crrt在严重感染中应用new58张

1、 东南大学附属中大医院危重病医学科郭凤梅CRRT在 重症感染和感染性休克中的应用第1页，共58页。定义发病机制治疗 -CRRT治疗内容提要第2页，共58页。定 义Systemic Inflammatory Response Syndrome (SIRS)At least 2 of the following 4 conditions: Oral temperature 38o or 20 breaths/min or PaCO2 of 90 beats/min WBC 12,000/uL or 10 percent bandsSepsis Severe sepsisSIRS that has

2、a proven or suspected microbial etiology Sepsis with one or more signs of organ dysfunctionhypoperfusion, or hypotension such as metabolic acidosisacute alteration in mental status, oliguria, coagulation abnormalities or adult respiratory distress syndrome第3页，共58页。Hypotension Systolic blood pressure

3、 90 mmHg - or 40 mmHg less than patients baseline blood pressureSeptic shock Sepsis with hypotension that is unresponsive to fluid resuscitation plus organ dysfunction or perfusion abnormalities as listed above for severe sepsisMultiple organ dysfunction syndrome (MODS)Dysfunction of more than one o

4、rgan, requiring intervention to maintain homeostasis定 义第4页，共58页。Sepsis =Infection+SIRSSevere sepsis =Sepsis + organ functionSeptic shock =Sepsis + hypotension第5页，共58页。损伤 SIRS Sepsis severe sepsis (septic shock) MODS MOF感染的全过程infection第6页，共58页。院内感染发生率普通病房中病人: 6-17%ICU病人：25-40%第7页，共58页。重症感染与MODS重症感染常并

5、发MODS心、肺、肾、肝、脑等器官发生单一器官衰竭死亡率是20随器官衰竭数量增加，死亡率逐渐上升，合并4个器官衰竭患者死亡率达100 Deitch EA. Surg Clin N Am, 2019, 79: 1471-88第8页，共58页。Rangel-Frausto, M, et al. JAMA, 2019, 273:117-123 感染与重症感染对患者预后的影响第9页，共58页。MODS对患者预后的影响第10页，共58页。定义发病机制治疗 -CRRT治疗内容提要第11页，共58页。炎症反应学说重症感染至感染性休克和MODS的发病机制第12页，共58页。The acute inflamma

6、tory responseA complex series of cellular, immune and metabolic responses which have evolved to be protective and promote repair processesStimuli of inflammation Infection Burns Toxins Pancreatitis Surgery Malignancy Trauma Poisoning Ischaemia/reperfusion第13页，共58页。第14页，共58页。Inflammatory mediator rel

7、easeAlbuminInjury，infectionH2ONaClSystemic capillary leak第15页，共58页。参与SIRS和MODS的可溶性介质体液性介质细胞性介质补体TNF-凝血系统IL-1，IL-6，IL-8激肽系统血小板活化因子 NO花生四烯酸代谢产物氧自由基抗炎介质IL-10等第16页，共58页。概述发病机制治疗 -CRRT治疗内容提要第17页，共58页。重症感染和感染性休克的治疗感染病灶的引流早期合理的抗生素应用改善器官灌注器官功能支持炎症调控-血液滤过治疗第18页，共58页。重症感染的治疗转归感染(细菌/毒素)组织损伤全身炎症反应和CARS引流、抗生素治疗引

8、流、抗生素治疗引流、抗生素治疗细菌有效清除，感染控制，炎症反应局限细菌有效清除，感染控制感染未控制康复炎症反应放大MODS引流、抗生素治疗肾脏替代治疗第19页，共58页。CVVH通过对流清除中小分子炎症介质(30-40KD)，另外还有滤过膜的吸附作用CRRT在重症感染和感染性休克中的作用第20页，共58页。重症感染和感染性休克部分主要炎症介质的分子量介质分子量(KD)TNF单体17TNF三聚体51IL-626IL-117IL-88C3a9C5a11D因子PAF230.6内皮素-1花生四烯酸代谢产物缓激肽小分子0.61.06第21页，共58页。CVVH对重症感染炎症介质的影响目的： CVVH对重

9、症感染炎症介质的清除方法： 检测患者与健康志愿者血滤开始(t0)与血滤60min (t60)滤器前(afferent)滤器后(efferent)与超滤液中炎症介质的浓度。滤器为金宝FH66D，聚酰胺膜，超滤率2L/hHoffmann JN, et al. Kidney International, 2019, 48: 1563-1570第22页，共58页。CVVH对重症感染炎症介质的影响重症感染患者IL-1(pg/ml)IL-6(U/ml)IL-8 (pg/ml)TNF (pg/ml)C3a(ng/ml)C3(mg/ml)C5a(ng/ml)TCC(ng/ml)滤器后浓度To66.021091

10、143933.14676.90.72326.582966T6063.241127144728.55545.4*0.72825.653362超滤液浓度T011.9c630c140.9c0.446ct60cc604c103.7*c0.183*c*与t0相比，P0.01，c没有检测到第23页，共58页。CVVH对重症感染炎症介质的影响健康志愿者IL-1(pg/ml)IL-6(U/ml)IL-8 (pg/ml)TNF (pg/ml)C3a(ng/ml)C3(mg/ml)C5a(ng/ml)TCC(ng/ml)滤器后浓度To0c41.2c54.820.4879.70363T600c31c33.91*0.

11、4958.82769超滤液浓度T0Cc30C18.22c0.552ct60CccC7.99*c0.059*cHoffmann JN, et al. Kidney International, 2019, 48: 1563-1570第24页，共58页。聚酰胺膜具有较好的生物相容性，不刺激机体产生大量的炎症介质CVVH可以部分清除IL-1，IL-8，C3a和C5aCVVH对炎症介质的清除作用除与炎症介质的分子量有关外，还与炎症介质的蛋白结合率、活性状态、跨膜压等有关CVVH对血滤前后炎症介质浓度无显著影响，可能与CVVH超滤率较低导致的清除效率低有关CVVH对重症感染炎症介质的影响Hoffmann

12、 JN, et al. Kidney International, 2019, 48: 1563-1570第25页，共58页。滤器膜对各种炎症介质的影响介质分子量(KD)LPSTNF单体1000 17.4TNF三聚体5560IL-626IL-117IL-88C3a9C5a11D因子PAF230.6滤器膜的影响超滤液中吸附吸附/滤过-+吸附-？吸附/滤过+吸附/滤过+？吸附/滤过+吸附/滤过+吸附/滤过+吸附吸附/滤过-+第26页，共58页。低流量CRRT对重症感染和感染性休克疗效的影响Low -flow hemofiltration作者动物模型治疗量主要结果Stein内毒素休克猪20ml/kg

13、/h血流动力学无改善Gomez大肠杆菌感染狗16ml/kg/h血流动力学无改善Gomez大肠杆菌感染狗27ml/kg/h心肌收缩力增强，其他血流动力学无改善Freeman感染性休克狗600ml/h血流动力学和存活率无改善Murphey内毒素休克猪33ml/kg/h心肺功能无改善第27页，共58页。低流量CVVH在重症感染中的临床应用目的：探讨CVVH对重症感染部分炎症 介质和器官功能的影响随机、控制研究24例早期重症感染或感染性休克患者 随机进行48hCVVH(2L/h，AN69膜，1.2m2) 或不进行CVVHBellomo R, et al. CCM, 2019, 30: 100-106第

14、28页，共58页。C3a和C5a的变化低流量CVVH在重症感染中的临床应用第29页，共58页。IL-6和IL-8的变化低流量CVVH在重症感染中的临床应用第30页，共58页。IL-10和TNF的变化低流量CVVH在重症感染中的临床应用第31页，共58页。低流量CVVH在重症感染中的临床应用第32页，共58页。低流量CVVH在重症感染中的临床应用血管活性药物的应用时间机械通气时间第33页，共58页。低流量CVVH在重症感染中的临床应用ICU住院时间低流量CVVH不显著改善重症感染和感染性休克动物与患者的血流动力学状态和预后第34页，共58页。Object: evaluate hemodynami

15、c and kinetics of TNF, IL1 and IL6 in septic shock patients and ARF undergoing CVVHF over 24-hourMethods: 11 Patients, AN69 , blood flow rate 240 mL/min and UF 1.650.33 L/h. MAP, PVR, SVR, CO before and after 2h, 4h, 6h, 12h and 24 h of CVVHF. the pre- and postfilter lines and ultrafiltrate samples

16、collected for the of TNF, IL-1 and IL6 CVVH improves hemodynamics in septic shock without modifying TNF* and IL6 plasma concentrations Klouche K, et al. J NEPHROL 2019; 15: 150-157 第35页，共58页。血流动力学结果temp CHeart rate beat/mMAP mmHgMPAP mmHgCI l/min/m2ISVR dyne/s/cm5IPVR dyne/s/cm5t0h38.20.241142267.36

17、.634.92.150.7571115325875t2h37.20.27*1181877.36.933.72.74.70.7295622824754.4t4h37.00.27*1202094.26.6*36.94.24.70.631353309*29074t6h36.70.27*12416846.6*37.92.44.70.6117720229869t12 h36.80.24*11515101.38*403.94.90.61324325*27669t24 h36.60.24*1192189.35.4*37.74.25.50.51200100*20528.4P0.05ns0.05nsns7.3

18、d) 4 hrs, 50% reduction in EP“responders” : attained four goals (11 of 20) “nonresponders” : did not (9 of 20)第45页，共58页。ResultsBase : age, APACHE II, predicted risk of death, SAPS II, epinephrine requirement no differences第46页，共58页。Twenty-Eight-Day Survival : 9 of 11 responder survived 9 nonresponde

19、rs died by T24 Body weight : responders (66.28.4)kg nonresponders (82.613.4)kg, (p .0031) Ultrafiltrate : responders (0.530.07)L/kg nonresponders (0.430.07)L/kg, (p .0031)Delay time : responders 6.5 hrs nonresponders 13.8 hrs (p .01) Responder was associated with : delay time, body weight, and ultra

20、filtrate doseResultsSTHVH may be of major therapeutic value in the treatment of intractable septic shockEarly initiation of therapy and adequate dose may improve hemodynamic and metabolic responses and 28-day survival 第47页，共58页。目的：评估高流量血滤对感染性休克患者血流动力学和细胞因子的影响方法：随机cross-over试验， 11例患者随机接受8h HVHF (6L/h

21、) (AN69滤器，1.6m2)或8h CVVH (1L/h) (AN69滤器，1.2m2)检测指标：血流动力学、去甲肾上腺素需要量、血清C3a、C5a、IL-2、IL-8、IL-10和TNF的含量高流量血滤在感染性休克患者中的作用Bellomo R, et al. Intensive Care Med, 2019, 27: 978-986第48页，共58页。结果：HVHF组与CVVH组期间CVP、CI、 PAWP和 液体平衡均无显著差异C3a, C5a, IL-10在治疗 2 h内均显著降低， C3a 和C5a在 HVHF期间降低更为明显 (p 70mmHg，HVHF组去甲肾上腺素需 要量显

22、著低于CVVH组(分别较血滤前降低10.5 ug/min和1.0ug/min， P=0.02)高流量血滤在感染性休克患者中的作用Bellomo R, et al. Inten Care Med, 2019, 27: 978-986高流量血滤部分清除感染性休克患者血清中补体成分，显著降低患者去甲肾上腺素的用量第49页，共58页。Impact of high volume hemofiltration on hemodynamic disturbance and outcome during septic shock Study design : 24 patients with septic s

23、hock, with dysfunction of more than two organsHVCVVH : ultrafiltration rate between 40 ml/kg/hr and 60 ml/kg/hr for 96hours Primary end point : mortality at 28 daysAll patients, increase in hemodynamic parameters was statistically significant(p0.05)With a significant decrease in norepinephrine doses (p 0.05). The predicted 28 day mortality by severity scores was more than 70%The mortality in the hemofiltration group was 46% (p 0.075) ASAIO Journal. 50(1):102-9, 2019 Jan-Feb 第50页，共58页。不同时期、流量血滤对伴呼吸循环衰竭的少尿急