脂肪酸在急重症的应用全面资料课件

N-3 Lipids in Critical Care MedicineDr.Konstantin MayerUniversity of Giessen Lung CenterPulmonary and Critical Care MedicineUniversity Hospital Giessen and MarburgN-3 Lipids in Critical Care M1Lipid Mediator SynthesisLipid Mediator Synthesis2Impact of n-3 vs.n-6 Fatty Acids on InflammationImpact of n-3 vs.n-6 Fatty Ac3Clinical CourseKey Features of ARDSAdapted from:Gadek JE.Enteral:N-3 Lipids vs.,Crit Care Med 1999;27:1409-20Am J Resp Cell Mol Biol 1997Addition of FO(0.dysfunctionLipid emulsions are a mainstay of parenteral nutrition,Crit Care Med 1999;27:1409-208 volunteers no infusioncoli intravenous injection(1.Clinical CourseFO-20=L-M+FO(20%)J Am Acad Dermatol 1998PaO2/Fi02=60 mmHg,further detoriationConclusion:Sepsis+n-3 lipidsleukocyte invasionKey Features of Acute Lung Injury pulmonary hypertension VQ-mismatch/Shuntvasomotor dysfunction vascular leakagegas exchange secundary bacterial invasionQO2O2O2 leukocyte invasionCapillary sequestrationAlveolar invasionN-3 LipidsClinical CourseKey Features of4Randomized,controlled study21 Pts with septic ARDS LCT or LCT/MCT 12g/hPulmonary hemodynamics/Ventilation parameterRandomized,controlled study5ResultsLCT(n-6)Increase in Pulmonary Artery Pressure(MPAP)Decrease in Oxygenation-Index(PaO2/FiO2)ResultsLCT(n-6)6Grimminger,Mayer et al.J Pharm Exp Ther 1993,Am J Physiol 1995Grimminger,Mayer et al.J Pha7Am J Resp Cell Mol Biol 1997Am J Resp Crit Care Med 1997,Am J Physiol 2000Protective impact of n-3 fatty acidson edema-formation in a model of septic lung failureLTB4+LTB4+LTB4+LTB5+Am J Resp Cell Mol Biol 1997P8Effects of Parenteral Application ofFish Oil versus Soy Bean Oil Emulsionson Bacterial Clearance FunctionsI.Kelbel,T.Koch,A.Prechtl,A.Heller,E.Schlotzer,H.G.Schiefer,H.Neuhof Infusion Therapy&Transfusion Medicine:26,226-232,1999Effects of Parenteral Applicat9Experimental Protocol(Kelbel et al.,1999)Design:36 rabbits,randomly assigned to 6 groupsTreatment:1.5 g/kg b.w./day for 3 days of a-fish oil emulsion(n-3 rich)-a soybean oil emulsion(n-6 rich)or-0.9%saline(Control)E.coli intravenous injection(1.3 x 108 CFU)Sacrifice of animals 3 or 6 h after bact.injectionParameters:Bacterial counts in lung,liver,spleen&kidneyExperimental ProtocolDesign:310Number of bacterial colonies in the lungKelbel et al.1999Number of bacterial colonies i11Design:36 rabbits,randomly assigned to 6 groupsUniversity Hospital Giessen and MarburgImprovement of bacterial killing in the liver in endotoxic rats by n-3 lipidsUniversity of Giessen Lung CenterEffect of SBO-based lipidsImpact of Sepsis and Infusion of Lipid Emulsions on Free Fatty AcidsLong-term lipid-infusion in miceDesign:36 rabbits,randomly a12Leukocyte Invasion in a Model of Acute Lung Injury Impact of n-3 LipidsLPS*Crit Care Med 2007BALBroncho alveolar lavageLPSlipopolysaccharideLeukocyte Invasion in a Model 13Enteral n-3 lipids+anti-oxidants:N-3 Lipids&ARDSRCT of 146 critically ill patients acute lung injury and positive bronchoalveolar lavage for leukocytesDouble-blindedEnteral:N-3 Lipids vs.high fat dietGadek,Crit Care Med 1999;27:1409Enteral n-3 lipids+anti-oxid14ARDS Enteral n-3 LipidsAdapted from:Gadek JE.et al.,Crit Care Med 1999;27:1409-20p=.011p=.016ARDS Enteral n-3 LipidsAdapt15Do lipids modulate acute lung injury?Should we have faith in fat?Key Features of ARDS pulmonary hypertension VQ-mismatch/Shuntvasomotor dysfunction vascular leakagegas exchange secundary bacterial invasionQO2O2O2 leukocyte invasionCapillary sequestrationAlveolar invasionLipid emulsions are a mainstay of parenteral nutritionused in many ventilated patients with acute lung injuryDo lipids modulate acute lung 16Immunologic Effects of lipid emulsions in ARDSn-3 lipids may have beneficial effects in ARDS in contrast to n-6 lipids.SCCM+Canadian Guidelines:N-3+ARDS:Grade A recommendationImmunologic Effects of lipid 17N-3 lipids and bacterial translocation/bacterial killing?Endo/ExotoxinFocusBacterialtranslocationnosocomialPneumonia1.barrier dysfunctionGut2.barrier dysfunctionN-3 lipids and bacterial trans18Improvement of blood flow in the intestine in endotoxic rats by n-3 lipidsL=SBOL-M=SBO+MCTFO-20=L-M+FO(20%)FO-40=L-M+FO(40%)Pscheidl,E et alImprovement of blood flow in t19Improvement of bacterial killing in the liver in endotoxic rats by n-3 lipidsL=SBOL-M=SBO+MCTFO-20=L-M+FO(20%)FO-40=L-M+FO(40%)Pscheidl,E et alImprovement of bacterial killi20Impact of Fish Oil on LPS-induced Response in Volunteers8 volunteers 0.5 g/kg/d FO for 2 d8 volunteers no infusionLPS 2 ng/kg intravenousreadout:cytokines,hormones,RR,HF,temperature,Pluess T et al.,Intensive Care Med.2007;33(5):789-97Impact of Fish Oil on LPS-indu21Fish Oil reduces LPS-induced fever-response in volunteersFish Oil reduces LPS-induced 22Effect of SBO-based lipidsIncreased inflammatory responseReduced bacterial killing/clearanceIncreased primary/seconday organ damageMay translate into clinical effectsEffect of SBO-based lipidsIncr23SIRSCARSBiphasic reaction of leukocytes in septic patientsHyperHypoEffective ResponseMayer,Curr Opin Clin Nutr Metab Care 1998 SIRS:systemic inflammatory response syndromeCARS:compensatory anti-inflammatory response syndromeSIRSCARSBiphasic reaction of l24Design:open label,randomized,pilot studySetting:Intensive Care UnitPatients:10 septic shock patients,8 healthy controlsNutrition:Parenteral nutrition over 10 days,total lipid intake 0.5 g/kg b.w./d Groups:1)Control:LCT 10%2)FO 10%Parameters:FFA,Leukotrienes,PAF,Thromboxane,.Mayer,K et alDesign:open label,randomize25InfectionSepsisFree Fatty Acids:Lipid Emulsions and Intensive CareFree Fatty AcidsTriglyceridesLPLHeparinLipid MediatoresInfectionFree Fatty Acids:Li26J Am Acad Dermatol 1998Intensive Care Med 2003Impact of Sepsis and Infusion of Lipid Emulsions on Free Fatty Acids*J Am Acad Dermatol 1998Impact 275-Lipoxygenase Metabolism in PMN*availability of free fatty acid(AA/EPA)*Eicosapentaenoic acid is the preferred substrate5-Lipoxygenase Metabolism in P28Design:controlled,randomised studySetting:Intensive Care UnitPatients:21 septic shock patients,6 healthy controlsNutrition:Parenteral nutrition over 5 days,total lipid intake 0.5 g/kg b.w./d Groups:1)Control:LCT 10%2)FO 10%Parameters:FFA,CytokinesMayer,K et alDesign:controlled,randomise29Mayer 2003,Am J Resp Crit Care MedMayer 2003,Am J Resp Crit Car30Mayer,Curr Opin Clin Nutr 2006Mayer,Curr Opin Clin Nutr 20031Biochemical BackgroundBiochemical Background32Use of RvE1 in a Colitis-ModelRead-out:Letality,weight,histologyinflammatory genesUse of RvE1 in a Colitis-Model33Mayer,Curr Opin Clin Nutr 2006Mayer,Curr Opin Clin Nutr 20034Impact of n-3 Lipids on ImmunityImpact of n-3 Lipids on Immuni35Female patient,*1939,Arterial hypertension,Smoker,Multiple herniates disks lower backPresented with acute abdomenBowel sounds presentPainTender AbdomenFemale patient,*1939,36CT thorax+abdomen Exsudative pancreatitis Lung edemaCT thorax+abdomen 37transferred to medical intensive care unittransferred to medical intensi38Clinical CourseUpon improvement transfer to step-down unit 3 days laterAfter 2 days development of acute dyspnoeaLow blood pressureClinical CourseUpon improvemen39脂肪酸在急重症的应用全面资料课件40Clinical CourseRe-Transfer to intensive care unitBeginning ARDSSevere necrotising pancreatitis(CT)Clinical CourseRe-Transfer to 41Clinical CourseIntubationDifficult respiratory situation FiO2 0,7-1,0;PaO2 50 70 mm Hg;Acute renal failureMODSClinical CourseIntubation42Clinical CourseSeptic courseAddition of FO(0.2 g/kg)i.v.on top of TPN(LCT/MCT 0.7 g/kg)Difficult ventilation,high oxygen(FiO2=100%,ARDS)Later:low grade enteral nutrition via gastric route installedClinical CourseSeptic course43Clinical CourseSlow improvement of the patientImprovement of ARDSSucessful weaning and extubationDischarge of the patient to a rehabilitation facilityClinical CourseSlow improvemen44Second caseTravel to Italy a week before admittancePresented with fever and cough to another hospitalSecond case45Clinical courseDevelopment of ARDSDifficult ventilation situationClinical course46PaO2/Fi02=60 mmHg,further detoriationInstallation of ECMO-therapyReceived diagnosis of legionella pneumonia due to positive urine test in other hospitalAddition of FO on top of TPN and ENPaO2/Fi02=60 mmHg,further d47Clinical course 07.2007Gradual improvement with therapyWeaning from ECMOWeaning from ventilationDischarge to rehabilitation centerClinical course 07.2007Gradual48Conclusion:Sepsis+n-3 lipidsBeneficial actions of n-3 FA containing lipid emulsions in models of acute lung injury and sepsisImproved organ function/integrityImproved bacterial killingImproved outcome due to n-3 FA containing diets in patients with acute lung injury and sepsisPossible benefits of n-3 containing lipid emulsions in septic patientsConclusion:Sepsis+n-3 lip49Thank you for your attentionThank you for your attention50脂肪酸在急重症的应用全面资料课件