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Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters

Introduction: The perioperative management of patients with pulmonary hypertension (PH) undergoing cardiac surgery represents one of the most challenging clinical scenarios. This fact mainly depends on the relationship existing between PH and right ventricular failure (RVF). Levosimendan (LS) is an...

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Autores principales: Ftikos, Panagiotis, Falara, Areti, Rellia, Panagiota, Leontiadis, Evangelos, Samanidis, George, Kamperi, Natalia, Piperakis, Artemios, Tamvakopoulos, Constantin, Antoniou, Theofani, Theodoraki, Kassiani
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305589/
https://www.ncbi.nlm.nih.gov/pubmed/37375762
http://dx.doi.org/10.3390/ph16060815
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author Ftikos, Panagiotis
Falara, Areti
Rellia, Panagiota
Leontiadis, Evangelos
Samanidis, George
Kamperi, Natalia
Piperakis, Artemios
Tamvakopoulos, Constantin
Antoniou, Theofani
Theodoraki, Kassiani
author_facet Ftikos, Panagiotis
Falara, Areti
Rellia, Panagiota
Leontiadis, Evangelos
Samanidis, George
Kamperi, Natalia
Piperakis, Artemios
Tamvakopoulos, Constantin
Antoniou, Theofani
Theodoraki, Kassiani
author_sort Ftikos, Panagiotis
collection PubMed
description Introduction: The perioperative management of patients with pulmonary hypertension (PH) undergoing cardiac surgery represents one of the most challenging clinical scenarios. This fact mainly depends on the relationship existing between PH and right ventricular failure (RVF). Levosimendan (LS) is an inodilator that might be an effective agent in the treatment of PH and RVF. The aim of this study was to examine the impact of the duration of cardiopulmonary bypass (CPB) on the therapeutic drug monitoring of LS and to evaluate the effect of preemptive administration of LS on perioperative hemodynamic and echocardiographic parameters in cardiac surgical patients with preexisting PH. Materials and Methods: In this study, LS was administered in adult patients undergoing cardiac surgery before CPB in order to prevent exacerbation of preexisting PH and subsequent right ventricular dysfunction. Thirty cardiac surgical patients with preoperatively confirmed PH were randomized to receive either 6 μg/kg or 12 μg/kg of LS after the induction of anesthesia. The plasma concentration of LS was measured after CPB. In this study, a low sample volume was used combined with a simple sample preparation protocol. The plasma sample was extracted by protein precipitation and evaporated; then, the analyte was reconstituted and detected using specific and sensitive bioanalytical liquid chromatography with mass spectrometry (LC-MS/MS) methodology. The clinical, hemodynamic, and echocardiographic parameters were registered and evaluated before and after the administration of the drug. Results: A fast bioanalytical LC-MS/MS methodology (a run time of 5.5 min) was developed for the simultaneous determination of LS and OR-1896, its main metabolite in human plasma. The LC-MS/MS method was linear over a range of 0.1–50 ng/mL for LS and 1–50 ng/mL for its metabolite OR-1896. Measured plasma concentrations of LS were inversely related to the duration of CPB. LS administration before CPB during cardiac surgery was effective in reducing pulmonary artery pressure and improving hemodynamic parameters after CPB, with a more pronounced and durable effect of the drug at the dose of 12 μg/kg. Additionally, administration of LS at a dose of 12 μg/kg in cardiac surgical patients with PH before CPB improved right ventricular function. Conclusion: LS administration decreases pulmonary artery pressure and may improve right ventricular function in patients with PH undergoing cardiac surgery.
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spelling pubmed-103055892023-06-29 Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters Ftikos, Panagiotis Falara, Areti Rellia, Panagiota Leontiadis, Evangelos Samanidis, George Kamperi, Natalia Piperakis, Artemios Tamvakopoulos, Constantin Antoniou, Theofani Theodoraki, Kassiani Pharmaceuticals (Basel) Article Introduction: The perioperative management of patients with pulmonary hypertension (PH) undergoing cardiac surgery represents one of the most challenging clinical scenarios. This fact mainly depends on the relationship existing between PH and right ventricular failure (RVF). Levosimendan (LS) is an inodilator that might be an effective agent in the treatment of PH and RVF. The aim of this study was to examine the impact of the duration of cardiopulmonary bypass (CPB) on the therapeutic drug monitoring of LS and to evaluate the effect of preemptive administration of LS on perioperative hemodynamic and echocardiographic parameters in cardiac surgical patients with preexisting PH. Materials and Methods: In this study, LS was administered in adult patients undergoing cardiac surgery before CPB in order to prevent exacerbation of preexisting PH and subsequent right ventricular dysfunction. Thirty cardiac surgical patients with preoperatively confirmed PH were randomized to receive either 6 μg/kg or 12 μg/kg of LS after the induction of anesthesia. The plasma concentration of LS was measured after CPB. In this study, a low sample volume was used combined with a simple sample preparation protocol. The plasma sample was extracted by protein precipitation and evaporated; then, the analyte was reconstituted and detected using specific and sensitive bioanalytical liquid chromatography with mass spectrometry (LC-MS/MS) methodology. The clinical, hemodynamic, and echocardiographic parameters were registered and evaluated before and after the administration of the drug. Results: A fast bioanalytical LC-MS/MS methodology (a run time of 5.5 min) was developed for the simultaneous determination of LS and OR-1896, its main metabolite in human plasma. The LC-MS/MS method was linear over a range of 0.1–50 ng/mL for LS and 1–50 ng/mL for its metabolite OR-1896. Measured plasma concentrations of LS were inversely related to the duration of CPB. LS administration before CPB during cardiac surgery was effective in reducing pulmonary artery pressure and improving hemodynamic parameters after CPB, with a more pronounced and durable effect of the drug at the dose of 12 μg/kg. Additionally, administration of LS at a dose of 12 μg/kg in cardiac surgical patients with PH before CPB improved right ventricular function. Conclusion: LS administration decreases pulmonary artery pressure and may improve right ventricular function in patients with PH undergoing cardiac surgery. MDPI 2023-05-30 /pmc/articles/PMC10305589/ /pubmed/37375762 http://dx.doi.org/10.3390/ph16060815 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ftikos, Panagiotis
Falara, Areti
Rellia, Panagiota
Leontiadis, Evangelos
Samanidis, George
Kamperi, Natalia
Piperakis, Artemios
Tamvakopoulos, Constantin
Antoniou, Theofani
Theodoraki, Kassiani
Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters
title Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters
title_full Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters
title_fullStr Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters
title_full_unstemmed Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters
title_short Monitoring of Levosimendan Administration in Patients with Pulmonary Hypertension Undergoing Cardiac Surgery and Effect of Two Different Dosing Schemes on Hemodynamic and Echocardiographic Parameters
title_sort monitoring of levosimendan administration in patients with pulmonary hypertension undergoing cardiac surgery and effect of two different dosing schemes on hemodynamic and echocardiographic parameters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305589/
https://www.ncbi.nlm.nih.gov/pubmed/37375762
http://dx.doi.org/10.3390/ph16060815
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