急性胰腺炎的臨床處理(美國胃腸病學(xué),2013.5)

華西醫(yī)院中西醫(yī)結(jié)合科ClinicalManagementofPatientsWithAcutePancreatitisGASTROENTEROLOGYMAY2013;144:1272–12811CenterforPancreaticCare,SouthernCaliforniaPermanenteMedicalGroup,DepartmentofGastroenterology,KaiserPermanenteLosAngelesMedicalCenter,LosAngeles,California（南加州,凱薩醫(yī)療機構(gòu)）;

and2CenterforPancreaticDisease,DivisionofGastroenterology,HepatologyandEndoscopy,BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts（波士頓，哈佛醫(yī)學(xué)院)Keywords:ClinicalManagement;FluidResuscitation;Necrosis;QualityImprovement.Abstract

AcutepancreatitisistheleadingcauseofhospitalizationforgastrointestinaldisordersintheUS,withmorethan280,000hospitalizationseachyear.TheaveragelengthofstayatUShospitalsin2010wasestimatedtobe5days,atanaggregatecostof$2.9billion.

高發(fā)病率；平均住院時間：5天；治療費用高昂

Mortalityrangesfrom3%forpatientswithinterstitial(edematous)pancreatitisto15%forpatientswhodevelopnecrosis.

死亡率：3%（間質(zhì)水腫性AP）-15%(壞死性AP)Astherateofhospitalizationforacutepancreatitiscontinuestoincrease,sodoesthedemandforeffectivemanagement.Thisdemandhasresultedinpublicationofatleast14clinicalpracticeguidelinesinthepastdecade.AnupdatetotheAmericanPancreasAssociationandInternationalAssociationofPancreatologyguidelinesisforthcoming.

急性胰腺炎診治指南需進一步規(guī)范1.PeeryAF,DellonES,LundJ,etal.BurdenofgastrointestinaldiseaseintheUnitedStates:2012update.Gastroenterology2012;143:1179–1187.2.SinghVK,BollenTL,WuBU,etal.Anassessmentoftheseverityofinterstitialpancreatitis.ClinGastroenterolHepatol2011;9:1098–1103.3.vanSantvoortHC,BakkerOJ,BollenTL,etal.Aconservativeandminimallyinvasiveapproachtonecrotizingpancreatitisimprovesoutcome.Gastroenterology2011;141:1254–1263ContentsDiagnosis1RiskandPrognosticFactors

2Treatment3Prevention4DiagnosisThediagnosisofacutepancreatitisrequiresatleast2ofthefollowing:

1.typicalupperabdominalpain

典型的上腹部疼痛

2.serumlevelsofamylaseorlipase>3timestheupperlimitofnormal,

胰腺酶水平>3倍正常值的上限3.con?rmatory?ndingsfromcrosssectionalimaginganalysis.

影像學(xué)支持ArecentlycompletedrevisionoftheAtlantaClassi?cationprovidesamoredetailedsystemthatemphasizesdiseaseseverityandincludescomprehensivede?nitionsofpancreaticandperipancreaticcollections.Therearealsomorecompletede?nitionsoflocalandsystemiccomplications.DiseaseDe?nitions:TheRevisedAtlantaClassi?cation

TheAtlantaClassi?cationsystemwasdevelopedataconsensusconferencein1992toestablishstandardde?nitionsforclassi?cationofacutepancreatitis.

最新修訂版的亞特蘭大分類標準提供了一個更加詳細的分類標準，它著重于疾病的嚴重程度，及包括胰腺和胰周液體聚集的綜合定義，而有更加完整的局部及系統(tǒng)性并發(fā)癥的定義。12.BanksPA,BollenTL,DervenisC,etal.Classi?cationofacutepancreatitis—2012:revisionoftheAtlantaclassi?cationandde?nitionsbyinternationalconsensus.Gut2013;62:102–111.13.MarshallJC,CookDJ,ChristouNV,etal.Multipleorgandysfunctionscore:areliabledescriptorofacomplexclinicaloutcome.CritCareMed1995;23:1638–1652.123De?nitionofLocalComplications

局部并發(fā)癥的定義

De?nitionofSystemicComplicationsandOrganFailure

全身并發(fā)癥及器官衰竭的定義De?nitionofSeverity嚴重程度分類4RolesofAdvancedImagingTechniques

影像學(xué)的作用

Diagnosis間質(zhì)水腫性胰腺炎De?nitionofLocalComplications急性胰腺炎急性胰周液體積聚（APFC）胰腺假性囊腫壞死性胰腺炎急性壞死物積聚（ANC）包裹性壞死（WON）

Avarietyoflocalcomplicationshavebeendelineated.Interstitialpancreatitisinvolvesacutecollectionofperipancreatic?uid（ACPF）andformationofpancreaticpseudocysts.

間質(zhì)水腫性胰腺炎涉及急性胰周液體積聚和胰腺假性囊腫的形成

APFCdevelopduringtheearlyphase早期ofinterstitialpancreatitis.Theyarehomogeneous

inappearancewithoutawell-de?nedwall,usuallyremainsterile,andfrequentlyresolve

spontaneously(FigureA).

急性胰周液體積聚（APFC）發(fā)生胰腺炎病程早期，滲出液均勻地而邊界模糊地分布于胰周，通常是無菌的，可以自行吸收Ifanacuteperipancreatic?uidcollectiondoesnotresolvespontaneously,itcoulddevelopintoapseudocystwithawellde?nedin?ammatorywallthatcontains?uidwithverylittle,ifany,solidmaterial(FigureB).

如果一旦胰周積液不能自行吸收，它將可能發(fā)展為有完整炎癥性包膜容納少量滲出液及極少量壞死組織的假性囊腫(發(fā)生AP后4周)間質(zhì)水腫性胰腺炎Figure(A)Interstitialpancreatitiswithacuteperipancreatic?uidcollection.Peripancreatic?uidcollection(arrows)ispoorlyde?nedwithhomogeneous?uiddensity.Figure(B)Resolvinginterstitialpancreatitiswithpseudocyst.Apseudocyst(arrow)istypicallyaroundorovalencapsulatedcollectionwithhomogeneous?uiddensity.急性胰周液體積聚（APFC）胰腺假性囊腫

Necrotizingpancreatitisinvolvesacutecollectionofnecrosisandwalled-offnecrosis.壞死性胰腺炎包括急性壞死物積聚（ANC）及包裹性壞死（WON）。

Anacutenecroticcollectionreferstothepresenceofnecrotictissueinvolvingpancreaticparenchymaandperipancreatictissues

(Figure2).Thesecollectionscanbesterileorinfected.Ifinfected,theyarecalledinfectednecrosis.急性壞死物積聚（ANC）指的是胰腺實質(zhì)及胰周組織的壞死（如表格2），壞死物的積聚可是無菌性和感染性，其中感染性的又叫感染壞死。After4ormoreweeks,anacutenecroticcollectioncanbecomesmallerbutrarelydisappearscompletelyandusuallyevolvesintowalled-offnecrosis.Walled-offnecrosishasawell-de?nedin?ammatorywallthatcontainsvaryingamountsof?uidandnecroticdebris(Figure3).在4周及之后，急性壞死物的積聚逐漸變小，但很少有被完全吸收，通常發(fā)展為有炎癥性包膜容納混合大量滲出液及少量壞死物碎片的包裹性壞死（WON）（如表格3）。Figure2.Pancreaticandperipancreaticnecrosis.Thisimageshowsanacutenecroticcollectioninvolvingboththepancreas(largearrow)andperipancreatictissue.

Figure3.Walled-offpancreaticnecrosisisanencapsulatedcollectionofnecrosis.Thistypeofcollectiontypicallyforms4to6weeksafterdiseaseonset.Thisimageshowspancreaticandperipancreaticnecrosis.壞死性胰腺炎急性壞死物積聚（ANC）包裹性壞死（WON）De?nitionofSystemicComplicationsandOrganFailureIntherevisedAtlantaClassi?cation,systemiccomplicationsarede?nedasexacerbationsofpreexistingcomorbiditiessuchaschroniclungdisease,chronicliverdisease,orcongestiveheartfailure,recognizingthefailureofrespiratory,cardiovascular,andrenalorgansystems.在修訂版的亞特蘭大分類標準，全身并發(fā)癥被定義為，先前存在的疾病諸如慢性肺部疾病、慢性肝病、充血性心力衰竭等的突然惡化，這些被認為是呼吸系統(tǒng)、心血管系統(tǒng)、腎臟功能系統(tǒng)的損害加重而衰竭。De?nitionofSystemicComplicationsandOrganFailure

Thescoringsystemthathasbeenchosentocharacterizeorganfailureisthemodi?edMarshallscoringsystem.Themodi?edMarshallsystemclassi?esdiseaseseverityonascalefrom0to4,sothattheoverallevaluation

oforgandysfunctioncanbemorecompletelydelineatedandcharacterizedovertime.Inthissystem,organfailureisde?nedbyascoreof≥2foroneormoreoftheseorgansystems.改良的馬歇爾評分系統(tǒng)用于器官衰竭的評分，該評分系統(tǒng)將急性胰腺炎的嚴重程度分為0—4級，以至于更能清晰及特征性地對器官功能障礙發(fā)展進行綜合評價。在該評分系統(tǒng)中，器官衰竭定義為有任何1個及多個器官功能評分≥

2分。13.MarshallJC,CookDJ,ChristouNV,etal.Multipleorgandysfunctionscore:areliabledescriptorofacomplexclinicaloutcome.CritCareMed1995;23:1638–1652.De?nitionofSeverityMAPMilddisease

isde?nedasacutepancreatitisnotassociatedwithorganfailure,localorsystemiccomplications.無器官衰竭、無局部或全身并發(fā)癥MSAPpresenceoftransientorganfailure(presentfor<48hours),localorsystemiccomplications.一過性器官衰竭（<48h）伴有局部或全身并發(fā)癥SAPpresenceofpersistentorganfailure(presentfor>48hours).Mostpatientswithpersistentorganfailurehavepancreaticnecrosis.持續(xù)性器官衰竭（>48h）,多伴有胰腺壞死Mostpatientswithmildacutepancreatitisdonotrequirepancreaticimaginganalysisandareusuallydischargedwithin3to5daysofonsetofillness.

輕型急性胰腺炎患者無需影像學(xué)檢查，住院時間通常為3-5天

Patientswithmoderatelysevereacutepancreatitisfrequentlyrequireextendedhospitalizationbuthavelowermortalityratesthanpatientswithsevereacutepancreatitis.

中度重癥急性胰腺炎需延長住院時間，但病死率低于重癥急性胰腺炎Ameta-analysisfoundpatientswithsevereacutepancreatitiswithpersistentorganfailurehavea30%mortalityrate;theriskofin-hospitaldeathdoubleswhentheyhavepersistentorganfailureandinfectednecrosis.

重癥急性胰腺炎有高達30%的病死率，當出現(xiàn)持續(xù)性器官功能衰竭和感染壞死時，住院期間死亡的風(fēng)險成倍增加。15.PetrovMS,ShanbhagS,ChakrabortyM,etal.Organfailureandinfectionofpancreaticnecrosisasdeterminantsofmortalityinpatientswithacutepancreatitis.Gastroenterology2010;139:813–820.RolesofAdvancedImagingTechniquesTheroleofCTinassessingpatientswithacutepancreatitishaschangedwithtime.CT的作用是用于評價急性胰腺炎發(fā)病及治療各階段的變化Acontrast-enhancedCTscanobtainedwithinthe?rstseveraldaysofillnesscannotbeusedtodeterminewhetherapatienthasnecrotizingorsevereinterstitialpancreatitis.Thismightbebecauseintrapancreatic?uidcausesheterogeneousenhancement,whichcanindicatenecrosis.在發(fā)病的前幾天，不能通過CT檢查判斷出胰腺壞死的存在及其范圍，這可能是由于胰腺內(nèi)液體滲出導(dǎo)致了CT的不均勻增強。

Overaperiodofseveraldays,the?uidcanbereabsorbedsuchthatasubsequentCTscanclearlyshowstheabsenceofnecrosis.Assuch,patientsshouldnotbeevaluatedbyCTwithinafewdaysaftertheonsetofdiseasetoestablishthepresenceorextentofpancreaticnecrosis.胰腺積液被重吸收后，后來的CT檢查才能夠區(qū)分液體積聚或胰腺壞死范圍。

Thebestuseofanearly-stageCTscanistocon?rmadiagnosisofacutepancreatitiswhentheclinicalsituation

isunclear.

發(fā)病早期行CT檢查僅能用于診斷不明時，以確診急性胰腺炎。ThebestuseofaCTscanafterthe?rst5to7daysistoevaluatethepresenceoflocalcomplicationsinpatientswithmoderatelysevereorseverepancreatitistoguideongoingcare.

發(fā)病的第一個5-7天后行CT檢查最大好處，用以評價中度重癥急性胰腺炎或重癥急性胰腺炎病人的局部并發(fā)癥，并指導(dǎo)治療。MRCPhasbecomeausefulprocedureforidentifyingretainedcommonbileductstones.

SelectiveuseofMRCPcanreducetheneedforERCPforpatientswithsuspectedgallstonepancreatitis.

MRCP對膽管結(jié)石敏感，能夠減少因懷疑為膽源性胰腺炎而行ERCP檢查。MRI

ishelpfulindistinguishingwalled-offnecrosisfromapseudocyst.Forexample,inwalled-offnecrosis,therearevariableamountsof?uidandsoliddebristhatcanbevisualizedusingT2-weightedimaging.MRI能用于鑒別是包裹性壞死（WON）或是胰腺假性囊腫，因為T2加權(quán)像能很直觀地看出含有大量滲液體及固體壞死物的包裹性壞死。

Endoscopicultrasonographyisahighlysensitivetestfordetectingcholelithiasisandcholedocholithiasis.19ItcouldbeanalternativetoMRCP,whichhaslimitedaccuracyfordetectingsmallergallstonesorsludge.超聲內(nèi)鏡對膽石病高度敏感，可以代替對細小結(jié)石或淤泥樣膽汁不敏感的MRCP檢查。123PrognosticFactors預(yù)后因素RiskandPrognosticFactorsClinicalscoringsystems

臨床系統(tǒng)性評分Riskfactors危險因素Riskfactors

AgeObesity

RiskfactorsAP？ComorbidillnessesAlcohol60yearsofageoroldercancer,heartfailure,andchronickidneyandliverdiseaseBMI>30kg/m2chronicalcoholconsumptionincreasestheriskofseverepancreatitis3-foldandmortality2-foldClinicalscoringsystems

Theinitial12to24hoursofhospitalizationiscriticalduringpatientmanagement,becausethehighestincidenceoforgandysfunctionoccursduringthisperiod.

發(fā)病第12-24h是臨床處理非常重要，器官功能障礙多發(fā)生于這個時段。Anumberofclinicalscoringsystemsandbiomarkers

havebeendevelopedtofacilitateriskstrati?cation

duringthisphase.WhereaspreviousscoringsystemssuchastheRansonorImrie–Glasgowscoresrequired48hourstocomplete,2scoringsystemswererecentlydevelopedandinvolveasimpli?edapproachthatcanbeperformedduringthe?rst24hoursofhospitalization——TheBedsideIndexofSeverityinAcutePancreatitis.

Ranson評分系統(tǒng)、Imrie–Glasgow評分系統(tǒng)對疾病的危險分層評分滯后，最新的AP嚴重程度床旁指數(shù)（BISAP）可在發(fā)病24h內(nèi)完成。26.HarrisonDA,D’AmicoG,SingerM.Casemix,outcome,andactivityforadmissionstoUKcriticalcareunitswithsevereacutepancreatitis:asecondaryanalysisoftheICNARCCaseMixProgrammeDatabase.CritCare2007;11(Suppl1):S1.27.WuBU,ConwellDL.Updateinacutepancreatitis.CurrGastroenterolRep2010;12:83–90.ClinicalscoringsystemsAP嚴重程度床旁指數(shù)BUN>25mg/dl(8.9mmol/L)Impairedmentalstatus精神狀態(tài)受損SIRSage60yearsorolderpleuraleffusion胸腔積液Score>2within24hoursisassociatedwitha7-foldincreaseinriskoforganfailureand10-foldincreaseinriskofmortality.發(fā)病24小時內(nèi)分數(shù)>2分，發(fā)生器官衰竭的風(fēng)險增加7倍，死亡的風(fēng)險增加10倍。

Anotherscoringsystem,theHarmlessAcutePancreatitisScore,usesadifferentapproachtoriskstrati?cation,identifyingpatientsatthetimeofadmissionwhoareunlikelytoexperiencecomplicationsrelatedtoacutepancreatitis.Speci?cally,patientswithanormalhematocrit

andnormalserumlevelofcreatininewithoutreboundtenderness

orguarding,areunlikelytodevelopseverepancreatitis(positivepredictivevalueof98%).

輕癥急性胰腺炎評分（HAPS）則注重于在入院時不會發(fā)生與急性胰腺炎相關(guān)并發(fā)癥的病人的評分，特別是Hct、Cre正常，無反跳痛體征的病人，將不再發(fā)展為重癥急性胰腺炎（陽性率高達98%）。Withrespecttoscoringsystems,themostwidelyvalidatedremainstheAcutePhysiologyandChronicHealthExaminationIIscore.Thesescoringsystemshavecomparablelevelsofoverallaccuracy.

最受到廣泛認同的評分系統(tǒng)為急性生理功能和慢性健康狀況評分系統(tǒng)

(APACHEII)，

這些評分系統(tǒng)具有相當?shù)乃降恼w精度。PrognosticFactorsAdditionalapproacheshavebeendevelopedtomonitor

diseaseprogression.Parametersthatareeasytodetermineandhavebeenvalidatedfortheirabilitytodeterminediseaseactivity

includethepresenceofSIRS,levelofBUNorCr,andhematocrit.

SIRS、尿素氮水平、肌酐水平、紅細胞壓積的參數(shù)，用于監(jiān)測疾病的進展。

ProspectivestudieshaveshownthatthelevelofBUNatadmissionandduringtheinitial24hoursofhospitalizationisastrongprognosticfactor.Forexample,patientswithalevelofBUNatadmission>20mg/dLthatincreasedduringtheinitial24hourshave9%to20%mortality.Bycontrast,patientswithanincreasedlevelofBUNatadmissionthatdecreasedatleast5mg/dLwithin24hourshave0%to3%mortality.入院時及入院后24小時內(nèi)BUN水平的高低是一個非常重要的預(yù)后因素。例如，入院時患者BUN>20mg/dL（7.14mmol/L），在發(fā)病最初24小時內(nèi)可增加9%-20%的病死率，相反，高BUN水平在入院后24小時內(nèi)至少下降5mg/dL(1.8mmol/L)則有0%-3%病死率。38.WuBU,BakkerOJ,PapachristouGI,etal.Bloodureanitrogenintheearlyassessmentofacutepancreatitis:aninternationalvalidationstudy.ArchInternMed2011;171:669–676.39.WuBU,JohannesRS,SunX,etal.Earlychangesinbloodureanitrogenpredictmortalityinacutepancreatitis.Gastroenterology2009;137:129–135.全身炎癥反應(yīng)綜合征(SIRS)

AnincreasingnumberofSIRScriteriaduringtheinitial24hoursofhospitalizationincreasestheriskofpersistentorganfailureandnecrosisaswellasmortality.PatientswithpersistentSIRS(beyond48hours)have11%to25%mortality.SIRS增加持續(xù)性器官衰竭、胰腺壞死、病死率（11-25%）的風(fēng)險。2ormoreofthefollowingcriteriaT>38.3°C

或<36°C脈搏>90次/分WBC>12×10^9/L或<4×10^9/L不成熟白細胞比例>10%呼吸>20次/分

AserumlevelofCr>1.8mg/dL（159umol/L）withinthe?rst24hoursofhospitalizationisassociatedwitha35-foldincreasedriskofdevelopmentofpancreaticnecrosis.ApersistentincreaseinHCT>44%hasalsobeenshowntoincreasetheriskofnecrosisandorganfailure.

研究表明，在發(fā)病的最初的24小時內(nèi)血肌酐>1.8mg/dL，發(fā)展為胰腺壞死的風(fēng)險增加35倍紅細胞壓積持續(xù)>44%也同樣增加了胰腺壞死及器官衰竭的風(fēng)險。33.MuddanaV,WhitcombDC,KhalidA,etal.Elevatedserumcreatinineasamarkerofpancreaticnecrosisinacutepancreatitis.AmJGastroenterol2009;104:164–170.34.BrownA,OravJ,BanksPA.Hemoconcentrationisanearlymarkerfororganfailureandnecrotizingpancreatitis.Pancreas2000;20:367–372.Treatment123InitialResuscitationandManagement早期治療

ManagementofLocalComplications

局部并發(fā)癥的治療ManagementofExtrapancreaticComplications

胰腺外并發(fā)癥的治療

4SpecialConsiderationsBasedonEtiology對因治療

InitialResuscitationandManagement

Aggressivevolumeresuscitationhasbeenacornerstoneoftherapy,basedonstudiesinanimalmodelsandobservationaldatafromclinicalstudies.However,approachesto?uidresuscitationrequireoptimization.

Under-resuscitationduringtheearlyphaseofacutepancreatitishasbeenassociatedwithincreasedriskofnecrosisandmortality.Incontrast,over-resuscitationcanleadtocomplicationssuchaspulmonarysequestration（肺隔離癥）.

積極的容量復(fù)蘇已經(jīng)成為治療的里程碑，疾病早期液體復(fù)蘇的容量不足會增加胰腺壞死及死亡的風(fēng)險，相反，如過度補液可能導(dǎo)致諸如肺隔離癥的并發(fā)癥，制定最優(yōu)化液體復(fù)蘇方案很重要。44.de-MadariaE,Soler-SalaG,Sanchez-PayaJ,etal.In?uenceof?uidtherapyontheprognosisofacutepancreatitis:aprospectivecohortstudy.AmJGastroenterol2011;106:1843–1850.45.MaoEQ,FeiJ,PengYB,etal.Rapidhemodilutionisassociatedwithincreasedsepsisandmortalityamongpatientswithsevereacutepancreatitis.ChinMedJ2010;123:1639–1644.NO.1InitialResuscitationInitialResuscitationandManagementAprospective,randomized,controlledtrialassessedtheeffectsofbolusinfusionof20mL/kgintheemergencydepartment,followedbycontinuousinfusionof3mL·kg-1·h-1,withintervalassessmentevery6to8hours(comprisingvitalsignmonitoring,pulseoximetry,

andphysicalexamination).RepeatvolumechallengewasadministeredifthelevelofBUNdidnotdecrease.Alternatively,iftheBUNleveldecreased,therateoftheinfusionwasreducedto1.5mL·kg-1·h-1.Thisapproachwasfoundtobesafeandfeasibleinanacutecaresetting.

研究表明，在急診科按20mL/kg進行開始補液，隨后按3mL·kg-1·h-1的速度進行持續(xù)補液，每間隔6-8小時進行病情評估（包括生命體征、血氧飽和度、身體狀況）：如果BUN水平?jīng)]有下降，需反復(fù)地補液；相反，如果BUN水平下降了，則補液速度減少至1.5mL·kg-1·h-1，最后證明此治療方案在急診治療中是安全可行的。

Ingeneral,patientsundergoingvolumeresuscitationshouldhavetheheadofthebedelevated,undergocontinuouspulseoximetry,andreceivesupplementaloxygen.

患者進行液體復(fù)蘇時，需抬高床頭，持續(xù)的血氧飽和度監(jiān)測及吸氧。

LactatedRinger’ssolutionreducestheincidenceofSIRSby>80%comparedwithsaline.Nevertheless,LR’ssolutionisareasonablechoiceforinitialresuscitation,basedonitspositiveeffectsonacid-basehomeostasis,comparedwithlarge-volumesalineresuscitation.BecauselactatedRinger’ssolutioncontainscalcium,itshouldnotbeadministeredinquantitytopatientswithhypercalcemia.

與用生理鹽水復(fù)蘇相比，乳酸林格氏液能減少80%的SIRS發(fā)生，乳酸林格氏液對維持酸堿平衡有積極的影響，更加適用于早期的液體復(fù)蘇，

高鈣血癥患者慎用。

Volumeexpansionwithcolloidhasnotbeenshowntobemoreeffectivethanwithcrystalloidsincriticallyillpatients.

對于危重病人，使用膠體液擴容的益處并不多于使用晶體液。NO.2IndicationsforIntensiveCare

重癥監(jiān)護的適應(yīng)癥Respiratoryfailureisthemostcommonformoforgandysfunction.Patientswithsignsofrespiratoryfailureorhypotensionthatfailtorespon