小兒內(nèi)科資料：兒童嚴(yán)重膿毒癥與膿毒性休克治療國(guó)際指南解讀

2012版兒童嚴(yán)重膿毒癥與膿毒性休克治療國(guó)際指南解讀陳攸濤2012版指南采用GRADE分級(jí)系統(tǒng)GRADE分級(jí)系統(tǒng)由推薦等級(jí)與證據(jù)強(qiáng)度兩部分構(gòu)成陳攸濤推薦等級(jí)1級(jí)——推薦(recomment)：指該措施有著良好的預(yù)期效果和經(jīng)濟(jì)效益。2級(jí)——建議(suggest)：指該措施可能有不可預(yù)知的不良反應(yīng)和較低的經(jīng)濟(jì)效益陳攸濤證據(jù)強(qiáng)度分級(jí)A級(jí)(強(qiáng))高質(zhì)量隨機(jī)對(duì)照研究B級(jí)(中等)中等質(zhì)量隨機(jī)對(duì)照或高質(zhì)量觀察性及隊(duì)列研究C級(jí)(弱)完成良好、設(shè)對(duì)照的觀察性及隊(duì)列研究D級(jí)(極弱)病例總結(jié)或?qū)＜乙庖?jiàn)陳攸濤PartGProteinCandactivatedproteinconcentrateG.ProteinCandactivatedproteinconcentrate.蛋白C和活化蛋白濃縮物指南中在兒童及成人均不推薦使用（已退市）See“HistoryofrecommendationsregardinguseofrecombinantactivatedproteinC”.參照“關(guān)于重組活化蛋白C（rhAPC）使用的舊版推薦”陳攸濤RecombinanthumanactivatedproteinC(rhAPC)wasapprovedforuseinadultpatientsinanumberofcountriesin2001followingtheRecombinantHumanActivatedProteinCWorldwideEvaluationinSevereSepsis(PROWESS)trial,whichenrolled1,690severesepsispatientsandshowedasignificantreductioninmortality(24.7%)withrhAPCcomparedwithplacebo(30.8%,P=0.005).PartGProteinCandactivatedproteinconcentrate陳攸濤2001年一些國(guó)家根據(jù)PROWESS研究結(jié)果開(kāi)始批準(zhǔn)重組活化蛋白（rhAPC）應(yīng)用于成人。PROWESS研究一共收集了1690例嚴(yán)重膿毒癥病例，證實(shí)rhAPC相對(duì)安慰劑可以明顯降低嚴(yán)重膿毒癥患者死亡率（24.7%vs.30.8%,P=0.005）。PartGProteinCandactivatedproteinconcentrate陳攸濤The2004SSCguidelinesrecommendeduseofrhAPCinlinewiththeproductlabelinginstructionsrequiredbytheUSandEuropeanregulatoryauthoritieswithagradeBqualityofevidence[7,8].2004版SSC指南將rhAPC使用等級(jí)定為1B。PartGProteinCandactivatedproteinconcentrate陳攸濤Bythetimeofpublicationofthe2008SSCguidelines,additionalstudiesofrhAPCinseveresepsis(asrequiredbyregulatoryagencies)hadshownitineffectiveinlessseverelyillpatientswithseveresepsisaswellasinchildren[229,230].到了2008年，又有一些新的研究表明rhAPC對(duì)一些疾病引起的嚴(yán)重膿毒癥中是無(wú)效的（包括兒童）。PartGProteinCandactivatedproteinconcentrate陳攸濤The2008SSCrecommendationsreflectedthesefindings,andthestrengthoftherhAPCrecommendationwasdowngradedtoasuggestionforuseinadultpatientswithaclinicalassessmentofhighriskofdeath,mostofwhomwillhaveAcutePhysiologyandChronicHealthEvaluation(APACHE)IIscoresC25ormultipleorganfailure(grade2C;qualityofevidencewasalsodowngradedfrom2004,fromBtoC).PartGProteinCandactivatedproteinconcentrate陳攸濤2008版SSC指南將rhAPC使用等級(jí)下調(diào)至2C，僅建議在具有死亡高風(fēng)險(xiǎn)（APACHEII評(píng)分C25）或合并多器官衰竭成人患者中使用。PartGProteinCandactivatedproteinconcentrate陳攸濤The2008guidelinesalsorecommendedagainstuseofrhAPCinlow-riskadultpatients,mostofwhomwillhaveAPACHEIIscoresB20orsingleorganfailures(grade1A),andagainstuseinallpediatricpatients(grade1B).同時(shí)2008版指南提出反對(duì)rhAPC在低風(fēng)險(xiǎn)（APACHEII評(píng)分B20）及單器官衰竭（1A）和兒童中使用（1B）。PartGProteinCandactivatedproteinconcentrate陳攸濤TheresultsofthePROWESSSHOCKtrial(1,696patients)werereleasedinlate2011,showingnobenefitofrhAPCinpatientswithsepticshock(mortality26.4%forrhAPC,24.2%placebo)witharelativeriskof1.09andaPvalueof0.31。2011年P(guān)ROWESSSHOCK研究顯示嚴(yán)重膿毒癥患者并沒(méi)有從rhAPC中受益，rhAPC組死亡率26.4%，安慰劑組死亡率24.2%（RR＝1.09，P＝0.31）PartGProteinCandactivatedproteinconcentrate陳攸濤Thedrugwaswithdrawnfromthemarketandisnolongeravailable,negatinganyneedforanSSCrecommendationregardingitsuse。這個(gè)藥物從此退出市場(chǎng)……PartGProteinCandactivatedproteinconcentrate陳攸濤PartHBloodproductsandplasmatherapies1.Wesuggestsimilarhemoglobintargetsinchildrenasinadults.Duringresuscitationoflowsuperiorvenacavaoxygensaturationshock（＜70%）,hemoglobinlevelsof10g/dLaretargeted.Afterstabilizationandrecoveryfromshockandhypoxemia,thenalowertarget7.0g/dLcanbeconsideredreasonable(grade1B)陳攸濤PartHBloodproductsandplasmatherapies建議兒童維持血紅蛋白量與成人相似（7.0～9.0g/dL）。在低上腔靜脈血氧飽和度（＜70%）的膿毒癥休克復(fù)蘇時(shí)，目標(biāo)血紅蛋白量為10g/dL。待病情穩(wěn)定，休克和低氧血癥糾正后，目標(biāo)血紅蛋白量可以考慮為7.0g/dL(1B)。陳攸濤PartHBloodproductsandplasmatherapiesTheoptimalhemoglobinforacriticallyillchildwithseveresepsisisnotknown.兒童膿毒癥最佳血紅蛋白值尚無(wú)定論。

Arecentmulti-centertrialreportednodifferenceinmortalityinhemodynamicallystablecriticallyillchildrenmanagedwithatransfusionthresholdof7g/dLcomparedwiththosemanagedwithatransfusionthresholdof9.5g/dL一項(xiàng)多中心研究報(bào)道在血液動(dòng)力血穩(wěn)定的重癥患兒HB7g/dL（輸血閾值）組與9.5g/dL在死亡率上無(wú)明顯差異。陳攸濤PartHBloodproductsandplasmatherapieshowever,theseveresepsissubgrouphadanincreaseinnosocomialsepsisandlackedclearevidenceofequivalenceinoutcomeswiththerestrictivestrategy陳攸濤PartHBloodproductsandplasmatherapiesBloodtransfusionisrecommendedbytheWorldHealthOrganizationforsevereanemia,hemoglobinvalue＜5g/dL,andacidosis.WHO建議嚴(yán)重貧血（HB＜5g/dL）及酸中毒時(shí)需要輸血。陳攸濤PartHBloodproductsandplasmatherapiesARCTofearlygoal-directedtherapyforpediatricsepticshockusingthethresholdhemoglobinof10g/dLforpatientswithaSvcO2saturationlessthan70%inthefirst72hofpediatricICUadmissionshowedimprovedsurvivalinthemultimodalinterventionarm.一項(xiàng)RCT研究顯示，早期目標(biāo)導(dǎo)向治療SvcO2＜70%的患兒，最初72小時(shí)內(nèi)HB低于10g/dL時(shí)輸血可提高生存率。陳攸濤PartHBloodproductsandplasmatherapies2.Wesuggestsimilarplatelettransfusiontargetsinchildrenasinadults(grade2C).建議兒童血小板計(jì)數(shù)目標(biāo)值與成人相似（2C）。PLT＜10×109／L，沒(méi)有出血表現(xiàn)

PLT＜20×109／L，有嚴(yán)重出血傾向

PLT＞50×109／L，但有活動(dòng)性出血、手術(shù)、侵襲性操作時(shí)陳攸濤PartHBloodproductsandplasmatherapies3.Wesuggesttheuseofplasmatherapiesinchildrentocorrectsepsis-inducedthromboticpurpuradisorders,includingprogressivedisseminatedintravascularcoag-ulation,secondarythromboticmicroangiopathy,andthromboticthrombocytopenicpurpura(grade2C).建議兒童膿毒癥導(dǎo)致的血栓性紫癜性疾病，包括DIC、繼發(fā)性血栓性血管病、血栓性血小板減少性紫癜的患兒給予血漿治療（2C）陳攸濤PartHBloodproductsandplasmatherapiesWegiveplasmatoreversethromboticmicro-angiopathiesinchildrenwiththrombocytopenia-associatedmultipleorganfailureandprogressivepurpurabecausefreshfrozenplasmacontainsproteinC,antithrombinIII,andotheranticoagulantproteins.新鮮冰凍血漿中含有蛋白C、抗凝血酶Ⅲ和其他抗凝蛋白，可用來(lái)逆轉(zhuǎn)血栓性微血管病導(dǎo)致的多臟器功能衰竭和進(jìn)行性紫癜。陳攸濤PartHBloodproductsandplasmatherapiesRapidresuscitationofshockreversesmostdisseminatedintravascularcoagula-tio