呼吸机相关性肺炎(已看,有必要再看)课件

呼吸机相关性肺炎HAP/VAP:概要流行病学诊断策略抗生素治疗HAP/VAP/HCAP:定义医院获得性肺炎(HAP)住院48小时后发生且住院时不处于潜伏期的肺炎呼吸机相关性肺炎(VAP)气管插管48小时以后发生的肺炎因重度HAP需要气管插管者应按照VAP处理医疗相关肺炎(HCAP)发生感染前90天内在急性病医院住院≥2天在养护院或长期医疗机构住院近期接受静脉抗生素治疗、化疗或发生感染前30天内接受伤口治疗就诊于医院门诊或透析门诊ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:流行病学KumpfG,etal.JClinEpidemiol1998;54:495-502LizioliA,etal.JHospInfect2003;54:141-148RichardsMJ,etal.CritCareMed1999;27:887-892HAP/VAP:流行病学机械通气510累积患病率(%)3%/d1%/d2%/dCookDJ,WalterSD,CookRJ,GriffithLE,GuyattGH,LeasaD,JaeschkeRZ,Brun-BuissonC.Incidenceofandriskfactorsforventilator-associatedpneumoniaincriticallyillpatients.AnnInternMed1998;129:440d迟发性HAP～50%早发性HAP～50%HAP/VAP:流行病学机械通气510累积患病率(%)d敏感菌引起,预后好致病菌常是多药耐药菌(MDR),病死率高HAP/VAP:病死率总病死率30-70%:

大多数HAP患者死于基础病

归因病死率33-50%

VAP的归因病死率升高与菌血症、耐药菌(如铜绿假单胞菌、不动杆菌属)感染、不恰当的抗生素治疗等因素相关。HAP/VAP:危险因素H2受体拮抗剂进行应激性溃疡预防“自由”输血去白细胞输血血糖控制不佳ARDS深度镇静或肌松HAP/VAP:病因学FagonKollefPapazianRelloTimsitTorres革兰阴性杆菌

55~85%铜绿假单胞菌192927501628不动杆菌属104501224嗜麦芽窄食单胞菌073000肠杆菌属168004流感嗜血杆菌61810130其他革兰阴性杆菌24102841032革兰阳性球菌20~30%金黄色葡萄球菌20302192620肺炎链球菌410744HAP/VAP:病因学支气管远端标本培养分离出口咽部定植菌（草绿色链球菌，凝固酶阴性葡萄球菌，奈瑟氏菌属，棒状杆菌属）难以解释在免疫抑制甚至免疫正常患者可能引起感染CabelloH,TorresA,CelissR,El-EbiaryM,delaBellacasaJP,XaubetA,GonzalezJ,AugustiC,SolerN.Bacterialcolonizationofdistalairwaysinhealthysubjectsandcroniclungdiseases:abronchoscopicstudy.EurRespirJ1997;10:1137–1144HAP/VAP:病因学金黄色葡萄球菌糖尿病，头颅创伤，住ICU厌氧菌：在VAP中的重要性尚不明确非插管患者误吸VAP罕见肺炎军团菌：发生率缺乏数据，但重要性受关注免疫抑制患者如器官移植，HIV，糖尿病，基础肺病，终末期肾病HAP/VAP:病因学真菌（包括念珠菌和曲霉菌）器官移植，免疫抑制，中性粒细胞缺乏免疫正常患者罕见病毒免疫正常者罕见流感病毒，副流感病毒，腺病毒，麻疹病毒，呼吸道合胞病毒占病毒的70%HAP/VAP:分类012345678Early-onsetHAPLate-onsetHAPTimefromhospitalization(days)012345678Early-onsetVAPLate-onsetVAPTimefromIntubation(days)ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:病因学早发性HAP/VAP迟发性HAP/VAP细菌学肺炎链球菌铜绿假单胞菌流感嗜血杆菌不动杆菌MSSAMRSA敏感GNB耐药肠杆菌科大肠杆菌肠杆菌属肺炎克氏菌ESBL+ve菌变形杆菌属克雷伯菌属肠杆菌属嗜肺军团菌粘质沙雷氏菌洋葱伯克霍尔德菌曲霉菌属预后病情较轻，对预后影响小归因病死率高病死率低罹患率高ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:问题2以下哪个不是呼吸机相关性肺炎确切的发病机制误吸直接吸入血行性播散胃肠道细菌移位以上答案均不对HAP/VAP:发病机制改变胃排空及胃液pH值的药物有生物膜的装置(气管插管,鼻胃管)既往应用抗生素宿主因素(免疫抑制,烧伤)消化道细菌定植细菌误吸细菌吸入医院获得性肺炎水,药物溶液及呼吸治疗装置污染感染控制措施不够(洗手,隔离衣,手套)医务人员不足经胸种植原发性菌血症胃肠道细菌移位HAP/VAP:影像学诊断对于可疑肺炎患者，如果根据其他临床表现不能确诊，影像学判断也不能提高诊断的正确性若胸片显示明显浸润影，则鉴别心源性肺水肿、非心源性肺水肿、肺挫伤和肺不张将非常困难各种影像学表现的敏感性和特异性差异很大，诊断准确性均不超过70%支气管气像诊断肺炎的准确性最高(64%)HAP/VAP:影像学诊断CXRvs.CT手术后肺实变：敏感性0.33–1.00，特异性>0.79不同医生判读的一致性放射科医生：kappa0.27ICU医生：12–39%WunderinkRG,WoldenbergLS,ZeissJ,etal.Theradiologicdiagnosisofautopsy-provenventilator-associatedpneumonia.Chest1992;101:458-63.FagonJ,ChastreJ,HanceA.Evaluationofclinicaljudgmentintheidentificationandtreatmentofnosocomialpneumoniainventilatedpatients.Chest1993;103:547-53.BeydonL,SaadaM,LiuN,etal.Canportablechestx-rayexaminationaccuratelydiagnoselungconsolidationaftermajorabdominalsurgery?:acomparisonwithcomputedtomographyscan.Chest1992;102:1698-703.HAP/VAP:细菌学诊断下呼吸道标本的半定量培养特异性低：培养结果阳性可能仅提示定植敏感性高：培养结果阴性有助于除外感染除非刚刚应用或更换抗生素常导致过度应用抗生素革兰染色结果结合培养结果有助于指导抗生素治疗HAP/VAP:细菌学诊断PSBETABAL诊断阈值103cfu/mL105–106cfu/mL104–105cfu/mL敏感性667673特异性907582特异敏感准确采样部位越远特异性越高敏感性越低诊断阈值越低HAP/VAP:细菌学诊断ETA(n=374)BAL(n=365)合计(n=739)明确VAP01(0.3)1(0.1)高度可疑VAP0180(49.3)180(24.4)可能VAP310(82.9)134(36.7)444(60.1)无VAP64(17.1)50(13.7)114(15.4)高度可疑VAP=临床诊断+BALF>104cfu/ml;可能VAP=临床诊断TheCanadianCriticalCareTrialsGroup.Arandomizedtrialofdiagnostictechniquesforventilator-associatedpneumonia.NEnglJMed2006;355:2619-2630HAP/VAP:细菌学诊断ETABALP值28天病死率18.4%18.9%0.946天时针对性治疗74.6%74.2%0.90无抗生素存活天数10.6±7.910.4±7.50.86最高MODS评分8.6±4.08.3±3.60.26TheCanadianCriticalCareTrialsGroup.Arandomizedtrialofdiagnostictechniquesforventilator-associatedpneumonia.NEnglJMed2006;355:2619-2630HAP/VAP:综合诊断CPIS评分012气管吸取物无无脓性分泌物脓性分泌物CXR浸润影无浸润影弥漫性浸润影局灶性浸润影肺部浸润影进展无进展有进展体温,°C≥36.5且≤38.4≥38.5且≤38.9≥39或≤36WCC,x109/L≥4.0且≤11.0<4.0或>11.0<4.0或>11.0+杆状核≥0.5PaO2/FiO2,mmHg>240或ARDS≤240且无ARDS的证据微生物学阴性或少量中等量或大量+革兰染色发现同样微生物PuginJ,AuckenthalerR,MiliN,JanssensJP,LewPD,SuterPM.Diagnosisofventilator-associatedpneumoniabybacteriologicanalysisofbronchoscopicandnon-bronchoscopic"blind"bronchoalveolarlavagefluid.AmRevRespirDis1991;143:1121-1129肺部感染评分HAP/VAP:鉴别诊断肿瘤结缔组织疾病血管炎综合征肺泡出血药物诱发肺泡炎肺不张血栓栓塞性疾病胃内容物误吸未治愈社区获得性肺炎充血性心力衰竭HAP/VAP:治疗LunaCM,VujacichP,NiedermanMS,etal.ImpactofBALdataonthetherapyandoutcomeofventilator-associatedpneumonia.Chest1997;111:676-685不充分的抗生素治疗2000名连续收治的MICU/SICU患者655(25.8%)罹患感染169(8.5%)抗生素治疗不充分KollefMH,ShermanG,WardS,etal.Inadequateantimicrobialtreatmentofinfections.Ariskfactorforhospitalmortalityamongcriticallyillpatients.Chest1999;115:462-474因此，临床高度怀疑VAP时，立即开始正确的经验性抗生素治疗至关重要HAP/VAP:经验性抗生素无MDR致病菌危险因素、任何严重程度、早发性HAP/VAP的初始抗生素可能致病菌推荐抗生素肺炎链球菌头孢曲松流感嗜血杆菌或MSSA左旋氧氟沙星，莫西沙星或环丙沙星敏感的肠道革兰阴性杆菌或大肠杆菌氨苄青霉素/舒巴坦肺炎克雷伯菌或肠杆菌属厄他培南变形杆菌属粘质沙雷氏菌ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:经验性抗生素有MDR致病菌危险因素、任何严重程度、迟发性HAP/VAP的初始抗生素可能致病菌推荐抗生素上表中致病菌及抗假单胞菌头孢菌素（头孢吡肟，头孢他啶）MDR致病菌或铜绿假单胞菌抗假单胞菌碳青霉烯（亚胺培南或美罗培南）肺炎克雷伯菌(ESBL+)或不动杆菌属β-内酰胺/β-内酰胺酶抑制剂（哌拉西林/他唑巴坦）加抗假单胞菌喹诺酮（环丙沙星或左旋氧氟沙星）或氨基糖甙（阿米卡星，庆大霉素或妥布霉素）加MRSA利奈唑烷或万古霉素嗜肺军团菌ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:抗生素剂量抗生素剂量抗假单胞菌头孢菌素头孢吡肟1–2g,q8–12h头孢他啶2gq8h抗假单胞菌碳青霉烯亚胺培南500mgq6h,1gq8h或美罗培南1gq8hβ-内酰胺/β-内酰胺酶抑制剂哌拉西林/他唑巴坦4.5q6h氨基糖甙阿米卡星20mg/kg/d，庆大霉素7mg/kg/d妥布霉素7mg/kg/d抗假单胞菌喹诺酮左旋氧氟沙星750mgqd环丙沙星400mgq8h万古霉素15mg/kgq12h利奈唑烷600mgq12hATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:治疗怀疑HAP/VAP迟发性HAP/VAP或MDR危险因素否是使用窄谱抗生素治疗使用广谱抗生素治疗ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:治疗怀疑HAP/VAP/HCAP采取下呼吸道(LRT)进行培养(定量或半定量)和显微镜检除非肺炎的临床概率低且LRT镜检阴性，否则应根据当地细菌流行病资料应用经验性抗生素第2/3天：培养结果并评价临床疗效(体温,WCC,CXR,氧合,脓痰,循环改变及器官功能)ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:治疗ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-41648-72小时临床改善寻找其他致病菌,并发症,其他诊断或其他感染灶调整抗生素,寻找其他致病菌,并发症,其他诊断或其他感染灶考虑停用抗生素如可能抗生素降阶梯,治疗7-8天后再次评估培养阴性培养阳性培养阴性培养阳性否是培养阴性培养阳性培养阴性培养阴性培养阳性培养阳性培养阴性培养阴性培养阳性HAP/VAP:局部抗生素局部注射氨基糖甙局部用药提高细菌学清除率，但不改变临床预后雾化吸入氨基糖甙或多粘菌素B治疗MDR致病菌副作用耐药率?诱发支气管痉挛HamerDH.Treatmentofnosocomialpneumoniaandtracheobronchitiscausedbymultidrug-resistantPseudomonasaeruginosawithaerosolizedcolistin.AmJRespirCritCareMed2000;162:328-330.BrownRB,KruseJA,CountsGW,RussellJA,ChristouNV,SandsML,EndotrachealTobramycinStudyGroup.Double-blindstudyofendotrachealtobramycininthetreatmentofgram-negativebacterialpneumonia.AntimicrobAgentsChemother1990;34:269-272KlickJM,duMoulinGC,Hedley-WhyteJ,TeresD,BushnellLS,FeingoldDS.Preventionofgram-negativebacillarypneumoniausingpolymyxinaerosolasprophylaxis.II.Effectontheincidenceofpneumoniainseriouslyillpatients.JClinInvest1975;55:514-519HAP/VAP:联合用药抗生素的协同效应体外试验证实有效中性粒细胞缺乏或血行性感染患者预防耐药发生增加抗菌谱β-内酰胺+氨基糖甙>β-内酰胺+喹诺酮?HAP/VAP:联合用药美罗培南+环丙沙星(n=369)vs.美罗培南(n=371)RR1.05,95%CI0.78–1.42MDR革兰阴性杆菌感染(n=56)28天细菌学清除：64.1%vs.29.4%机械通气时间：10.7(3.3)vs.15.0(9.3)ICU住院日：14.2(8.1)vs.21.2(14.1)ICU病死率：23.1%vs.29.4%住院病死率：33.3%vs.41.2%HeylandD,DodekP,MuscedereJ,etal.Randomizedtrialofcombinationversusmonotherapyfortheempirictreatmentofsuspectedventilator-associatedpneumonia.CritCareMed2008;36(3):737-744HAP/VAP:联合用药PaulM,Benuri-SilbigerI,Soares-WeiserK,etal.β-lactammonotherapyversusβ-lactam-aminoglycosidecombinationtherapyforsepsisinimmunocompetentpatients:systematicreviewandmeta-analysisofrandomisedtrials.BMJ2004;328:668总病死率RR0.9095%CI0.77–1.06临床失败率RR0.8795%CI0.78–0.97细菌学失败率RR0.8695%CI0.72–1.02HAP/VAP:联合用药PaulM,Benuri-SilbigerI,Soares-WeiserK,etal.β-lactammonotherapyversusβ-lactam-aminoglycosidecombinationtherapyforsepsisinimmunocompetentpatients:systematicreviewandmeta-analysisofrandomisedtrials.BMJ2004;328:668针对VAP经验性治疗时，应根据当地细菌耐药情况，选择适当的抗生素进行单药治疗HAP/VAP:问题3呼吸机相关性肺炎的抗生素疗程应为8天15天肺部感染评分

CPIS评分<6血清降钙素原

PCT<0.1以上答案都不对HAP/VAP:抗生素疗程ProbabilityofSurvival0102030405060DaysafterBronchoscopy0.00.20.40.60.81.015-day8-dayChastreJ,WolffM,FagonJY,etal.Comparisonof8vs15daysofantibiotictherapyforventilator-associatedpneumoniainadults:arandomizedtrial.JAMA2003;290(19):2588-2598结果：8天与15天抗生素疗程相比:

病死率、住院日和机械通气时间无显著差别减少了抗生素使用避免了细菌耐药的发生

8天：亚组发现非发酵G-杆菌复发（铜绿、不动）HAP/VAP:抗生素疗程HAP/VAP:抗生素疗程对于接受适当的初始经验性治疗的呼吸机相关性肺炎患者，推荐抗生素疗程为8天如果患者初始的经验性抗生素治疗不正确，需要对抗生素进行调整时，没有足够的资料推荐适宜的抗生素疗程。HAP/VAP:抗生素疗程环丙沙星x3天抗生素10–21天抗生素10–21天CPIS>6CPIS≤6可疑HAP/VAP3天后重新评估CPISCPIS>6:按照肺炎治疗CPIS≤6:停用环丙沙星SinghN,RogersP,AtwoodCW,etal.Short-courseempiricantibiotictherapyforpatientswithpulmonaryinfiltratesintheintensivecareunit.AmJRespirCritCareMed2000;162(2):505-511HAP/VAP:抗生素疗程PCT指导抗生素治疗社区获得性下呼吸道感染不良预后相似(15.4%vs.18,9%)，抗生素疗程缩短(5.7dvs.8.7d)AECOPD减少抗生素使用(40%vs.72%)，减少6个月内抗生素使用(RR0.76;95%CI0.64–0.92)社区获得性肺炎减少抗生素使用(RR0.52,95%CI0.48–0.58)SchuetzP,Christ-CrainM,ThomannR,etal.Effectofprocalcitonin-basedguidelinesvsstandardguidelinesonantibioticuseinlowerrespiratorytractinfections:TheProHOSPrandomizedcontrolledtrial.JAMA2009;302(10):1059-1066StolzD,Christ-CrainM,BingisserR,etal.AntibiotictreatmentofexacerbationsofCOPD.Chest2007;131:9-19Christ-CrainM,StolzD,BingisserR,etal.Procalcitoningu