CRRT在-重癥感染和感染性休克中應(yīng)用危重病醫(yī)課件

危重病醫(yī)學(xué)科CRRT在重癥感染和感染性休克中的應(yīng)用1PPT課件定義發(fā)病機(jī)制治療--CRRT治療內(nèi)容提要2PPT課件定義SystemicInflammatoryResponseSyndrome(SIRS)Atleast2ofthefollowing4conditions:Oraltemperature>38oor<36oCRR>20breaths/minorPaCO2of<32torrHeartrateof>90beats/minWBC>12,000/uLor<4000/uLor>10percentbandsSepsis

SeveresepsisSIRSthathasaprovenorsuspectedmicrobialetiology

Sepsiswithoneormoresignsoforgandysfunctionhypoperfusion,orhypotensionsuchasmetabolicacidosisacutealterationinmentalstatus,oliguria,coagulationabnormalitiesoradultrespiratorydistresssyndrome3PPT課件Hypotension

Systolicbloodpressure<90mmHg-or40mmHglessthanpatient'sbaselinebloodpressureSepticshockSepsiswithhypotensionthatisunresponsivetofluidresuscitationplusorgandysfunctionorperfusionabnormalitiesaslistedaboveforseveresepsisMultipleorgandysfunctionsyndrome(MODS)Dysfunctionofmorethanoneorgan,requiringinterventiontomaintainhomeostasis定義4PPT課件Sepsis=Infection+SIRSSeveresepsis=Sepsis+organfunctionSepticshock=Sepsis+hypotension5PPT課件

損傷SIRSSepsisseveresepsis(septicshock)MODSMOF感染的全過(guò)程infection6PPT課件院內(nèi)感染發(fā)生率普通病房中病人:

6-17%ICU病人：25-40%7PPT課件重癥感染與MODS重癥感染常并發(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(gè)器官衰竭患者死亡率達(dá)100％

DeitchEA.Surg

ClinNAm,1999,79:1471-888PPT課件Rangel-Frausto,M,etal.JAMA,1995,273:117-123

感染與重癥感染對(duì)患者預(yù)后的影響9PPT課件MODS對(duì)患者預(yù)后的影響10PPT課件定義發(fā)病機(jī)制治療--CRRT治療內(nèi)容提要11PPT課件炎癥反應(yīng)學(xué)說(shuō)重癥感染至感染性休克和MODS的發(fā)病機(jī)制12PPT課件

Theacuteinflammatoryresponse'Acomplexseriesofcellular,immuneandmetabolicresponseswhichhaveevolvedtobeprotectiveandpromoterepairprocesses'Stimuliofinflammation Infection Burns Toxins Pancreatitis

Surgery Malignancy Trauma Poisoning

Ischaemia/reperfusion13PPT課件14PPT課件InflammatorymediatorreleaseAlbuminInjury，infectionH2ONaClSystemiccapillaryleak15PPT課件參與SIRS和MODS的可溶性介質(zhì)體液性介質(zhì)細(xì)胞性介質(zhì)補(bǔ)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(chǎn)物氧自由基抗炎介質(zhì)IL-10等16PPT課件概述發(fā)病機(jī)制治療--CRRT治療內(nèi)容提要17PPT課件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(yīng)用改善器官灌注器官功能支持炎癥調(diào)控--血液濾過(guò)治療18PPT課件重癥感染的治療轉(zhuǎn)歸感染(細(xì)菌/毒素)組織損傷全身炎癥反應(yīng)和CARS引流、抗生素治療引流、抗生素治療引流、抗生素治療細(xì)菌有效清除，感染控制，炎癥反應(yīng)局限細(xì)菌有效清除，感染控制感染未控制康復(fù)炎癥反應(yīng)放大MODS引流、抗生素治療腎臟替代治療19PPT課件CVVH通過(guò)對(duì)流清除中小分子炎癥介質(zhì)(<30-40KD)，另外還有濾過(guò)膜的吸附作用CRRT在重癥感染和感染性休克中的作用20PPT課件重癥感染和感染性休克部分主要炎癥介質(zhì)的分子量介質(zhì)分子量(KD)TNF單體17TNF三聚體51IL-626IL-117IL-88C3a9C5a11D因子PAF230.6內(nèi)皮素-1花生四烯酸代謝產(chǎn)物緩激肽小分子0.61.0621PPT課件CVVH對(duì)重癥感染炎癥介質(zhì)的影響目的：CVVH對(duì)重癥感染炎癥介質(zhì)的清除方法：檢測(cè)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(zhì)的濃度。濾器為金寶FH66D，聚酰胺膜，超濾率2L/hHoffmannJN,etal.KidneyInternational,1995,48:1563-157022PPT課件CVVH對(duì)重癥感染炎癥介質(zhì)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To66.021091143933.14676.90.72326.582966T6063.241127144728.55545.4*0.72825.653362超濾液濃度T011.9c630c140.9c0.446ct60cc604c103.7*c0.183*c*與t0相比，P<0.01，c沒(méi)有檢測(cè)到23PPT課件CVVH對(duì)重癥感染炎癥介質(zhì)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*0.4958.82769超濾液濃度T0Cc30C18.22c0.552ct60CccC7.99*c0.059*cHoffmannJN,etal.KidneyInternational,1995,48:1563-157024PPT課件聚酰胺膜具有較好的生物相容性，不刺激機(jī)體產(chǎn)生大量的炎癥介質(zhì)CVVH可以部分清除IL-1，IL-8，C3a和C5aCVVH對(duì)炎癥介質(zhì)的清除作用除與炎癥介質(zhì)的分子量有關(guān)外，還與炎癥介質(zhì)的蛋白結(jié)合率、活性狀態(tài)、跨膜壓等有關(guān)CVVH對(duì)血濾前后炎癥介質(zhì)濃度無(wú)顯著影響，可能與CVVH超濾率較低導(dǎo)致的清除效率低有關(guān)CVVH對(duì)重癥感染炎癥介質(zhì)的影響HoffmannJN,etal.KidneyInternational,1995,48:1563-157025PPT課件濾器膜對(duì)各種炎癥介質(zhì)的影響介質(zhì)分子量(KD)LPSTNF單體~100017.4TNF三聚體55~60IL-626IL-117IL-88C3a9C5a11D因子PAF230.6濾器膜的影響超濾液中吸附吸附/濾過(guò)-+吸附-？吸附/濾過(guò)+吸附/濾過(guò)+？吸附/濾過(guò)+吸附/濾過(guò)+吸附/濾過(guò)+吸附吸附/濾過(guò)-+26PPT課件低流量CRRT對(duì)重癥感染和感染性休克療效的影響Low-flowhemofiltration作者動(dòng)物模型治療量主要結(jié)果Stein內(nèi)毒素休克豬20ml/kg/h血流動(dòng)力學(xué)無(wú)改善Gomez大腸桿菌感染狗16ml/kg/h血流動(dòng)力學(xué)無(wú)改善Gomez大腸桿菌感染狗27ml/kg/h心肌收縮力增強(qiáng)，其他血流動(dòng)力學(xué)無(wú)改善Freeman感染性休克狗600ml/h血流動(dòng)力學(xué)和存活率無(wú)改善Murphey內(nèi)毒素休克豬33ml/kg/h心肺功能無(wú)改善27PPT課件低流量CVVH在重癥感染中的臨床應(yīng)用目的：探討CVVH對(duì)重癥感染部分炎癥介質(zhì)和器官功能的影響隨機(jī)、控制研究24例早期重癥感染或感染性休克患者隨機(jī)進(jìn)行48hCVVH(2L/h，AN69膜，1.2m2)

或不進(jìn)行CVVHBellomoR,etal.CCM,2002,30:100-10628PPT課件C3a和C5a的變化低流量CVVH在重癥感染中的臨床應(yīng)用29PPT課件IL-6和IL-8的變化低流量CVVH在重癥感染中的臨床應(yīng)用30PPT課件IL-10和TNF的變化低流量CVVH在重癥感染中的臨床應(yīng)用31PPT課件低流量CVVH在重癥感染中的臨床應(yīng)用32PPT課件低流量CVVH在重癥感染中的臨床應(yīng)用血管活性藥物的應(yīng)用時(shí)間機(jī)械通氣時(shí)間33PPT課件低流量CVVH在重癥感染中的臨床應(yīng)用ICU住院時(shí)間低流量CVVH不顯著改善重癥感染和感染性休克動(dòng)物與患者的血流動(dòng)力學(xué)狀態(tài)和預(yù)后34PPT課件Object:evaluatehemodynamicandkineticsofTNF,IL1?andIL6insepticshockpatientsandARFundergoingCVVHFover24-hourMethods:11Patients,AN69,bloodflowrate240

mL/minandUF1.65±0.33L/h.MAP,PVR,SVR,CObeforeandafter2h,4h,6h,12hand24hofCVVHF.thepre-andpostfilter

linesandultrafiltratesamplescollectedfortheofTNF,IL-1?andIL6

CVVHimproveshemodynamicsinsepticshockwithoutmodifyingTNF*andIL6plasmaconcentrations

KloucheK,etal.JNEPHROL2002;15:150-157

35PPT課件血流動(dòng)力學(xué)結(jié)果

temp°CHeartratebeat/mMAPmmHgMPAPmmHgCIl/min/m2ISVRdyne/s/cm5IPVRdyne/s/cm5t0h38.2±0.24114±2267.3±6.634.9±2.15±0.75711±153258±75t2h37.2±0.27*118±1877.3±6.933.7±2.74.7±0.72956±228247±54.4t4h37.0±0.27*120±2094.2±6.6*36.9±4.24.7±0.631353±309*290±74t6h36.7±0.27*124±1684±6.6*37.9±2.44.7±0.61177±202298±69t12h36.8±0.24*115±15101.3±8*40±3.94.9±0.61324±325*276±69t24h36.6±0.24*119±2189.3±5.4*37.7±4.25.5±0.51200±100*205±28.4P<0.05ns<0.05nsns<0.05ns36PPT課件氧代謝結(jié)果

lactatesmmol/LSaO2%SvO2%DO2

mL/min/m2VO2

mL/min/m2O2E%t0h6.3±1.896.5±1.567.5±3.9551±80147±2330±4.2t2h6.5±1.897.6±0.669±5.1529±82.4144±2331±5.1t4h7.1±2.195.9±2.169±3527±68.5149±27.528±3t6h6.4±1.898.4±0.370.4±3.9541±57.7143±2029±4t12h5.6±1.598.5±0.367.2±3.3543±57.7163±2232±3.3t24h5.8±1.897.7±0.671±3.3585±66179±21.427±3.3Pnsnsnsnsnsns低流量CVVH部分改善感染性休克患者血流動(dòng)力學(xué)狀態(tài)37PPT課件高流量CRRT對(duì)重癥感染和感染性休克療效的影響作者動(dòng)物模型治療量主要結(jié)果Lee金葡菌感染豬133ml/kg/h存活率顯著升高Grootendont內(nèi)毒素休克豬162ml/kg/h動(dòng)脈壓升高,右室射血分?jǐn)?shù)和心輸出梁增加Grootendont小腸缺血再灌注豬150ml/kg/h動(dòng)脈壓升高,心輸出量增加，小腸缺血減輕,24h存活率升高Rogiers急性內(nèi)毒素休克狗107ml/kg/h或214ml/kg/h血流動(dòng)力學(xué)改善38PPT課件CVVH不同治療量對(duì)內(nèi)毒素休克狗血流動(dòng)力學(xué)的影響動(dòng)物模型：LPS靜脈注射復(fù)制感染性休克狗模型分組：對(duì)照組(A)：內(nèi)毒素休克組CVVH1組(B)：CVVH3l/h270min(0.7m2聚砜膜濾器，40KD)CVVH2組(C)：CVVH3l/h150min+6l/h120min觀察指標(biāo)：MAP、MPAP、CO、SVR、PVR、SV、LVSWI、Lac、肝動(dòng)脈血流量RogiersP,etal.CritCareMed,1999,27:1848-185539PPT課件CVVH不同治療量對(duì)內(nèi)毒素休克狗血流動(dòng)力學(xué)的影響40PPT課件CVVH不同治療量對(duì)內(nèi)毒素休克狗血流動(dòng)力學(xué)的影響41PPT課件CVVH不同治療量對(duì)內(nèi)毒素休克狗血流動(dòng)力學(xué)的影響42PPT課件CVVH不同治療量對(duì)內(nèi)毒素休克狗血流動(dòng)力學(xué)的影響CVVH3L/h顯著改善感染性休克狗CO和SV，但對(duì)動(dòng)脈血壓無(wú)明顯改善與CVVH3L/h相比，6L/h顯著改善感染性休克狗動(dòng)脈血壓和左心室做功指數(shù)43PPT課件對(duì)象：33例難治的感染性休克和MODS患者HVHF方法：置換液量108L/24h，濾器面積2.3m2結(jié)果：HVHF4h后MAP從8.40.94KPa上升至10.32.3KPa

PaO2/FiO2從10.12.0KPa升至11.83.0KPa

患者存活率無(wú)顯著改變HVHF對(duì)感染性休克和MODS的影響B(tài)ellomoR,etal.KidneyInt,1998,53(S66):S182.44PPT課件STHVHonhemodynamicsandoutcomeinintractablecirculatoryfailurepatientsresultingfromsepticshockObjective:evaluateeffectsofSTHVHonhemodynamics,metabolic,28-daysurvivalinrefractorysepticpatientsshockDesign:Prospective,interventionalPatients:20withintractablesepticshock,whohadfailedtorespondtoconventionaltherapyInterventions:STHVH4-hr35LofultrafiltrateandneutralfluidbalanceismaintainedSubsequentCVVHcontinuedforatleast4days(1.6m2，聚砜膜，35KD)PatrickM,etal.CCM.2000,28:3581-3587

Measure:CI,SVR,PVR,DO2,SvO2,pHa,andlactateTherapeuticendpointsSTHVH:a)2hrs,50%increaseinCIb)2hrs,25%increaseinSvO2c)4hrs,increaseinpHato>7.3d)4hrs,50%reductioninEP“responders”:attainedfourgoals(11of20)“nonresponders”

:didnot(9of20)45PPT課件ResultsBase:age,APACHEII,predictedriskofdeath,SAPSII,

epinephrinerequirementnodifferences46PPT課件Twenty-Eight-DaySurvival

:

9of11respondersurvived

9nonrespondersdiedbyT24

Bodyweight:responders

(66.2±8.4)kg

nonresponders

(82.6±13.4)kg,(p<.0031)

Ultrafiltrate

:responders

(0.53±0.07)L/kg

nonresponders(0.43±0.07)L/kg,(p<.0031)Delaytime:

responders6.5hrs

nonresponders13.8hrs

(p<.01)Responderwasassociatedwith:delaytime,bodyweight,

andultrafiltratedoseResultsSTHVHmaybeofmajortherapeutic

valueinthetreatmentofintractable

septicshockEarlyinitiationoftherapyand

adequate

dosemayimprovehemodynamicand

metabolicresponsesand28-daysurvival

47PPT課件目的：評(píng)估高流量血濾對(duì)感染性休克患者血流動(dòng)力學(xué)和細(xì)胞因子的影響方法：隨機(jī)cross-over試驗(yàn)，11例患者隨機(jī)接受8hHVHF(6L/h)(AN69濾器，1.6m2)或8hCVVH(1L/h)(AN69濾器，1.2m2)檢測(cè)指標(biāo)：血流動(dòng)力學(xué)、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BellomoR,etal.IntensiveCareMed,2001,27:978-98648PPT課件結(jié)果：HVHF組與CVVH組期間CVP、CI、PAWP和液體平衡均無(wú)顯著差異C3a,C5a,IL-10在治療2h內(nèi)均顯著降低，C3a和C5a在HVHF期間降低更為明顯(p<0.01)維持MAP>70mmHg，HVHF組去甲腎上腺素需要量顯著低于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BellomoR,etal.IntenCareMed,2001,27:978-986高流量血濾部分清除感染性休克患者血清中補(bǔ)體成分，顯著降低患者去甲腎上腺素的用量49PPT課件Impactofhighvolumehemofiltrationonhemodynamicdisturbanceandoutcomeduringsepticshock

Studydesign:24patientswithsepticshock,withdysfunctionofmorethantwoorgansHVCVVH:ultrafiltrationratebetween40ml/kg/hrand60ml/kg/hrfor96hoursPrimaryendpoint:mortalityat28daysAllpatients,incre