 29868972 DOI: 10.1007/s00134-018-5242-5] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 05/22/2018] [Indexed: 01/09/2023]
Abstract
PURPOSE We set out to summarize the current knowledge on vasoactive drugs and their use in the management of shock to inform physicians' practices. METHODS This is a narrative review by a multidisciplinary, multinational-from six continents-panel of experts including physicians, a pharmacist, trialists, and scientists. RESULTS AND CONCLUSIONS Vasoactive drugs are an essential part of shock management. Catecholamines are the most commonly used vasoactive agents in the intensive care unit, and among them norepinephrine is the first-line therapy in most clinical conditions. Inotropes are indicated when myocardial function is depressed and dobutamine remains the first-line therapy. Vasoactive drugs have a narrow therapeutic spectrum and expose the patients to potentially lethal complications. Thus, these agents require precise therapeutic targets, close monitoring with titration to the minimal efficacious dose and should be weaned as promptly as possible. Moreover, the use of vasoactive drugs in shock requires an individualized approach. Vasopressin and possibly angiotensin II may be useful owing to their norepinephrine-sparing effects.
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Affiliation(s)
- Djillali Annane
- General ICU, Raymond Poincaré Hospital (APHP), School of Medicine Simone Veil U1173 Laboratory of Infection and Inflammation (University of Versailles SQY, University Paris Saclay/INSERM), CRICS-TRIGERSEP Network (F-CRIN), 104 boulevard Raymond Poincaré, 92380, Garches, France.
| | | | - Daniel de Backer
- Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
| | - Bin DU
- Medical ICU, Peking Union Medical College Hospital, 1 Shuai Fu Yuan, 100730, Beijing, China
| | - Anthony C Gordon
- Section of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK
| | - Glenn Hernández
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Tiffany M Osborn
- Section of Acute Care Surgical Services, Surgical/Trauma Critical Care, Barnes Jewish Hospital, St. Louis, MI, USA
| | - Sandra Peake
- Department of Intensive Care, The Queen Elizabeth Hospital School of Medicine, University of Adelaide, Adelaide, SA, Australia
- School of Epidemiology and Preventive Medicine, Monash University, Victoria, Australia
| | - James A Russell
- Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada
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Pharmacodynamic and -kinetic Behavior of Low-, Intermediate-, and High-Dose Landiolol During Long-Term Infusion in Whites. J Cardiovasc Pharmacol 2018; 70:42-51. [PMID: 28437278 DOI: 10.1097/fjc.0000000000000495] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Pharmacokinetics, pharmacodynamics, safety, and tolerability of long-term administration of landiolol, a fast-acting cardioselective β-blocker, were investigated for the first time in white subjects in a prospective clinical trial. Blood concentrations of landiolol and its metabolites, heart rate (HR), blood pressure (BP), and electrocardiogram parameters were studied in 12 healthy volunteers receiving continuous infusions of a new 12-mg/mL formulation of landiolol using a dose-escalation regimen (10 μg/kg BW/min for 2 hours, 20 μg/kg BW/min for 2 hours, 40 μg/kg BW/min for 20 hours, 6 hours follow-up). Landiolol blood concentrations were dose proportional. Time until steady state decreased with increasing doses. Pharmacokinetic parameters were t1/2 = 4.5 minutes, VD = 366 mL/kg, and total body clearance = 53 mL·kg·min. Maximal blood concentrations of the inactive main metabolite M1 were 10-fold higher than those of landiolol, with t1/2 = 126 minutes, VD = 811 mL/kg, and total body clearance = 4.5 mL·kg·min. HR reduction from baseline was fast (significant after 16 minutes) and sustained throughout the administration period. Systolic and diastolic BP reductions and electrocardiogram parameter changes were less pronounced and became significant only occasionally. Recovery after discontinuation of infusion was fast with little (HR) or no (BP) rebound. The new formulation showed excellent local and general tolerability.
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Abstract
New-onset atrial fibrillation (NOAF) is the most common perioperative complication of heart surgery, typically occurring in the perioperative period. NOAF commonly occurs in patients who are elderly, or have left atrial enlargement, or left ventricular hypertrophy. Various factors have been identified as being involved in the development of NOAF, and numerous approaches have been proposed for its prevention and treatment. Risk factors include diabetes, obesity, and metabolic syndrome. For prevention of NOAF, β-blockers and amiodarone are particularly effective and are recommended by guidelines. NOAF can be treated by rhythm/rate control, and antithrombotic therapy. Treatment is required in patients with decreased cardiac function, a heart rate exceeding 130 beats/min, or persistent NOAF lasting for ≥ 48 h. It is anticipated that anticoagulant therapies, as well as hemodynamic management, will also play a major role in the management of NOAF. When using warfarin as an anticoagulant, its dose should be adjusted based on PT-INR. PT-INR should be controlled between 2.0 and 3.0 in patients aged < 70 years and between 1.6 and 2.6 in those aged ≥ 70 years. Rate control combined with antithrombotic therapies for NOAF is expected to contribute to further advances in treatment and improvement of survival.
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Affiliation(s)
- Takeshi Omae
- Department of Anesthesiology and Pain Clinic, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan. .,Department of Anesthesiology and Pain Medicine, School of Medicine, Juntendo University, Tokyo, Japan.
| | - Eiichi Inada
- Department of Anesthesiology and Pain Medicine, School of Medicine, Juntendo University, Tokyo, Japan
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Pharmacokinetics and Pharmacodynamics of Low-, Intermediate-, and High-Dose Landiolol and Esmolol During Long-Term Infusion in Healthy Whites. J Cardiovasc Pharmacol 2018; 71:137-146. [DOI: 10.1097/fjc.0000000000000554] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Domanovits H, Wolzt M, Stix G. Landiolol: pharmacology and its use for rate control in atrial fibrillation in an emergency setting. Eur Heart J Suppl 2018; 20:A1-A3. [PMID: 30188959 PMCID: PMC5909771 DOI: 10.1093/eurheartj/sux037] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
This article provides new insight on landiolol, an ultra-short acting injectable betablocker, recently approved in Europe, with regard to its pharmacokinetic and pharmacodynamic profile, along with its first experience in Caucasian healthy volunteers and patients with atrial fibrillation. Landiolol as iv formulation exhibited in an emergency setting rapid rate reduction in patients with tachycardic atrial fibrillation without pronounced blood pressure drop both in caucasian and asian populations in similar manner.
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Affiliation(s)
- Hans Domanovits
- Department of Emergency Medicine, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria
| | - Michael Wolzt
- Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria
| | - Günter Stix
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
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Koyoshi R, Shiga Y, Idemoto Y, Ueda Y, Tashiro K, Kuwano T, Kitajima K, Fujimi K, Kawamura A, Ogawa M, Miura SI. Safety of Landiolol Hydrochloride as a Premedication for Producing an Appropriate Heart Rate for Multidetector-Row Computed Tomography Coronary Angiography. J Clin Med Res 2017; 10:22-26. [PMID: 29238430 PMCID: PMC5722041 DOI: 10.14740/jocmr3213w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Accepted: 10/12/2017] [Indexed: 11/11/2022] Open
Abstract
Background We evaluated the safety of a bolus injection of landiolol hydrochloride, an ultrashort-acting β1-selective antagonist, as a premedication prior to multidetector-row computed tomography coronary angiography (CTA). Methods The subjects consisted of 176 patients (M/F = 64:112, 67 ± 11 years) who had heart rate (HR) at rest ≥ 70 beats/min (bpm) and underwent CTA. Systolic/diastolic blood pressure (SBP/DBP) and HR were measured before and after the administration of landiolol. Results SBP/DBP and HR upon entry to the CT room were 136 ± 17/80 ± 11 mm Hg and 83 ± 10 bpm, respectively. HR was significantly reduced at the time of CTA scan (62 ± 7 bpm). Next, we divided the patients into three groups according to HR upon entry to the CT room: 70 - 79 bpm (n = 76), 80 - 89 bpm (n = 60) and ≥ 90 bpm (n = 40). HR at the time of CTA scan was significantly lower than that upon entry to the CT room in all three groups: 70 - 79 bpm (74 ± 3 bpm upon entry to the CT room to 61 ± 6 bpm at the time of CAT scan), 80 - 89 bpm (84 ± 3 to 63 ± 7 bpm) and ≥ 90 bpm (98 ± 6 to 65 ± 7 bpm). Although SBP/DBP was significantly decreased after the CTA scan (123 ± 18/72 ± 12 mm Hg), landiolol had no severe adverse events throughout CTA. Conclusion In conclusion, a bolus injection of landiolol reduced HR by about 20 bpm without any severe adverse effects. Thus, a bolus injection of landiolol hydrochloride may be a suitable pretreatment for controlling HR in CTA.
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Affiliation(s)
- Rie Koyoshi
- Division of Medical Safety Management, Fukuoka University Hospital, Fukuoka, Japan.,These authors contributed equally to this work
| | - Yuhei Shiga
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan.,These authors contributed equally to this work
| | - Yoshiaki Idemoto
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Yoko Ueda
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Kohei Tashiro
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Takashi Kuwano
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Ken Kitajima
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Kanta Fujimi
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan.,Division of Rehabilitation, Fukuoka University Hospital, Fukuoka, Japan
| | - Akira Kawamura
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Masahiro Ogawa
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Shin-Ichiro Miura
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan.,Department of Molecular Cardiovascular Therapeutics, Fukuoka University School of Medicine, Fukuoka, Japan
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Krumpl G, Ulc I, Trebs M, Kadlecová P, Hodisch J. Pharmacokinetics and pharmacodynamics of two different landiolol formulations in a healthy Caucasian group. Eur J Pharm Sci 2016; 92:64-73. [PMID: 27373605 DOI: 10.1016/j.ejps.2016.06.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 06/24/2016] [Accepted: 06/25/2016] [Indexed: 11/25/2022]
Abstract
BACKGROUND To date, no data have been reported on the pharmacokinetic and pharmacodynamic properties of landiolol, a fast-acting cardioselective β1-adrenergic antagonist, in non-Asian subjects. The aim of this study was to compare two landiolol formulations in healthy Caucasian subjects. MATERIALS AND METHODS We conducted a single-center, prospective, double-blinded, randomized study in two cross-over periods with 12 healthy subjects (7 women and 5 men) each receiving three doses (0.1, 0.2, and 0.3mg/kg BW) of Onoact® 50 Lyophilized powder (50mg) or Rapibloc® concentrate IV (20mg/2mL) to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of the two landiolol formulations. RESULTS For both formulations, maximum blood concentrations of landiolol were rapidly reached (median tmax 2.3±0.65 and 2.8±1.13min for the high dose of each formulation). The compounds had a short half-life (t1/2=3.2±1.2min and 3.0±1.1min for the low dose of the concentrate formulation and the lyophilized powder, respectively). The results showed no statistically significant differences between both formulations of landiolol for any PK parameters, at study doses. Both formulations dose-dependently and significantly decreased the heart rate values from 62.2bpm at baseline to minimum values of 55-56, 52-53, and 50-52bpm after 0.1, 0.2, and 0.3mg/kg respectively. This bradycardic effect was achieved within 1 to 3min. The decrease in systolic blood pressure (baseline: 107mmHg, minimum values were around 99mmHg) was significant but not dose dependent, and occurred within 3 to 12min. Seven mild to moderate AEs occurred after administration of the concentrate formulation. No SAEs were reported in this study. CONCLUSION In Caucasians, both landiolol formulations showed similar pharmacokinetic behaviours, displaying very short half-lives (3.0 to 3.6min). In addition, after administration of both formulations, the landiolol-induced heart rate reduction showed fast onset and dose dependence, whilst the decrease of systolic blood pressure occurred more slowly, was less pronounced, and dose independent. In summary, both landiolol formulations delivered comparable plasma concentration profiles and showed good local tolerability. Overall, the pharmacokinetic and pharmacodynamic reactions observed in Caucasians were comparable to those described in Japanese subjects.
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Affiliation(s)
| | - Ivan Ulc
- Center for Pharmacology and Analysis s.r.o, Czech Republic
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Marvanova P, Padrtova T, Pekarek T, Brus J, Czernek J, Mokry P, Humpa O, Oravec M, Jampilek J. Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts. Molecules 2016; 21:molecules21060707. [PMID: 27258242 PMCID: PMC6273361 DOI: 10.3390/molecules21060707] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 05/16/2016] [Accepted: 05/23/2016] [Indexed: 12/05/2022] Open
Abstract
Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of 13C-CP/MAS and 15N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated.
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Affiliation(s)
- Pavlina Marvanova
- Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic.
| | - Tereza Padrtova
- Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic.
| | - Tomas Pekarek
- Zentiva k.s., U kabelovny 130, 10237 Prague 10, Czech Republic.
| | - Jiri Brus
- Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky sq. 2, 16206 Prague 6, Czech Republic.
| | - Jiri Czernek
- Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky sq. 2, 16206 Prague 6, Czech Republic.
| | - Petr Mokry
- Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic.
| | - Otakar Humpa
- CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 753/5, 62500 Brno, Czech Republic.
| | - Michal Oravec
- Global Change Research Institute CAS, Belidla 986/4a, 60300 Brno, Czech Republic.
| | - Josef Jampilek
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia.
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Effects of landiolol on refractory tachyarrhythmia after total cavopulmonary connection: a retrospective, observational, cohort study. J Anesth 2015; 30:331-6. [DOI: 10.1007/s00540-015-2119-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Accepted: 12/02/2015] [Indexed: 10/22/2022]
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Okajima M, Takamura M, Taniguchi T. Landiolol, an ultra-short-acting β1-blocker, is useful for managing supraventricular tachyarrhythmias in sepsis. World J Crit Care Med 2015; 4:251-257. [PMID: 26261777 PMCID: PMC4524822 DOI: 10.5492/wjccm.v4.i3.251] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 02/05/2015] [Accepted: 04/29/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether landiolol, an ultra-short-acting β1-antagonist, can safely and effectively control heart rate in septic patients with supraventricular tachyarrhythmias.
METHODS: We reviewed all patients with sepsis who admitted to our intensive care unit between January 2006 and December 2011. Sixty one septic patients suffered from supraventricular tachyarrhythmias (heart rate ≥ 120 bpm for > 1 h). Among 61 patients, 39 patients were treated with landiolol (landiolol group) and 22 patients were not treated with landiolol (control group). Arterial pressure, heart rate, cardiac rhythm, pulmonary arterial pressure and cardiac output (if a pulmonary arterial catheter was inserted) were compared between the 2 groups at 1, 8 and 24 h after the initiation of tachyarrhythmias.
RESULTS: Mean age and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were similar between the 2 groups. Paroxysmal atrial fibrillation/flutter (87%), paroxysmal atrial tachycardia (10%), and paroxysmal supraventricular tachycardia (3%) were observed. The initial landiolol dose administered was 6.3 ± 5.8 g/kg per minute. Rapid and substantial reduction of heart rate was observed in the landiolol group without any deterioration of hemodynamics. Landiolol significantly reduced heart rate (from 145 ± 14 bpm to 90 ± 20 bpm) compared to the control group (from 136 ± 21 bpm to 109 ± 18 bpm, P < 0.05). The conversion to sinus rhythm was observed more frequently in the landiolol group than in the control group at every point (P < 0.01 at 8 h; P < 0.05 at 1 and 24 h).
CONCLUSION: Landiolol safely reduced heart rate and, in part, converted to sinus rhythm in septic patients with supraventricular tachyarrhythmias.
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Xiao J, He P, Zou Q, Zhao Y, Xue Z, Deng X, Li S, Guo Q, Tao G, Yang T, Lang Z, He J, Wang X. Landiolol in the treatment of the intraoperative supraventricular tachycardia: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Anesth 2015; 27:120-8. [DOI: 10.1016/j.jclinane.2014.07.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 07/17/2014] [Accepted: 07/18/2014] [Indexed: 10/24/2022]
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Nakamura Y, Yamaji K, Saho T, Matsuzaki Z, Yuda I, Soga Y, Shirai S, Ando K, Nobuyoshi M. A comparison of bolus injection of landiolol versus oral administration of propranolol before cardiac computed tomography. SPRINGERPLUS 2014; 3:93. [PMID: 24634807 PMCID: PMC3951651 DOI: 10.1186/2193-1801-3-93] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Accepted: 01/28/2014] [Indexed: 11/25/2022]
Abstract
Heart rate (HR) reduction is essential to achieve good image quality for cardiac computed tomography (CCT). We evaluated the efficacy of a bolus injection of landiolol, an ultra-short acting β-blocker, without the administration of oral β-blocker to reduce HR prior to CCT. We enrolled 678 consecutive patients who underwent CCT from December 2011 to March 2012 and divided them into three groups, which were a propranolol group (n = 277), a low-dose landiolol group (n = 188), and a high-dose landiolol group (n = 213). Patients in the propranolol group received oral propranolol (10–20 mg) prior to CCT. Patients in the low-dose and high-dose landiolol groups were administered a bolus injection of landiolol (0.125 mg/kg), while the high-dose group received an additional 3.75 mg of landiolol if the baseline HR was ≥75/min. Although the average HR was significantly lower in the propranolol group (61.6 ± 8.0/min) than in the low-dose landiolol group (64.1 ± 7.4/min, P < 0.001), there was no significant difference in the image quality (P = 0.91). Among patients with baseline HR ≥75/min, the average HR tended to be lower in the high-dose landiolol group (67.2 ± 6.9/min) compared with the low-dose landiolol group (69.0 ± 6.9/min, P = 0.10), and there was a corresponding difference in image quality between these two groups (P = 0.02). In conclusion, Although the decrease of HR was significantly larger in the propranolol group than in the landiolol groups, the image quality was similar. Among the patients who received landiolol, a higher dose was associated with a lower HR and better image quality. Further investigation to assess higher-dose bolus injection of landiolol or bolus injection following oral administration of a β-blocker would be needed.
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Osumi M, Tashiro T, Morita Y, Kamiya S, Minematsu N, Nishimi M, Wada H. Preventive effect of intraoperative landiolol administration on atrial fibrillation after off-pump coronary artery bypass grafting. Adv Ther 2014; 31:1109-17. [PMID: 25319249 PMCID: PMC4209088 DOI: 10.1007/s12325-014-0158-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Postoperative atrial fibrillation (AF) is a common complication of cardiac surgery that is associated with an increased incidence of other complications. This study evaluated the safety and efficacy of landiolol hydrochloride--an ultrashort-acting β1-selective blocker and highly regulated drug, positioned as a class 1 antiarrhythmic in Japan guidelines--for the prevention of AF after off-pump coronary artery bypass grafting (CABG). METHODS Between January 2011 and November 2013, 116 patients underwent CABG at Fukuoka University Hospital. They were divided into two groups: group L consisted of patients who were administered landiolol hydrochloride at 2 μg/kg/min after completion of all distal anastomoses; group C was the control group consisting of patients who were not administered landiolol. Patient backgrounds, intraoperative variables and incidence of postoperative complications were compared. RESULTS No significant between-group differences were observed in patient backgrounds or incidence of complications other than postoperative AF, which occurred significantly less frequently in group L. After administration of landiolol, heart rate decreased but no change was observed in arterial pressure or other parameters, and patient hemodynamics remained stable. CONCLUSION Intraoperative and perioperative administration of low-dose landiolol has a preventive effect on the development of AF after CABG surgery.
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Affiliation(s)
- Masahiro Osumi
- Department of Cardiovascular Surgery, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0133, Japan,
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Dose-dependent effect of landiolol, a new ultra-short-acting β(1)-blocker, on supraventricular tachyarrhythmias in postoperative patients. Clin Drug Investig 2014; 33:505-14. [PMID: 23728899 PMCID: PMC3691491 DOI: 10.1007/s40261-013-0093-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
BACKGROUND β-Adrenoceptor antagonists (β-blockers) have been reported to be effective for regulation of heart rate (HR) and restoring sinus rhythm in postoperative atrial fibrillation and atrial flutter, as well as in the prevention of those arrhythmias after open-heart surgery. OBJECTIVES The objectives of this study were to evaluate the dose-dependent effects of landiolol, an ultra-short-acting β1-blocker, as well as the effectiveness and safety of the drug in suppressing supraventricular tachyarrhythmias (SVT) in postoperative patients. METHODS Landiolol was administered as a four-dose titration regimen (LL, L, M, and H doses) to postoperative patients who developed SVT. The titration sequence began with a 1-min loading infusion at a rate of 0.015 mg/kg/min, followed by a 10-min continuous infusion at 0.005 mg/kg/min (the LL dose). Infusions at progressively higher doses followed in sequence until 20 % reduction in HR was achieved. The L dose was a 1-min loading infusion at 0.03 mg/kg/min, followed by a 10-min continuous infusion at 0.01 mg/kg/min. The M dose was a 1-min loading infusion at 0.06 mg/kg/min, followed by a 10-min continuous infusion at 0.02 mg/kg/min. The H dose was a 1-min loading infusion at 0.125 mg/kg/min, followed by a 10-min continuous infusion at 0.04 mg/kg/min. The patient was then observed for 30 min to determine the cardiovascular responses to withdrawal of the medication. After completion of this follow-up period, additional maintenance infusion for up to 6 h was permitted if considered necessary by the investigator. RESULTS A total of 108 patients were enrolled in this study. The cumulative improvement rates (percentage of patients obtaining ≥20 % reduction in HR) were 11.4, 32.4, 63.1, and 87.3 % at the LL, L, M, and H doses, respectively, demonstrating the dose-dependent effectiveness of landiolol. Additional infusion for up to 6 h was conducted in 16 patients. HR was maintained between 95.5 and 116.8 beats/min during the maintenance period (mean 259.8 min). Landiolol was generally well tolerated, although one patient with sick sinus syndrome developed an approximately 5-s cardiac arrest. CONCLUSIONS The overall results, including those pertaining to patient safety, demonstrate that landiolol is effective and useful for the treatment of postoperative SVT.
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Plosker GL. Landiolol: a review of its use in intraoperative and postoperative tachyarrhythmias. Drugs 2014; 73:959-77. [PMID: 23760735 DOI: 10.1007/s40265-013-0077-4] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Landiolol (Onoact(®)) is an intravenously administered, ultra short-acting β1-blocker with an elimination half-life of 3-4 min and ≈8-fold greater cardioselectivity than esmolol in vitro. It is approved in Japan for the treatment of intraoperative and postoperative tachyarrhythmias, but in clinical practice is also used to prevent postoperative tachyarrhythmias, such as atrial fibrillation after coronary artery bypass grafting. Randomized controlled trials in patients undergoing open-heart surgery demonstrated that various dosages of landiolol (0.0005-0.04 mg/kg/min) [0.5-40 μg/kg/min] were more effective than diltiazem in converting postoperative atrial fibrillation to normal sinus rhythm during the first 8 h after surgery, and were more effective than placebo (or no landiolol) in preventing the development of atrial fibrillation during the first week after surgery (primary efficacy endpoints). In patients undergoing surgical procedures, landiolol 0.125 mg/kg/min for 1 min followed by 0.04 mg/kg/min for 10 min was superior to placebo in improving intraoperative tachycardia in randomized double-blind trials. The beneficial effects of landiolol in attenuating adverse haemodynamic or other changes that can occur during surgery or invasive procedures (e.g. percutaneous coronary intervention) have been demonstrated in a large number of randomized controlled trials. For example, several studies showed that landiolol attenuated the increase in heart rate associated with tracheal intubation, without adversely affecting blood pressure or other haemodynamic parameters. Landiolol was generally well tolerated in clinical trials, with a relatively low risk of hypotension and bradycardia, although routine monitoring of cardiac function during landiolol administration is important. In general, adverse events such as reduced blood pressure resolve quickly after discontinuation of landiolol. Thus, as an ultra short-acting β1-blocker with a rapid onset of action and readily titratable and rapidly reversible effects, landiolol represents an important agent for the management of intraoperative and postoperative tachyarrhythmias.
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Affiliation(s)
- Greg L Plosker
- Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand.
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Landiolol hydrochloride for early postoperative tachycardia after transthoracic esophagectomy. Surg Today 2013; 44:848-54. [DOI: 10.1007/s00595-013-0615-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2012] [Accepted: 03/08/2013] [Indexed: 11/26/2022]
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Hifumi T, Okada I, Kiriu N, Kato H, Inoue J, Koido Y. Clinical experience with landiolol hydrochloride in conservative management of blunt aortic injury. Am J Emerg Med 2013; 31:1290.e3-5. [PMID: 23909979 DOI: 10.1016/j.ajem.2013.03.044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Accepted: 03/23/2013] [Indexed: 11/17/2022] Open
Affiliation(s)
- Toru Hifumi
- Department of Critical Care Medicine and Trauma, National Hospital Organization Disaster Medical Center, Tachikawa, Tokyo, Japan.
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Effects of landiolol hydrochloride on intractable tachyarrhythmia after pediatric cardiac surgery. Ann Thorac Surg 2013; 95:1685-8. [PMID: 23506630 DOI: 10.1016/j.athoracsur.2013.01.057] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 01/18/2013] [Accepted: 01/29/2013] [Indexed: 11/22/2022]
Abstract
BACKGROUND While β-blockers can be effective in controlling tachyarrhythmias after pediatric cardiac surgery, a negative inotropic influence sometimes complicates their use. Landiolol hydrochloride is a novel, ultra-short-acting β-blocker recently developed in Japan. The drug has higher β1:β2 selectivity ratio and a less negative inotropic effect. This study retrospectively evaluates the efficacy and safety of landiolol in the management of tachyarrhythmias after pediatric cardiac surgery. METHODS A retrospective analysis was performed on 312 consecutive patients undergoing surgery for congenital heart disease. Twelve patients were treated with landiolol for critical tachyarrhythmia. The mean age of patients was 28.7 ± 10.6 months. Five junctional ectopic tachycardia, 2 atrial flutters, 1 paroxysmal supraventricular tachycardia, 1 atrial fibrillation, 1 atrioventricular reciprocating tachycardia with Wolff-Parkinson-White syndrome and 2 excessive sinus tachycardia were treated. RESULTS The mean loading and maintenance doses were 11.3 ± 4.0 and 6.8 ± 0.9 μg/kg per minute, respectively. Rate control was achieved in all patients. Landiolol reduced the heart rate from 169.7 ± 11.4 to 127.7 ± 7.5 beats per minute (p < 0.05) while blood pressure did not significantly change. Tachyarrhythmias were converted to sinus rhythm in 70.0% of the cases and the average time needed to achieve heart rate reduction was 2.3 ± 0.5 hours. CONCLUSIONS Landiolol was efficacious in treating tachyarrhythmia in pediatric cardiac surgery. The desired negative chronotropic effect was achieved without significant hemodynamic compromise. The ultra-short half-life of landiolol provided rapid dose manipulation. This study suggests that landiolol is a promising option for the management of postoperative tachyarrhythmias in pediatric patients.
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Nakanishi K, Takeda S, Kim C, Kohda S, Sakamoto A. Postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting or cardiac valve surgery: intraoperative use of landiolol. J Cardiothorac Surg 2013; 8:19. [PMID: 23347432 PMCID: PMC3564867 DOI: 10.1186/1749-8090-8-19] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 01/11/2013] [Indexed: 12/02/2022] Open
Abstract
Background Landiolol hydrochloride is a new β-adrenergic blocker with a pharmacological profile that suggests it can be administered safely to patients who have sinus tachycardia or tachyarrhythmia and who require heart rate reduction. This study aimed to investigate whether intraoperative administration of landiolol could reduce the incidence of atrial fibrillation (AF) after cardiac surgery. Methods Of the 200 consecutive patients whose records could be retrieved between October 2006 and September 2007, we retrospectively reviewed a total of 105 patients who met the inclusion criteria: no previous permanent/persistent AF, no permanent pacemaker, no renal insufficiency requiring dialysis, and no reactive airway disease, etc. Landiolol infusion was started after surgery had commenced, at an infusion rate of 1 μg/kg/min, titrated upward in 3–5 μg/kg/min increments. The patients were divided into 2 groups: those who received intraoperative β-blocker therapy with landiolol (landiolol group) and those who did not receive any β-blockers during surgery (control group). An unpaired t test and Fisher’s exact test were used to compare between-group differences in mean values and categorical data, respectively. Results Seventeen of the 105 patients (16.2%) developed postoperative atrial fibrillation: 5/57 (8.8%) in the landiolol group and 12/48 (25%) in the control group. There was a significant difference between the two groups (P=0.03). The incidence of AF after valve surgery and off-pump coronary artery bypass grafting was lower in the landiolol group, although the difference between the groups was not statistically significant. Conclusions Our retrospective review demonstrated a marked reduction of postoperative AF in those who received landiolol intraoperatively. A prospective study of intraoperative landiolol for preventing postoperative atrial fibrillation is warranted.
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Affiliation(s)
- Kazuhiro Nakanishi
- Department of Anesthesiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
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Hoshi T, Sato A, Nishina H, Kakefuda Y, Wang Z, Noguchi Y, Aonuma K. Acute hemodynamic effects of landiolol, an ultra-short-acting beta-blocker, in patients with acute coronary syndrome: Preliminary study. J Cardiol 2012; 60:252-6. [DOI: 10.1016/j.jjcc.2012.06.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 05/17/2012] [Accepted: 06/03/2012] [Indexed: 11/30/2022]
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Hasegawa T, Oshima Y, Maruo A, Matsuhisa H, Kadowaki T, Noda R. Landiolol for junctional ectopic tachycardia refractory to amiodarone after pediatric cardiac surgery. Gen Thorac Cardiovasc Surg 2012; 61:350-2. [PMID: 22893321 DOI: 10.1007/s11748-012-0141-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2012] [Accepted: 08/06/2012] [Indexed: 11/28/2022]
Abstract
Postoperative junctional ectopic tachycardia (JET) in children undergoing cardiac surgery is a serious arrhythmia that is associated with considerable morbidity and mortality. We present here a case of successful landiolol therapy for postoperative JET in a 3-month-old infant who underwent ventricular septal defect closure and right pulmonary artery plasty. His left ventricular function was poor postoperatively. The JET was refractory to amiodarone and caused severe hypotension, which was required cardiac massage. Continuous intravenous infusion of low-dose landiolol reduced the persistent JET rate immediately, and restored to sinus rhythm with stable hemodynamics.
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Affiliation(s)
- Tomomi Hasegawa
- Department of Cardiovascular Surgery, Kobe Children's Hospital, 1-1-1 Takakuradai, Suma-ku, Kobe 654-0081, Japan.
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Very-low-dose continuous drip infusion of landiolol hydrochloride for postoperative atrial tachyarrhythmia in patients with poor left ventricular function. Gen Thorac Cardiovasc Surg 2012; 60:386-90. [PMID: 22566247 DOI: 10.1007/s11748-012-0011-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2011] [Accepted: 06/13/2011] [Indexed: 10/28/2022]
Abstract
Three patients with poor left ventricular function (left ventricular ejection fraction <30 %) developed postoperative atrial tachyarrhythmia in intensive care. Case 1 was a 64-year-old man who underwent a modified Bentall procedure and mitral valve annuloplasty. Case 2 was a 63-year-old woman who underwent quintuple coronary artery bypass grafting. Case 3 was a 65-year-old man who underwent mitral valve replacement. Preoperative intra-aortic balloon pumping was required in Cases 2 and 3. Excellent heart rate control with no hemodynamic deterioration was achieved in all three cases by very-low-dose continuous drip infusion of landiolol hydrochloride (2-5 μg/kg/min). Very-low-dose continuous drip infusion of landiolol hydrochloride is a safe and useful alternative for the control of perioperative atrial tachyarrhythmias in patients with poor left ventricular function.
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Goyagi T, Horiguchi T, Nishikawa T, Tobe Y, Masaki Y. Neuroprotective effects of selective β-1 adrenoceptor antagonists, landiolol and esmolol, on transient forebrain ischemia in rats; a dose-response study. Brain Res 2012; 1461:96-101. [PMID: 22583856 DOI: 10.1016/j.brainres.2012.04.040] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Revised: 04/19/2012] [Accepted: 04/20/2012] [Indexed: 10/28/2022]
Abstract
Although selective beta-1 adrenoceptor antagonists are known to provide neuroprotective effects after brain ischemia, dose-response relationships of their neuroprotective effects have not been examined. The present study was conducted to evaluate whether the degree of brain protection against transient forebrain ischemia would be influenced by different doses of selective beta-1 adrenoceptor antagonists, esmolol and landiolol, in rats. Adult male S.D. rats received intravenous infusion of saline 0.5 ml/h, esmolol 20, 200, 2,000 μg/kg/min, or landiolol 5, 50, 500 μg/kg/min. Infusion was initiated 30 min prior to ischemia and continued for 24h. Ten-minute forebrain ischemia was induced by hemorrhagic hypotension and occlusion of the bilateral carotid arteries. Neurological and histological examinations were performed. Neurological deficit scores at 1, 4 and 7 days were lower, and the number of intact neurons in CA1 hippocampal region was larger in the rats treated with esmolol and landiolol after ischemia, compared with saline-treated rats (P<0.05), whereas no difference was found among different doses of esmolol and landiolol. These results suggested that selective beta-1 adrenoceptor antagonists improved neurological and histological outcomes following forebrain ischemia in rats, irrespective of their doses.
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Affiliation(s)
- Toru Goyagi
- Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine, Japan.
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Akaishi M. Intravenous infusion of ultra-short-acting β-blocker for postoperative atrial fibrillation is the one of choice. Circ J 2012; 76:1083-4. [PMID: 22361919 DOI: 10.1253/circj.cj-12-0142] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Omae T, Kanmura Y. Management of postoperative atrial fibrillation. J Anesth 2012; 26:429-37. [PMID: 22274170 PMCID: PMC3375013 DOI: 10.1007/s00540-012-1330-9] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2011] [Accepted: 01/09/2012] [Indexed: 11/24/2022]
Abstract
The impact of postoperative atrial fibrillation (PAF) on patient outcomes has prompted intense investigation into the optimal methods for prevention and treatment of this complication. In the prevention of PAF, β-blockers and amiodarone are particularly effective and are recommended by guidelines. However, their use requires caution due to the possibility of drug-related adverse effects. Aside from these risks, perioperative prophylactic treatment with statins seems to be effective for preventing PAF and is associated with a low incidence of adverse effects. PAF can be treated by rhythm control, heart-rate control, and antithrombotic therapy. For the purpose of heart rate control, β-blockers, calcium-channel antagonists, and amiodarone are used. In patients with unstable hemodynamics, cardioversion may be performed for rhythm control. Antithrombotic therapy is used in addition to heart-rate maintenance therapy in cases of PAF >48-h duration or in cases with a history of cerebrovascular thromboembolism. Anticoagulation is the first choice for antithrombotic therapy, and anticoagulation management should focus on maintaining international normalized ratio (INRs) in the 2.0–3.0 range in patients <75 years of age, whereas prothrombin-time INR should be controlled to the 1.6–2.6 range in patients ≥75 years of age. In the future, dabigatran could be used for perioperative management of PAF, because it does not require regular monitoring and has a quick onset of action with short serum half-life. Preventing PAF is an important goal and requires specific perioperative management as well as other approaches. PAF is also associated with lifestyle-related diseases, which emphasizes the ongoing need for appropriate lifestyle management in individual patients.
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Affiliation(s)
- Takeshi Omae
- Department of Anesthesiology, Fujimoto Hayasuzu Hospital, Miyakonojo, Miyazaki, Japan.
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He Q, Shi M, Liu X, Sun Y, Hu L, Yang Y, Fawcett JP, Gu J, Zhao L. Determination of landiolol, an ultra-short-acting β₁-receptor antagonist, in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2011; 891-892:7-11. [PMID: 22418070 DOI: 10.1016/j.jchromb.2011.12.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2011] [Revised: 12/21/2011] [Accepted: 12/22/2011] [Indexed: 11/18/2022]
Abstract
A method for the determination of landiolol, an ultra-short-acting β₁-adrenoreceptor antagonist, in human plasma has been developed and validated. With the addition of pyridostigmine bromide to stabilize landiolol in the blood/plasma samples, and bisoprolol as internal standard, plasma samples were subjected to liquid-liquid extraction with diethyl ether:dicholoromethane (60:40, v/v) prior to assay by liquid chromatography-tandem mass spectrometry. Separation was performed on a TC-C₁₈ column (150 mm × 4.6 mm, 5 μm) using a mobile phase of methanol:10 mM ammonium acetate containing 1% formic acid (65:35, v/v) in a run time of 3.5 min. Detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring of the precursor-to-product ion transitions of landiolol at m/z 510.1→157.2 and bisoprolol at m/z 326.3→116.1. The method was linear over the concentration range 0.5-500 ng/ml with a lower limit of quantitation of 0.5 ng/ml. Intra- and inter-day precisions (as relative standard deviation, RSD) were <4.4% and <10.0%, respectively, with accuracy (as relative error, RE) <10.0%. The method was successfully applied to a clinical pharmacokinetic study involving a continuous infusion of landiolol hydrochloride to healthy Chinese volunteers.
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Affiliation(s)
- Qun He
- Clinical Pharmacology Center, Institute for Translational Medicine, Norman Bethune First Hospital, Jilin University, 519 Dongminzhu Street, Changchun 130061, PR China
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Nakano T, Shimizu K, Kawashima O, Kamiyoshihara M, Nagashima T, Ibe T, Takeyoshi I. Effect of landiolol hydrochloride, an ultra-short-acting beta 1-selective blocker, on supraventricular tachycardia, atrial fibrillation and flutter after pulmonary resection. J Clin Pharm Ther 2011; 37:431-5. [PMID: 22059486 DOI: 10.1111/j.1365-2710.2011.01315.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Supraventricular tachycardia is a common complication after pulmonary resection. The objective of this study was to investigate the efficacy of landiolol hydrochloride, an ultra-short-acting β1-blocker, in patients with post-operative supraventricular tachycardia after pulmonary resection. METHODS The response to continuous intravenous infusion of landiolol was evaluated in 25 patients who developed post-operative atrial fibrillation or atrial flutter after major pulmonary resection. Four patients had preoperative rate-controlled chronic atrial fibrillation. The heart rate and blood pressure were compared before and after infusion of landiolol. Side effects and recurrence of supraventricular tachycardia after termination of landiolol infusion were also monitored. RESULTS AND DISCUSSION The heart rate was reduced from 135±24 bpm before landiolol infusion to a plateau rate of 85±19 bpm during infusion (P<0·0001). Heart rate reduction occurred in all but two patients. Conversion to normal sinus rhythm from supraventricular tachycardia occurred in 14 patients (56%). Recurrence of supraventricular tachycardia after stopping landiolol infusion was observed in 17 patients (68%), but all patients without preoperative AF were cured of post-operative AF. There were no detectable side effects, including no adverse influence on the circulatory and respiratory systems. WHAT IS NEW AND CONCLUSION Continuous intravenous infusion of landiolol was found to be effective and safe for supraventricular tachycardia after pulmonary resection.
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Affiliation(s)
- T Nakano
- Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Gunma, Japan
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Wajima Z, Tsuchida H, Shiga T, Imanaga K, Inoue T. Intravenous landiolol, a novel β(1)-adrenergic blocker, reduces the minimum alveolar concentration of sevoflurane in women. J Clin Anesth 2011; 23:292-6. [PMID: 21663813 DOI: 10.1016/j.jclinane.2010.11.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Revised: 09/30/2010] [Accepted: 11/09/2010] [Indexed: 11/18/2022]
Abstract
STUDY OBJECTIVE To investigate the effect of intravenous (IV) landiolol, a novel β(1)-adrenergic blocker, on the minimum alveolar concentration (MAC) of sevoflurane in adult women. DESIGN Prospective, randomized study. SETTING University hospital. PATIENTS 42 ASA physical status 1 and 2 women, aged 24-57 years, who were scheduled to undergo elective abdominal surgery. INTERVENTIONS Anesthesia was induced in all patients by vital capacity rapid inhalation induction of sevoflurane. In the landiolol group, administration of landiolol began when patients took a vital-capacity breath: 0.125 mg/kg/min for one minute and then 0.04 mg/kg/min. Normal saline was administered in the control group. MEASUREMENTS MAC was determined by a technique adapted from the conventional up-down method. MAIN RESULTS The MAC of sevoflurane was 2.2% ± 0.2% in the control group and 1.7% ± 0.2% in the landiolol group, a statistically significant difference (P = 0.0005). CONCLUSIONS IV landiolol reduces the MAC of sevoflurane in women by approximately 20%.
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Affiliation(s)
- Zen'ichiro Wajima
- Department of Anesthesiology, Shioya Hospital, International University of Health and Welfare, Tochigi 329-2145, Japan.
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Safety and Efficacy of Low-Dose Continuous Infusion of Landiolol, an Ultra-Short-Acting β-blocker, in Cardiac Surgery. J Arrhythm 2011. [DOI: 10.1016/s1880-4276(11)80008-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Wajima Z, Shiga T, Imanaga K, Inoue T. Prophylactic continuous administration of landiolol, a novel β1 blocker, blunts hyperdynamic responses during electroconvulsive therapy without altering seizure activity. Int J Psychiatry Clin Pract 2010; 14:132-6. [PMID: 24922473 DOI: 10.3109/13651500903494531] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Abstract Objective. In previous reports, it has been shown that many drugs may act against hyperdynamic responses during electro-convulsive therapy (ECT). The aim of this study was to conduct a randomized, placebo-controlled crossover study to investigate the hemodynamic responses and seizure duration during ECT by continuous administration of two doses of landiolol, a novel short-acting β1-adrenergic blocker, including standard and high-dose. Methods. Thirty-two patients undergoing ECT participated in this study. The control treatment was infusion of saline alone. The standard-dose of landiolol, 0.125 mg/kg per min, was infused over a 1-min period as a standard treatment. The high-dose landiolol treatment was 0.25 mg/kg per min, also infused over a 1-min period. After landiolol treatments, patients received landiolol at 0.04 mg/kg per min. Propofol and succinylcholine was then administered, and electrical stimulation was applied. Results. Both peak heart rate and mean arterial pressure after ECT was lowest with high-dose landiolol treatment. Motor and EEG seizure duration did not differ among the treatments. Conclusion. The results of this study show that high-dose landiolol treatment blunts hyperdynamic responses during ECT. Furthermore, landiolol does not reduce the seizure duration.
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Affiliation(s)
- Zen'ichiro Wajima
- Department of Anesthesiology, Shioya Hospital, International University of Health and Welfare, Tochigi, Japan
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Inoue S, Tanaka Y, Kawaguchi M, Furuya H. The efficacy of landiolol for suppressing the hyperdynamic response following laryngoscopy and tracheal intubation: a systematic review. Anaesth Intensive Care 2010; 37:893-902. [PMID: 20014594 DOI: 10.1177/0310057x0903700621] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Landiolol is a recently developed, selective short-acting beta1-antagonist. The aim of the study was to evaluate the efficacy of landiolol for suppressing haemodynamic changes induced by laryngoscopy and tracheal intubation (LTI) in Japanese patients. A comprehensive search was undertaken to identify all randomised comparisons of landiolol with placebo that examined effects on haemodynamic responses following LTI. MEDLINE, Cochrane CENTRAL, EMBASE and the Japanese Central Review of Medicine were searched from their date of inception to February 2009. Trials were included in the review if heart rate, systolic blood pressure or mean blood pressure was recorded at three different stages: pre-induction, just before intubation and in the post-intubation period. Weighted mean differences and 95% confidence intervals (CI) were calculated for changes in haemodynamic variables between treatment and placebo groups. Seven randomised controlled trials involving 325 patients were included in the study. Of these, five trials that used the same continuous infusion regimen for landiolol (0.125 mg/kg/minute for one minute followed by 0.04 mg/kg/minute) showed efficacy in attenuation of heart rate and blood pressure following LTI (heart rate weighted mean difference: -21.18 bpm, 95% CI -18.59 to -14.20; systolic blood pressure weighted mean difference: -23.03 mmHg, 95% CI -43.59 to -2.47; mean blood pressure weighted mean difference: -16.26 mmHg, 95% CI -23.96 to -8.55). The other two studies used bolus administration of landiolol (0.1 to 0.3 mg/kg), but it was difficult to evaluate the efficacy because of the limited amount of data. Landiolol administration at 0.125 mg/kg/minute for one minute followed by 0.04 mg/kg/minute effectively suppresses the increases in heart rate and blood pressure following LTI. For a bolus regimen of landiolol, further studies are required to determine the efficacy and the optimal dose and timing for suppression of haemodynamic responses following LTI.
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Affiliation(s)
- S Inoue
- Department ofAnesthesiology, Nara Medical University, Nara, Japan
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Kadoi Y, Saito S. Possible indications of beta-blockers in the perioperative period other than prevention of cardiac ischemia. J Anesth 2010; 24:81-95. [DOI: 10.1007/s00540-009-0865-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Miwa Y, Ikeda T, Mera H, Miyakoshi M, Hoshida K, Yanagisawa R, Ishiguro H, Tsukada T, Abe A, Yusu S, Yoshino H. Effects of Landiolol, an Ultra-Short-Acting .BETA.1-Selective Blocker, on Electrical Storm Refractory to Class III Antiarrhythmic Drugs. Circ J 2010; 74:856-63. [DOI: 10.1253/circj.cj-09-0772] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Yosuke Miwa
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Takanori Ikeda
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Hisaaki Mera
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Mutsumi Miyakoshi
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Kyoko Hoshida
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Ryoji Yanagisawa
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Haruhisa Ishiguro
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Takehiro Tsukada
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Atsuko Abe
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Satoru Yusu
- Second Department of Internal Medicine, Kyorin University School of Medicine
| | - Hideaki Yoshino
- Second Department of Internal Medicine, Kyorin University School of Medicine
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Conversion of atrial flutter to sinus rhythm during landiolol infusion. J Anesth 2009; 24:107-9. [PMID: 20039082 DOI: 10.1007/s00540-009-0824-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2008] [Accepted: 07/20/2009] [Indexed: 10/20/2022]
Abstract
A 73-year-old male patient with a past history of hypertension and atrial premature contraction underwent endoscopic restoration of the left bubonocele. Sinus rhythm was confirmed by preoperative electrocardiography, but paroxysmal atrial flutter developed when abdominoscopy was started. Continuous administration of landiolol hydrochloride at a dose of 0.005 mg kg(-1) min(-1) after a loading dose of 0.04 mg kg(-1) min(-1) for 1 min resulted in control of heart rate without a decrease in blood pressure. Atrial flutter was converted to sinus rhythm 3 min after the start of administration. Landiolol hydrochloride was administered continuously until the morning of the following day and sinus rhythm was maintained postoperatively.
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Kaneko M, Yamaguchi S, Hamaguchi S, Egawa H, Fujii K, Ishikawa K, Kitajima T, Minami J. Effects of landiolol on QT interval and QT dispersion during induction of anesthesia using computerized measurement. J Clin Anesth 2009; 21:555-61. [PMID: 20122586 DOI: 10.1016/j.jclinane.2008.12.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2008] [Revised: 12/26/2008] [Accepted: 12/30/2008] [Indexed: 10/20/2022]
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Ichikawa M, Ishiyama T, Shibuya K, Matsukawa T. Transient sinus arrest during continuous infusion of landiolol in an elderly patient. J Anesth 2009; 23:637-8. [PMID: 19921388 DOI: 10.1007/s00540-009-0814-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2009] [Accepted: 06/29/2009] [Indexed: 11/29/2022]
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Wariishi S, Yamashita K, Nishimori H, Fukutomi T, Yamamoto M, Radhakrishnan G, Sasaguri S. Postoperative administration of landiolol hydrochloride for patients with supraventricular arrhythmia: the efficacy of sustained intravenous infusion at a low dose. Interact Cardiovasc Thorac Surg 2009; 9:811-3. [PMID: 19666952 DOI: 10.1510/icvts.2009.212837] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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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Affiliation(s)
- Seiichiro Wariishi
- Department of Surgery II, Kochi University, Kohasu, Nankoku, Kochi, Japan.
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Effect of landiolol hydrochloride on suxamethonium-induced neuromuscular block. J Anesth 2009; 23:188-91. [PMID: 19444555 DOI: 10.1007/s00540-008-0727-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2008] [Accepted: 11/26/2008] [Indexed: 10/20/2022]
Abstract
PURPOSE The aim of this study was to examine the effect of landiolol hydrochloride, an ultrashort-acting beta(1)-blocker, on suxamethonium-induced neuromuscular block. METHODS Thirty patients were randomly allocated to receive a loading dose of landiolol, 0.125 mg x kg(-1) x min(-1) for 1 min, followed by an infusion at 0.04 mg x kg(-1) x min(-1), or placebo. Twenty minutes after the infusion of landiolol or placebo, suxamethonium 1 mg x kg(-1) was administered during propofolfentanyl-nitrous oxide anesthesia. Neuromuscular block was monitored by train-of-four (TOF) responses of the adductor pollicis muscle, applying acceleromyographic stimuli to the ulnar nerve. RESULTS The onset of neuromuscular block did not differ between the groups. The time from administration of suxamethonium to spontaneous recovery to the first twitch of TOF (T1) of control was significantly longer in the landiolol group (mean [SD]; 12.2 [2.5] min), when compared with the control group (9.8 [2.6] min). However, the TOF ratios measured when the T1 had spontaneously recovered to 10%, 25%, 50%, 75%, 90%, and 100% of control was comparable between the groups. CONCLUSION Landiolol delayed recovery from suxamethonium-induced paralysis. However, the interaction between the drugs seemed to be small in the clinical setting.
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