急性胰腺炎的临床处理(美国胃肠病学,2013.5)

华西医院中西医结合科ClinicalManagementofPatientsWithAcutePancreatitisGASTROENTEROLOGYMAY2013;144:1272–12811CenterforPancreaticCare,SouthernCaliforniaPermanenteMedicalGroup,DepartmentofGastroenterology,KaiserPermanenteLosAngelesMedicalCenter,LosAngeles,California（南加州,凯萨医疗机构）;

and2CenterforPancreaticDisease,DivisionofGastroenterology,HepatologyandEndoscopy,BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts（波士顿，哈佛医学院)Keywords:ClinicalManagement;FluidResuscitation;Necrosis;QualityImprovement.Abstract

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

高发病率；平均住院时间：5天；治疗费用高昂

Mortalityrangesfrom3%forpatientswithinterstitial(edematous)pancreatitisto15%forpatientswhodevelopnecrosis.

死亡率：3%（间质水肿性AP）-15%(坏死性AP)Astherateofhospitalizationforacutepancreatitiscontinuestoincrease,sodoesthedemandforeffectivemanagement.Thisdemandhasresultedinpublicationofatleast14clinicalpracticeguidelinesinthepastdecade.AnupdatetotheAmericanPancreasAssociationandInternationalAssociationofPancreatologyguidelinesisforthcoming.

急性胰腺炎诊治指南需进一步规范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.confirmatoryfindingsfromcrosssectionalimaginganalysis.

影像学支持ArecentlycompletedrevisionoftheAtlantaClassificationprovidesamoredetailedsystemthatemphasizesdiseaseseverityandincludescomprehensivedefinitionsofpancreaticandperipancreaticcollections.Therearealsomorecompletedefinitionsoflocalandsystemiccomplications.DiseaseDefinitions:TheRevisedAtlantaClassification

TheAtlantaClassificationsystemwasdevelopedataconsensusconferencein1992toestablishstandarddefinitionsforclassificationofacutepancreatitis.

最新修订版的亚特兰大分类标准提供了一个更加详细的分类标准，它着重于疾病的严重程度，及包括胰腺和胰周液体聚集的综合定义，而有更加完整的局部及系统性并发症的定义。12.BanksPA,BollenTL,DervenisC,etal.Classificationofacutepancreatitis—2012:revisionoftheAtlantaclassificationanddefinitionsbyinternationalconsensus.Gut2013;62:102–111.13.MarshallJC,CookDJ,ChristouNV,etal.Multipleorgandysfunctionscore:areliabledescriptorofacomplexclinicaloutcome.CritCareMed1995;23:1638–1652.123DefinitionofLocalComplications

局部并发症的定义

DefinitionofSystemicComplicationsandOrganFailure

全身并发症及器官衰竭的定义DefinitionofSeverity严重程度分类4RolesofAdvancedImagingTechniques

影像学的作用

Diagnosis间质水肿性胰腺炎DefinitionofLocalComplications急性胰腺炎急性胰周液体积聚（APFC）胰腺假性囊肿坏死性胰腺炎急性坏死物积聚（ANC）包裹性坏死（WON）

Avarietyoflocalcomplicationshavebeendelineated.Interstitialpancreatitisinvolvesacutecollectionofperipancreaticfluid（ACPF）andformationofpancreaticpseudocysts.

间质水肿性胰腺炎涉及急性胰周液体积聚和胰腺假性囊肿的形成

APFCdevelopduringtheearlyphase早期ofinterstitialpancreatitis.Theyarehomogeneous

inappearancewithoutawell-definedwall,usuallyremainsterile,andfrequentlyresolve

spontaneously(FigureA).

急性胰周液体积聚（APFC）发生胰腺炎病程早期，渗出液均匀地而边界模糊地分布于胰周，通常是无菌的，可以自行吸收Ifanacuteperipancreaticfluidcollectiondoesnotresolvespontaneously,itcoulddevelopintoapseudocystwithawelldefinedinflammatorywallthatcontainsfluidwithverylittle,ifany,solidmaterial(FigureB).

如果一旦胰周积液不能自行吸收，它将可能发展为有完整炎症性包膜容纳少量渗出液及极少量坏死组织的假性囊肿(发生AP后4周)间质水肿性胰腺炎Figure(A)Interstitialpancreatitiswithacuteperipancreaticfluidcollection.Peripancreaticfluidcollection(arrows)ispoorlydefinedwithhomogeneousfluiddensity.Figure(B)Resolvinginterstitialpancreatitiswithpseudocyst.Apseudocyst(arrow)istypicallyaroundorovalencapsulatedcollectionwithhomogeneousfluiddensity.急性胰周液体积聚（APFC）胰腺假性囊肿

Necrotizingpancreatitisinvolvesacutecollectionofnecrosisandwalled-offnecrosis.坏死性胰腺炎包括急性坏死物积聚（ANC）及包裹性坏死（WON）。

Anacutenecroticcollectionreferstothepresenceofnecrotictissueinvolvingpancreaticparenchymaandperipancreatictissues

(Figure2).Thesecollectionscanbesterileorinfected.Ifinfected,theyarecalledinfectednecrosis.急性坏死物积聚（ANC）指的是胰腺实质及胰周组织的坏死（如表格2），坏死物的积聚可是无菌性和感染性，其中感染性的又叫感染坏死。After4ormoreweeks,anacutenecroticcollectioncanbecomesmallerbutrarelydisappearscompletelyandusuallyevolvesintowalled-offnecrosis.Walled-offnecrosishasawell-definedinflammatorywallthatcontainsvaryingamountsoffluidandnecroticdebris(Figure3).在4周及之后，急性坏死物的积聚逐渐变小，但很少有被完全吸收，通常发展为有炎症性包膜容纳混合大量渗出液及少量坏死物碎片的包裹性坏死（WON）（如表格3）。Figure2.Pancreaticandperipancreaticnecrosis.Thisimageshowsanacutenecroticcollectioninvolvingboththepancreas(largearrow)andperipancreatictissue.

Figure3.Walled-offpancreaticnecrosisisanencapsulatedcollectionofnecrosis.Thistypeofcollectiontypicallyforms4to6weeksafterdiseaseonset.Thisimageshowspancreaticandperipancreaticnecrosis.坏死性胰腺炎急性坏死物积聚（ANC）包裹性坏死（WON）DefinitionofSystemicComplicationsandOrganFailureIntherevisedAtlantaClassification,systemiccomplicationsaredefinedasexacerbationsofpreexistingcomorbiditiessuchaschroniclungdisease,chronicliverdisease,orcongestiveheartfailure,recognizingthefailureofrespiratory,cardiovascular,andrenalorgansystems.在修订版的亚特兰大分类标准，全身并发症被定义为，先前存在的疾病诸如慢性肺部疾病、慢性肝病、充血性心力衰竭等的突然恶化，这些被认为是呼吸系统、心血管系统、肾脏功能系统的损害加重而衰竭。DefinitionofSystemicComplicationsandOrganFailure

ThescoringsystemthathasbeenchosentocharacterizeorganfailureisthemodifiedMarshallscoringsystem.ThemodifiedMarshallsystemclassifiesdiseaseseverityonascalefrom0to4,sothattheoverallevaluation

oforgandysfunctioncanbemorecompletelydelineatedandcharacterizedovertime.Inthissystem,organfailureisdefinedbyascoreof≥2foroneormoreoftheseorgansystems.改良的马歇尔评分系统用于器官衰竭的评分，该评分系统将急性胰腺炎的严重程度分为0—4级，以至于更能清晰及特征性地对器官功能障碍发展进行综合评价。在该评分系统中，器官衰竭定义为有任何1个及多个器官功能评分≥

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

isdefinedasacutepancreatitisnotassociatedwithorganfailure,localorsystemiccomplications.无器官衰竭、无局部或全身并发症MSAPpresenceoftransientorganfailure(presentfor<48hours),localorsystemiccomplications.一过性器官衰竭（<48h）伴有局部或全身并发症SAPpresenceofpersistentorganfailure(presentfor>48hours).Mostpatientswithpersistentorganfailurehavepancreaticnecrosis.持续性器官衰竭（>48h）,多伴有胰腺坏死Mostpatientswithmildacutepancreatitisdonotrequirepancreaticimaginganalysisandareusuallydischargedwithin3to5daysofonsetofillness.

轻型急性胰腺炎患者无需影像学检查，住院时间通常为3-5天

Patientswithmoderatelysevereacutepancreatitisfrequentlyrequireextendedhospitalizationbuthavelowermortalityratesthanpatientswithsevereacutepancreatitis.

中度重症急性胰腺炎需延长住院时间，但病死率低于重症急性胰腺炎Ameta-analysisfoundpatientswithsevereacutepancreatitiswithpersistentorganfailurehavea30%mortalityrate;theriskofin-hospitaldeathdoubleswhentheyhavepersistentorganfailureandinfectednecrosis.

重症急性胰腺炎有高达30%的病死率，当出现持续性器官功能衰竭和感染坏死时，住院期间死亡的风险成倍增加。15.PetrovMS,ShanbhagS,ChakrabortyM,etal.Organfailureandinfectionofpancreaticnecrosisasdeterminantsofmortalityinpatientswithacutepancreatitis.Gastroenterology2010;139:813–820.RolesofAdvancedImagingTechniquesTheroleofCTinassessingpatientswithacutepancreatitishaschangedwithtime.CT的作用是用于评价急性胰腺炎发病及治疗各阶段的变化Acontrast-enhancedCTscanobtainedwithinthefirstseveraldaysofillnesscannotbeusedtodeterminewhetherapatienthasnecrotizingorsevereinterstitialpancreatitis.Thismightbebecauseintrapancreaticfluidcausesheterogeneousenhancement,whichcanindicatenecrosis.在发病的前几天，不能通过CT检查判断出胰腺坏死的存在及其范围，这可能是由于胰腺内液体渗出导致了CT的不均匀增强。

Overaperiodofseveraldays,thefluidcanbereabsorbedsuchthatasubsequentCTscanclearlyshowstheabsenceofnecrosis.Assuch,patientsshouldnotbeevaluatedbyCTwithinafewdaysaftertheonsetofdiseasetoestablishthepresenceorextentofpancreaticnecrosis.胰腺积液被重吸收后，后来的CT检查才能够区分液体积聚或胰腺坏死范围。

Thebestuseofanearly-stageCTscanistoconfirmadiagnosisofacutepancreatitiswhentheclinicalsituation

isunclear.

发病早期行CT检查仅能用于诊断不明时，以确诊急性胰腺炎。ThebestuseofaCTscanafterthefirst5to7daysistoevaluatethepresenceoflocalcomplicationsinpatientswithmoderatelysevereorseverepancreatitistoguideongoingcare.

发病的第一个5-7天后行CT检查最大好处，用以评价中度重症急性胰腺炎或重症急性胰腺炎病人的局部并发症，并指导治疗。MRCPhasbecomeausefulprocedureforidentifyingretainedcommonbileductstones.

SelectiveuseofMRCPcanreducetheneedforERCPforpatientswithsuspectedgallstonepancreatitis.

MRCP对胆管结石敏感，能够减少因怀疑为胆源性胰腺炎而行ERCP检查。MRI

ishelpfulindistinguishingwalled-offnecrosisfromapseudocyst.Forexample,inwalled-offnecrosis,therearevariableamountsoffluidandsoliddebristhatcanbevisualizedusingT2-weightedimaging.MRI能用于鉴别是包裹性坏死（WON）或是胰腺假性囊肿，因为T2加权像能很直观地看出含有大量渗液体及固体坏死物的包裹性坏死。

Endoscopicultrasonographyisahighlysensitivetestfordetectingcholelithiasisandcholedocholithiasis.19ItcouldbeanalternativetoMRCP,whichhaslimitedaccuracyfordetectingsmallergallstonesorsludge.超声内镜对胆石病高度敏感，可以代替对细小结石或淤泥样胆汁不敏感的MRCP检查。123PrognosticFactors预后因素RiskandPrognosticFactorsClinicalscoringsystems

临床系统性评分Riskfactors危险因素Riskfactors

AgeObesity

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

Theinitial12to24hoursofhospitalizationiscriticalduringpatientmanagement,becausethehighestincidenceoforgandysfunctionoccursduringthisperiod.

发病第12-24h是临床处理非常重要，器官功能障碍多发生于这个时段。Anumberofclinicalscoringsystemsandbiomarkers

havebeendevelopedtofacilitateriskstratification

duringthisphase.WhereaspreviousscoringsystemssuchastheRansonorImrie–Glasgowscoresrequired48hourstocomplete,2scoringsystemswererecentlydevelopedandinvolveasimplifiedapproachthatcanbeperformedduringthefirst24hoursofhospitalization——TheBedsideIndexofSeverityinAcutePancreatitis.

Ranson评分系统、Imrie–Glasgow评分系统对疾病的危险分层评分滞后，最新的AP严重程度床旁指数（BISAP）可在发病24h内完成。26.HarrisonDA,D’AmicoG,SingerM.Casemix,outcome,andactivityforadmissionstoUKcriticalcareunitswithsevereacutepancreatitis:asecondaryanalysisoftheICNARCCaseMixProgrammeDatabase.CritCare2007;11(Suppl1):S1.27.WuBU,ConwellDL.Updateinacutepancreatitis.CurrGastroenterolRep2010;12:83–90.ClinicalscoringsystemsAP严重程度床旁指数BUN>25mg/dl(8.9mmol/L)Impairedmentalstatus精神状态受损SIRSage60yearsorolderpleuraleffusion胸腔积液Score>2within24hoursisassociatedwitha7-foldincreaseinriskoforganfailureand10-foldincreaseinriskofmortality.发病24小时内分数>2分，发生器官衰竭的风险增加7倍，死亡的风险增加10倍。

Anotherscoringsystem,theHarmlessAcutePancreatitisScore,usesadifferentapproachtoriskstratification,identifyingpatientsatthetimeofadmissionwhoareunlikelytoexperiencecomplicationsrelatedtoacutepancreatitis.Specifically,patientswithanormalhematocrit

andnormalserumlevelofcreatininewithoutreboundtenderness

orguarding,areunlikelytodevelopseverepancreatitis(positivepredictivevalueof98%).

轻症急性胰腺炎评分（HAPS）则注重于在入院时不会发生与急性胰腺炎相关并发症的病人的评分，特别是Hct、Cre正常，无反跳痛体征的病人，将不再发展为重症急性胰腺炎（阳性率高达98%）。Withrespecttoscoringsystems,themostwidelyvalidatedremainstheAcutePhysiologyandChronicHealthExaminationIIscore.Thesescoringsystemshavecomparablelevelsofoverallaccuracy.

最受到广泛认同的评分系统为急性生理功能和慢性健康状况评分系统

(APACHEII)，

这些评分系统具有相当的水平的整体精度。PrognosticFactorsAdditionalapproacheshavebeendevelopedtomonitor

diseaseprogression.Parametersthatareeasytodetermineandhavebeenvalidatedfortheirabilitytodeterminediseaseactivity

includethepresenceofSIRS,levelofBUNorCr,andhematocrit.

SIRS、尿素氮水平、肌酐水平、红细胞压积的参数，用于监测疾病的进展。

ProspectivestudieshaveshownthatthelevelofBUNatadmissionandduringtheinitial24hoursofhospitalizationisastrongprognosticfactor.Forexample,patientswithalevelofBUNatadmission>20mg/dLthatincreasedduringtheinitial24hourshave9%to20%mortality.Bycontrast,patientswithanincreasedlevelofBUNatadmissionthatdecreasedatleast5mg/dLwithin24hourshave0%to3%mortality.入院时及入院后24小时内BUN水平的高低是一个非常重要的预后因素。例如，入院时患者BUN>20mg/dL（7.14mmol/L），在发病最初24小时内可增加9%-20%的病死率，相反，高BUN水平在入院后24小时内至少下降5mg/dL(1.8mmol/L)则有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.全身炎症反应综合征(SIRS)

AnincreasingnumberofSIRScriteriaduringtheinitial24hoursofhospitalizationincreasestheriskofpersistentorganfailureandnecrosisaswellasmortality.PatientswithpersistentSIRS(beyond48hours)have11%to25%mortality.SIRS增加持续性器官衰竭、胰腺坏死、病死率（11-25%）的风险。2ormoreofthefollowingcriteriaT>38.3°C

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

AserumlevelofCr>1.8mg/dL（159umol/L）withinthefirst24hoursofhospitalizationisassociatedwitha35-foldincreasedriskofdevelopmentofpancreaticnecrosis.ApersistentincreaseinHCT>44%hasalsobeenshowntoincreasetheriskofnecrosisandorganfailure.

研究表明，在发病的最初的24小时内血肌酐>1.8mg/dL，发展为胰腺坏死的风险增加35倍红细胞压积持续>44%也同样增加了胰腺坏死及器官衰竭的风险。33.MuddanaV,WhitcombDC,KhalidA,etal.Elevatedserumcreatinineasamarkerofpancreaticnecrosisinacutepancreatitis.AmJGastroenterol2009;104:164–170.34.BrownA,OravJ,BanksPA.Hemoconcentrationisanearlymarkerfororganfailureandnecrotizingpancreatitis.Pancreas2000;20:367–372.Treatment123InitialResuscitationandManagement早期治疗

ManagementofLocalComplications

局部并发症的治疗ManagementofExtrapancreaticComplications

胰腺外并发症的治疗

4SpecialConsiderationsBasedonEtiology对因治疗

InitialResuscitationandManagement

Aggressivevolumeresuscitationhasbeenacornerstoneoftherapy,basedonstudiesinanimalmodelsandobservationaldatafromclinicalstudies.However,approachestofluidresuscitationrequireoptimization.

Under-resuscitationduringtheearlyphaseofacutepancreatitishasbeenassociatedwithincreasedriskofnecrosisandmortality.Incontrast,over-resuscitationcanleadtocomplicationssuchaspulmonarysequestration（肺隔离症）.

积极的容量复苏已经成为治疗的里程碑，疾病早期液体复苏的容量不足会增加胰腺坏死及死亡的风险，相反，如过度补液可能导致诸如肺隔离症的并发症，制定最优化液体复苏方案很重要。44.de-MadariaE,Soler-SalaG,Sanchez-PayaJ,etal.Influenceoffluidtherapyontheprognosisofacutepancreatitis: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，在急诊科按20mL/kg进行开始补液，随后按3mL·kg-1·h-1的速度进行持续补液，每间隔6-8小时进行病情评估（包括生命体征、血氧饱和度、身体状况）：如果BUN水平没有下降，需反复地补液；相反，如果BUN水平下降了，则补液速度减少至1.5mL·kg-1·h-1，最后证明此治疗方案在急诊治疗中是安全可行的。

Ingeneral,patientsundergoingvolumeresuscitationshouldhavetheheadofthebedelevated,undergocontinuouspulseoximetry,andreceivesupplementaloxygen.

患者进行液体复苏时，需抬高床头，持续的血氧饱和度监测及吸氧。

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

与用生理盐水复苏相比，乳酸林格氏液能减少80%的SIRS发生，乳酸林格氏液对维持酸碱平衡有积极的影响，更加适用于早期的液体复苏，

高钙血症患者慎用。

Volumeexpansionwithcolloidhasnotbeenshowntobemoreeffectivethanwithcrystalloidsincriticallyillpatients.

对于危重病人，使用胶体液扩容的益处并不多于使用晶体液。NO.2IndicationsforIntensiveCare

重症监护的适应症Respiratoryfailureisthemostcommonformoforgandysfunction.Patientswithsignsofrespiratoryfailureorhypotensionthatfailtorespon