血管活性药物对脓毒症羊乳酸林格氏液体动力学的影响

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，30 min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（k₁₂），而降低从组织间液返回到血浆的速率（k₂₁）。α₁-受体激动剂促进, 而β₁-受体激动剂减缓RL的分布和排泄。E_max药效动力学模型分析显示RL增加心脏每博量13 mL/次；α₁-受体激动剂和β₁-受体激动剂均可增加平均动脉压（MAP），只有α₁-受体激动剂可以增加心搏量；β₁-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。

Effects of vasoactive drugs on crystalloid fluid kinetics in septic sheep

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 (k12); while decreased the distribution rate opposite direction (k21). Adrenergic α1-receprtor accelerated, while β1-receptors retarded, the distribution and elimination of the fluid. The pharmacodynamics Emax model showed that RL increased stroke volume by 13 mL/beat, α1-receptors but not β1-receptors further increased stroke volume, while both raised the mean arterial pressure, modulation of the β1-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.