感染性休克时“血管瀑布”的血流动力学基础与临床研究

发布时间：2018-07-09 21:18

本文选题：感染性休克 + 平均动脉压　；参考：《北京协和医学院》2013年博士论文

【摘要】：目的： 1.第一部分：探讨平均动脉压对早期目标导向治疗(EGDT)达标末仍有组织灌注异常的患者组织灌注和预后的影响。 2.第二部分：证实感染性休克时存在“血管瀑布”现象,探讨扩容和加用去甲肾上腺素对小血管临界闭合压(Pcc)和循环平均充盈压(Pmsf)的影响及其临床意义。方法： 1.第一部分：回顾性分析2012年1月-2012年12月北京协和医院重症医学科连续诊治EGDT达标末有组织灌注异常的感染性休克患者126例。EGDT末记为0时,应用去甲肾上腺素提高MAP的方法进一步复苏6个小时,记为6时。按照感染性6时乳酸是否2mmoL/L分为乳酸正常组和高乳酸组。记录0时和6时血流动力学资料、乳酸(Lac)、急性生理状况和慢性健康状态(APACHE Ⅱ)评分、6小时内去甲肾上腺素平均用量(NE)和休克诊断后第28d生存状况。 2.第二部分：(1)前瞻性观察2012年7月1日-2012年8月1日北京协和医院重症医学科诊治的感染性休克且休克时间小于6小时的20例患者。前瞻性观察2012年7月1日-2013年2月1日北京协和医院重症医学科诊治的感染性休克且休克时间小于6小时的62患者。(2)所有患者均经右颈内静脉放置中心静脉导管、经左股动脉放置股动脉导管行脉搏指示持续心排血量(PiCCO)监测；(3)待患者完全没有自主呼吸,且镇静深度达到能够屏气12s时,调节吸气末平台压分别达到5、15、25、35cmH2O,按住吸气末屏气键,在屏气开始后7-12s时,读取心输出量(CO)、中心静脉压(CVP)、平均动脉压(Pa)；对4个平台压下得到的4对心输出量(CO)和CVP数值构建静脉回流(VR)曲线。VR曲线在流速为零时压力轴的截值即为循环平均充盈压(Pmsf);对同时得到的4对CO和Pa值进行线性回归曲分析构建心室输出(VO)曲线。心室输出曲线在流速为零时压力轴的截值为小血管临界闭合压(Pcc)。(4)根据Pcc和Pmsf的差值,确定感染性休克患者中有无“血管瀑布”现象。(5)对62例患者行500m1晶体进行扩容,按照上述方法估测Pcc和Pmsf,行血流动力学、皮肤氧分压监测。(6)对62例患者应用去甲肾上腺素逐步上调Pa65→75→85→95mmHg,每个压力位点稳定30min,待血流动力学平稳后,按照上述方法估测Pcc和Pmsf,行血流动力学、皮肤氧分压监测。结果： 1.第一部分：126例患者28d天死亡率为46.03%。两组患者0时乳酸和APACHⅡ及血流动力学指标方面的差异均无统计学意义。6时存活组的MAP为86.5±9.8mmHg,高于死亡组的75.2±10.5mmHg,差异有统计学意义。存活组NE为0.72(0.43,1.6) ug/kg/min显著高于死亡组0.48(0.45,1.4) ug/kg/min,差异有统计学意义。存活组UO显著高于死亡组(1.8±1.lml/kg/hr vs.1.38±1.2ml/kg/hr),差异有统计学意义。存活组Lac显著低于死亡组(5.3±3.8mmol/L vs.2.1±1.7mmol/L),差异有统计学意义。两组患者其他血流动力学参数方面的差异均无统计学意义。多因素回归分析显示MAP是本组患者28天死亡的独立危险因素。乳酸正常组患者28d死亡率为29%,乳酸增高组患者28d死亡率为62.5%,差异有统计学意义；两组患者0时血流动力学指标方面的差异均无统计学意义。乳酸正常组的MAP为85.6±10.3mmHg,死亡组为77.2±10.7mmHg,差异有统计学意义。乳酸正常组UO显著高于乳酸增高组(1.8±1.2ug/kg/min vs.1.3±0.9ug/kg/min),差异有统计学意义。相关性分析显示,MAP与6时乳酸高度负相关。两组患者6时其他血流动力学参数方面的差异均无统计学意义。按6时血压分三组,三组在0时血流动力学指标及乳酸的差异无显著性。MAP在75-85mmHg组乳酸显著低于MAP75mmHg组,MAP85mmHg与MAP在75-85mmHg乳酸的差异无统计学意义。6时三组患者其他血流动力学指标方面的差异无显著性。 2.第二部分：(1)①感染性休克中Pcc和Pmsf分别为49.59±13.6mmHg和28.31±6.3mmHg,(P0.0001)。Pcc-Pmsf为21.27±11.1mmHg,提示感染性休克中存在“血管瀑布”；②动脉阻力(Ra)与全身血管阻力指数(SVRI)之间呈显著正相关(P0.0001);③Pcc与外周血管阻力指数不相关,R=0.27(P=0.032)。(2)①扩容后Pcc由42.9±10.0mmHg变为44.8±8.9mmHg,(P=0.188);②扩容后Pcc-Pmsf由21.5±8.6mmHg变为20.5±7.9mmHg,(P=0.899);③扩容后Pmsf-CVP由增加12.2±6.1mmHg增加到14.5±7.0mmHg,(P=0.002); CO由6.0±1.9L.min-1增加到,(P0.0001);④扩容后Pa-Pcc由22.9±10.1mmHg增加到37.2±10.5mmHg,(P0.0001);扩容后Ra降低,Rv无显著变化,同时SVRI降低到1383.7±643.8dyn.sec.cm-5. m-2,(P0.0001),提示动脉阻力降低,静脉阻力无显著变化。⑤扩容后ScvO2由75.9±9.3%增加到81.6±4.2%,(P0.05)。(3)①在Pa由65mmHg升高到95mmHg的整个过程中,需要的NE依次增加,且各压力位点所用剂量之间均有显著性差异,(P0.0001)；试验整个过程中血温无显著改变。②Pa由65mmHg增加到75mmHg时：Pmsf和CVP均显著增加,(P0.05)；但Pmsf-CVP和CO无显著改变,(P0.05); Pcc由42.8±10.0变为44.5±8.8mmHg,(P0.05); Pa-Pcc由22.8±10.1mmHg增加到32.6±9.1mmHg,(P0.0001)。Ra、Rs显著增加,Rv无明显改变；皮肤氧合指数(PtcO2/PaO2)和尿量(UO)增加,(P0.05); Lac和Pv-aCO2显著降低,(P0.05); ScvO2碱剩余(BE)、PH无明显变化。③Pa由75mmHg增加到85mmHg时：Pmsf-CVP、Pcc-Pmsf、Rv. CO值均无显著增加,(P0.05); Pmsf-CVP和Rv均大于Pa65mmHg的位点值；Pcc由44.5±8.8mmHg变为45.4±8.8mmHg,(P0.05); Pa-Pcc由22.8±10.1mmHg增加到41.9±8.9mmHg,(P0.0001); SVRI和Ra增加。PtcO2/PaO2、UO增加；Lac降低(P0.05),ScvO2、 Pv-aCO2、BE、PH无明显改变。④Pa由85mmHg增加到95mmHg时：Pmsf, CVP Pmsf-CVP、Rv、CO均显著增加,与前三个压力位点值的差异均有统计学意义,(P0.05)。Pcc由45.4±8.8mmHg增加到59.1±14.8mmHg,差异有统计学意义,(P0.05); Pa-Pcc由41.9±8.9mmHg降低为40.6±1.1mmHg,差异无统计学意义,(P0.05); Pcc-Pmsf由17.0±1.8mmHg增加到24.5±4.mmHg,差异有统计学意义,(P0.0001)。该过程中血清乳酸水平没有进一步降低,PtcO2/PaO2降低,UO没有进一步增加,Pv-aCO2没有进一步降低,(P0.05)。结论： 1.第一部分：(1)EGDT末有组织灌注异常的感染性休克患者死亡率很高；(2)一定程度提高血压能够降低血清乳酸水平,进而降低该类患者28d的死亡率；(3)目前寻找灌注压的方法改善组织灌注的效果并不理想,进一步寻找反应最佳灌注压的方法是临床中亟待解决的问题。 2.第二部分：(1)感染性休克时Pcc和Pmsf存在压力梯度,提示存在“血管瀑布”(2)通过扩容增加心输出量不改变小血管临界闭合压；(3)联合应用小血管临界闭合压和外周血管阻力能够评估血管收缩药的血管作用位点；(4)应用血管收缩药,提高MAP的过程中,临界闭合压的突然增大,提示组织灌注可能开始恶化；(5)以平均动脉压与小血管临界闭合压最大差值作为灌注压能够最有效的改善组织灌注,该灌注压对应的平均动脉压范围75-85mmHg;(6) Pcc可以使最佳灌注压的选择实现量化和个体化。
[Abstract]:Objective:
1. part I: To investigate the effect of mean arterial pressure on tissue perfusion and prognosis in patients with early stage target directed therapy (EGDT) with abnormal perfusion at the end of standard.
2. the second part: to confirm the phenomenon of "vascular waterfall" in septic shock, and to explore the effect and clinical significance of dilatation and addition of norepinephrine on the critical closed pressure (Pcc) and circulating mean filling pressure (Pmsf) of small vessels.
Method:
1.. Part one: retrospective analysis of 126 cases of septic shock in the Department of severe medicine of Peking Union Medical College Hospital in December -2012 January 2012. The end of.EGDT was recorded at the end of EGDT, and the end of.EGDT was recorded as 0. The method of using norepinephrine to improve MAP was further resuscitation for 6 hours. It was recorded at 6 when the infection was 6 of 2mmoL. /L was divided into normal lactate group and high lactic acid group. The hemodynamic data at 0 and 6 hours, lactic acid (Lac), acute physiological status and chronic health state (APACHE II) score, average dosage of norepinephrine within 6 hours (NE) and 28d survival after shock diagnosis were recorded.
2. second parts: (1) prospective observation of 20 patients with septic shock and shock time less than 6 hours in the Department of severe medicine, Peking Union Medical College Hospital, August 1st -2012 July 1, 2012. A prospective observation of septic shock and less than 6 hours of shock time in the Department of intensive medicine in February 1st July 1, 2012 62 patients. (2) all the patients placed the central venous catheter in the right internal jugular vein and placed the femoral artery catheterization through the left femoral artery for continuous cardiac output (PiCCO) monitoring. (3) when the patients were completely free of breathing, and the sedative depth reached the ability to hold the breath of 12s, the pressure of the terminal platform was reached to 5,15,25,35cmH2O, respectively. At the end of the breath holding key, the heart output (CO), central venous pressure (CVP) and mean arterial pressure (Pa) are read at the beginning of the breath holding 7-12s; the 4 pairs of cardiac output (CO) and the CVP value of the 4 platforms are constructed to construct the VR curve.VR curve at zero velocity when the velocity is zero, and the 4 pairs of CO are obtained at the same time. The ventricular output (VO) curve was constructed by linear regression analysis with the Pa value. The cut-off value of the pressure axis of the ventricular output curve at zero velocity was small critical closed pressure (Pcc). (4) according to the difference between Pcc and Pmsf, there was no "vascular waterfall" in the patients with septic shock. (5) 62 patients were treated with 500m1 crystal expansion, according to the above Methods Pcc and Pmsf were estimated, and the hemodynamics and oxygen partial pressure of skin were monitored. (6) 62 patients with norepinephrine were gradually up-regulated by norepinephrine, and each pressure loci was stable 30min. After the hemodynamics were stable, Pcc and Pmsf were estimated according to the above methods, and the hemodynamics and oxygen partial pressure were monitored.
Result:
1. first part: the mortality of 126 patients with 28d days was 46.03%. two, and there was no significant difference in lactate, APACH II and hemodynamic indexes at 0. The MAP of the survival group was 86.5 + 9.8mmHg when.6, higher than the 75.2 + 10.5mmHg in the death group, the difference was statistically significant. NE in the survival group was 0.72 (0.43,1.6) ug/kg/min significantly higher than death. Group 0.48 (0.45,1.4) ug/kg/min, the difference was statistically significant. The survival group UO was significantly higher than that of the death group (1.8 + 1.lml/kg/hr vs.1.38 + 1.2ml/kg/hr), the difference was statistically significant. The survival group Lac was significantly lower than the death group (5.3 + 3.8mmol/L vs.2.1 + 1.7mmol/L), the difference was statistically significant. The difference of other hemodynamic parameters in the two groups of patients There was no statistical significance. Multivariate regression analysis showed that MAP was an independent risk factor for 28 days of death in this group. The mortality of 28d in the normal lactate group was 29%, and the mortality of 28d in the higher lactate group was 62.5%, the difference was statistically significant. There was no statistically significant difference in the hemodynamic index in the two groups at 0. The MAP was 85.6 + 10.3mmHg, and the death group was 77.2 + 10.7mmHg, and the difference was statistically significant. The UO in the normal lactate group was significantly higher than that of the higher lactate group (1.8 + 1.2ug/kg/min vs.1.3 + 0.9ug/kg/min). The difference was statistically significant. The correlation analysis showed that MAP and 6 were negatively correlated with lactic acid. The difference of other hemodynamic parameters in the two group was 6. There was no statistical significance. There was no significant difference in the hemodynamic index and lactic acid between the three groups at 6 hours and the three groups at 6. The lactic acid in the group 75-85mmHg was significantly lower than that in the group MAP75mmHg, and there was no significant difference between the MAP85mmHg and MAP in the difference of other blood flow mechanics indexes in the three groups of patients with 75-85mmHg lactate difference.6.
2. second parts: (1) (1) (1) Pcc and Pmsf in septic shock were 49.59 + 13.6mmHg and 28.31 + 6.3mmHg respectively, and (P0.0001).Pcc-Pmsf was 21.27 + 11.1mmHg, suggesting that there was a "vascular waterfall" in septic shock; (2) there was a significant positive correlation between arterial resistance (Ra) and systemic vascular resistance index (SVRI); (3) Pcc and peripheral vascular resistance index (P0.0001) Number is unrelated, R=0.27 (P=0.032). (2) (2) (1) after dilatation, Pcc changes from 42.9 + 10.0mmHg to 44.8 + 8.9mmHg, (P=0.188); and after expansion, Pcc-Pmsf changes from 21.5 + 8.6mmHg to 20.5 + 7.9mmHg, (P=0.899); thirdly, Pmsf-CVP increases 12.2 + 6.1mmHg to 14.5 +. .9 + 10.1mmHg increased to 37.2 + 10.5mmHg, (P0.0001), Ra decreased, Rv had no significant change, and SVRI decreased to 1383.7 + 643.8dyn.sec.cm-5. m-2, (P0.0001), suggesting that arterial resistance decreased and venous resistance had no significant change. (5) ScvO2 increased from 75.9 + 9.3% to 81.6 + 4.2%, (P0.05). (3) During the process, the required NE increased in turn, and there was a significant difference between the dosage of the stress loci (P0.0001), and there was no significant change in the blood temperature in the whole process. (2) when Pa increased from 65mmHg to 75mmHg, Pmsf and CVP increased significantly (P0.05), but Pmsf-CVP and CO did not change significantly (P0.05); Pcc changed from 42.8 + 10 to 44.5 +. (05): Pa-Pcc increased from 22.8 + 10.1mmHg to 32.6 + 9.1mmHg, (P0.0001).Ra, Rs significantly increased, Rv had no obvious changes, the skin oxygenation index (PtcO2/PaO2) and urine volume (UO) increased, (P0.05), Lac and Pv-aCO2 significantly decreased. Significantly increased, (P0.05); both Pmsf-CVP and Rv were greater than the locus of Pa65mmHg; Pcc changed from 44.5 + 8.8mmHg to 45.4 + 8.8mmHg, (P0.05); Pa-Pcc increased from 22.8 + 10.1mmHg to 41.9 + 8.9mmHg. MSF, CVP Pmsf-CVP, Rv, CO were all significantly increased, and the differences in the values of the first three pressure loci were statistically significant. (P0.05).Pcc increased from 45.4 + 8.8mmHg to 59.1 + 14.8mmHg, and the difference was statistically significant, (P0.05); Pa-Pcc was reduced to 40.6 + from 41.9 + 8.9mmHg, and the difference was increased from 17 + to 24.5. The difference was statistically significant (P0.0001), (P0.0001). The level of serum lactic acid was not further reduced, PtcO2/PaO2 decreased, UO did not further increase, and Pv-aCO2 did not further decrease, (P0.05).
Conclusion:
1. first part: (1) the death rate of patients with septic shock with abnormal tissue perfusion at the end of EGDT is very high; (2) a certain degree of blood pressure can reduce the level of serum lactic acid, and then reduce the mortality of 28d in this type of patient; (3) the effect of perfusion pressure seeking to improve tissue perfusion is not ideal at present, and the best perfusion pressure is further sought. The method is an urgent problem to be solved in the clinic.
2. second parts: (1) there is a pressure gradient in Pcc and Pmsf during septic shock, suggesting that there is a "vascular waterfall" (2) not changing the critical closed pressure of the small vessels by enlarging the volume of the heart, and (3) the critical closed pressure of the small vessels and the resistance of the peripheral vessels can be used to evaluate the vascular site of the vasoconstrictor; (4) the application of vasoconstriction. During the process of improving MAP, the sudden increase of critical closure pressure suggests that tissue perfusion may begin to deteriorate; (5) the maximum difference between the mean arterial pressure and the critical close pressure of the small vessels can be the most effective improvement of tissue perfusion, and the mean arterial pressure range corresponding to the perfusion pressure is 75-85mmHg; (6) Pcc can make the best perfusion pressure selected. Choose to quantify and individualized.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R459.7

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