N-3脂肪酸在急重症的应用

N-3Lipidsin

CriticalCareMedicineDr.KonstantinMayerUniversityofGiessenLungCenterPulmonaryandCriticalCareMedicineUniversityHospitalGiessenandMarburg第一页，共五十一页。LipidMediatorSynthesis第二页，共五十一页。Impactofn-3vs.n-6FattyAcidsonInflammation第三页，共五十一页。KeyFeaturesofAcuteLungInjurypulmonaryhypertensionVQ-mismatch/Shuntvasomotordysfunction

vascularleakagegasexchangesecundarybacterialinvasionQO2O2O2

leukocyteinvasionCapillarysequestrationAlveolarinvasionN-3Lipids第四页，共五十一页。Randomized,controlledstudy21PtswithsepticARDSLCTorLCT/MCT@12g/hPulmonaryhemodynamics/Ventilationparameter第五页，共五十一页。ResultsLCT(n-6)IncreaseinPulmonaryArteryPressure(MPAP)DecreaseinOxygenation-Index(PaO2/FiO2)第六页，共五十一页。Grimminger,Mayeretal.JPharmExpTher1993,AmJPhysiol1995第七页，共五十一页。AmJRespCellMolBiol1997AmJRespCritCareMed1997,AmJPhysiol2000Protectiveimpactofn-3fattyacidsonedema-formationinamodelofsepticlungfailureLTB4++++LTB4++LTB4+LTB5++++第八页，共五十一页。EffectsofParenteralApplicationofFishOilversusSoyBeanOilEmulsionsonBacterialClearanceFunctionsI.Kelbel,T.Koch,A.Prechtl,A.Heller,E.Schlotzer,H.G.Schiefer,H.NeuhofInfusionTherapy&TransfusionMedicine:26,226-232,1999第九页，共五十一页。ExperimentalProtocol(Kelbeletal.,1999)Design: 36rabbits,randomlyassignedto6groupsTreatment: 1.5g/kgb.w./dayfor3daysofa -fishoilemulsion(n-3rich) -asoybeanoilemulsion(n-6rich)or -0.9%saline(Control)

E.coliintravenousinjection(1.3x108CFU) Sacrificeofanimals3or6hafterbact.injectionParameters:Bacterialcountsinlung,liver,spleen&kidney

第十页，共五十一页。NumberofbacterialcoloniesinthelungKelbeletal.1999第十一页，共五十一页。Long-termlipid-infusioninmice第十二页，共五十一页。LeukocyteInvasioninaModelofAcuteLungInjury–Impactofn-3LipidsLPS*CritCareMed2007BALBronchoalveolarlavageLPSlipopolysaccharide第十三页，共五十一页。Enteraln-3lipids+anti-oxidants:

N-3Lipids&ARDSRCTof146criticallyillpatientsacutelunginjuryandpositivebronchoalveolarlavageforleukocytesDouble-blindedEnteral:N-3Lipidsvs.highfatdietGadek,CritCareMed1999;27:1409第十四页，共五十一页。ARDS–Enteraln-3LipidsAdaptedfrom:GadekJE.etal.,CritCareMed1999;27:1409-20p=.011p=.016第十五页，共五十一页。Dolipidsmodulateacutelunginjury?

Shouldwehavefaithinfat?KeyFeaturesofARDSpulmonaryhypertensionVQ-mismatch/Shuntvasomotordysfunction

vascularleakagegasexchangesecundarybacterialinvasionQO2O2O2

leukocyteinvasionCapillarysequestrationAlveolarinvasionLipidemulsionsareamainstayofparenteralnutritionusedinmanyventilatedpatientswithacutelunginjury第十六页，共五十一页。ImmunologicEffects

oflipidemulsionsinARDSn-3lipidsmayhavebeneficialeffectsinARDSincontrastton-6lipids.SCCM+CanadianGuidelines:N-3+ARDS:GradeArecommendation第十七页，共五十一页。N-3lipidsandbacterialtranslocation/bacterialkilling?Endo/ExotoxinFocusBacterialtranslocationnosocomialPneumonia1.barrierdysfunctionGut2.barrierdysfunction第十八页，共五十一页。Improvementofbloodflowintheintestineinendotoxicratsbyn-3lipidsL=SBOL-M=SBO+MCTFO-20=L-M+FO(20%)FO-40=L-M+FO(40%)Pscheidl,Eetal第十九页，共五十一页。Improvementofbacterialkillingintheliver

inendotoxicratsbyn-3lipidsL=SBOL-M=SBO+MCTFO-20=L-M+FO(20%)FO-40=L-M+FO(40%)Pscheidl,Eetal第二十页，共五十一页。ImpactofFishOilonLPS-inducedResponseinVolunteers8volunteers0.5g/kg/dFOfor2d8volunteersnoinfusionLPS2ng/kgintravenousreadout:cytokines,hormones,RR,HF,temperature,…PluessTetal.,IntensiveCareMed.2007;33(5):789-97第二十一页，共五十一页。FishOilreducesLPS-inducedfever-responseinvolunteers第二十二页，共五十一页。EffectofSBO-basedlipidsIncreasedinflammatoryresponseReducedbacterialkilling/clearanceIncreasedprimary/secondayorgandamageMaytranslateintoclinicaleffects第二十三页，共五十一页。SIRSCARSBiphasicreactionofleukocytesinsepticpatientsHyperHypoEffectiveResponseMayer,CurrOpinClinNutrMetabCare1998SIRS:systemicinflammatoryresponsesyndromeCARS:compensatoryanti-inflammatoryresponsesyndrome第二十四页，共五十一页。Design: openlabel,randomized,pilotstudySetting: IntensiveCareUnitPatients: 10septicshockpatients,8healthycontrolsNutrition: Parenteralnutritionover10days, totallipidintake0.5g/kgb.w./dGroups: 1)Control:LCT10% 2)FO10%

Parameters: FFA,Leukotrienes,PAF,Thromboxane,…..Mayer,Ketal第二十五页，共五十一页。InfectionSepsisFreeFattyAcids:

LipidEmulsionsandIntensiveCareFreeFattyAcidsTriglyceridesLPLHeparinLipidMediatores第二十六页，共五十一页。JAmAcadDermatol1998IntensiveCareMed2003ImpactofSepsisandInfusionofLipidEmulsionsonFreeFattyAcids**第二十七页，共五十一页。5-LipoxygenaseMetabolisminPMN*availabilityoffreefattyacid(AA/EPA)*Eicosapentaenoicacidisthepreferredsubstrate第二十八页，共五十一页。Design: controlled,randomisedstudySetting: IntensiveCareUnitPatients: 21septicshockpatients,6healthycontrolsNutrition: Parenteralnutritionover5days, totallipidintake0.5g/kgb.w./dGroups: 1)Control:LCT10% 2)FO10%

Parameters: FFA,CytokinesMayer,Ketal第二十九页，共五十一页。Mayer2003,AmJRespCritCareMed第三十页，共五十一页。Mayer,CurrOpinClinNutr2006第三十一页，共五十一页。BiochemicalBackground第三十二页，共五十一页。UseofRvE1inaColitis-ModelRead-out:Letality,weight,histologyinflammatorygenes第三十三页，共五十一页。Mayer,CurrOpinClinNutr2006第三十四页，共五十一页。Impactofn-3LipidsonImmunity第三十五页，共五十一页。CaseHistory07.11.2006Femalepatient,*1939,Arterialhypertension,Smoker,MultipleherniatesdiskslowerbackPresentedwithacuteabdomenBowelsoundspresentPainTenderAbdomen第三十六页，共五十一页。CaseHistory07.11.2006CTthorax+abdomenExsudativepancreatitisLungedema第三十七页，共五十一页。CaseHistory07.11.2006transferredtomedicalintensivecareunit第三十八页，共五十一页。ClinicalCourseUponimprovementtransfertostep-downunit3dayslaterAfter2daysdevelopmentofacutedyspnoeaLowbloodpressure第三十九页，共五十一页。第四十页，共五十一页。ClinicalCourseRe-TransfertointensivecareunitBeginningARDSSeverenecrotisingpancreatitis(CT)第四十一页，共五十一页。ClinicalCourseIntubationDifficultrespiratorysituationFiO20,7-1,0;PaO250–70mmHg;AcuterenalfailureMODS第四十二页，共五十一页。ClinicalCourseSepticcourseAdditionofFO(0.2g/kg)i.v.ontopofTPN(LCT/MCT0.7g/kg)Difficultventilation,highoxygen(FiO2=100%,ARDS)Later:lowgradeenteralnutritionviagastricrouteinstalled第四十三页，共五十一页。ClinicalCourseSlowimprovementofthepatientImprovementofARDSSucessfulweaningandextubationDischargeofthepatienttoarehabilitationfacility第四十四页，共五十一页。SecondcasePatient,male,*14.12.1961TraveltoItalyaweekbeforeadmittancePresentedwithfeverandcoughtoanotherhospital第四十五页，共五十一页。ClinicalcourseIntubation01.07.2007DevelopmentofARDSDifficultventilationsituationTransfertoourfacility02.07.2007第四十六页，共五十一页。Clinicalcourse02.07.2007PaO2/Fi02=60mmHg,furtherdetoriationInstallationofECMO-therapyReceiveddiagnosisoflegionellapneumoniaduetopositiveurinet