心脏瓣膜病患者体外循环对舒芬太尼药动学的影响

目的:研究心脏瓣膜置换术患者低温体外循环对舒芬太尼药动学的影响。方法:随机选择NYHAⅡ～Ⅲ级的心脏瓣膜置病患者16例,随机分为普通外科手术组(Ⅰ组,n=7)和体外循环下心脏瓣膜置换组(Ⅱ组,n=9)两组。入室后建立前臂静脉通路,麻醉后一次性静脉注射舒芬太尼5μg.kg-1。在静脉注射舒芬太尼后1,3,5,10,20,30,60,120,180,240,360 min,采肝素抗凝血浆1 mL置入密封真空试管中,-80℃低温保存直至分析。用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药动学软件计算药动学参数。结果:舒芬太尼在两组患者的药动学可用三室模型完整描述,其三指数函数方程分别为:Cp(t)=27.7e-1.871t+6.9e-0.117t+2.3e-0.019t和Cp(t)=24.8e-0.526t+5.4e-0.053t+0.16e-0.0017t,2组间的π,α,β,t1/2α、t1/2β和CL差异有统计学意义(P<0.05或P<0.01)。结论:舒芬太尼在心脏瓣膜病患者药动学可用三室模型描述,低温体外循环与血液稀释及剧烈的血液动力学变化均可影响其药动学特征。

Effect of cardiopulmonary bypass on the pharmacokinetics of sufentanil in patients underwent heart valve replacement

OBJECTIVE To study the effect of cardiopulmonary bypass on the pharmacokinetics of sufentanil in patients with heart valve disease.METHODS Sixteen NYHA grade Ⅱor Ⅲ patients with cardiac valvular disease were divided into general surgery group(groupⅠ,n=7) and cardiac valve prosthesis group(groupⅡ,n=9).Intravenous and intra-arterial cannulae were placed.After general anesthesia sufentanil 5 μg· kg-1 was administered as a rapid bolus intravenously.Blood samples were obtained at 1,3,5,10,20,30,60,120,180,240 min and 360 min after sufentanil injection.1mL plasma was immediately separated from blood samples and stored at-80 ℃ until analyzed.Plasma sufentanil concentration were determined by liquid chromatography-mass spectrometry,pharmacokinetic parameters were calculated by 3P97 pharmacological program.RESULTS Pharmacokinetics of sufentanil in patients with heart valve disease fitted to three-compartment open model,the tri-exponential equation were Cp(t)= 27.7e-1.871t+6.9e-0.117t +2.3e-0.019t and Cp(t)=24.8e-0.526t+5.4e-0.053t +0.16e-0.0017t,respectively.There were significant difference in π α,β,t1/2α,t 1/2β and CL between two groups(P<0.05 or P<0.01).CONCLUSION Pharmacokinetics of domestic sufentanil in patients with heart valve disease fitted to three-compartment open models,cardiopulmonary bypass and haemodilution and drastic haemodynamics could affect its pharmacokinetics characteristics.