感染性休克时心脏和微循环的功能变化及β受体阻滞剂的血流动力学效应

发布时间：2018-09-13 06:35

【摘要】：目的：脓毒症、感染性休克直至发展至脓毒症心肌抑制阶段各个阶段患者能否从β-受体阻滞剂治疗中获益,以及β-受体阻滞剂对心脏收缩和舒张功能、动脉系统、静脉回流系统以及血管瀑布各个位点影响。方法：临床部分：连续选择2014年2月-2014年4月入住北京协和医院重症医学科脓毒症、严重脓毒症、感染性休克并经过标准治疗,且可除外容量不足,Ramsay镇静评分2～4分,但仍心率≥100次/分32例患者。给予艾司洛尔泵入治疗,目标心率下降较基础值低10%-15%。实验全程维持患者其余输液、血管活性药物、降温、镇静、呼吸支持等治疗不变。采用前瞻性研究方法,所有患者采集用药前1h内,及用药后达到目标心率时2h内经胸超声(TTE)及组织灌注参数。动物实验部分：杂种犬8只,麻醉满意后给予气管插管接呼吸机辅助呼吸,建立应用肺动脉导管技术和脉搏指示剂持续心排量(PICCO)监测系统；应用经食道超声(TEE)监测心脏收缩及舒张功能的变化；给狗在无菌状态下行开腹手术,在左肾动脉放置超声血流量仪探头,实时监测左肾动脉肾血流量(RBF)变化,给狗做机械通气4个不同水平气道压的10秒吸气末屏气,选用5cmH20、15cmH20,25cmH20、35cmH20这四个水平的气道压,用稳态CVP代替肾静脉回流压力,用平均动脉压力替代肾灌注压。建立一元线性回归方程,测量每只狗的动脉临界闭合压(critical closing pressure, Pcc)和体循环平均充盈压(mean systemic filling pressure, MSFP),并计算血管瀑布,及动脉系统、静脉回流系统各参数,并检测动脉、中心静脉、混合静脉,监测乳酸、静动脉二氧化碳分压差、代酸等组织灌注指标。本实验给狗泵入内毒素(LPS)总剂量为5.3ug/Kg,以制造感染性休克模型,分别研究基线期、感染性休克基线期、感染性休克高动力阶段、感染性休克低动力阶段各阶段动脉系统、静脉回流系统特点及血管瀑布的演变过程。并重点研究感染性休克低动力阶段(脓毒症心肌抑制阶段),在LVEF下降至45%以下达到脓毒症心肌抑制标准,分2组(对照组、β-受体阻滞剂组)干预治疗,并对比两组整体循环参数变化,以了解β-受体阻滞剂组能否使脓毒症心肌抑制期动物获益。结果：临床部分：给脓毒症患者使用β-受体阻滞剂后测左室流出道速度时间积分(velocity time integral) VTI较用药前上升,心室舒张功能评估可知顺应性改善是VTI上升的基础。但用β受体阻滞剂后伴随心率的下降尽管心输出量(cardiac output, CO)降低是明确的,但乳酸水平有明显下降。另外本研究认为VTI上升是心功能综合改善的结果,故将VTI上升组和VTI不升组两组用药前超声资料进行对比,发现二尖瓣环侧壁侧位移(MAPSElat)可做为预测用β-受体阻滞剂VTI上升的参数,做ROC曲线分析cutoff值为MAPSElat=1.34;另外给β-受体阻滞剂前没有容量过负荷的患者更容易获VTI上升。动物实验部分：伴随脓毒症的发生,血管瀑布现象消失及组织灌注变差,此过程始终伴随感染性休克整体进程。感染性休克高动力状态时高C0并不能改善组织灌注,且高CO不能使瀑布复现,而低动力状态脓毒症心肌抑制时低CO使组织灌注进一步恶化。感染性休克系统流量的高低同体循环张力容量多少有关,而张力容量状态和休克复苏及系统顺应性相关。结论：研究给脓毒症患者使用β-受体阻滞剂后使CO下降,但可使部分患者VTI上升。MAPSElat1.34可作为预测VTI上升的阈值,使得β-受体阻滞剂能更安全应用于临床治疗。β-受体阻滞剂使用后心室顺应性改善,舒张功能改善。CO下降可以和组织灌注改变不平行。感染性休克时Pcc下降,导致血管瀑布效应消失。C0改变,不改变血管瀑布效应,不改变瀑布起点和终点的压力；瀑布上、下游阻力随CO改变而改变；张力容量的改变影响C0变化。CO变化与组织灌注改变并不平行。除CO之外,微循环的血管瀑布效应是影响组织灌注的重要因素。脓毒症心肌抑制阶段,β-受体阻滞剂治疗：可改善心室顺应性,使Pcc增加,恢复血管瀑布效应；瀑布效应存在与组织灌注改善相关。存在瀑布现象时,瀑布高度高有利于组织灌注,机制尚不完全清楚。
[Abstract]:Objective:
Whether patients at all stages of sepsis, septic shock, and myocardial suppression develop to sepsis benefit from beta-blockers, and the effects of beta-blockers on cardiac systolic and diastolic function, arterial system, venous return system, and vascular waterfall sites.
Method:
Clinical section: 32 patients with sepsis, severe sepsis, septic shock and standard treatment, who were admitted to the Department of Critical Medicine of Peking Union Medical College Hospital from February 2014 to April 2014, were selected. The Ramsay sedation score was 2-4, but the heart rate was still above 100 beats/minute. Esmolol was given to 32 patients, and the target heart rate was lower than the baseline. All patients received transthoracic echocardiography (TTE) and tissue perfusion parameters within 1 hour before administration and 2 hours after reaching the target heart rate.
Animal experiment: Eight mongrel dogs were given tracheal intubation and ventilator to assist respiration after anesthesia, and the monitoring system of pulmonary artery catheterization and pulse indicator continuous cardiac output (PICCO) was established; the changes of cardiac contraction and diastolic function were monitored by transesophageal echocardiography (TEE); the dogs were operated on under aseptic condition and left ventricle was operated on. The left renal artery renal blood flow (RBF) was monitored in real time with a probe placed in the renal artery. The dogs were ventilated for 10 seconds at four different levels of airway pressure. The four levels of airway pressure (5 cm H20, 15 cm H20, 25 cm H20, 35 cm H20) were selected. Steady state CVP was used instead of renal venous reflux pressure and mean arterial pressure was used instead of renal perfusion. Pressure. A linear regression equation was established to measure the critical closing pressure (Pcc) and mean systemic filling pressure (MSFP) in each dog. The parameters of vascular cascade, arterial system and venous reflux system were calculated. The arteries, central veins, mixed veins, lactic acid and static arteries were detected. The total dose of LPS was 5.3 ug/Kg. The characteristics of arterial system and venous reflux system in baseline stage, baseline stage of septic shock, hyperdynamic stage of septic shock, hypodynamic stage of septic shock were studied. The development of vascular waterfall was also studied. The low dynamic stage of septic shock (myocardial suppression stage) was studied, and the LVEF decreased to below 45% to reach the standard of myocardial inhibition in septic shock. Animals with toxic myocardial arrest benefit.
Result:
Clinical part: The left ventricular outflow velocity time integral (VTI) of sepsis patients after beta-blocker administration was higher than that before administration. Ventricular diastolic function assessment showed that improved compliance was the basis of VTI elevation. In addition, this study considered that the increase of VTI was the result of comprehensive improvement of cardiac function. Therefore, we compared the ultrasonic data of the two groups before treatment and found that MAPSElat could be used as a parameter to predict the increase of VTI and ROC curve. The cut off value was MAPSElat = 1.34, and VTI was more likely to rise in patients who did not have excess capacity before beta-blockers were given.
Animal experiment: with sepsis, vascular waterfall disappears and tissue perfusion becomes worse. This process is always accompanied by the whole process of septic shock. High C0 does not improve tissue perfusion in septic shock with hyperdynamic state, and high CO does not make the waterfall recur, while low CO makes tissue perfusion in septic myocardial suppression with hypodynamic state. Further deterioration. Systemic flow in septic shock is related to the volume of circulatory tension, while the volume of tension is related to shock resuscitation and system compliance.
Conclusion:
MAPSElat 1.34 can be used as a threshold to predict the rise of VTI, making beta-receptor blockers safer for clinical use. Ventricular compliance and diastolic function improved after the use of beta-receptor blockers. Decreased CO and tissue perfusion can be altered. Not parallel.
In septic shock, Pcc decreases, resulting in the disappearance of vascular cascade effect. C0 changes, does not change vascular cascade effect, does not change the pressure at the beginning and the end of the cascade; upstream and downstream resistance of the cascade changes with the change of CO; the change of tension capacity affects the change of C0. The change of CO is not parallel to the change of tissue perfusion. Effect is an important factor affecting tissue perfusion.
In the myocardial suppression stage of sepsis, beta-blocker therapy can improve ventricular compliance, increase Pcc and restore the vascular cascade effect; the cascade effect is related to the improvement of tissue perfusion.
【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】：2014
【分类号】：R459.7

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