AusderKinderklinikundKinderpoliklinikimDr.v.HaunerschenKinderspitalder LudwigMaximiliansUniversitätMünchen Direktor:Prof.Dr.Dr.C.Klein Microcirculatory assessment of red blood cell transfusion in children with severe anemia Dissertation zumErwerbdesDoktorgradesderMedizin anderMedizinischenFakultät derLudwigMaximilianUniversitätMünchen vorgelegtvon Carina Madelen Schinagl aus Oslo 2015 Index 1. INTRODUCTION 1 1.1. ANEMIA 1 1.1.1. DEFINITION 1 1.1.2. ETIOLOGY 1 1.1.3. EPIDEMIOLOGYANDMORBIDITY 2 1.1.4. PHYSIOLOGY 2 1.1.5. SIGNSANDSYMPTOMS 3 1.1.6. THERAPY 3 1.2. DEFINITIONOFPEDIATRICINFECTION 5 1.3. MICROCIRCULATION 6 1.3.1. INANUTSHELL 6 1.3.2. STRUCTUREOFTHECAPILLARYSYSTEM 6 1.3.3. CHARACTERISTICSOFTHEMICROCIRCULATION 7 1.3.4. DYSFUNCTIONOFTHEMICROCIRCULATION 10 1.3.5. MICROCIRCULATIONOFTHEPEDIATRICPATIENT 13 1.3.6. THEEFFECTOFBLOODTRANSFUSIONONTHEMICROCIRCULATION 13 1.3.7. DIAGNOSTICSINMICROCIRCULATORYASSESSMENT 14 1.3.8. IMAGINGTECHNIQUE 16 1.4. AIMSOFDISSERTATION 19 2. MATERIALSANDMETHODS 20 2.1. PATIENTPOPULATION 20 2.1.1. RECRUITMENT 20 2.1.2. INFORMEDCONSENT 20 2.2. STUDYDESIGN 21 2.3. ASSESSMENTOFTHEMICROCIRCULATION 22 2.3.1. FUNCTIONALPRINCIPLE 22 2.3.2. EXPERIMENTALSETUP 23 2.3.3. MEASUREMENTPROCEDURES 25 2.3.4. CLINICALDATA 26 2.3.5. VIDEORECORDINGS 26 2.4. ANALYZINGDATA 27 2.4.1. SOFTWARECONFIGURATION 27 2.4.2. ANALYSIS 27 2.4.3. STORINGANDREVIEWINGANALYSISRESULTS 29 2.4.4. STATISTICALANALYSIS 29 3. RESULTS 31 3.1. STUDYPOPULATION 31 3.2. CLINICALDATA–GROUPANALYSIS 33 3.2.1. LABORATORYDATA 33 3.2.2. VITALSIGNS 37 3.2.3. BLOODUNITS 38 3.3. MICROCIRCULATORYRESULTS–GROUPANALYSIS 39 3.3.1. FUNCTIONALVESSELDENSITY(FVD) 39 3.3.2. ΔFVD 43 3.3.3. CORRELATIONHB-‐FVD 46 3.3.4. CORRELATION∆FVD-‐AGEOFRBCS 47 4. DISCUSSION 48 4.1. STUDYDESIGN 48 4.1.1. STATISTICALANALYSIS 50 4.2. MATERIALSANDMETHODS 51 4.2.1. MEASUREMENT 51 4.2.2. ANALYSIS 52 4.3. MICROCIRCULATORYCHANGES 54 4.3.1. DOESRBC-‐TXIMPROVETHEMICROCIRCULATIONOFANEMICCHILDREN? 54 4.3.2. DOESINFECTIONINFLUENCETHEMICROCIRCULATION? 57 4.3.3. DOESTHEHBCORRELATEWITHTHEFVD? 61 4.3.4. DOTHEMIRCROCIRCUALTORYCHANGESCORRELATEWITHTHEAGEOFRBCS? 62 4.4. OUTLOOK 65 5. CONCLUSION 66 6. SUMMARY 67 7. SUMMARYINGERMAN/DEUTSCHEÜBERSETZUNG 69 8. ABSTRACT 71 9. APPENDIX 72 9.1. LISTOFABBREVIATIONS 72 9.2. CLINICALDATA 73 9.3. VESSELLENGTHANDVESSELSURFACEAREA 75 9.4. RBCVELOCITY 76 9.5. ΔFVD/VOLUME 79 10. LISTOFREFERENCES 81 11. ACKNOWLEDGEMENT 92 12. CURRICULUMVITAE 93 List of figures 1.Figure,Schematicrepresentationofthemicrocirculation...............................................7 2.Figure,SchematicrepresentationofATPdependentvasodilatation……………………....…...9 3.Figure,Principalmechanismsimplicatedinthedevelopmentofmicrocirculatory alterations…………………………………………………………………………………………………….…………...……11 4.Figure,Developmentofmicrocirculatorydysfunction…………………………………...….....….…12 5.Figure,SchematicrepresentationofOPSimaging...........................................................17 6.Figure,OPSimagingversusSDFimagingofthesublingualmicrocirculation….…….….…..18 7.Figure,TheSidestreamDarkField(SDF)imagingdevice…………………………………….....…….23 8.Figure,SDFdevice………………………………………………………………………………………….…....………23 9.Figure,Microscan……………………………………………………………………………………………….….…...24 10.Figure,ExampleofsublingualmicrocirculationwiththeSDF-‐imagingtechnique….…..24 11.Figure,Overviewofstudygroups……………………………………………….……………….....…........32 12.Figure,Timechartofmeasurements…………………………………………………………..…...……..…33 13.Figure,Hbvaluesoftheanemicstudygroupbeforeand48-‐72haftertransfusionin comparisonwithHbvaluesofcontrolgroup(..…………………………….………………………………..…34 14.Figure,ComparisonofCRPvaluesbetweenanemicpatientswithoutinfectionsandwith infection………………………………………….………………..…………………………………………………...………..36 15.Figure,ComparisonofFVDbeforeandafterRBCtransfusion..…………..…………..….……….39 16.Figure,AbeforeandaftergraphshowingFVDvaluesbeforeandaftertransfusion…...40 17.Figure,FVDvaluesofsubgroups………………………………………………………………….……..………42 18.Figure,Scatterdotplotof∆FVD……………………………………………………………........................43 19.Figure,Scatterdotplotof∆FVD(InfvsnInf)…………………………………………………………..…..44 20.Figure,ImageofthesublingualmicrocirculationpriortoRBC-‐Tx....................................45 21.Figure,ImageofthesublingualmircocirculationrightafterRBC-‐Tx................................45 22.Figure,CorrelationofFVDandHemoglobin…………………………………………….………….46 23.Figure,CorrelationofΔFVDandRBCage………………………………………….…………………47 24.Figure,Imageofsublingualmicrocirculationbeforeandaftertransfusion….………68 25.Figure,Velocityinmediumandlargevessels……………………………………………………..76 26.Figure,LinearregressionandcorrelationofΔFVD(preTx-‐pTx1)/Vol………………..….79 27.Figure,LinearregressionandcorrelationofΔFVD(pTx1-‐pTx2)/Vol........................80 List of tables 1.Table,Patientcharacteristics………………………………………………………………………………………………31 2.Table,Laboratorydatapresentedasmeanvaluesand95%CI……………………………………………33 3.Table,Meanand95%CIofhemoglobinvaluesofsubgroups……………………………………………..35 4.Table,Meanand95%CIofheartrate…………………………………………………………………………………37 5.Table,Meanand95%CIoftemperatureintheTxandsubgroups………………………………………37 6.Table, Mean,95%CIandStandardDeviation(SD)ofFVD………………………………………………….39 7.Table,MeanFVDvaluesand95%CIforbothgroups(InfandnInf)…………………………………….41 8.Table,Mean,StandardDeviationand95%CIofΔFVDforallGroups…….……………………………43 9.Table,Diagnosis,gender,ageandweightofeachanemicchild…………………………………………..73 10.Table,MeanlaboratorydataofTx-‐group…………………………………………………………………………74 11.Table,Meanand95%CIofvessellengthandvesselsurfacearea…………………………………….75 12.Table,VelocityvaluesoftransfusiongroupbeforeandafterTx……………………………………….76 13.Table,Velocityvaluesmediumvessels(InfvsnInf)…………………………………………………………..77 14.Table,Velocityvalueslargevessels(InfvsnInf)………………………………………………………………..77
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