应用响应曲面模型法研究丙泊酚与瑞芬太尼的最佳配伍剂量

目的:应用响应曲面模型法研究丙泊酚与瑞芬太尼合用抑制喉镜置入刺激的体动反应、循环反应及出现循环抑制副作用，评估两药相互作用方式和程度，并探索丙泊酚与瑞芬太尼最佳配伍剂量范围。方法:ASA Ⅰ-Ⅱ级患者70例，随机平行分组，选择一个预设的丙泊酚靶控输注浓度并维持丙泊酚靶浓度不变，阶梯式增加瑞芬太尼的靶浓度，评估喉镜置入刺激的体动反应、循环反应和循环抑制副作用。应用响应曲面模型分析丙泊酚与瑞芬太尼的药效学相互作用，构建最佳反应阈值范围。结果:响应曲面模型显示丙泊酚（≤9 μg/mL）和瑞芬太尼（≤10 ng/mL）联合使用在抑制喉镜置入体动反应、循环反应和产生循环抑制副作用有明显协同作用，Imax分别为2.89、5.02和2.55。将不同药效学观察指标的响应曲面相结合，构建出最佳配伍剂量范围。结论:响应曲面模型可以定性并定量的研究丙泊酚与瑞芬太尼之间的药物相互作用，并创建最佳反应阈值范围。

Response surface model to optimize the concentration range of propofol and remifentanil

AIM: To investigate the pharmacodynamic interactions between propofol and remifentanil by response surface methodology. The response surface for inhibition of somatic, hemodynamic responses to laryngoscopy and response surface of cardiovascular side effects were combined to identify the optimal combination of propofol and remifentanil. METHODS: Seventy ASA I-II patients were grouped randomly and parallelly. The patients received target-controlled infusion (TCI) of propofol (0-9 μg/mL) at a fixed concentration, then remifentanil was administrated with TCI device from 0 to 10 ng/mL in a stepwise ascending fashion. After reaching pseudo-steady-state drug levels, the somatic and hemodynamic responses to laryngoscopy and cardiovascular side effects were observed. The pharmacodynamic interactions were investigated by response surface methodology. RESULTS:Response surface models revealed significant synergy between propofol and remifentanil. Imax were 2.89, 5.02 and 2.55 for the somatic and hemodynamic responses to laryngoscopy and cardiovascular side effects. Based on the results of response surface method, the optimal dose range of propofol and remifentanil was constructed.CONCLUSION: Response surface method can analyze the pharmacodynamic interactions qualitatively and quantitatively and provide the optimal dose range.