第一个小时的脓毒性休克复苏

2018-05-08 梁宇鹏 重症医学

综述目的 我们对最近的脓毒症和脓毒性休克初始复苏策略进行综述


综述目的

我们对最近的脓毒症和脓毒性休克初始复苏策略进行综述.

近期的研究结果

脓毒症和脓毒性休克是一类致命性急症。第一个小时内的两项关键干预措施包括及时的抗感染治疗和复苏。在得到实验室检查结果之前,于体格检查中发现伴有低血压或外周循环障碍的,怀疑存在感染的患者均应考虑进行复苏。迄今为止,这种脓毒症和脓毒性休克的早期复苏仍被来自目标导向治疗对患者结局的改善所支持。但最近三个目标导向治疗研究未能重复最初报道的死亡率的降低,由此推动了是否应该进行早期复苏的争论。因复苏聚焦于例如优化中心静脉压等大循环目标,复苏期间微循环和大循环优化间的不一致是一个较新的临床研究缺乏结局获益的可能论点。血管活性药物的剂量和复苏相关的液体正平衡与重症脓毒症和脓毒性休克患者较差的临床结局均独立相关。基于较低的血压目标和限制性容量复苏具有可行性并耐受良好,我们是否应该考虑一个更低的血压目标来降低儿茶酚胺的副作用和复苏液体的过量。可对液体种类、血管活性药物和正性肌力药物选择进行指导的证据仍然有限。

总结

尽管早期复苏对脓毒症和脓毒性休克的结局改善至关重要,目前仍未能找到理想的复苏目标。应该对微循环和大循环的变化进行区别并制定相应的目标。包括大容量复苏和高剂量的血管活性药物并不总是能给患者带来益处。微循环目标,个体化复苏目标和应用更新的脓毒性休克诊断标准对所有的研究进行重新评估应该是将来的研究所关注的焦点。

要点

@SSC指南提出了脓毒症患者治疗的框架。

@早期抗感染药物和液体复苏是脓毒症治疗的重要干预措施.

@新的证据表明微循环和大循环在复苏后的优化间存在不同。

@复苏相关的液体正平衡和高剂量的血管活性药物与脓毒症和脓毒性休克的不良后果相关,已有与限制液体,更低的血压目标相关的研究正在进行。

前言

脓毒症被定义为机体对感染的失调的炎症反应引起的致命的器官功能障碍。在这个背景下,器官功能衰竭在临床上被定义为SOFA评分≥2分。脓毒性休克被定义为脓毒症的一个亚组,其特点为存在持续的循环、细胞和代谢异常,与脓毒症相比,具有更高的死亡风险。诊断脓毒性休克的标准为不伴低血容量情况下需要血管活性药物来获得平均动脉压≥65mmHg和乳酸浓度>2mmol/L (>18mg/dl)。复苏是改善在脓毒症和脓毒性休克患者中常见的大循环和微循环障碍重要干预措施。复苏也是SSC指南3小时和6小时bundle的组成部分。本文将对脓毒症相关的大循环和微循环异常、指南中的复苏目标,微循环作为复苏早期的关注点和最近的关于液体、血管活性药物以及脓毒症和脓毒性休克复苏过程中的综合目标进行综述。

微循环和大循环障碍在脓毒症和脓毒性休克中非常常见。微循环指直径小于100-150um的血管(例如小动脉、毛细血管、小静脉和淋巴管)和包括血管内皮细胞、血管平滑肌细胞、红细胞、白细胞和血小板等在内的相关细胞的循环状态。能够直接进行微循环血流检测的工具在并不总是可用的。但包括乳酸、混合/中心静脉氧饱和度(ScvO2)和中心静脉—动脉二氧化碳分压差(dPCO2) 等基于组织灌注的指标仍然构成了全身微循环的非直接指标。微循环状态也可通过被称为功能毛细血管密度的方式了解血流的一致性进行评估。.

脓毒症状况下,因为局部和全身性宿主反应,微循环存在持续改变。健康人体中,内皮细胞在循环血液和组织间起连续和抗凝的屏障作用。脓毒症背景下内皮屏障出现障碍,导致凝血激活、液体外渗和活化白细胞的粘附造成恶性循环。这使炎症、凝血和内皮损伤持续存在。与此相关的血管平滑肌张力、相对的血容量不足和功能性毛细血管密度降低导致微循环单位间出现异质性,导致微循环丧失血管张力调节能力。收缩的小动脉与舒张的毛细血管共存。这些改变导致微循环的效率变得低下,从而出现一个可被毛细血管氧分压降低,静脉氧分压升高和线粒体摄氧能力下降所证实的氧分压 。

大血管内的循环被称为大循环。大循环的血流动力学参数包括中心静脉压(CVP),肺楔压,动脉血压(BP),心输出量(CO),动脉氧摄取和氧供。同微循环的变化类似,脓毒症的大循环异常也存在异质性。另外,还存在急性可逆,可同时影响两个心室的心肌抑制以及提示肌节收缩和兴奋—收缩偶联受损的心肌细胞及基因表达异常。

脓毒症和脓毒性休克的早期复苏

2001年,Rivers等发表了一项在263例严重脓毒症或脓毒性休克患者中,对早期目标导向治疗与标准治疗进行对比的EGDT单中心、随机对照研究(RCT)。该研究结果显示EGDT降低了16%的院内绝对死亡率。EGDT方案包括首先达到大循环目标(CVP 8-12mmHg,MAP≥65mmHg),而后达到ScvO2≥70%的微循环指标。达到这些目标的干预手段包括液体和血管活性药物,以及为达到微循环目标的,通过输注红细胞将血红蛋白提升至10g/L和/或应用正性肌力药物改善心输出量。EGDT与常规治疗组间在0-6小时间干预措施的关键区别在于—显著增加的液体、红细胞输注量及血管活性药物。这个研究构建了之前SSC指南的复苏目标的基础。复苏的第一个6小时内的目标包括:CVP=8-12,MAP至少65mmHgL,尿量至少0.5 ml/kg/h以及上腔静脉或混合静脉氧饱和度各自分别大于70%和65%。

2008到2014年间,三个分别在美国(RROCESS),澳大利亚(ARISE)和英国(PROMISS)进行的,共纳入了4211例患者的多中心随机对照研究应用与Rivers等类似的方案进一步对EGDT与常规治疗进行了评估。除了实验水平的 Meta分析外,作者还通过合成这三个研究的数据进行了患者水平的Meta分析,以评估EGDT同常规治疗组比较,对所有患者以及关键的预设亚组的影响。EGDT组(24.9%)和常规治疗组(25.4%)患者的90天死亡率之间不存在有意义的校正比值比[95% CI 0.97 (0.82–1.14)]。EGDT治疗的作用并未随着疾病严重程度而有所变化。基于这些研究结果,最新的SSC指南虽然称仍这是基于低质量证据,但仍强烈推荐在治疗的前3个小时内给予至少30ml/kg的晶体液。这些指南也推荐目标MAP≥65mmHg并建议对乳酸升高的患者,应将乳酸水平降至正常,这(乳酸水平降至正常)也是基于低质量证据,但是毕竟提出了一个微循环的指标。

早期针对微循环的复苏有意义吗?

RCT中设置的微循环目标包括乳酸浓度以及分别在急诊室(LactATES研究)或ICU中的常规治疗与其进行对比的ScvO2。LactATES研究是一项在300例患者中进行的非劣效研究。该研究将接受以CVP,随后MAP,进而ScvO2≥70%为目标的对照组与以类似的CVP,MAP,进而乳酸清除率大于10%为目标的乳酸清除组进行了对比。此研究强调乳酸清除率不劣于基于ScvO2的复苏。值得注意的是,来自这个研究的,一个预设的亚组分析强调,仅达到目标ScvO2相比仅达到乳酸清除率的目标与更高的死亡率相关[41% vs 8%,比例差=33%;95%CI 9-55%]。尽管这些支持力度不足的亚组分析在应用于临床之前需要经过RCT检测,其确实强调了对乳酸的代谢进行研究的价值。Jansen等在ICU中评估了一个复杂的,目标为乳酸清除率大于等于20%的复苏程序。尽管常规治疗组和乳酸清除组未调整的死亡率间没有差别,但乳酸清楚组协变量调整的OR显著低于常规治疗组。乳酸清除组患者在第一个以“开放微循环”为目的8小时复苏时间内接受了更多的液体,并依据实验程序的要求,42.5%的患者接受了血管扩张药物的应用。这个方法挑战了更传统的复苏目标(例如,65mmHg的MAP)。通常用于达到MAP目标血管活性药物,其用量可以降低至能维持最小灌注的更低的MAP值,并且最终血管扩张药物能够改善微循环血流的程度。但尽管乳酸清除率已成为一个良好的预后指标,高乳酸水平在脓毒症状态下并不与组织的严重缺氧密切相关,并且儿茶酚胺通过增加糖代谢直接促进乳酸水平的上升。此外,SSC指南委员会基于低质量的证据,对于以乳酸为导向的复苏程序作出了低等级推荐,并且因引用的支持文献在方法学上的局限,没有对血管扩张药物做出推荐。

动静脉CO2梯度构成了另外一个潜在的复苏目标。理论上讲,静脉和动脉血二氧化碳含量差的增加同CO和CO2产生之间的不匹配比例相关。升高的dPCO2梯度(正常值范围为2-6 mmHg)可能在乳酸水平上升之前就提示血流与代谢需求相比的不足。但是,CO2代谢是一个复杂的过程并且将dPCO2值作为复苏目标与无数的假设相关。而且,以dPCO2梯度作为复苏目标的复苏程序的整体效应仍属未知。最后,Marik等在一个激动人心的研究中强调了早期联用维生素C,激素和维生素B1的临床益处,并指出这种干预方式的微循环效应具有其生物学合理性。总体而言,设计良好并具有足够效能的,关于脓毒症和脓毒性休克微循环复苏的作用的研究仍在被热切期待。

液体

脓毒症和脓毒性休克初始复苏期间液体治疗理论目标包括恢复血管内的压力容量和心室前负荷的优化。液体治疗的用量和种类选择仍然存在争议。尽管液体的bolus应用可迅速改善患者的血流动力学状况,但(临床医生存在)对于(液体的bolus应用对血流动力学改善的)作用的短暂和(液体的bolus应用)对微循环的影响以及医源性并发症的影响存在顾虑。同样,目前有关何种液体最适合于脓毒性休克早期复苏的结论仍不明确。因缺乏综合获益并可能带来伤害,羟乙基淀粉已经不再被广泛推荐。类似的,在近期的一个RCT中,基于白蛋白的复苏没有能够在脓毒症亚组中显示出获益的可能。因胶体液的应用缺乏明确的获益,尽管对其多种潜在的,包括肾脏、促进炎症反应、抗凝和与其酸性相关的副作用的担忧持续存在,但2016年SSC指南仍推荐初始的晶体液复苏。平衡液具有理论上的优点,尽管其明确获益有待不断论证。无论选择了那种液体和多大量,因其在脓毒性休克背景下有限和矛盾的证据,重要的是其应被认为是一种药物并谨慎应用。

对脓毒性休克患者进行的大量液体复苏会导致液体的累积正平衡。这种正平衡可对微循环造成损伤并且是脓毒症和脓毒性休克患者独立的死亡危险因素。此外,在严重感染的儿童患者中,无论盐水或白蛋白bolus应用超量,均可造成48小时死亡率的显著升高。这些观察性研究促生了有关对比脓毒性休克保守与自由液体复苏的RCT(CLASSIC研究)。CLASSIC研究的结果显示随机后第5天(-1.21,95%CI-2.0— -0.4)和整个ICU停留时间内(-1.41,95%CI -2.4--0.4,P<0.001)限制组的累积复苏液体量显著低于标准治疗组并且限制组并没有增加不良后果的风险。包含通过被动抬腿实验来评估液体反应性的复苏方法可降低脓毒症和脓毒性休克患者的总液体用量。

血管活性药物和正性肌力药物

血管活性药物,同液体一样,是复苏bundle中的直观组成部分。理论上而言,血管活性在所谓的病理病因根源上纠正了血管的国度扩张。但是,低血压并不意味着器官灌注一定受损,而血压正常并不能保证器官灌注的足够。根据泊肃叶定律,血管的半径对血流的影响远较血管两端的压力差为大。因血管活性药物诱导了血管收缩(换句话说,降低了血管的半径),尽管达到了血压目标,但其可能降低了器官灌注。另外,血管活性药物本身可对微循环血流造成损伤。例如,临床医生倾向与把休克加重的信号归因于疾病本身并增加治疗强度,而对他们的治疗正是造成(休克加重)的罪魁祸首一无所知。因此,在应用血管活性药物时,临床医生应对病情恶化是否源自医源性并发症做出鉴别。最近的研究引起了人们对脓毒症背景下血管活性药物的随意应用的灌注。在足够有力的临床研究确定更严格的MAP目标的整体获益之前,目前的推荐MAP目标的整体效应仍来源于少量证据。当我们讨论血管活性药物的应用时,必须将脓毒性休克背景下各种血管活性药物的缺点和血管加压素的应用考虑在内。

在一个应用析因实验设计,以非肾衰天数为首要终点指标的,将血管加压素与去甲肾上腺素和激素与安慰剂进行对比的研究中,血管加压素对比去甲肾上腺素未能改善非肾衰天数。来自对更早应用血管加压素研究进行的亚组分析的假设表明疾病严重程度较低的患者可能获益最大。这个假设应该在脓毒性休克患者中增加血管加压素应用的背景下进行验证。

脓毒症中循环的变化也可能由肾素-血管紧张素系统的异常所致,并且外源性的血管紧张素II可以作为一个对脓毒性休克患者有意义的血管活性药物。最近的研究表明,在儿茶酚胺抵抗的血管舒张性休克患者中,血管紧张素II的应用与作为主要结果的BP的改善相关。在这个研究中,接近75%的儿茶酚胺抵抗状态的原因是脓毒性休克。这暗示了一旦血管紧张素II改善死亡率的益处得到承认,其在脓毒性休克中的应用前景。

左西孟旦是一个可能对脓毒症有益的,除正性肌力以外还有多种作用的钙增敏剂。例如,在最近的一项纳入了20例患者的试验性RCT中,左西孟旦降低了乳酸/丙酮酸比例,这表明其对脓毒性休克细胞代谢的改变具有有益作用。但是,在这之前进行过一个大型的,纳入516例成人脓毒症患者,评估左西孟旦是否能够改善成人脓毒症患者器官功能障碍的研究。在该研究中,同安慰剂相比,左西孟旦与器官功能障碍严重程度或死亡率的降低并不相关。重要的是,在这个研究中左西孟旦组患者室上性心律失常和脱机失败的风险更高。鉴于缺乏左西孟旦在左心室功能受损患者心脏手术中的疗效观察,在广泛临床应用之前进行需要进一步的研究以丰富脓毒症患者是否可从左西孟旦中获益的证据。

结论

脓毒性休克是一个常见并具有高死亡风险的急症。早期的抗生素和目标复苏仍然是其治疗的基石。越来越多的证据表明,一些传统的,大容量复苏和高剂量血管活性药物的应用并不总是有益甚至可能有害。应该对微循环和大循环的改变和复苏进行区别。关注于微循环的个体化复苏和更低的血压目标在适用于所有患者方面具有理论上的优越性。但证据需要从足够的有说服力的研究中获得。

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1687097, encodeId=c880168e0972e, content=<a href='/topic/show?id=b038851865c' target=_blank style='color:#2F92EE;'>#脓毒性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85186, encryptionId=b038851865c, topicName=脓毒性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dd9828318255, createdName=1249857fm41暂无昵称, createdTime=Tue Oct 09 19:55:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314626, encodeId=3b5b31462625, content=好文献.谢谢学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 06:54:59 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290280, encodeId=d01f12902807e, content=<a href='/topic/show?id=7d058518e56' target=_blank style='color:#2F92EE;'>#脓毒性休克#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85187, encryptionId=7d058518e56, topicName=脓毒性休克)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1305443, encodeId=36b9130544349, content=<a href='/topic/show?id=270342e249d' target=_blank style='color:#2F92EE;'>#复苏#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42724, encryptionId=270342e249d, topicName=复苏)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1d01326, createdName=lizhou0204, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313405, encodeId=eb34313405db, content=好文献.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Wed May 09 07:05:54 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313244, encodeId=883e313244f5, content=感谢分享., beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f1941433532, createdName=susu8093, createdTime=Tue May 08 21:52:34 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313190, encodeId=811b31319077, content=脓毒症和脓毒性休克是一类致命性急症.第一个小时内的两项关键干预措施包括及时的抗感染治疗和复苏., beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Tue May 08 15:25:34 CST 2018, time=2018-05-08, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1687097, encodeId=c880168e0972e, content=<a href='/topic/show?id=b038851865c' target=_blank style='color:#2F92EE;'>#脓毒性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85186, encryptionId=b038851865c, topicName=脓毒性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dd9828318255, createdName=1249857fm41暂无昵称, createdTime=Tue Oct 09 19:55:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314626, encodeId=3b5b31462625, content=好文献.谢谢学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 06:54:59 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290280, encodeId=d01f12902807e, content=<a href='/topic/show?id=7d058518e56' target=_blank style='color:#2F92EE;'>#脓毒性休克#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85187, encryptionId=7d058518e56, topicName=脓毒性休克)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1305443, encodeId=36b9130544349, content=<a href='/topic/show?id=270342e249d' target=_blank style='color:#2F92EE;'>#复苏#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42724, encryptionId=270342e249d, topicName=复苏)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1d01326, createdName=lizhou0204, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313405, encodeId=eb34313405db, content=好文献.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Wed May 09 07:05:54 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313244, encodeId=883e313244f5, content=感谢分享., beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f1941433532, createdName=susu8093, createdTime=Tue May 08 21:52:34 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313190, encodeId=811b31319077, content=脓毒症和脓毒性休克是一类致命性急症.第一个小时内的两项关键干预措施包括及时的抗感染治疗和复苏., beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Tue May 08 15:25:34 CST 2018, time=2018-05-08, status=1, ipAttribution=)]
    2018-05-13 张新亮1853311252142e2fm

    好文献.谢谢学习了

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1687097, encodeId=c880168e0972e, content=<a href='/topic/show?id=b038851865c' target=_blank style='color:#2F92EE;'>#脓毒性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85186, encryptionId=b038851865c, topicName=脓毒性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dd9828318255, createdName=1249857fm41暂无昵称, createdTime=Tue Oct 09 19:55:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314626, encodeId=3b5b31462625, content=好文献.谢谢学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 06:54:59 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290280, encodeId=d01f12902807e, content=<a href='/topic/show?id=7d058518e56' target=_blank style='color:#2F92EE;'>#脓毒性休克#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85187, encryptionId=7d058518e56, topicName=脓毒性休克)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1305443, encodeId=36b9130544349, content=<a href='/topic/show?id=270342e249d' target=_blank style='color:#2F92EE;'>#复苏#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42724, encryptionId=270342e249d, topicName=复苏)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1d01326, createdName=lizhou0204, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313405, encodeId=eb34313405db, content=好文献.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Wed May 09 07:05:54 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313244, encodeId=883e313244f5, content=感谢分享., beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f1941433532, createdName=susu8093, createdTime=Tue May 08 21:52:34 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313190, encodeId=811b31319077, content=脓毒症和脓毒性休克是一类致命性急症.第一个小时内的两项关键干预措施包括及时的抗感染治疗和复苏., beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Tue May 08 15:25:34 CST 2018, time=2018-05-08, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1687097, encodeId=c880168e0972e, content=<a href='/topic/show?id=b038851865c' target=_blank style='color:#2F92EE;'>#脓毒性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85186, encryptionId=b038851865c, topicName=脓毒性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dd9828318255, createdName=1249857fm41暂无昵称, createdTime=Tue Oct 09 19:55:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314626, encodeId=3b5b31462625, content=好文献.谢谢学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 06:54:59 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290280, encodeId=d01f12902807e, content=<a href='/topic/show?id=7d058518e56' target=_blank style='color:#2F92EE;'>#脓毒性休克#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85187, encryptionId=7d058518e56, topicName=脓毒性休克)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1305443, encodeId=36b9130544349, content=<a href='/topic/show?id=270342e249d' target=_blank style='color:#2F92EE;'>#复苏#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42724, encryptionId=270342e249d, topicName=复苏)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1d01326, createdName=lizhou0204, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313405, encodeId=eb34313405db, content=好文献.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Wed May 09 07:05:54 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313244, encodeId=883e313244f5, content=感谢分享., beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f1941433532, createdName=susu8093, createdTime=Tue May 08 21:52:34 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313190, encodeId=811b31319077, content=脓毒症和脓毒性休克是一类致命性急症.第一个小时内的两项关键干预措施包括及时的抗感染治疗和复苏., beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Tue May 08 15:25:34 CST 2018, time=2018-05-08, status=1, ipAttribution=)]
    2018-05-10 lizhou0204
  5. [GetPortalCommentsPageByObjectIdResponse(id=1687097, encodeId=c880168e0972e, content=<a href='/topic/show?id=b038851865c' target=_blank style='color:#2F92EE;'>#脓毒性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85186, encryptionId=b038851865c, topicName=脓毒性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dd9828318255, createdName=1249857fm41暂无昵称, createdTime=Tue Oct 09 19:55:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314626, encodeId=3b5b31462625, content=好文献.谢谢学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 06:54:59 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290280, encodeId=d01f12902807e, content=<a href='/topic/show?id=7d058518e56' target=_blank style='color:#2F92EE;'>#脓毒性休克#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85187, encryptionId=7d058518e56, topicName=脓毒性休克)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1305443, encodeId=36b9130544349, content=<a href='/topic/show?id=270342e249d' target=_blank style='color:#2F92EE;'>#复苏#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42724, encryptionId=270342e249d, topicName=复苏)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1d01326, createdName=lizhou0204, createdTime=Thu May 10 04:55:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313405, encodeId=eb34313405db, content=好文献.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Wed May 09 07:05:54 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313244, encodeId=883e313244f5, content=感谢分享., beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f1941433532, createdName=susu8093, createdTime=Tue May 08 21:52:34 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313190, encodeId=811b31319077, content=脓毒症和脓毒性休克是一类致命性急症.第一个小时内的两项关键干预措施包括及时的抗感染治疗和复苏., beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Tue May 08 15:25:34 CST 2018, time=2018-05-08, status=1, ipAttribution=)]
    2018-05-09 张新亮1853311252142e2fm

    好文献.学习了

    0

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    2018-05-08 susu8093

    感谢分享.

    0

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    2018-05-08 有备才能无患

    脓毒症和脓毒性休克是一类致命性急症.第一个小时内的两项关键干预措施包括及时的抗感染治疗和复苏.

    0

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