SINIAI临床特征与对策PPT文档格式.ppt
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-2,3-糖苷唾液酸,influenzaV,HostcellwithVirusattachment,NI和AI(H5)现状,H5:
大陆首例2005.10.27,40例,病死率65%(26/40);
WHO1997HK,2003年后高发,病死率58.5%(330/564)H1:
WHOSI-NI-AI-BI现状,WHOSI-NI现状,二、临床特征,上呼吸道鼻、咽、喉下呼吸道肺炎,包括SARI(严重急性呼吸感染综合症)细支气管炎严重肺病和全身表现ARDSMODS严重性:
AINISI,南京医科大学鼓楼医院蔡后荣教授提供,H5N1infection,诊断,流行病学暴露史临床ILI症状危重症病例肺炎/ALI/ARDS/MODS实验室诊断RT-PCR/病毒分离/双份血清,三、应对策略,治疗:
对症:
药物、氧疗(鼻面罩、无创、有创、ECMO)抗病毒:
神经氨酸酶抑制剂、阿比多尔等特异性治疗:
恢复期血浆/免疫血浆辅助:
激素?
他汀类药物等感控:
做好个人防护预防:
疫苗接种,抗病毒治疗,神经氨酸酶抑制剂M2通道阻滞剂广谱抗病毒,抗RNA病毒,MosconaA.NeuraminidaseInhibitorsforInfluenza.NEJM2005;
353:
1363-73.,神经氨酸酶抑制剂,奥司他韦扎那米韦(10mgBID吸入;
600mgbid静脉;
由于是乳糖悬液,不能给予呼吸机雾化治疗)帕拉米韦(peramivir,iv600mg/dx5-10)Laninamivir(20mg/40mg长效),达菲治疗可降低抗生素治疗下呼吸道感染的比率,JeffersonT,etal.Neuraminidaseinhibitorsforpreventingandtreatinginfluenzainhealthyadults:
systematicreviewandmeta-analysis.BMJ2009;
339:
b5106,抗病毒治疗,M2通道阻滞剂:
抑制病毒在胞内包装成病毒颗粒金刚烷胺金刚乙胺,广谱抗病毒,利巴韦林,机制磷酸化产物为病毒合成酶的竞争性抑制剂抑制肌苷单磷酸脱氢酶流感病毒RNA聚合酶mRNA鸟苷转移酶抑制病毒RNA和蛋白质合成广谱抗RNA病毒,其主要作用于抗HCV感染,对流感病毒等作用均有限,阿比多尔(arbidol),抗病毒机制主要是增加流感病毒HA构象转换的稳定性抑制病毒外壳HA与与宿主细胞膜的融合作用阻断流感病毒的复制穿入细胞核直接抑制病毒RNA和DNA的合成调节免疫和诱导干扰素表达,增加抗病毒效果广谱抗病毒:
流感病毒、呼吸道合胞病毒、鼻病毒、柯萨奇病毒、腺病毒,其抗RNA病毒的作用较抗DNA病毒的作用更有效剂量:
200mg/d,5-10d,Arbidol:
abroad-spectrumantiviralcompoundthatblocksviralfusion.,BoriskinYS,etal.CurrMedChem2008;
15(10):
997-1005.,恢复期血浆/免疫血浆治疗,我国2例接受免疫血浆,2接受恢复期血浆,均存活,Thiswasa31yearsoldmanwithH5infection.HedevelopedtoARDSalso,andwasadministratedwithinvasivemechanicalventilation,buthisclinicalsituationwasstillunstable.Onday13and14afteronsetofillness,hewasadministratedwith3unitsofconvalescentplasma.,AnnInternMed.2006;
145:
599-609.,与对照组相比,恢复期血浆治疗对1919H1N1死亡率影响,早期和晚期恢复期血浆治疗对1919H1N1死亡率的影响,AnnInternMed.2006;
599-609.,辅助治疗探求新方法,激素辅助治疗的利与弊,我国重症和危重症H1患者的管理,25篇文献406例,男208(51.2%),孕妇44(10.8%)年龄:
3M-72Y治疗达菲401(98.8%):
75mgBidx5;
150mgBidx10激素306(75.4%):
40-500mg/d,3-10dormoreIVIG,小儿病例,1g/kg.dx2恢复期血浆8(2%),7例治愈机械通气:
无创41(10.1%),有创79(19.5%)ECMO:
5例,2例存活Outcome:
治愈363(89.4%),病死43(10.6%),我国H5病例的临床管理,37cases,F21(56.8%),pregnant4(10.8%)Age:
2Y-62YManagementOseltamivir17(45.9%):
75mgBidx5Corticosteroids36(97.3%):
20-1000mg/d,3-10dormoreIVIG21(56.8%)3-25g/d,1-44dConvalescent/vaccinatedplasma4(10.8%),allrecoveredMechanicalventilation:
NIPPV18(48.6%),IPPV29(78.4%)Outcome:
recovered13(35.1%),died24(64.9%),AmJRespirCritCareMedVol183.pp12001206,2011,40%,83例2009H1N1感染所致ARDS患者激素使用状况,AmJRespirCritCareMedVol183.pp12001206,2011,83例2009H1N1感染所致ARDS患者激素使用状况,AmJRespirCritCareMedVol183.pp12001206,2011,结论,noevidenceofabeneficialeffectofcorticosteroidsinpatientswithARDSsecondarytoinfluenzapneumonia,butsuggeststhatveryearly(3d)corticosteroidtherapymaybeharmful.,28家医院ICUinSouthKoreafrom2009.09-2010.02Atotalof245patients,107(44%)receivedadjuvantsteroidtreatment90-daymortalityrateofpatientsgivensteroids(58%,62of107)wassignificantlyhigherthanthatofthosenotgivensteroids(27%,37of138)(P,0.001).,AmJRespirCritCareMedVol183.pp12071214,2011,结论,AdjuvantcorticosteroidsweresignificantlyassociatedwithhighermortalityincriticallyillpatientswithpH1N1infection.,免疫调节剂,他汀类HMG-CoA(羟甲基戊二酰辅酶A)inhibitors-HDLcholesterolandpreventcardiovascularandcerebrovasculardisease-anti-inflammatory(pleiotropic)effects贝特类PPARagonists(过氧化物酶体增生物激活受体)-regulatelipidmetabolism,fattyacidoxidation-anti-inflammatoryandimmunomodulatoryeffects格列酮类PPARagonists-increasesensitivitytoinsulin-anti-inflammatoryandimmunomodulatoryeffects,炎性分子间的相互作用,Ac-CoA,HMG-CoA,Mevalonate甲羟戊酸,Farnesyl-PP,Statin,SREBP-2,Cholesterol,LDLR,LDL-C,Normolipidemiceffect(liver),Pleiotropiceffects(vascularwall),TG,HDL-C,IL6iNOS,TNF-MCP-1,L-FABP,ApoA1,PPAR,PPAR,15d-PGJ2,COX-2,MARK,PKC,GeranylatedproteinsRhoA,Cdc42,Rac,Geranylgeranyl-PP二牛龙牛儿基-胰多肽,HMG-CoA羟甲基戊二酰辅酶APPAR过氧化物酶体增生物激活受体MARK微管亲和性调节激酶FABP脂肪酸结合蛋白,固醇调节元件结合蛋白,38,实验性急性肺损伤以及Statins&
PPAR激动剂的作用,HO-1:
hemeoxygenase-1血红素加氧酶-1,39,流感免疫发病机制以及Statins&
PPAR激动剂的作用,LaGrutaNL,etal.ImmunolCellBiol2007;
85:
85-92.,STATINs临床应用,BrettSJ,etal.Pre-admissionstatinuseandin-hospitalseverityof2009pandemicinfluenzaA(H1N1)disease.PloSONE2011;
6(4):
e18120FrostFJ,etal.InfluenzaandCOPDmortalityprotectionaspleitropic,dose-dependenteffectsofstatins.Chest2007;
131:
1006-12.KwongJC,etal.Influenzamorbidityandmortalityinelderlypatientsreceivingstatins:
acohortstudy.PloSONE2009;
4(11):
e8087,肺炎时短期Statins治疗对死亡率的影响,1995-2006:
9073例肺炎,年龄4090Y,1398例statin治疗,DouglasI,etal.BMJ2011;
342:
d1642,烷胺类药物,对新H1N1耐药,国外H5N1耐药国内H5N1尚有效,预防,WHOSI-NI现状,预防VaccineStrainsforthe201112InfluenzaSeason,201112U.S.季节流感疫苗病毒株与2010-11相同A/California/7/2009(H1N1)-likeantigensA/Perth/16/2009(H3N2)-likeantigensB/Brisbane/60/2008-likeantigens新A(H1N1)疫苗病毒株来源于