Garraza-Obaldia Maite, Jaramillo Sebastian, Parra-Guillen Zinnia P, Valencia José F, Gambús Pedro L, Trocóniz Iñaki F
Department of Pharmaceutical Sciences, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
Pharmaceutics. 2024 Dec 19;16(12):1615. doi: 10.3390/pharmaceutics16121615.
: Despite the known impact of propofol and remifentanil on hemodynamics and patient outcomes, there is a lack of comprehensive quantitative analysis, particularly in surgical settings, considering the influence of noxious stimuli. The aim of this study was to develop a quantitative semi-mechanistic population model that characterized the time course changes in mean arterial pressure (MAP) and heart rate (HR) due to the effects of propofol, remifentanil, and different types of noxious stimulation related to the clinical routine. : Data from a prospective study were used; the study analyzed the effects of propofol and remifentanil general anesthesia on female patients in physical status of I-II according to the American Society of Anesthesiologists (ASA I-II) undergoing gynecology surgery. Patients were consecutively assigned to different administration schemes of propofol and remifentanil targeted at different effect-site concentrations. Esophageal instrumentation, laryngeal mask airway insertion, hysteroscopy, and tetanus stimuli were applied. Data from patients with chronic hypertension were discarded. : MAP and HR observations from 77 patients were analyzed. The hemodynamic effects were described using turn-over models incorporating feedback mechanisms. Analyses revealed that propofol and remifentanil elicited effects on the turn-over of MAP and HR, respectively, with estimates of plasma drug concentrations causing an inhibition-half of the maximum effect (50) of 8.79 µg∙mL and 4.57 ng∙mL. Hysteroscopy exerted an increase in MAP (but not in HR), which was well-characterized by the model, with a predicted typical increase of 28 mmHg and a dissipation half-life of 33 min. The impact of other noxious stimuli on MAP or HR could not be identified. Model simulations indicated that propofol and remifentanil, titrated to inhibit the motor response to noxious stimuli, regardless of dose combinations, cause a significant risk of hypotension, especially following induction and at the end of surgery (when surgical intervention is completed, before the awakening phase). : The developed semi-mechanistic and fully identifiable model provides quantitative information on how propofol, remifentanil, and surgical stimulus (hysteroscopy) interact to produce the hemodynamic changes (of MAP and HR) commonly observed in clinical practice.
尽管丙泊酚和瑞芬太尼对血流动力学和患者预后的影响已为人所知，但考虑到有害刺激的影响，尤其是在手术环境中，仍缺乏全面的定量分析。本研究的目的是建立一个定量半机制群体模型，以描述由于丙泊酚、瑞芬太尼的作用以及与临床常规相关的不同类型有害刺激导致的平均动脉压（MAP）和心率（HR）随时间的变化过程。：使用了一项前瞻性研究的数据；该研究分析了丙泊酚和瑞芬太尼全身麻醉对根据美国麻醉医师协会（ASA I-II）身体状况为I-II级的接受妇科手术的女性患者的影响。患者被连续分配到针对不同效应部位浓度的丙泊酚和瑞芬太尼不同给药方案。进行了食管插管、喉罩置入、宫腔镜检查和破伤风刺激。患有慢性高血压的患者的数据被剔除。：分析了77例患者的MAP和HR观察结果。使用包含反馈机制的周转模型描述血流动力学效应。分析表明，丙泊酚和瑞芬太尼分别对MAP和HR的周转产生影响，导致最大效应抑制一半（IC50）的血浆药物浓度估计值分别为8.79μg∙mL和4.57 ng∙mL。宫腔镜检查使MAP升高（但HR未升高），该模型对此有很好的描述，预测典型升高为28 mmHg，消散半衰期为33分钟。无法确定其他有害刺激对MAP或HR的影响。模型模拟表明，滴定丙泊酚和瑞芬太尼以抑制对有害刺激的运动反应，无论剂量组合如何，都会导致显著的低血压风险，尤其是在诱导后和手术结束时（手术干预完成后，苏醒阶段之前）。：所建立的半机制且完全可识别的模型提供了关于丙泊酚、瑞芬太尼和手术刺激（宫腔镜检查）如何相互作用以产生临床实践中常见的血流动力学变化（MAP和HR）的定量信息。
