【摘要】 目的评价丙泊酚复合瑞芬太尼用于经阴道取卵术麻醉的临床效果,根据给药时间、剂量和药代动力学模型,用计算机模拟药物浓度,建立并分析药效学模型及其特点。方法静脉麻醉下行经阴道取卵术患者42例,ASAⅠ或Ⅱ级,随机分为两组,分别静脉注射瑞芬太尼1.5μg/kg+丙泊酚1.5mg/kg（PR15组,n=24）或瑞芬太尼1.0μg/kg+丙泊酚1.0 mg/kg（PR10组,n=18）。根据患者体动反应和自诉疼痛情况,酌情追加瑞芬太尼0.5μg/kg和/或丙泊酚0.5 mg/kg。麻醉质量评价主要指标包括睫毛反射消失时间、定向力恢复时间、低氧发生率（SpO₂<92%）及其他不良反应。基于模拟浓度、非线性混合效应模型、采用NONMEM软件建立药效学模型。结果PR15组患者定向力恢复时间明显慢于PR10组[（4.9±1.3）min vs（3.6±1.2）min,P<0.05];但两组睫毛反射消失时间[（58±14）s vs（64±13）s]、低氧（12.5%vs 16.7%）和咳嗽（16.7%vs11.1%）发生率差异无统计学意义。50%患者有效镇静的丙泊酚浓度和有效镇痛的瑞芬太尼浓度(EC₅₀)分别是1.71μg/ml、2.57ng/ml;95%患者有效镇静的丙泊酚浓度和有效镇痛的瑞芬太尼浓度(EC₉₅)分别为4.30μg/ml、4.57ng/ml。丙泊酚1.0 mg/kg产生的峰效应位浓度低于EC₅₀,而1.5mg/kg产生的峰效应位则高于EC₅₀;但瑞芬太尼1.0、1.5μg/kg产生的峰效应位浓度均高于EC₅₀,后者接近EC₉₅。结论基于患者恢复时间,经阴道取卵术麻醉时瑞芬太尼1.0μg/kg复合丙泊酚1.0mg/kg较为合适。更多还原

【Abstract】 Objective To evaluate the clinical anesthetic efficacy of a combination of propofol and remifentanil for ultrasound-guided transvaginal oocyte retrieval.Pharmacodynamic（PD）model was established and its characteristics were analyzed based on the simulated concentrations of propofol and remifentanil in respective pharmacokinetic models,so as to guide further study.Methods Forty-two female patients undergoing transvaginal oocyte retrieval were divided into groups PR15（n=24）and PR10（n=18）,who were received intravenous bolus of remifentanil 1.5μg/kg + propofol 1.5 mg/kg and remifentanil 1.0μg/kg+propofol 1.0mg/kg,respectively.The anesthesia quality evaluation was based on the following indicators:onset time（loss of eyelash reflex）,recovery time of orientation,the incidence of hypoxemia（SpO₂< 92%）and adverse reactions.Nonlinear mixed-effects model was used to evaluate the time courses of the simulated propofol and remifentanil concentrations-effect and to establish the PD model with NONMEM software.Results The time of recovering orientation in the patients of group PR10 was significantly faster compared with the patients in group PR15 [（3.6±1.2）min vs（4.9±1.3）min,P<0.05];the time of loss of eyelash reflex [（58±14）s vs（64±13）s],incidence of hypoxemia（12.5% vs 16.7%）and cough（16.7% vs 11.1%）had no significant differences between the both groups.With the final PD model,the estimated parameters as following:EC₅₀ of propofol and remifentanil for effective sedation and analgesia were 1.71μg/ml and 2.57ng/ml,respectively.EC₉₅ of propofol and remifentanil for effective sedation and analgesia were 4.30g/ml and 4.57ng/ml,respectively.The effect site concentration of propofol 1mg/kg was lower than EC₅₀,but the effect site concentration of 1.5mg/kg was higher than EC₅₀.The peak effect site of 1.0μg/kg and 1.5μg/kg remifentanil was higher than EC₅₀,and 1.5μg/kg concentration was close to EC₉₅.Conclusion Based on patients’ recovery time,propofol 1.0mg/kg combined with fentanyl 1.0μg/kg is appropriate in patients undergoing transvaginal oocyte retrieval.更多还原