crrt在嚴重感染中應用new58張

1、 東南大學附屬中大醫(yī)院危重病醫(yī)學科郭鳳梅CRRT在 重癥感染和感染性休克中的應用第1頁，共58頁。定義發(fā)病機制治療 -CRRT治療內容提要第2頁，共58頁。定 義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頁，共58頁。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 義第4頁，共58頁。Sepsis =Infection+SIRSSevere sepsis =Sepsis + organ functionSeptic shock =Sepsis + hypotension第5頁，共58頁。損傷 SIRS Sepsis severe sepsis (septic shock) MODS MOF感染的全過程infection第6頁，共58頁。院內感染發(fā)生率普通病房中病人: 6-17%ICU病人：25-40%第7頁，共58頁。重癥感染與MODS重癥感染常并

5、發(fā)MODS心、肺、腎、肝、腦等器官發(fā)生單一器官衰竭死亡率是20隨器官衰竭數(shù)量增加，死亡率逐漸上升，合并4個器官衰竭患者死亡率達100 Deitch EA. Surg Clin N Am, 2019, 79: 1471-88第8頁，共58頁。Rangel-Frausto, M, et al. JAMA, 2019, 273:117-123 感染與重癥感染對患者預后的影響第9頁，共58頁。MODS對患者預后的影響第10頁，共58頁。定義發(fā)病機制治療 -CRRT治療內容提要第11頁，共58頁。炎癥反應學說重癥感染至感染性休克和MODS的發(fā)病機制第12頁，共58頁。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頁，共58頁。第14頁，共58頁。Inflammatory mediator rel

7、easeAlbuminInjury，infectionH2ONaClSystemic capillary leak第15頁，共58頁。參與SIRS和MODS的可溶性介質體液性介質細胞性介質補體TNF-凝血系統(tǒng)IL-1，IL-6，IL-8激肽系統(tǒng)血小板活化因子 NO花生四烯酸代謝產物氧自由基抗炎介質IL-10等第16頁，共58頁。概述發(fā)病機制治療 -CRRT治療內容提要第17頁，共58頁。重癥感染和感染性休克的治療感染病灶的引流早期合理的抗生素應用改善器官灌注器官功能支持炎癥調控-血液濾過治療第18頁，共58頁。重癥感染的治療轉歸感染(細菌/毒素)組織損傷全身炎癥反應和CARS引流、抗生素治療引

8、流、抗生素治療引流、抗生素治療細菌有效清除，感染控制，炎癥反應局限細菌有效清除，感染控制感染未控制康復炎癥反應放大MODS引流、抗生素治療腎臟替代治療第19頁，共58頁。CVVH通過對流清除中小分子炎癥介質(30-40KD)，另外還有濾過膜的吸附作用CRRT在重癥感染和感染性休克中的作用第20頁，共58頁。重癥感染和感染性休克部分主要炎癥介質的分子量介質分子量(KD)TNF單體17TNF三聚體51IL-626IL-117IL-88C3a9C5a11D因子PAF230.6內皮素-1花生四烯酸代謝產物緩激肽小分子0.61.06第21頁，共58頁。CVVH對重癥感染炎癥介質的影響目的： CVVH對重

9、癥感染炎癥介質的清除方法： 檢測患者與健康志愿者血濾開始(t0)與血濾60min (t60)濾器前(afferent)濾器后(efferent)與超濾液中炎癥介質的濃度。濾器為金寶FH66D，聚酰胺膜，超濾率2L/hHoffmann JN, et al. Kidney International, 2019, 48: 1563-1570第22頁，共58頁。CVVH對重癥感染炎癥介質的影響重癥感染患者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)濾器后濃度To66.021091

10、143933.14676.90.72326.582966T6063.241127144728.55545.4*0.72825.653362超濾液濃度T011.9c630c140.9c0.446ct60cc604c103.7*c0.183*c*與t0相比，P0.01，c沒有檢測到第23頁，共58頁。CVVH對重癥感染炎癥介質的影響健康志愿者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)濾器后濃度To0c41.2c54.820.4879.70363T600c31c33.91*0.

11、4958.82769超濾液濃度T0Cc30C18.22c0.552ct60CccC7.99*c0.059*cHoffmann JN, et al. Kidney International, 2019, 48: 1563-1570第24頁，共58頁。聚酰胺膜具有較好的生物相容性，不刺激機體產生大量的炎癥介質CVVH可以部分清除IL-1，IL-8，C3a和C5aCVVH對炎癥介質的清除作用除與炎癥介質的分子量有關外，還與炎癥介質的蛋白結合率、活性狀態(tài)、跨膜壓等有關CVVH對血濾前后炎癥介質濃度無顯著影響，可能與CVVH超濾率較低導致的清除效率低有關CVVH對重癥感染炎癥介質的影響Hoffmann

12、 JN, et al. Kidney International, 2019, 48: 1563-1570第25頁，共58頁。濾器膜對各種炎癥介質的影響介質分子量(KD)LPSTNF單體1000 17.4TNF三聚體5560IL-626IL-117IL-88C3a9C5a11D因子PAF230.6濾器膜的影響超濾液中吸附吸附/濾過-+吸附-？吸附/濾過+吸附/濾過+？吸附/濾過+吸附/濾過+吸附/濾過+吸附吸附/濾過-+第26頁，共58頁。低流量CRRT對重癥感染和感染性休克療效的影響Low -flow hemofiltration作者動物模型治療量主要結果Stein內毒素休克豬20ml/kg

13、/h血流動力學無改善Gomez大腸桿菌感染狗16ml/kg/h血流動力學無改善Gomez大腸桿菌感染狗27ml/kg/h心肌收縮力增強，其他血流動力學無改善Freeman感染性休克狗600ml/h血流動力學和存活率無改善Murphey內毒素休克豬33ml/kg/h心肺功能無改善第27頁，共58頁。低流量CVVH在重癥感染中的臨床應用目的：探討CVVH對重癥感染部分炎癥 介質和器官功能的影響隨機、控制研究24例早期重癥感染或感染性休克患者 隨機進行48hCVVH(2L/h，AN69膜，1.2m2) 或不進行CVVHBellomo R, et al. CCM, 2019, 30: 100-106第

14、28頁，共58頁。C3a和C5a的變化低流量CVVH在重癥感染中的臨床應用第29頁，共58頁。IL-6和IL-8的變化低流量CVVH在重癥感染中的臨床應用第30頁，共58頁。IL-10和TNF的變化低流量CVVH在重癥感染中的臨床應用第31頁，共58頁。低流量CVVH在重癥感染中的臨床應用第32頁，共58頁。低流量CVVH在重癥感染中的臨床應用血管活性藥物的應用時間機械通氣時間第33頁，共58頁。低流量CVVH在重癥感染中的臨床應用ICU住院時間低流量CVVH不顯著改善重癥感染和感染性休克動物與患者的血流動力學狀態(tài)和預后第34頁，共58頁。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頁，共58頁。血流動力學結果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頁，共58頁。ResultsBase : age, APACHE II, predicted risk of death, SAPS II, epinephrine requirement no differences第46頁，共58頁。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頁，共58頁。目的：評估高流量血濾對感染性休克患者血流動力學和細胞因子的影響方法：隨機cross-over試驗， 11例患者隨機接受8h HVHF (6L/h

21、) (AN69濾器，1.6m2)或8h CVVH (1L/h) (AN69濾器，1.2m2)檢測指標：血流動力學、去甲腎上腺素需要量、血清C3a、C5a、IL-2、IL-8、IL-10和TNF的含量高流量血濾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頁，共58頁。結果：HVHF組與CVVH組期間CVP、CI、 PAWP和 液體平衡均無顯著差異C3a, C5a, IL-10在治療 2 h內均顯著降低， C3a 和C5a在 HVHF期間降低更為明顯 (p 70mmHg，HVHF組去甲腎上腺素需 要量顯

22、著低于CVVH組(分別較血濾前降低10.5 ug/min和1.0ug/min， P=0.02)高流量血濾在感染性休克患者中的作用Bellomo R, et al. Inten Care Med, 2019, 27: 978-986高流量血濾部分清除感染性休克患者血清中補體成分，顯著降低患者去甲腎上腺素的用量第49頁，共58頁。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頁，共58頁。不同時期、流量血濾對伴呼吸循環(huán)衰竭的少尿急