低分子量治疗研究doc

1、低分子量治疗研究.doc低分子量治疗研究.doc低分子量治疗研究.doc感谢赏析低分子量肝素联合IPC对妇科肿瘤手术后DVT的预防Arandomizedtrialoflow-doseheparinandintermittentpneumaticcalfcompressionforthepreventionofdeepvenousthrombosisaftergynecologiconcologysurgeryDanielL.Clarke-Pearson,MD,aIngridS.Synan,RN,aRichardDodge,MS,bacJohnT.Soper,MD,AndrewBerchuck,

2、MD,andR.EdwardColeman,MDDurham,NorthCarolinaOBJECTIVE:Ouraimwastodeterminetherelativeefficacyandcomplicationsoflowdoseheparinandintermittentpneumaticcalfcompressionforthepreventionofpostoperativevenousthrombosisinpatientsundergoingsurgeryforgynecologicmalignancy.STUDYDESIGN:Randomizedtrialcomparing1

3、07patientstreatedwithlow-doseheparinto101patientstreatedwithintermittentpneumaticcalfcompressionwasperformed.Allpatientswereevaluatedwithiodine-125fibrinogenscanningofthelegs.Clinicalandlaboratoryvariablesassociatedwithbleedingcomplicationswererecordedprospectively.RESULTS:Venousthrombosiswasdiagnos

4、edinsevenpatientsreceivinglow-doseheparinandinfourreceivingintermittentpneumaticcalfcompression(p=0.54).Low-doseheparinpatientsreceivedmorebloodtransfusionspostoperatively(p=0.02),hadincreasedvolumeofretroperitonealdrainage(p=0.02),andtheactivatedpartialthromboplastintimewasmorefrequentlyprolonged(p

5、=0.001).CONCLUSIONS:Low-doseheparinandintermittentpneumaticcalfcompressionprovidesimilarreductioninreducingtheincidenceofpostoperativevenousthrombosis.However,Iow-doseheparinismorefrequentlyassociatedwithpostoperativebleedingcomplications.(AmJOBSTETGYNECOL1993;168:1146-54.)Keywords:Venousthrombosisp

6、rophylaxis,low-doseheparin,intermittentpneumaticcalfcompression,bleedingcomplicationsDeepveinthrombosisandpulmonaryembolismareseriousandsometimesfatalcomplicationsthatcanoccuraftergynecologicsurgery.Overthepastdecadewehaveperformedseveralprospective,controlled,randomizedtrialstoevaluatetheefficacyof

7、varioustherapeuticmodalitiesaimedatpreventingpostoperativedeepveinthrombosis.Inwomenwithgynecologicmalignancieswefoundthatlow-doseheparingivenevery12hourspostoperativelyisineffectiveinpreventingdeepvenousthrombosis.1Wealsofoundthatintermit-tentpneumaticcalfcompressionusedintraoperativelyandfor24hour

8、spostoperativelydidnotpreventdeepvenousthrombosis?Subsequentlywedemonstratedthatgynecologiconcologypatientsdidbenefitfromeitherlow-doseheparinwhengivenastreeddosesevery8hourspreoperativelyandevery8hourspostoperativelyorintermittentpneumaticcallcompressionappliedintraoperativelyandmaintaine(ltotthefi

9、rst5postoperativedays.4FromtheDivisionofGynecologicOncology,DepartmentofObstetricsandGynecology,Biostatistics,ComputingandDataManagement,DukeComprehensiveCancerCenter,bandtheDivisionofNuclearMedicine,DepartmentofRadiology,DukeUniversityMedicalCenter.PresentedbyinvitationattheEleventhAnnualMeetingoft

10、he感谢赏析感谢赏析AmericanGynecologicalandObstetricalSocietyHotSprings,Virginia,September10-12,1992.Reprintrequests:D.L.Clarke-Pearson,MD,Box3079,DukeUniversityMedicalCenter,Durham,NC27710.Copyright1993byMosby-YearBook,Inc.0002-9378/93$1.00+.206/6/44822Althoughthecostsofthesetwoprophylacticmethodsareapproxi

11、matelythesamethesideeffectsandpatientcompliancediffer.Thecurrentstudywasbasedonthehypothesisthatlow-doseheparinandintermittentpneumaticcalfcompressionhavesimilarefficacyinpreventingpostoperativedeepvenousthrombosisingynecologiconcologypatients.Becauseofthedifferencesinthemechanismsofactionofthesetwo

12、methods,however,theremightbesignificantdifferencesincomplicationsoftherapy,especiallybleedingcomplications.Furthermore,thesecomplicationsmightinfluencetheoveralluseandtherapeuticindexofthetwomethodsandresultinchangesinmanagementinthefuture.MaterialandmethodsAllpatientsadmittedtotheDivisionofGynecolo

13、gicOncologyformajorsurgeryforknownorpresumedgynecologicmalignancieswereeligibleforthisstudyafterinformedwrittenconsentwasobtained,asapprovedbytheInstitutionalReviewBoard.Becauseoftheveryhighincidenceofdeepveinthrombosisassociatedwithpelvicexenteration,patientswerestratifiedbeforerandomizationiftheyw

14、eretoundergoapelvicexenteration.Patientswerethenassignedrandomlybymeansoftherandomnumbertabletooneofthetwotreatmentregimens.Regimen1(low-doseheparin)wasadministeredidenticallytoourprevioussuccessfultrial3andwasgiveninthefollowingmanner:5000unitsofheparinwasgivensubcutaneouslyat2PM,10pm,and6AMbefores

15、tartingsurgeryat8Au.Ifapatientwasadmittedseveraldaysbeforesurgery,heparinwasstartedonadmissionandcontinuedevery8hoursuntilsurgeryPostoperativelythepatientreceived5000unitsofheparinsubcutaneouslyevery8hoursfor7postoperativedays.Ifthepatientwasnotfullyambulatorybytheseventhpostoperativeday,heparinwasc

16、ontinueduntilfullambulationwasestablished.Ontheotherhand,ifthepatientwasdischargedfromthehospitalbeforetheseventhpostoperativeday,theheparinwasdiscontinuedatthetimeofhospitaldischarge.Patientsassignedtoregimen2hadintermittentpneumaticcalfcompression(Venodyne,Needham,Mass.)initiatedattheinductionofan

17、esthesiaandcontinuedwhilethepatientwasinambulatorybythefifthpostoperativeday,intermittentpneumaticcalfcompressioncontinueduntilthepatientambulatedcompletely.Ifthepatientwasdischargedfromthehospitalbeforethefifthpostoperativcday,pneumaticcalfcompressionwasterminatedatthetimeofhospitaldischarge.Histor

18、yandphysicalexaminationwereperformedattiletimeofthehospitaladmission,withspecificattentiontocoexistingriskfactorsthethromboemboliccomplications6Anypatientwithapasthistoryofableedingdiathesis,thromboembolismwithinthepast3months,oranticoagulant(warfarinorheparin)useintheprevious6weekswasexcludedfromth

19、estudy.Patientsalsounderwentlaboratorytesting,includingevaluationofhematocrit,plateletcount,activatedpartialthromboplastintime,andprothrombintime.Patientswereexcludedfromthistrialiftheirplatelet感谢赏析感谢赏析procedureundergeneralanesthesia.Deepveinthrombosiswasassessedbymeansofthefibrinogenuptaketest,onth

20、ebasisofidentificationbyscintillationcountingofiodine-125-labeledfibrinogenincorporatedintoacutethrombiforminginthelegveins.Theaccuracyofthistest,whencorrelatedwithvenography,hasbeenestablished,andcriteriafordiagnosishavebeendescribed.7125Ifibrinogencountingwasperformedat2-inchintervalsoverthedeepve

21、insofthecalfandthigh.Oralsupersaturatedpotassiumiodinewasgivenpreoperativelytoblockthyroiduptakeof125Iiodide.125Ifibrinogen(100uCi)wasadministeredintravenouslytoallpatientsimmediatelyaftersurgery.Beginningonthefirstpostoperativeday,thefibrinogenuptaketestwasperformeddailyuntilthepatientwasdischarged

22、.Deepveinthrombosiswasdiagnosedwhen125Icountswereincreased20%overcountsintheadjacentscansiteorinthesamesiteonthecontralaterallegoroverthepreviousdayscountsatthesamelocation,withpersistencefor2consecutivedays.Ifthefibrinogenstudysuggestedthrombusformationinthepoplitealregionorthigh,ascendingvenograph

23、ywasusedtoconfirmdeepveinthrombosis.WeperformedvenographyaccordingtothetechniquesdescribedbyRabinovandPaulin.8Patientswerefollowedbythefibrinogenuptaketestthroughouttheirhospitalizationandwerefollowedclinicallyforthefirst30dayspost-operatively.Signsandsymptomsofdeepveinthrombosisandpulmonaryembolism

24、werealsoevaluateddaily.Symptomsofdeepveinthrombosiswereevaluatedbyimpedanceplethysmography,duplexDopplerultrasonography,andascendingcontrastvenography,ifclinicallyindicated.Symptomsandsignsofpulmonaryembolismwereassessedfurtherbyventilation-perfusionlungscanandpulmonaryarteriography.Clinicalevidence

25、ofbleedingcomplicationswereassesseddaily,includingestimatedoperativebloodloss,transfusionsduringsurgeryandpostoperatively,woundhematomaandseparation,pelvichematomaorlymphocyst,andretroperitonealsuctiondrainagevolume.Laboratorystudies,includinghematocrit,prothrombintime,activatedpartialthromboplastin

26、time,andplateletcount,wererecordedpreoperativelyandeveryotherdaybeginningonthefirstpostoperativeday.Toassesstheeffectsofcategoricvariablessuchastreatmentandraceontheoccurrenceofdeepveinthrombosis,weusedtheFisherexacttest.Forcontinuousvariables,suchasageandweight,logisticregressionwasused,withthedepe

27、ndentvariablebeingthepresenceorabsenceofdeepveinthrombosis.Then,tocontrolforpotentialconfoundingfactorsandtoinvestigatesimultaneouseffectsofseveralofthesevariables,weperformedmultiplelogisticregressionanalyses.Clinicalhemorrhagicparameterssuchasestimatedbloodlosswerecomparedbetweenthetwogroupsbymean

28、sofrank-sumtestsforcontinuousvariablesandbytheFisherexacttestfordiscretevariables.Analysisoflaboratoryparametersthatwererepeatedovertimewascomplicatedbythefactthattheseparametersdidnotshowconsistentpostoperativepatternsforallpatients.Forexample,insomepatientsthevaluewouldincreasepostoperativelyandth

29、enwoulddecrease,whereasinothersitwoulddecreaseinitially.Theseinconsistenciesoccurredwithineachofthetreatmentgroupsandsuggestedthatmodelinglinearorquadratictrendswouldbeinfeasible.Furthermore,althoughmeasurementswerescheduledtobetakeneveryotherdayuntildischarge,insomecaseslaboratorytestswereomitted.N

30、odifferencebetweentreatmentgroupscouldbediscernedwithrespecttomissingvalues.Thusforeachpatientandforeachoftheselaboratoryparametersamaximum,minimum,andfinalvalueduringthepost-operativecoursewascalculated.Amaximum(mini-mum)wasdefinedonlyifthemaximum(minimum)postoperativevaluewaslarger(smaller)thanthe

31、pre-operativebaselinevalue.Thefinalvaluewasdefinedasthelastvalue感谢赏析感谢赏析recordedpostoperatively.Table1.DistributionofvenousthrombosisriskfactorsLow-doseheparinIntermittentpneumatic(n=107)calfcompression(n=I01)Age(yr)Median5755Range22-8927-84RaceWhite8579Other2222DiagnosisBenigndisease2624Primarycanc

32、er6766Recurrentcancer1412PasthistoryPulmonaryembolus00Deepvenousthrombosis22Pelvicradiationtherapy1510PhysicalexaminationWeight(kg)Median70.771.2Range44-13935-132Varicoseveins2017Ankleedema34Theaimoftheanalysiswastodeterminewhich,ifany,ofthenineindexesthusconstructed(maximum,minimum,andfinalforeacho

33、fthethreelaboratoryparameters)variedsignificantlybetweenthelow-doseheparinandtheintermittentpneumaticcalfcompressiongroups.Becausetheseindexeswouldprobablybeinfluencedbybaselinevaluesandbecausepatientswerefollowedforvaryinglengthsoftime,regressionanalysiswasusedtoadjustforbaselinevaluesandforthenumb

34、erofdaysthepatientwasobservedbeforethevalueinquestionwasobtained.Theestimatedmeandifferenceinparametersmeasuredovertime,thestandarderrorofthedifference,andthetestofsignificancewereobtainedfromtheregressionanalysis.ResultsTwohundredeighteenpatientswereenteredintothisstudy.Tenpatientswereexcludedfromf

35、urtheranalysisafterrandomizationbecausetheirsurgerieswerecancelled.Noneofthepatientsexcludedfromanalysisdevelopedevidenceofdeepveinthrombosisorpulmonaryembolismduring30daysoffollow-up.The208evaluablepatientsarethesubjectofthisreport.Onehundredsevenpatientsreceivedlow-doseheparin,and101patientsreceiv

36、edintermittentpneumaticcalfcompression.Initialevaluationofvenousthrombosisriskfactors:showedasimilardistributionbetweenthetwogroups(TableI).FableIIliststhesurgicalproceduresper-formedandthedurationofanesthesia.Therewerenosignificantdifferencesbetweenthetwostudygroupsinnumbersor感谢赏析感谢赏析typesofprocedu

37、resperformedorinthedurationofgeneralanesthesia.Fibrinogenuptaketestofthelegswaspositiveinsixpatientsinthelow-doseheparingroup.Thisincludedfourpatientswiththrombiconfinedtothecalfandtwopatientswhohadthrombiextendingintothefemoralvein.Threepatientsintheintermittentpneumaticcalfcompressiongroupdevelope

38、dabnormalfibrinogenup-taketests,whichdetectedthrombithatwereconfinedtothecalfinallcases.Clinicallysymptomaticfemoralveinthrombosiswasdiagnosedinonepatientinthelow-doseheparingrouponthetwenty-sixthpostoperativeday.andinonepatientintheintermittentpneumaticcalfcompressiongrouponthetwenty-eighthpostoper

39、ativeday.Thesethrombiwereconfirmedbyvenography.Therewerenopulmonaryembolidiagnosedineithertreatmentgroup.Overall,venousthrombosiswasdiagnosedinsevenpatients(6.5%)inthelow-doseheparingroupandfourpatients(4%)intheintermit-tentpneumaticcalfcompressiongroup(p=0.54).TableII.SurgicalproceduresperformedLow

40、-doseheparinIntermittentpneumatic(n=107)calfcompression(n=101)SignificancePelvicexenteration42Radicalvulvectomy56Radicalhysterectomy,pelvicandparaaortic1513lymphadenectomyTotalabdominalhysterectomy,bilateral1712salpingo-oophorectomy,seletivepelvicandparaaorticiymphadenectomyTotalabdominalhysterectom

41、y,bilateral3232salpingooophorectomyIntestinalresectionorbypass1011Exploratorylaparotomy2425Durationofanesthesia(min)Median230235Range90-85580-510p=0.72TableIII.IncidenceandtypeofdeepvenousthrombosisLow-doseheparinIntermittentpneumatic(n=107)calfcompression(n=101)SignificanceLocation.Calf43Thigh31p=1

42、.0Totaldeepvenousthrombosis74p=0.54Deepvenousthrombosisduringprophylaxis52p=0.45Thrombidevelopedduringthetimeofactiveprophylaxisinfivepatientsreceivinglow-doseheparinandintwopatientsreceivingintermittentpneumaticcalfcompression.Theincidenceof感谢赏析感谢赏析thrombiarisingproximaltothecalf(whichareconsidered

43、moreserious)wasnotsignificantlydifferentinthetwotreatmentgroups(TableIII).TableIVshowstheincidenceofdeepvenousthrombosisastheyrelatetootherhigh-riskclinicalvariables.Apasthistoryofdeepveinthrombosis(p=0.04),thepresenceofvaricoseveins(p=0.005),andincreasedage(p=0.01)wereassociatedwiththeoccurrenceofp

44、ostoperativedeepveinthrombosis.Inamultivariatelogisticregressionanalysis,afteradjustingforage,thepresenceofvaricoseveinsremainsasignificantpredictorofthelikelihoodofdevelopingvenousthrombosis(p=0.02).Afteradjustingforage,historyofdeepvenousthrombosisisnolongersignificantlyassociatedwiththeoccurrence

45、ofpostoperativevenousthrombosis(p0.10).ClinicalcomplicationsassociatedwiththetwoprophylacticregimensareshowninTableV.Intraoperativeestimatedbloodloss,intraoperativebloodtransfusions,postoperativewoundseparations,pelvichematomas,andfebrilemorbiditywerenotsignificantlydifferentbetweenthetwotreatmentgr

46、oups.However,postoperativetransfusionsweregivento34patientswhoreceivedlow-doseheparin,comparedwithonly17patientswhoreceivedintermittentpneumaticcalfcompressionprophylaxis(p=0.03).Patientsreceivinglow-doseheparinalsorequiredtransfusionofmoreunitsofbloodpostoperatively(p=0.02).Thetotalvolumeofretroper

47、itonealsuctiondrainageandtheaveragedailysuctionoutputwerealsosignificantlygreaterinthelow-doseheparingroup(p=0.02).Lymphocystswerenotsignificantlymorecommoninthepatientswhoreceivedlow-doseheparin,althoughtheyoccurredinthreepatients,comparedwithonlyoneintheintermit-tentpneumaticcalfcompressiongroup.I

48、nadditiontotheincreasedincidenceofbleedingcomplicationsobservedwiththeuseoflow-doseheparininthisstudy,laboratorydatarevealedthatpatientsreceivinglow-doseheparinweremorelikelytohaveaprolonged,activatedpartialthromboplastintime.Anactivatedpartialthromboplastintime1.5timesthecontrolvaluewasfoundpostope

49、rativelyin25patientsreceivinglow-doseheparin(23%)andinonlyfourpatients(4%)receivingintermittentpneumaticcalfTableIV.IncidenceofvenousthrombosisinrelationshiptoclinicalvariablesNo.VenousthrombosisLogisticregressionsignificancecoefficientRaceWhite1649p=1.00Other442DiagnosisBenign501p=0.30Cancer15810Pr

50、eviousradiationtherapyNo18311p=0.37Yes250HistoryofdeepvenousthrombosisNo1928p=0.04Yes163Varicoseveinsp=0.005感谢赏析感谢赏析No1715Yes376ContinuousvariablesAge0.07p=0.01Weight0.004p=0.82compression(p0,001).Apostoperativeplateletcountof100,000/mm3wasnotedinthreelow-doseheparinpatientsandinfourtreatedwithintermittentpneumaticcalfcompression.TableVIshowstheresultsoflinearregr