机构地区:[1]温岭市第一人民医院麻醉科 [2]绍兴市人民医院医学研究中心 [3]绍兴市人民医院麻醉科 [4]昆明理工大学医学院
出 处:《中国临床药理学与治疗学》2019年第4期424-432,共9页Chinese Journal of Clinical Pharmacology and Therapeutics
基 金:浙江省科技厅动物平台项目(2017C37160);浙江省医药卫生科技计划项目(2018KY173);绍兴市科技局公益项目(2017B70038)
摘 要:目的:探索炎性疾病患者的乳酸林格氏液(Ringer's lactate,RL)液体动力学特征以及炎性生物标记物是否可以作为协变量影响RL分布和排泄。方法:本研究为前瞻性队列研究。选择40例美国麻醉医师分级(ASA)I-II级,腹腔镜下择期胆囊切除术(胆囊炎组,n=20)或者腹腔镜下急诊阑尾切除术(阑尾炎组,n=20)。所有患者麻醉诱导前开始输注RL,按15 mL/kg,35 min内输毕。采用酶联免疫(enzyme-linked immunosorbent assay,ELISA)方法测定血浆炎症(TNF-α,IL-10和CRP)或者内皮损伤生物标记物(syndecan-1,SDC-1);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RL液体动力学参数和协变量的影响。结果:与胆囊炎组相比,阑尾炎组RL从组织间隙到血浆的转运速率常数(k_(21))显著降低(14×10^(-3)min^(-1)versus 35×10^(-3)min^(-1);P=0.012)。阑尾炎组C反应蛋白(CRP)升高[中位数38.1(1.8-143.6)μg/mL versus 1.3(0.1-159.0)μg/mL;P<0.001];与清醒状态相比,麻醉期间(输液开始后30~45 min),液体从中央室中到外周室的转运速率常数(k_(12))显著增加(57×10^(-3)min^(-1)versus 32×10^(-3)min^(-1);P<0.01)。清除速率常数(k_(10))降低90%(0.6×10^(-3)min^(-1)versus 5.3×10^(-3)min^(-1);P<0.001)。无论在清醒状态还是麻醉状态下低血压均能降低液体清除;炎症或者内膜损伤的生物标记物不能作为显著影响RL液体动力学参数的协变量。结论:阑尾炎或者胆囊炎患者术前输入液体后"炎症反应的生物标记物"不是RL的液体动力学的协变量,但是两组患者中,全身麻醉期间输入液体的清除率下降。AIM : To explore the volume kinetics of Ringer's lactate (RL) in acute inflammatory disease and whether the inflammatory biomarker would be associated with altered distribution and elimination of RL. METHODS : In this prospective cohort study, we enrolled 40 ASA physical status Ⅰ-Ⅱ patients undergoing elective laparoscopic cholecystectomy (cholecystitis group, n =20) or emergency laparoscopic appendectomy (appendicitis group, n =20). All of the patients were infused RL (15 mL/kg) intravenously over 35 min, starting before the induction of general anesthesia. Plasma concentrations of inflammatory (tumor necrosis factor-α, interleukin-10, and C-reactive protein) and endothelial damage (syndecan-1, SDC-1) biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA). The kinetics of RL and the effects of covariates were calculated by plasma dilution based on the dilution of hemoglobin-time curve, urinary excretion by using Phoenix software for mixed effects modeling. RESULTS :Compared with the cholecystitis group, the rate constant for fluid transfer from the peripheral fluid space to the central fluid space ( k 21 ) decreased significantly in the appendicitis group (14×10^-3 min -1 versus 35×10^-3 min^-1;P = 0.012 ), in whom higher plasma concentrations of C-reactive protein (CRP) were measured [median: 38.1(1.8-143.6)μg/mL versus 1.3 ( 0.1 - 159.0 )μg/mL, P < 0.001 ]. Compared with conscious period, ongoing anesthesia (duration: 30 min-45 min after beginning of infusion) increased the rate constant for fluid transfer from the plasma to the extravascular space ( k 12 ) significantly (57×10^-3 min -1 versus 32×10^-3 min^-1 ), and decreased the elimination rate constant ( k 10 : from 0.6 ×10^-3 min^-1 to 5.3 ×10^-3 min^-1;P < 0.001 ). A lower mean arterial pressure was associated with reduced elimination, independent of conscious/anaesthetized state. However, no biomarkers for inflammation or endothelial damage were significantly associated covariates in the kinetic model. CONCLUSION : No assoc
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