Table Of ContentAusderKinderklinikundKinderpoliklinikimDr.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
Description:der Ludwig Maximilian Universität München . Anemia is classically defined as a deficiency of red blood cells or hemoglobin leading to a cancer frequently develop anemia both from the disease and chemo-‐ and radiotherapy.
