20%脂肪乳对家兔持续异丙酚输注血药浓度、分布容积及药理效应的影响

Influence of 20% Lipid Emulsion on Drug Concentration,Distribution Volume and Pharmacology Effect of Continuous Infusion of Propofol in Rabbits

目的探讨20%脂肪乳对家兔持续恒速输注异丙酚血药浓度、分布容积及药理效应的影响。方法 52只家兔随机分为4组(n=13):异丙酚组(P组),低剂量脂肪乳组(L组),高剂量脂肪乳组(H组),生理盐水组(S组)。每组家兔以70mg/(kg.h)持续恒速输注异丙酚120min。恒速输注异丙酚60min后,P组维持原速率继续输注异丙酚,L组和H组输注异丙酚同时输注20%脂肪乳,速率分别为0.3mL/(kg.h)和15mL/(kg.h);S组输注异丙酚同时输注生理盐水,速率为15mL/(kg.h),3组输注不同液体时间为60min。各组取8只家兔于异丙酚输注后30、60、65、70、80、90、105、120min以及停药后10、20、30、60、120、180min采血测定异丙酚血药浓度,计算相关药代动力学参数;用平均动脉压(MAP)、心率(HR)、神经反射率评价药理效应;各组另取5只家兔于异丙酚输注120min时获取家兔脑组织、测量异丙酚脑组织浓度。结果 H组经20%脂肪乳输注后,血药浓度上升,消除相分布容积(V)〔各组分别为(34.56±16.11)mL、(33.37±29.87)mL、(7.29±3.20)mL和(35.46±13.58)mL〕、稳态分布容积(Vss)〔各组分别为(11.13±3.21)mL、(13.87±4.09)mL、(4.82±1.46)mL和(11.61±4.11)mL〕降低(P<0.05);MAP、HR上升(P<0.05);90、120min痛觉反射存在率与其余3组比较差异有统计学意义(P<0.05);120min时异丙酚脑组织浓度降低〔各组分别为(1.92±0.41)μg/g、(1.90±0.53)μg/g、(1.27±0.40)μg/g和(2.02±0.49)μg/g,P<0.05〕。结论当20%脂肪乳以高剂量输注时,可降低异丙酚药物分布容积,升高血药浓度,降低异丙酚脑组织浓度,导致药理效应减弱。以临床营养支持相类似的低速率输注时,并不会对以上指标产生影响。

Objective To investigate the influence of 20% lipid emulsion on drug plasma concentration, distribution volume and pharmacology effect of propofol administered with constant rate intravenous infusion in rabbits. Methods Propofol was intravenously administrated at a constant rate of 70 mg/（kg · h） in propofol group （P group, n=8）,low rate lipid group （L group, n=8）,high rate lipid group （H group,n=8） and saline group（S group, n=8） within 2 h. After 60 rain, different agents were administrated in L group （20% lipid emulsion with rate of 0.3 mL/（kg ·h）], H group [20% lipid emulsion with rate of 15 mL/（kg · h）3 ,S group [saline with rate of 15 mL/（kg · h）3 for another 60 rain respectively. Blood samples were taken to measure the plasma concentration and calculate the pharmacokinetic parameters at the following time points ： 30,60,65,70,80,90,120 min after the start of propofol infusion and 10,20,30,60,120,180 min after the termination of propofol infusion. Brain tissues were also taken to measure propofol concentration. Related information about vital signs and pharmaceutical effects were recorded. Results High rate lipid infusion was associated with elevated propofol plasma concentration and reduced volume of distribution. The volume of distribution based on the terminal phase （V）：P group, （34.56 =[= 16.11） mL;L group,（33.37±29.87） mL;H group,（7.29±3.20） mL;S group, （35.46±13.58） mL;P〈0.05）. The volume of distribution at steady state（Vss ） ： P group, （ 11. 13 ± 3. 21 ） mL; L group, （ 13. 87± 4. 09） mL; H group,（4.82±1.46） mL;Sgroup,（11.61±4. 11） mL;P±0.05） ）. Painful stimulation existences were higher at 90,120 rain and the mean arterial pressure and heart rate were higher in H group （P〈0. 05）. The propofol concentration in brain tissue was lower in H group at 120 rain （P〈0. 05）. Conclusion Amelioration of pharmacology effect of propofol with high rate lipid infusion is associated with reduced V,Vss, elevated propofol plasma concentration and lowered propofol brain tissue concentration. 20% lipid will not influence these indice when infused with low rate, indicating that lipid in TPN will not change the sedation effects of propofol.