重症甲型H1NI流感的诊治

重症甲型H1NI流感的诊治内容提要概述与流行病学临床表现及诊断重症患者的临床特征与早期识别重型甲型H1NI流感的监测与治疗TheOriginsofPandemicInfluenza—Lessonsfromthe1918Virus2009年3月墨西哥暴发“人感染猪流感”疫情，迅速在全球蔓延09-4-25WHO向我国通报人感染猪流感疫情美国、墨西哥宣布卫生紧急状态WHO宣布为严重公共卫生事件胡锦涛主席批示：成立人感染猪流感防控小组09-4-29上海首先从口岸到医院进行物质准备、演练--全国防控工作以应对疫情出现甲型H1NI流感09-04-30中科院和中国CDC已建立了快速诊断方法09-05-01WHO宣布将“猪流感”改称“A型（H1N1）流感”09-05-01晚香港宣布首例甲型H1N1流感确诊病例09-05-11我国四川省确诊一例甲型H1N1流感病例09-05-20台湾时确认其感染了甲型Ｈ１Ｎ１流感09-09-0915:00内地31个省市自治区累计报告6457例甲型H1N1流感确诊病例，已治愈4137例无甲型H1N1流感所致的死亡病例

NEnglJMed2009;361:279-285.易感人群(CDC-USA)

人群普遍易感高危病例：甲型Ｈ１Ｎ１流感后可能病情较重，病死率较高的人群年龄小于５岁的儿童年龄大于或等于６５岁的老年人妊娠妇女合并以下情况：慢性呼吸系统疾病，心血管系统疾病（高血压除外）、肾病、肝病、血液系统疾病、神经系统及神经肌肉疾病、代谢及内分泌系统疾病、免疫功能抑制、１９岁以下长期服用阿司匹林者集体生活于养老院或其他慢性病疗养机构的人员

TwopathwayDirectinjurySIRS:inflammatorystormMODS病理与病理生理

(PathogenesisofsevereH1N1infections)甲型H1N1流感病毒和季节性H1N1的区别季节性H1N1主要在鼻腔复制，甲型H1N1除在鼻腔复制外在器气管、支气管和细支气管复制Science.2009,325:481-483.NEnglJMed2009;361:680-9.DiffusealveolardamagewithprominenthyalinemembranesThespecimenhematoxylinandeosin)showsnecrosisofbronchiolarwallsaneutrophilicinfiltrate病理与病理生理

(PathogenesisofsevereH1N1infections)Moreover,somepatientshaverequiredhospitalizationBecauseofseverepneumoniaandrespiratoryfailureFatalityrate:0.5%oflaboratory-confirmedcases病理与病理生理

(PathogenesisofsevereH1N1infections)Science2009,325:481重症甲型H1N1患者病死率PatientswithpneumoniaandALIMortality39％PatientswithmechanicalventilationMortality58%NEnglJMed2009;361:680-9.重症甲型H1N1流行病学至09-09-05，全世界因甲型H1N1发病25万余人，死亡达2837人从09-08-28到09-09-05一周内死亡652人，占总死亡人数的23％钟南山院士及中国疾控中心流行病学首席专家曾光认为甲型H1N1开始第二波流行内容提要概述与流行病学临床表现及诊断重症患者的临床特征与早期识别重型甲型H1NI流感的监测与治疗临床表现潜伏期一般为1-7天，多为1-3天流感样症状：发热、咳嗽、咽痛、咯痰、流涕、鼻塞、头痛、全身酸痛、乏力部分病例出现呕吐和/或腹泻约10%病例可不发热体征主要包括咽部充血和扁桃体肿大，肺炎(我国５％的病人出现了以轻症为主的程度不同的肺炎)少数为重症病例：实验室检查

外周血象：白细胞总数一般不高或降低血生化：部分低钾，肝酶升高病原学检查：病毒核酸检测：RT-PCR病毒分离血清学检查动态检测血清甲型H1N1流感病毒特异性中和抗体水平呈4倍或4倍以上升高胸部影像学重症甲型H1NI流感当确诊或疑似病例出现以下情况之一时为重症病例：合并肺炎和/或低氧血症、呼吸衰竭合并感染中毒性休克合并多脏器功能不全或多脏器功能衰竭Day1Day2内容提要概述与流行病学临床表现及诊断重症患者的临床特征与早期识别重型甲型H1NI流感的监测与治疗Timebetweenonsetofsymptomsandadmissiontothehosp:4to25daysThemediantimeofpresentationtothehosp:6daftertheonsetofsymptomsNEnglJMed2009;361:680-9.发生重症表现的时间vsinMexicoCase122-yearsoldpregnantwomanPulmonaryedemaandRespirfailure3dafteronsetofsymptomsCase240years-oldman1weekafterOnsetofsymptomsCase340years-oldmanRespirfailureandARDS10dafteronsetofsymptoms发生重症表现的时间vsChina重症患者的年龄分布MexicovsChinaALLpatsinMexicono.%<=5yr3/1817%>5to<=5yr1/186%>10to<=15yr1/186%>15to<=50yr11/1861%>50yr2/1811%ALLseverepatsinChinaAgeCase122Case240Case340Fever,withTemperatureshigherthan38°C,coughinALLpatsDyspneaOrrespiratorydistressinALLpatsSpO2:71%(roomair)Wheezing:twopatients(11%)Diarrhea:Fourofthefivechildren(allunder14yearsofage)APACHEII:14(range,4to32)SequentialOrganFailureAssessment:6(range,1to13)重症患者的早期线索(MexicovsChina)NEnglJMed2009;361:680-9.Only3severecasesinChinaFever,withTemperatureshigherthan38°C,coughinALLpatsDyspneaorrespiratorydistressinALLpatsSpO2:56%(roomair)Wheezing:twopatients重症患者的早期线索(MexicovsChina)重症患者的早期线索呼吸困难或呼吸窘迫口唇紫绀咯粉红色泡沫痰或血性痰胸片出现斑片状阴影重症患者的早期线索具有基础疾病高原地区（2220m）基础的呼吸系统疾病妊娠先心病误吸重症患者的临床特征inMexico

NEnglJMed2009;361:680-9.RadiologicallyconfirmedpneumoniaBilateralpatchyalveolaropacities(predominantlybasal)ORLinear,reticular,ornodularshadows(interstitialopacities)Affectthreeorfourlungquadrantsin11pats.重症患者的临床特征inMexico

NEnglJMed2009;361:680-9.重症患者的临床特征inMexicoNEnglJMed2009;361:680-9.Coughandfever(3)bloodinsputum(1)Suddenonsetofsymptom(3)Dyspneaandrespirdistress(3)MVonadmission(3)Hypotension(1?)Ventricularfibrillation/CardiacarrestHepaticdysfunction(2)重症患者的临床特征inChinaIncreasedLDHandCK(2)WBC:normalorincreased(3)Lymphopenia:?重症患者的临床特征inChina临床特征Pneumonia/RespiratoryfailurePulmonaryedemaMyotitis/MyocarditisHepaticdysfuntionCardiopulmonarycollapseSepticshockVentricularfibrillationIn18patients,7died,and11recoveredandweredischargedfromthehospital.Patientsdiedwithin10to23days(mean,14)aftertheonsetofillnessbetween4and18days(mean,9days)afteradmission.重症患者的转归NEnglJMed2009;361:680-9.S-OIV阳性与阴性

年龄分布及肺炎发生情况病毒RNA阳性\载量vs严重程度TheclinicalcourseofSevereH1N1influenzaAStage1:Onset:Influenza-likesymptom.Stage2:PneumoniaandARDSStage3:MultipleorganfailureStage4:Convalescence内容提要概述与流行病学临床表现及诊断重症患者的早期识别与临床特征重型甲型H1NI流感的监测与治疗严密监测治疗重点提前遏制病毒的复制与炎症反应风暴预防ARDS和呼吸衰竭对于已发生MODS强化治疗和支持衰竭的多个器官临床监测与救治Patientsrequiresymptomatictreatmentonly抗病毒治疗药物对症治疗：发热、呕吐、腹泻等处理注意排除其他感染性和神经系统疾病发病3～5天后继发感染的防治(特别是应用激素)Stage1:Influenza–like病因治疗---抗病毒奥司他韦EmergencyUseAuthorization(EUA)ReviewOseltamivirPhosphateforSwineInfluenzaA

Resp:RR(HighvsLow)OximeterreadingsExaminationoflungMetabolismbloodsugarlevelsshouldbecloselymonitoredUrineoutputandbladderstateTissuseperfusionExtermityperfusionArteriallactate/ScvO2Monitoringatstage1Stage1:Influenza–likeMostpatientswhopresentinstage1recoverwithoutsequelaewithin1week.Onlyaveryfewprogresstothenextstage.Stage1:Influenza–likeWithsignsandsymptomsofcirculatoryandrespfailure(dyspneaorrespirdistress)orpoorperfusionAdmittohospital/ICUInsult(infection,injury)LocalorsystemicinflammatoryresponseHighpermeabilitypuledemaAlveolarcollapseandshuntingHypoxemiaandrespiratorydistressStage2:PneumoniaandARDSStage2:PneumoniaandARDSAntivirustherapyRespiratorysupportAnti-inflammatorySteroidImmunoglobulin/AprotininFluidrestrictionanddiuretics/albuminSedativestopatswithagitation呼吸支持治疗氧疗

无创机械通气

有创机械通气

肺保护性通气肺复张PEEP的选择自主呼吸、半卧位、俯卧位通气

体外膜氧合技术(ECMO)

ALI/ARDSImmunoglobulin:Nodatafromcontrolledstudiesareavailablethatsupporttheuse.UntilcontrolledevidenceisavailablewerecommendCanbeusedonlyforseverecasesandonlyintheearlystagesofthedisease.5-20g/dfor3~5dSteroid:Methyprednisoline

1~2mg/kg.d/highdoseforseverecasesAprotinin:20~30万U，TidThymosina1(Thymopeptids)Stage2:PneumoniaandARDSSteroidBMJ2008;336;1006-1009.ApossibilityofreducedmortalityandincreasedventilatorfreedayswithsteroidsstartedaftertheonsetofARDSwassuggested.Timing:Steroid

Latestage(>7d)ofARDSPersistentARDS:excessivefibroproliferation,ongoinginflammation---prolongedMV,andasubstantialriskofdeath.multicenter,randomizedcontrolledtrialPatswithpersistentARDS(day

7-28aftertheonsetofARDS),n=180Methylprednisolone2mg/kg,0.5mg/kgq6hfor14d,0.5mg/kgq12hfor7days,andthentaperingofthedose.Groups:Randomizationwithin7–13DaysafterARDSOnsetRandomizationwithin14–28DaysafterARDSOnset180-DaymortalityaccordingtobaselineBALprocollagenpeptidetypeIIIlevel(PCPIII)<Median>MedianNEnglJMed2006;354:1671-84糖皮质激素明显改善呼吸和循环功能P=0.04P=0.02P=0.02OutcomevsSteroidatARDSonset7-13dvs>14d液体治疗与肺水肿Qf=Kf[(Pc-PIF)–(c-IF)]影响肺水肿的主要因素

Starlingequation静水压对肺水肿的影响CircRes1959,7:649-57通透性vs肺静水压对肺水肿的影响RelationshipbetweenpulmonaryhydrostaticpressureandlungedemaformationundernormalconditionsandincreasedpermeabilityChest2007;131;913-920IncreasedEVLWhasbeenassociatedwithpooroutcomeinARDSpatsReductioninPCWPassociatedwithincreasedsurvivalinARDSpatsincreasededemadecreasedvitalorganperfusionwithalowerintravascularpressurebalancingARDS的液体管理策略问题：是否应该限制液体，限制性的液体管理是否影响其他器官功能Randomizedstudyn=1000patswithALIConservativevsliberalstrategyoffluidmanagementNEnglJMed2006;354限制性液体管理

－不改善预后，但改善呼吸功能胶体渗透压对肺水肿的影响CircRes1959,7:649-57Resp:RR(HighvsLow)OximeterreadingsExaminationoflungChestX-ray

Circulation:Bloodpressure(highorlow)HR(HighvsLow),EKGCkMB/TnITissuseperfusionExtermityperfusionArteriallactate/ScvO2Monitoringatstage2Temperiture:SustainedhighfeverMetabolismBloodsugarlevelsshouldbecloselymonitoredUrineoutputandrenal/hepaticfunctionImmuno-statesHLA-DRTcellsubtypeMonitoringatstage2Patientswhopresentwithtachypneaorapnea,hypotension,hypoxemia,andrenalfailureShouldbeadmittedtotheICU.Stage2:PneumoniaandARDSStage3:MODSThelandmarksarehypertension,renalfailure,etcFluidresuscitationtorestoreintravascularbloodvolumePositive-pressureMVwithincreasedPEEPfortreatmentofpulmonaryedema.CRRTforrenalandextra-renalsupportEGDTEGDT感染所致组织低灌注患者复苏的最初6h内达中心静脉压8~12mmHg平均动脉压>=65mmHg尿量>=0.5ml/kg.h-1中心静脉或混合静脉血氧饱和度>=70%若液体复苏后ScvO2或SvO2仍未达到70%输注浓缩红细胞使血细胞比容达到30%以上输注多巴酚丁胺(最大剂量至20ug/kg/min)NEnglJMed200;345:1368-77.Sepsisbundle--Goldenhours黄金6小时血清乳酸水平测定抗生素使用前留取病原学标本急诊在3小时内、ICU在1小时内开始广谱抗生素治疗如果低血压不能纠正，加用血管活性药物，达到EGDT目标Sepsisbundle-Silverday白银24小时积极的血糖控制糖皮质激素应用机械通气患者平台压<30cmH2O有条件情况下使用APCBothearlyandlatefluidmanagementofsepticshockcomplicatedbyALIcaninfluencepatientoutcomesFluidmanagementinALIsecondaryt