等容量血液稀释对犬异丙酚药代动力学的影响  

Effect of normovolemic hemodilution on propofol pharmacokinetics in dogs

作　　者：曹晖[1] 蒋豪[1] 缪长虹[1] 张鸿[1] 薛张纲[1] 

机构地区：[1]复旦大学附属中山医院麻醉科

出　　处：《中华麻醉学杂志》2005年第8期589-592,共4页Chinese Journal of Anesthesiology

摘　　要：目的观察等容量血液稀释对犬异丙酚药代动力学的影响。方法13只雄性犬随机分为对照组(n=7)与等容量血液稀释组(n=6)。静脉注射地西泮0.5 mg/kg、氯胺酮5mg/kg麻醉后, 股静脉与股动脉穿刺,乳酸钠林格氏液5—7 ml·kg-1·h-1持续静脉滴注。麻醉后0.5 h等容量血液稀释组由股动脉放血,同时经股静脉1:1快速输入6%羟乙基淀粉,直至红细胞压积达25%。两组持续恒速静脉输注异丙酚10mg·kg-1·h-130 min,分别于输注2、5、10、15、20、30、31、32、35、40、50、70、90、120、150、180、240、300min采动脉血,测定异丙酚血浆浓度并计算药代动力学参数。一周后两组均根据各自药代动力学参数靶控输注异丙酚60 min,分别于靶控输注5、15、30、45、60 min测定两组异丙酚血浆浓度、游离浓度、脑脊液浓度及脑组织含量。结果与对照组比较,恒速给药时等容量血液稀释组异丙酚血浆浓度降低,中央室分布容积、稳态分布容积与全身清除率均升高(P<0.05或0.01);靶控输注时两组异丙酚血浆浓度与血浆靶浓度一致,但等容量血液稀释组异丙酚游离药物浓度、脑脊液浓度、脑组织含量及脑/血浆分配系数升高(P<0.05),脑/血浆分配系数与游离药物百分比[异丙酚游离浓度/(异丙酚游离浓度+异丙酚血浆浓度)]呈正相关(r=0.87,P<0.05)。结论等容血液稀释提高了异丙酚中央室分布容积、稳态分布容积和全身清除率,降低了分布项系数和浓度-时间曲线下面积,中枢药物浓度升高,可能导致药效增强。Objective To investigate the changes in pharmacokinetics of propofol and propofol concentration in the brain induced by normovolemic hemodilution （NHD）.Melllods Thirteen healthy male mongrel dogs weighing 10-15 kg were randomly divided into 2 groups： control group （ n = 7） and NHD group （ n = 6）. The animals were anesthetized with intravenous diazepam 0.5 mg·kg^-1 and ketamine 5 mg·kg^-1 . The femoral artery and vein were cannulated. Lactated Ringer＇ s solution was infused at 5-7 ml · kg^- 1 · h^- 1 . 30 min after induction of anesthesia NHD was conducted by removing blood from femoral artery and replacing it with 6% hydroxyethyl starch （HES） until Her was reduced to 25%. Propefol was then infused at 10 mg·kg^-1 ·h^-1 for 30 min after NHD. Arterial blood samples were taken immediately before and at 1, 2, 5, 10, 15, 20, 30, 31, 32, 35, 40, 50, 70, 90, 120, 150, 180, 240 and 300 min after propefol infusion was started for determination of plasma propefol concentrations. One week later the same NHD was repeated. Propefol was administered by TCI via Graseby 3500 infusion pump incorporated with Stanpump TCI software. Target plasma propefol concentration was set at 5 μg·ml^-1. Arterial blood and CSF samples were obtained at 5, 15, 30, 45 and 60 rain after the start of propefol infusion for determination of plasma propefol concentration （bound and free ）, plasma free propofol concentration and CSF propefol concentration. At the end of 60 min, after the collection of blood and CSF samples, brain tissue was obtained from the cerebral cortex of right frontal lobe for determination of brain propefol content. EGG, BP, arterial blood gases and body temperature were monitored during experiment. Results The plasma propefol concentrations were significantly lower during and after propefol infusion at 10 mg· kg^- 1 · h^- 1 in NHD group than in control group （ P 〈 0.05 or 0.01 ）. Vc, Vdss and CLs were significantly larger in NHD group than in control group （ P 〈 0.05）. During TCI of pr

关 键 词：血液稀释 二异丙酚 药代动力学 等容量血液稀释 药代动力学参数 异丙酚 游离药物浓度 脑脊液浓度 血浆浓度 乳酸钠林格氏液 

分 类 号：R614[医药卫生—麻醉学]