血管活性药物对脓毒症羊乳酸林格氏液体动力学的影响
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摘要
目的:探讨血管活性药对脓毒症羊输入乳酸林格氏液体(RL)分布和排泄的影响。方法:本研究为随机、双盲前瞻性研究。将实验羊25只随机分成5组:生理盐水组(Control组)、生理盐水稀释去甲肾上腺素组(Nor组)、苯肾上腺素组(Phe组)、多巴胺组(Dop组)和艾司洛尔组(Esm组),每组5只动物。实验羊全身麻醉和气管切开插管后,采用盲肠结扎穿孔法(CLP)和静脉输注内毒素(LPS)构建羊脓毒症模型。造模成功后,每组分别微泵持续输入生理盐水或相应的血管活性药物,10 min后,输入RL,按20 mL/kg,30min内输毕。利用血红蛋白(Hb)稀释-时间曲线和尿量使用Phoenix软件,采用非线性混合效应模型分析计算液体动力学参数及协变量的影响。结果:与Control组相比,Nor组和Dop组加速RL从血浆到组织间隙的分布速率(k_(12)),而降低从组织间液返回到血浆的速率(k_(21))。α_1-受体激动剂促进,而β_1-受体激动剂减缓RL的分布和排泄。Emax药效动力学模型分析显示RL增加心脏每博量13 mL/次;α_1-受体激动剂和β1-受体激动剂均可增加平均动脉压(MAP),只有α_1-受体激动剂可以增加心搏量;β_1-受体激动剂可以减少酸中毒的发生。结论:脓毒症羊对RL的分布和排泄减慢,液体在外周组织积聚,苯肾上腺素和多巴胺促进液体在组织间液积聚,去甲肾上腺素可以降低酸中毒。
AIM: To explore how vasoactive drugs influence the distribution and clearance of lactated Ringer ' s solution( RL) in septic sheep.METHODS: This was a prospective randomized double-blinded study. Twenty-five experimental sheep were randomized into five groups: no drug( Control group), norepinephrine( Nor group),phenylephrine( Phe group), dopamine( Dop group),or esmolol( Esm group),with five animals for each group. After general anesthesia and tracheostomy tube for all sheep,septic model was established through cecal ligation puncture( CLP) method and a short infusion of lipopolysaccharide( LPS). Then a continuous intravenous administration of saline or corresponding vasoactive drugs were given to five groups respectively. 10 min later 20 mL/kg of RL solution over 30 min was given. The kinetics of RL and the effects of covariates were calculated by plasma dilution based on dilution of hemoglobin-time curve, urinary excretion by using Phoenix software for mixed effects modeling. RESULTS: Compared with Control group,Nor group and Dop group accelerated the distribution rate from plasma to peripheral tissue( k_(12)); while decreased the distribution rate opposite direction( k_(21)). Adrenergic α_1-receprtor accelerated,while β_1-receptors retarded,the distribution and elimination of the fluid. The pharmacodynamics Emaxmodel showed that RL increased stroke volume by 13 mL/beat,α_1-receptors but not β_1-receptors further increased stroke volume,while both raised the mean arterial pressure,modulation of the β_1-receptors limited the acidosis. CONCLUSION: The distribution and elimination of RL is slow in septic sheep. The tendency to peripheral accumulation of fluid is pronounced,in particular when phenylephrine and dopamine are given,and norepinephrine can alleviate acidosis.
AIM: To explore how vasoactive drugs influence the distribution and clearance of lactated Ringer ' s solution( RL) in septic sheep.METHODS: This was a prospective randomized double-blinded study. Twenty-five experimental sheep were randomized into five groups: no drug( Control group), norepinephrine( Nor group),phenylephrine( Phe group), dopamine( Dop group),or esmolol( Esm group),with five animals for each group. After general anesthesia and tracheostomy tube for all sheep,septic model was established through cecal ligation puncture( CLP) method and a short infusion of lipopolysaccharide( LPS). Then a continuous intravenous administration of saline or corresponding vasoactive drugs were given to five groups respectively. 10 min later 20 mL/kg of RL solution over 30 min was given. The kinetics of RL and the effects of covariates were calculated by plasma dilution based on dilution of hemoglobin-time curve, urinary excretion by using Phoenix software for mixed effects modeling. RESULTS: Compared with Control group,Nor group and Dop group accelerated the distribution rate from plasma to peripheral tissue( k_(12)); while decreased the distribution rate opposite direction( k_(21)). Adrenergic α_1-receprtor accelerated,while β_1-receptors retarded,the distribution and elimination of the fluid. The pharmacodynamics Emaxmodel showed that RL increased stroke volume by 13 mL/beat,α_1-receptors but not β_1-receptors further increased stroke volume,while both raised the mean arterial pressure,modulation of the β_1-receptors limited the acidosis. CONCLUSION: The distribution and elimination of RL is slow in septic sheep. The tendency to peripheral accumulation of fluid is pronounced,in particular when phenylephrine and dopamine are given,and norepinephrine can alleviate acidosis.
引文
[1]Dellinger RP,Levy MM,Rhodes A,et al.Surviving sepsis campaign guidelines committee including pediatric subgroup.Surviving sepsis campaign;international guidelines for management of severe sepsis and septic shock[J].Crit Care Med,2013,39(2):165-228.
[2]Martin-Loaches I,Levy MM,Artigas A.Management of severe sepsis:advances,challenges,and current status[J].Drug Des Devel Ther,2015,9:2079-2088.
[3]Beale RJ,Hollenberg SM,Vincent JL,et al.Vasopressor and inotropic support in septic shock:an evidence-based review[J].Crit Care Med,2004,32(11 Suppl):S455-465.
[4]Patel GP,Grahe JS,Sperry M,et al.Efficacy and safety of dopamine versus norepinephrine in the treatment of septic shock[J].Shock,2010;33(4):375-380.
[5]Ewaldsson CA,Vane LA,Kramer GC,et al.Adrenergic drugs alter both the fluid kinetics and the hemodynamic responses to volume expansion in sheep[J].J Surg Res,2006,131(1):7-14.
[6]金惠铭.盲肠结扎穿刺后的大鼠败血症模型[J].中国病理生理杂志,1990,6(2):126-127.
[7]Li Y,Zhu HB,Zheng X,et al.Low doses of esmolol and phenylephrine act as diuretics during intravenous anesthesia[J].Crit Care,2012,16:R18.
[8]Hahn RG.Volume kinetics for infusion fluids(review)[J].Anesthesiology,2010,113(2):470-481.
[9]Hahn RG,Drobin D,Zdolsek J.Distribution of crystalloid fluid changes with the rate of infusion:a population-based study[J].Acta Anaesthesiol Scand,2016,60(5):569-578.
[10]Heeremans EH,Proost JH,Eleveld DJ,et al.Absalom AR,Struys MRF.Population pharmacokinetics and pharmacodynamics in anesthesia,intensive care and pain medicine[J].Curr Opin Anesthesiol,2010,23(4):479-484.
[11]Evers AS,Maze M,Kharasch ED.Anesthetic pharmacology:basic principles and clinical practice[M].2nd Ed.Cambridge;Cambridge University Press,2011,648-665.
[12]Brauer KI,Svensen C,Hahn RG,et al.Volume kinetic analysis of the distribution of 0.9%saline in conscious versus isoflurane-anesthetized sheep[J].Anesthesiology,2002,96(2):442-449.
[13]Hahn RG.Clinical fluid therapy in the perioperative setting[M].2nd Ed.Cambridge;Cambridge University Press,2016:82-91.
[14]Hahn RG,Geback T.Fluid volume kinetics of dilutional hyponatremia;a shock syndrome revisited[J].Clinics,2014,69(12):120-127.
[15]Hahn RG,Lyons G.The half-life of infusion fluids:an educational review[J].Eur J Anaesthesiol,2016,33(7):475-482.
[16]Li Y,Hahn RG,Hu Y,et al.Plasma and renal clearances of lactated Ringer's solution in pediatric and adult patients just before anesthesia is induced[J].Paediatr Anaesth,2009,19(7):682-687.
[17]王军会,李玉红,茹国美,等.成人与儿童乳酸林格氏液液体动力学的比较[J].中国临床药理学和治疗学,2015;20(8):909-915.
[18]Li Y,Zhu S,Hahn RG.The kinetics of Ringer's solution in young and elderly patients during induction of general anesthesia with propofol and epidural anesthesia with ropivacaine[J].Acta Anaesthesiol Scand,2007,51(7):880-887.
[19]Drobin D,Hahn RG.Distribution and elimination of crystalloid fluid in pre-eclampsia[J].Clin Sci(Lond),2004,106(3):307-313.
[2]Martin-Loaches I,Levy MM,Artigas A.Management of severe sepsis:advances,challenges,and current status[J].Drug Des Devel Ther,2015,9:2079-2088.
[3]Beale RJ,Hollenberg SM,Vincent JL,et al.Vasopressor and inotropic support in septic shock:an evidence-based review[J].Crit Care Med,2004,32(11 Suppl):S455-465.
[4]Patel GP,Grahe JS,Sperry M,et al.Efficacy and safety of dopamine versus norepinephrine in the treatment of septic shock[J].Shock,2010;33(4):375-380.
[5]Ewaldsson CA,Vane LA,Kramer GC,et al.Adrenergic drugs alter both the fluid kinetics and the hemodynamic responses to volume expansion in sheep[J].J Surg Res,2006,131(1):7-14.
[6]金惠铭.盲肠结扎穿刺后的大鼠败血症模型[J].中国病理生理杂志,1990,6(2):126-127.
[7]Li Y,Zhu HB,Zheng X,et al.Low doses of esmolol and phenylephrine act as diuretics during intravenous anesthesia[J].Crit Care,2012,16:R18.
[8]Hahn RG.Volume kinetics for infusion fluids(review)[J].Anesthesiology,2010,113(2):470-481.
[9]Hahn RG,Drobin D,Zdolsek J.Distribution of crystalloid fluid changes with the rate of infusion:a population-based study[J].Acta Anaesthesiol Scand,2016,60(5):569-578.
[10]Heeremans EH,Proost JH,Eleveld DJ,et al.Absalom AR,Struys MRF.Population pharmacokinetics and pharmacodynamics in anesthesia,intensive care and pain medicine[J].Curr Opin Anesthesiol,2010,23(4):479-484.
[11]Evers AS,Maze M,Kharasch ED.Anesthetic pharmacology:basic principles and clinical practice[M].2nd Ed.Cambridge;Cambridge University Press,2011,648-665.
[12]Brauer KI,Svensen C,Hahn RG,et al.Volume kinetic analysis of the distribution of 0.9%saline in conscious versus isoflurane-anesthetized sheep[J].Anesthesiology,2002,96(2):442-449.
[13]Hahn RG.Clinical fluid therapy in the perioperative setting[M].2nd Ed.Cambridge;Cambridge University Press,2016:82-91.
[14]Hahn RG,Geback T.Fluid volume kinetics of dilutional hyponatremia;a shock syndrome revisited[J].Clinics,2014,69(12):120-127.
[15]Hahn RG,Lyons G.The half-life of infusion fluids:an educational review[J].Eur J Anaesthesiol,2016,33(7):475-482.
[16]Li Y,Hahn RG,Hu Y,et al.Plasma and renal clearances of lactated Ringer's solution in pediatric and adult patients just before anesthesia is induced[J].Paediatr Anaesth,2009,19(7):682-687.
[17]王军会,李玉红,茹国美,等.成人与儿童乳酸林格氏液液体动力学的比较[J].中国临床药理学和治疗学,2015;20(8):909-915.
[18]Li Y,Zhu S,Hahn RG.The kinetics of Ringer's solution in young and elderly patients during induction of general anesthesia with propofol and epidural anesthesia with ropivacaine[J].Acta Anaesthesiol Scand,2007,51(7):880-887.
[19]Drobin D,Hahn RG.Distribution and elimination of crystalloid fluid in pre-eclampsia[J].Clin Sci(Lond),2004,106(3):307-313.