Ftikos Panagiotis, Falara Areti, Rellia Panagiota, Leontiadis Evangelos, Samanidis George, Kamperi Natalia, Piperakis Artemios, Tamvakopoulos Constantin, Antoniou Theofani, Theodoraki Kassiani
Department of Anesthesiology, Onassis Cardiac Surgery Center, 176 74 Athens, Greece.
Department of Cardiology, Onassis Cardiac Surgery Center, 176 74 Athens, Greece.
Pharmaceuticals (Basel). 2023 May 30;16(6):815. doi: 10.3390/ph16060815.
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.
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.
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.
LS administration decreases pulmonary artery pressure and may improve right ventricular function in patients with PH undergoing cardiac surgery.
接受心脏手术的肺动脉高压（PH）患者的围手术期管理是最具挑战性的临床情况之一。这一事实主要取决于PH与右心室衰竭（RVF）之间的关系。左西孟旦（LS）是一种血管扩张剂，可能是治疗PH和RVF的有效药物。本研究的目的是研究体外循环（CPB）时间对LS治疗药物监测的影响，并评估在患有PH的心脏手术患者中预先给予LS对围手术期血流动力学和超声心动图参数的影响。
在本研究中，在CPB前对接受心脏手术的成年患者给予LS，以防止术前存在的PH恶化及随后的右心室功能障碍。30例术前确诊为PH的心脏手术患者在麻醉诱导后随机接受6μg/kg或12μg/kg的LS。CPB后测量LS的血浆浓度。在本研究中，使用了低样本量并结合简单的样本制备方案。血浆样本通过蛋白沉淀法提取并蒸发；然后，使用特异性和灵敏的生物分析液相色谱-质谱联用（LC-MS/MS）方法对分析物进行重构和检测。在给药前后记录并评估临床、血流动力学和超声心动图参数。
开发了一种快速生物分析LC-MS/MS方法（运行时间为5.5分钟），用于同时测定人血浆中的LS及其主要代谢产物OR-1896。LC-MS/MS方法在LS浓度范围为0.1-50 ng/mL、其代谢产物OR-1896浓度范围为1-50 ng/mL时呈线性。测得的LS血浆浓度与CPB时间呈负相关。心脏手术期间CPB前给予LS可有效降低肺动脉压并改善CPB后的血流动力学参数，药物在12μg/kg剂量时效果更显著且持久。此外，在CPB前对患有PH的心脏手术患者给予12μg/kg剂量的LS可改善右心室功能。
给予LS可降低肺动脉压，并可能改善接受心脏手术的PH患者的右心室功能。
