IPC預防婦科腫瘤術后靜脈栓

1/1IPC預防婦科腫瘤術后靜脈栓IPC預防婦科腫瘤術后靜脈血栓PreventionofPostoperativeVenousThromboembolismbyExternalPneumaticCalfCompressioninPatientsWithGynecologicMalignancyDANIELL.CLARKE-PEARSON,MD,INGRIDS.SYNAN,RN,WANDAM.HINSHAW,MS,R.EDWARDCOLEMAN,MD,ANDWILLIAMT.CREASMAN,MDOnehundredsevenpatientsundergoingmajorsurgeryforgynecologicmalignancyparticipatedinacontrolledtrialevaluatingtheeffectivenessofpneumaticcalfcompressioninthepreventionofpostoperativedeepvenousthrombosisandpulmonaryembolism.Externalpneumaticcalfcompressionwasappliedintraoperativelyandforfivepostoperativedays.Allpatientswereprospectivelyscreenedfordeepvenousthrombosiswithimpedanceplethysmographyand125I-fibrinogenlegcounting.Deepvenousthrombosisand/orpulmonaryemboliweredetectedin18of52controlgrouppatients(34.6%)whereasinsevenof55(12.7%)ofthosetreatedwithexternalpneumaticcalfcompression(P.005).Externalpneumaticcalfcompressionwasmosteffectiveduringthefirstfivedayspostoperativelyandalsoreducedtheincidenceofdeepvenousthrombosisinpatientsathighestrisk.Whenappliedduringsurgeryandforfivedayspostoperatively,externalpneumaticcalfcompressionsignificantlyreducestheincidenceofpostoperativevenousthrombosis.(ObstetGynecol63:92,1984)Thepreventionofpulmonaryembolianddeepvenousthrombosismustbeanimportanteffortofthepelvicsurgeoncaringforthehigh-riskgroupofpatientswhohavepelvicmalignancies.Overthepastdecadeinvestigatorshavefoundlow-doseheparintopreventfatalpulmonaryemboli1and125I-fibrinogen-detectedlegthrombi.2-4Thesestudieshaveledtoageneralrecommendationoflow-doseheparinprophylaxisforhigh-riskgroups.5Low-doseheparinhasbeenfoundtobeineffectiveinpreventingvenousthrombosisandpulmonaryemboliaftermajorsurgeryforgynecologicmalignancies?6.7Anotherprophylacticmethod,externalpneumaticcalfcompression,hasalsobeendemonstratedtoreducelegthrombi,8-14Ascomparedwithbleedingcomplicationsassociatedwithlowdoseheparin,pneumaticcalfcompressionhasnosignificantsideeffects.1.15Thepresentstudywasundertakentoevaluatetheefficacyofexternalpneumaticcalfcompressioninpreventionofdeepvenousthrombosisandpulmonaryemboliinpatientsundergoingmajorsurgeryforgynecologicmalignancies.MaterialsandPatientsPatientsadmittedtotheDivisionofGynecologicOncology,DukeUniversityMedicalCenter,whoweretoundergomajorsurgeryforknownorpresumedgynecologicmalignancieswereeligibletoenterthestudyprotocol.Excludedfromstudyentrywerepatientswhohadreceivedanticoagulants(heparinorsodiumwarfarin)withinsixweeksofsurgery,orpatientswithacutevenousthromboemboliccomplications.Afterobtaininginformedwrittenconsent,amedicalhistorywastakenandaphysicalexaminationperformedwithparticularemphasisonpossiblethromboembolicriskfactors:age,race,stageandsiteofmalignancy,concur-rentmedicalillnesses,apasthistoryofdeepvenousthrombosisorpulmonaryembolus,andcurrentmedications.Physicalfindingsofvenousvaricosities,venousstasischanges,weight,andheightwererecord-ed.Usinga1:1allocationscheme,patientswererandomlyassignedtoeitheracontrolgrouporexternalpneumaticcalfcompressiongroup.Thecontrolgroupreceivednospecificthromboembolicprophylaxis.Patientsassignedtoeternalpneumaticcalfcompressionhadthepneumaticsleevesappliedatthetimeofinductionofanesthesiaintheoperatingroom.Externalpneumaticcalfcompressionwasdeliveredbyapneumaticcompressor(Venodyne,Lyne-Nicholson,Inc,NeedhamHeights,MA),whichcycledtoachieveapressureof40to45mmHgdeliveredtosleevesemcompassingthecalvesofthepatients’legs.Durationofcompressionwas12secondsofeveryminute.Calfcompressionwasmaintainedintraoperativelyandthroughoutthefirstfivepostoperativedays.Thecompressionsleeveswereremovedonlywhenthepatientwasoutofbedtoambulate.Bothgroupsofpatientshadthefootoftheirbedselevated20to30degreesandwereencouragedtoambulateintheimmediatepost-operativeperiod.FromtheDivisionofGynecologicOncology,DepartmentofObstetricsandGynecology,theComprehensiveCancerCenterDatabase,andtheDepartmentofRadiology,DukeUniversityMedicalCenter,Durham,NorthCarolina.Becauseofthenatureofthetherapeuticinterventionstudied,thistrialcouldnotbecarriedoutinadouble-blindfashion.Inaddition,theclinicaldiagnosisofdeepvenousthrombosisorpulmonaryembolismisoftenerroneous.Wethereforebasedthediagnosisofthromboembolionobjectivenoninvasiveandinvasivediagnosticmethods.Nopatientwasconsideredtohavedevelopedthromboembolusbasedonclinicalimpressionalone.Surveillanceforclinicallyoccultdeepvenousthrombosiswasconductedby125l-fibrinogencountingandimpedanceplethysmography,125l-fibrinogenlegcountingwasperformedattwo-inchintervalsoverthedeepveinsofthethighandcalfasdescribedbyFlancetal16andKakkar.17Preoperatively,fourdropsofsuper-saturatedpotassiumiodidewereadministeredorallyor100mgofsodiumiodidegivenintravenouslytoblockthyroiduptakeof125iodine.Immediatelypostoperatively,intherecoveryroom,125l-fibrinogen(100uCi)wasinjectedintravenously.Onthefirstpostoperativeday,12to24hoursafter125I-fibrinogenadministration,theconditionofthepatients’legswasassessed.Allcountswerenormalizedtotheprecordiacount.125I-fibrinogenwascountedonthefirstpostoperativedayandonalternatedaysuntilthepatientwasdischargedfromthehospital.Ifanareaofincreasedactivitysuggestiveofthrombosiswasencountered,125[fibrinogencountingwasrepeateddaily.Thediagnosisofdeepveinthrombosiswasmadewhenthe125iodinecountswereincreasedmorethan20%ewertheadjacentscansite,overthesamesiteonthecontralateralleg,oroverthepreviousday’scountatthesamelocationwithpersistenceoftheincreasedcountfortwoconsecutivedays.Ifthefibrinogenscansuggestedthrombusformationinthepoplitealregionorthigh,ascendingcontrast,venographywasper-formedtoconfirmdeepvenousthrombosis.125I-fibrin-ogen-detectedthrombosisinthecalfwasfolloweddailywith125I-fibrinogencountingandimpedanceplethysmography.Ifthe125l-fibrinogen-detectedthrombuspropagatedtothepoplitelregionoriftheimpedanceplethysmogrambecameabnormal,contrastvenographywasobtained.AscendingcontrastvenographywasperformedusingthetechniquedescribedbyRabinovandPaulin.18Impedanceplethysmography(IPG-200,StimTechProductsbyCodmanandSchurtleff,Inc.,Hingham,MA)wasperformedpreoperativelyandonthefifthpostoperativedayusingthemethodsdescribedbyWheeleretal19andthepresentauthors?Ifanabnormalimpedanceplethysmogramwasobtained,venographywasusedtoconfirmtheoccurrenceanddocumentthelocationandextentofdeepveinthrombosis.Patientswithclinicalsignsandsymptomsofdeepveinthrombosisorpulmonaryemboliwereevaluatedwithvenography,ventilationperfusionlungscanning,and/orpulmonaryarteriographyaswasappropriatetoconfirmthediagnosis.Patientswithnormal125l-fibrinogenstudies,impedanceplethysmography,andnoclinicalevidenceofthromboemboliccomplicationswereassignedafinaldiagnosisofnothromboembolism.Thosepatientswith125I-fibrinogen-detectedcalfthrombithatdidnotpropagatetothepoplitealregionormoreproximallywereclassifiedashavingcalfveinthrombosis.Allotherpatientswitheitherabnormal125l-fibrinogencountingoranabnormalimpedanceplethysmogramunderwentvenographytoachieveafinaldiagnosis.Patientswithsignsorsymptomsofpulmonaryemboliandthosewithproximaldeepveinthrombosisunderwentventilationperfusionlungscanning.ThediagnosisofpulmonaryembolismwasgiventothosepatientswithahighprobabilityscanasdefinedbyBielloetal.TMPatientswithindeterminantlungscansunderwentpulmonaryarteriographyandreceivedafinaldiagnosisbasedonangiographicfindings.PatientswithnormalorIowprobabilitylungscansreceiveddiagnosesofnopulmonaryembolism.Interpre-tationofvenography,lungscans,andpulmonaryarteriographywasmadebytworadiologistsunawareofthepatient’smethodOfthromboembolismprophylaxisorresultsofnoninvasivesurveillance.Allpatientswerefollowedclinicallyforatleast42dayspostoperatively.Afterhospitaldischarge,symptomssuggestiveofdeepvenousthrombosisorpulmonaryembolismwereevaluatedbyappropriatenoninvasiveandinvasivestudies,asdescribedabove,toachieveadiagnosis.Anydeepvenousthrombosisorpulmonaryembolismdetectedwithinthefirst42dayspostoperativelywasincludedasapostoperativethromboembolus.Statisticalmethodsusedcontingencytableanalysesandassociated~2statisticstomeasuretheeffectsofvariousriskfactorsontheincidenceofthromboembolism.Amultiplelogisticregressionanalysiswasusedtotestfortreatmentdifferences,adjustingfortheriskfactorsidentified.Table1.SummaryofPatientsExcludedAfterStudyEntryTreatmentgroupExternalpneumaticcalfcompressionReasonexcludedfromstudyControlSurgerycanceled23Impedanceplethysmographyabnormal11preoperativelyRefusedfurther125I-fibrinogenscans01EPCremovedafter1daybecauseof1equipmentmalfunctionTotal45EPC=ExternalpneumaticcalfcompressionResultsOnehundredsixteenpatientswereenteredintothestudyprotocol.Ninepatientswereexcludedafterrandomization(fivepatientsfromthecontrolgroupandfourfromtheexternalpneumaticcalfcompressiongroup).ThespecificreasonsforexclusionareshowninTable1.Noneofthesepatientssubsequentlydevelopeddeepvenousthrombosisorpulmonaryemboli.Onehundredsevenpatientscompletedthestudyprotocol,with52inthecontrolgroupand55intheexternalpneumaticcompressiongroup.Table2.Age,Race,andPhysicalFindingsofPatientsintheControlandExternalPneumaticTreatmentGroupsTreatmentgroupExternalpneumaticcalfcom-Controlpression(N=52)(N=55)Age(yr)2O-293l30-392540-499850-59101760--69191670+98Mean58.256.1RaceWhite3538Black1614Other13PhysicalfindingsVaricoseveinsMild712Moderate46Severe22Venousstasischangesinlegs56Meanweight(kg)71.869.2Table3.OrganSiteandClinicalStageofMalignancyintheControlandExternalPneumaticCompressionTreatmentGroupsTreatmentgroupExternalPneumaticControlCalfcompression(N=52)(N=55)OrgansiteUterus2315Ovary1219Cervix1218Vulva53ClinicalstageBenignorintraepithelial96I2228Il47III137IV24Recurrent23Deepvenousthrombosisand/orpulmonaryemboluswasdiagnosedin18of52(34.6%)controlgrouppatientsandinsevenof55(12.7%)externalpneumaticcompressionpatients(P.05).Thirteenof52controlpatients(25%)andfourof55(7.3%)ofexternalpneumaticcalfcompressionpatientsdevelopedthrombiinthecalfveinsonly.Deepvenousthrombosiswasfoundinthepoplitealregionormoreproximallyinfourcontrolgrouppatients(7.7%)andinoneexternalpneumaticcalfcompressionpatient(1.8%).Allcalfandproximaldeepveinthrombiweredetectedbeforethedevelopmentofclinicalsymptoms.Therewasonepulmonaryembolusinthecontrolgroupandtwopulmonaryemboliintheexternalpneumaticcalfcompressiongroup.Therewerenopostoperativedeaths.Riskfactors15reviouslyreportedtobeassociatedwiththromboemboliccomplications22.23weredistributedbetweenthecontrolandtheexternalpneumaticcompressiongroupsasshowninTables2to5.Examinationofthefactorsitemizedinthesetablesdemonstratesnoappreciabledifference(P.05)inthedistributionofanyparameterbetweenthetwostudygroups.Thesepotentialriskfactorswerefurtherexaminedfortheireffectsontheincidenceofdeepvenousthrombosisandpulmonaryemboli,bothaloneandinconjunctionthroughthelogisticregressionanalysis.Ageover60(P.05),varicoseveins(P.01),andadvancedclinicalstageofdisease(P.05)werefoundtobeindependentlyassociatedwithanincreasedincidenceofvenousthrombosisandpulmonaryembolism(Table6).Table4.CurrentandPastMedicalProblemsandCurrentMedicationsUsedbyPatientsinStudyGroupsTreatmentgroupExternalpneumaticControlcalfcompressionCurrentorpastmedicalproblemsHistoryofdeepveinthrombosis24Historyofpulmonaryembolus02Hypertension2921Diabetesmellitus104Congestiveheartfailure(compensated)33HistoryofmyocardialinfarctI1DrugsAspirin2330Digoxin34Antihypertensive2420Insulin63Estrogensororalcontraceptives31TheincidenceofdeepvenousthrombosisandpulmonaryembolismrelatedtovarioussurgicalproceduresisshowninTable7.Whenadjustmentismadeforotherriskfactors,nosurgicalprocedurewasmoreoftenassociatedwithvenousthrombosisorpulmonaryembolism.Externalpneumaticcompressionresultedinareductionintheincidenceofdeepvenousthrombosisascomparedwiththecontroltreatment,afteradjustmentfortheseimportantprognosticfactors(P.005).ThepostoperativedayonwhichthethromboemboliccomplicationwasdiagnosedinthetwostudygroupsisshowninFigure1.Themediantimeofoccurrencewaspostoperativeday3inthecontrolgroupandday4intheexternalpneumaticcompressiongroup.Duringthefirstfivepostoperativedays,fourof55externalpneumaticcalfcompressionpatientsdevelopedathromboemboliccomplication(7.3%),whileduringthesametimeperiod13of52controlgrouppatients(25%)sufferedathromboemboliccomplication(P.02).Ofpatientswithnothromboemboliccomplicationduringthefirstfivepostoperativedays,threeof51externalpneumaticcompressionpatients(5.9%)andfiveof39controlgrouppatients(12.8%)subsequentlydevelopedathromboemboliccomplication(P=.08).Nosignificantsideeffectsfromtheexternalpneumaticcompressionequipmentwerefoundexceptforperspirationbeneaththecalfsleeve.DiscussionVenousthromboemboliccomplicationsareoneoftheleadingcausesofmorbidityandmortalityfollowingmajorsurgicalprocedures.Theirsignificanceisevengreateringroupsofhigh-riskpatientssuchasthoseundergoingsurgeryforpelvicmalignancies.Withtheadventofsensitivenoninvasivediagnosticmethodssuchas125l-fibrinogencountingandimpedanceplethysmography,thenaturalhistoryandincidenceofdeepvenousthrombosishasbeenmoreclearlydelineated.Theincidenceofdeepvenousthrombosisandpulmonaryemboliinthe52untreatedcontrolgrouppatientsof35%issimilartoapriorprospectivestudyusing125l-fibrinogencountingin45gynecologiconcologypatientsinGreatBritain.24However,theincidenceofthromboembolismmayvarywithtime,eveninsimilargroupsofpatients.Forexample,apreviousprospectiverandomizedclinicaltrialfromtheauthors’institutionfounda12%incidenceofthromboemboliccomplicationsin97controlpatientsundergoingsimilarsurgeryforgynecologicmalignancies.7ThevaryingincidenceofthromboembolismhasalsobeenreportedbyLittleandBinns25andLawrenceetal.26Prospectivestudieswithconcurrentcontrolgroupsthusallowamoredefinitiveevaluationoftherapeuticmeasures.Theuseoflow-doseheparinhasbeenfoundtobeeffectiveinthepreventionoffatalpulmonaryemboli1and125I-fibrinogenscandetectedthrombosisingeneralsurgerypatients2-4andintwostudiesofpatientsTable5.OperativeProcedure,AnesthesiaTime,andEstimatedOperativeBloodLossintheControlandExternalPneumaticCompressionTreatmentGroupsTreatmentgroupExternalpneumaticcalfcompres-ControlsionOperation(N=52)(N=551Vaginalhysterectomy20TotalabdominalhysterectomyzBSO1413Totalabdominalhysterectomyandse-1212lectivenodes*Exploratorylaparotomy+intestinal916surgeryRadicalhysterectomyandP+PA1012lymphadenectomyRadicalvulvectomyinguinallymph-52adenectomyMeananesthesiatime(min)242227Range85-59090-480Medianestimatedbloodloss(ml)575450Range50-270050-4000BSO=bilateralsalpingo-oophorectomy;P+PAlymphadenectomy=pelvicandparaaorticlymphadenectomy.Nodes=selectivepelvicandparaaorticlymphadenectomy.Table6.IncidenceofThromboembolismintheControlandExternalPneumaticTreatmentGroups.RelatedloPreoperaliveFactorsSignificantlyAssociatedWithPostoperativeThromboembolismTreatmentgroupControlExternalpneumaticcallcompression(N=52)(N=55)Totalno.PatientswithTEPatientswithTEOfpatientsNo.PercentTotalno.ofpatientsNo.Percent:Age(yr)6024312.53139.760281553.624416.7:VaricoseveinsNone391230.83538.6Mild7228.61218.3Moderate42506116.7Severe2210022100StageofdiseaseBenignorintra-9006116.7epithelial122522.728310.7II42507228.61II1386l.5700IV22100.0400Recurrent2150.03133.3TE=thromboembolism.undergoinggynecologicsurgeryforbenigndisease.27,2sHowever,aretrospectivereviewandaprospectivecontrolledtrialhavefoundlow-doseheparinnottobeofanybenefitinpreventingdeepvenousthrombosisorpulmonaryemboliinpatientswithgynecologicmalignancy.6’7Therefore,thepresentauthorsunder-tookthe’currentstudytoevaluatewhetherornotanothertreatmentmethod,externalpneumaticcalfcompression,mightreducetheincidenceofthromboemboliccomplications.Overthepastdecade,variousmethodsofexternalpneumaticcalfcompressionhavebeenevaluatedandfoundtobeeffectiveinpreventingpostoperativedeepvenousthrombosis,s-m4Thepro-posedmechanismofprophylaxisisthereductionofTable7.IncidenceofThromboembolismintheControlandExternalPneumaticTreatmentGroupstoSurgicalProcedureTreatmentgroupControlExternalpneumaticcalfcompression(N=52)(N=55)Totalno.PatientswithTETotalno.PatientswithTEofpatientsNo.PercentofpatientsNo.PercentSurgicalprocedureVaginalhysterectomy2000Totalabdominalhysterecto-14428.61317.7my+BSOTotalabdominalhysterecto-12541.71218.3myandselectivenodes*Exploratorylaparotomy+9444.41616.3intestinalsurgeryRadicalhysterectomyandP1011012216.7+PAlymphadenectomyRadicalvulvectomyinguinal548022100lymphadenectomyBSO=bilateralsalpingo-oophorectomy;P+PAlymphadenectomy=pelvicandparaaorticlymphadenectomy.*Nodes=selectivepelvicandparaaorticlymphadenectomy.Figure1.Dayofdetectionofspecificthromboemboliccomplicationincontrolandexternalpneumaticcompressiongroups.Openboxesindicatecalfthrombus;closedboxesindicatepulmonaryembolus;hatchedboxesindicateproximaldeepveinthrombus.Venousstasis,particularlyinthecalfveinsofthelegs.Electromagneticflowstudieshavedemonstratedthatthepulsatilepressure‘deliveredbythepneumaticpumpaugmentsvenousflowmeasuredinthefemoralvein29andthevenacava.3~Intermittentvenouscompressionalsoappearstoincreaseapatient’sownfibrinolyticactivity,31.32whichmayalsocontributetothereductionofvenousthrombosis.Externalpneumaticcalfcompressionreducedtheincidenceofdeepvenousthrombosisthreefoldascomparedwithaconcurrentcontrolgroup.Theseresultsaresimilartoothercontrolledstudiesofpneumaticcalfcompressioningeneralsurgical,neurosurgical,urologic,andorthopedicsurgerypatients,5,4Themajorbenefitofexternalpneumaticcompressionwasinreducingtheoccurrenceofcalfveinthrombi.Whilenotall125I-fibrinogen-detectedcalfveinthrombileadtoproximalextensionorembolization,Kakkaretal33andNicholaidesetal34foundthatmostsignificantthrombiandpulmonaryemboliinitiallystartinthecalfveins.Thepreventionofcalfveinthrombosisshouldthere-foreleadtoareductioninproximalthrombusextensionandsubsequentembolization.Indeed,therewasonlyoneproximaldeepveinthrombosisfoundintheexternalpneumaticcompressiongroup,whilefouroccurredinthecontrolgroup.Theincidenceofpulmonaryemboliinthisstudywassolowastoprecludefurtherevaluationwithoutalargermulticentertrial.Thedurationofpneumaticcompressionpostoperativelywaschosenbasedontheunderstandingthatmostthromboemboliccomplicationsoriginateintheoperativeortheearlypostoperativeperiod33’34andthatmostpatientsarealmostfullyambulatoryaftergynecologicproceduresbythefifthpostoperativeday.Duringthefivedaysofexternalpneumaticcompressiontreatment,onlyfourpatients(7.3%)developeddeepveinthrombosisorpulmonaryemboli,whereas13(25%)ofthecontrolgrouppatientsdid.Afterfivedaysofexternalpneumaticcompr