1、急性肾衰竭CHF:充血性心衰SIRS:系统性炎症反应综合征ARDS:急性呼吸窘迫综合征SEPSIS:脓毒血症TPE:治疗性血浆置换感染、SIRS与脓毒症关系 促炎介质过度产生原始病因感染非感染抗炎介质过度产生全全 身身 反反 应应 全身炎症反应综合征 （SIRS）代偿性炎症反应综合征（CARS）混合性抗炎反应综合征（MARS）平平 衡衡 SIRS、CARS 细胞调亡细胞调亡 SIRS过度免疫功能障碍免疫功能障碍 CARS过度 MODS SIRS过度休休 克克 SIRS过度局部促炎介质局部促炎介质 局部抗炎介质 SIRS临床发病过程SepsisTherapyantibiotics/surgica
2、l drainageantibiotics/surgical drainagegeneral ICU supportgeneral ICU supportsteroidssteroids-high dose-high dose-low dose-low doseBacterial sepsisBacterial sepsisexotoxinexotoxinLPSLPSmediatorsmediatorsIMMUNOMODULATIONIMMUNOMODULATIONmonoclonal antibodiesmonoclonal antibodiesother anti-inflammatori
3、esother anti-inflammatoriesmediator adsorption/removalmediator adsorption/removal 血液净化的功能1.清除致病介质，维持内环境稳定2.调节机体免疫内稳态平衡3.稳定血流动力学，保护重要脏器功能血液净化免疫调节机制峰浓度假说免疫调节阈值假说介质传递假说峰浓度假说免疫调理阈值假说在血液的细胞因子和炎症介质清除后，间质和组织中的炎症介质及其前体转移到血液，再被清除，直至间质和组织中的炎症介质降低到一定水平（即阈值），此水平的炎症介质对组织器官不产生损害。Honore,PM&Matson,JR.Critical Care
4、Medicine 2004;32:896-897介质传递假说高容量血液滤过（HVHF）的置换流量如果达到3-5L/h，可使淋巴液流动速度提高20-40倍，随着炎症介质和细胞因子被快速传递到血液，可增加其清除量。Di Carlo,JV&Alexander,SR.Int J Artif Organs 2005;28:777-7861.清除炎症介质2.解除单核细胞功能抑制状态，恢复其功能抗原提呈能力分泌功能3.逆转抗炎反应（Th2）过度活化状态，恢复Th2/Th1平衡IL-10/TNF-CBP治疗重建机体免疫内稳态机制CRRT免疫调节策略治疗时机模式剂量滤器治疗时机Timing of initiat
5、ion of RRTKarvellas.Acomparisonofearlyversuslateinitiationofrenalreplacementtherapyincriticallyillpatientswithacutekidneyinjury.CriticalCare2011,15:R72Meta-analysisof15studiespEarlyRRTinitiationassociatedwithmortality（pooledOR0.45）pHowever,significantheterogeneityandbiaspSomestudiesshowedgreaterrena
6、lrecovery,durationRRTandICUlengthofstayTiming of initiation of RRTImpact of Early High Dose CRRT on Cytokines in Adult Sepsis:RCT ResultsIL-6IL-8TNF-aIL-10-Coleetal.,CritCareMed2002Early CRRT in Sepsis:RCT-Payenetal.,CritCareMed,2009CVVH治疗急性胰腺炎急性胰腺炎动物分组未治疗组晚期CVVH组（MAP下降20%后开始）早期CVVH组（模型建立后即开始）治疗模式CR
7、RT的原理与机制弥散对流吸附500500050000原理与机制:小分子物质氯化钠SodiumChloride58.5尿素Urea60磷酸PhosphateAcid96肌酐Creatinine113尿酸UricAcid168葡萄糖Glucose180原理与机制:中分子物质多肽PeptideA778维生素B12VitaminB121355菊糖Inulin5200微球蛋白B2-microglobulin11800肝素Heparin11200肌球蛋白Myoglobin17000因子DFactorD24000白介素1Interleukin-131000蛋白酶Pepsin35000肿瘤坏死因子TumorN
8、ecrosisFactor39000-225000 原理与机制:大分子物质前白蛋白Pre-albumin55000抗凝血酶原3Antithrombin365000白蛋白Albumin66000血红蛋白Hemoglobin68000凝血酶原Prothrombin68000转铁蛋白Transferrin76500免疫球蛋白GIgG160000纤维蛋白原Fibrinnogen341000纤维连接蛋白Fibronectin（dimer）450000 肾脏替代治疗的原理机制清除物质对流（convection）小分子物质,中分子物质,大分子物质弥散（diffusion）小分子物质吸附（adsorption
9、）特殊分子CRRT的基本作用原理滤过-对流基础上的溶质与水分清除透析-弥散基础上的溶质清除吸附-炎性介质、内毒素CBP几种常用方式的比较方式原理补充液体清除物质CVVH对流为主，压力梯度（TMP）为驱动力置换液（分前、后稀释法）小、中、大分子物质（水溶性）CVVHD弥散为主，浓度梯度为驱动力透析液（同置换液成分）小分子物质（水溶性）CVVHDF对流+弥散透析液，置换液大、中、小分子物质清除能力CVVHD+CVVH血液灌流吸附？Continuous vs intermittent dialysis OngoingdebateTheoreticalbenefitstobothAtleast7RCT
10、sand3meta-analyseshavenotdemonstrateddifferenceinoutcomeEgBagshawCrit Care Med 2008,36:610-617:metaanalysisof9randomizedtrials:Noeffectonmortality（OR0.99）orrecoverytoRRTindependence（OR0.76）.suggestionthatcontinuousRRThadfewerepisodesofhemodynamicinstabilityandbettercontroloffluidbalanceMaybepreferab
11、leinspecificsubpopulationsVanholderetal.Pro/condebate:Continuousvsintermittentdialysisforacutekidneyinjury.CriticalCare2011,15:204Outcome with IRRT vs CRRT Vinsonneau,S et al.Lancet 2006;368:379-385双重血浆滤过吸附（CPFA）几乎可100%吸附清除SIRS患者血浆TNF-、IL-6、IL-10、IL-1显著减少SEPSIS病人血管活性药的剂量，改善病人的血流动力学明显改善单核细胞分泌功能和抗原呈递功
12、能，调节过度活跃或过度抑制状态，调节细胞的免疫功能重建机体免疫内稳状态 剂量Effect of Filtration Rate on Outcome in Septic Adults with CVVH:Is More Better?-Ronco et al.Lancet 2000;351:26-30Therapy Dose in CVVH20ml/kg/hr35ml/kg/hr45ml/kg/hrRonco,C et al.Lancet 2000;355:26-30Optimal dosingVA/NIHAcuteRenalFailureTrialNetworkIntensiveRRT=IR
13、RTorSLEDD6x/wkorCRRTat35ml/kg/hrLessintensiveRRT=IRRTorSLEDD3x/wkorCRRTat20ml/kg/hrNodifferenceinmortality,recoveryofkidneyfunction,ornonrenalorganfailureVA/NIHAcuteRenalFailureTrialNetwork.NEJM2008;359:7Optimal dosingTheRENALReplacementTherapyStudyRCTof1508criticallyillptstoCRRTofhighvslowintensity
14、（40vs25ml/kg/hr）Nodifferencein90dmortalityorRRTindependenceNEnglJMed.2009Oct22;361（17）:1627-38Figure 1.Possible relationship between delivered dose ofcontinuous renal replacement therapy and survival,with resultsfrom the ATN and RENAL trials illustrated.ProwleJR,et al.:Optimaldoseofcontinuousrenalre
15、placementtherapyinacutekidneyinjury.Critical Care 2011,15:207.Meta-Analysis:No Benefit of High Dose CRRT in Adult SepsisRRT in Sepsis/MODS:High Volume HemofiltrationPilotRCTof20adultswithsepticshockandARFtohighvolumehemofiltrationHVHF65ml/（kgh）vslowvolumehemofiltrationLVHF35ml/（kgh）.HVHF:decreasedvasopre
