1、N-3 Lipids in Critical Care Medicine,Dr.Konstantin MayerUniversity of Giessen Lung CenterPulmonary and Critical Care MedicineUniversity Hospital Giessen and Marburg,第一页，共五十一页。,Lipid Mediator Synthesis,第二页，共五十一页。,Impact of n-3 vs.n-6 Fatty Acids on Inflammation,第三页，共五十一页。,Key Features of Acute Lung I
2、njury,第四页，共五十一页。,Randomized,controlled study21 Pts with septic ARDS LCT or LCT/MCT 12g/hPulmonary hemodynamics/Ventilation parameter,第五页，共五十一页。,Results,LCT(n-6)Increase in Pulmonary Artery Pressure(MPAP)Decrease in Oxygenation-Index(PaO2/FiO2),第六页，共五十一页。,Grimminger,Mayer et al.J Pharm Exp Ther 1993,
3、Am J Physiol 1995,第七页，共五十一页。,Am J Resp Cell Mol Biol 1997Am J Resp Crit Care Med 1997,Am J Physiol 2000,Protective impact of n-3 fatty acidson edema-formation in a model of septic lung failure,LTB4+,LTB4+,LTB4+LTB5+,第八页，共五十一页。,Effects of Parenteral Application ofFish Oil versus Soy Bean Oil Emulsion
4、son Bacterial Clearance FunctionsI.Kelbel,T.Koch,A.Prechtl,A.Heller,E.Schlotzer,H.G.Schiefer,H.Neuhof Infusion Therapy&Transfusion Medicine:26,226-232,1999,第九页，共五十一页。,Experimental 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-
5、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&kidney,第十页，共五十一页。,Number of bacterial colonies in the lung,Kelbel et al.1999
6、,第十一页，共五十一页。,Long-term lipid-infusion in mice,第十二页，共五十一页。,Leukocyte Invasion in a Model of Acute Lung Injury Impact of n-3 Lipids,LPS,*,Crit Care Med 2007,BALBroncho alveolar lavageLPSlipopolysaccharide,第十三页，共五十一页。,Enteral n-3 lipids+anti-oxidants:N-3 Lipids&ARDS,RCT of 146 critically ill patients a
7、cute lung injury and positive bronchoalveolar lavage for leukocytesDouble-blindedEnteral:N-3 Lipids vs.high fat dietGadek,Crit Care Med 1999;27:1409,第十四页，共五十一页。,ARDS Enteral n-3 Lipids,Adapted from:Gadek JE.et al.,Crit Care Med 1999;27:1409-20,p=.011,p=.016,第十五页，共五十一页。,Do lipids modulate acute lung
8、injury?Should we have faith in fat?,Lipid emulsions are a mainstay of parenteral nutritionused in many ventilated patients with acute lung injury,第十六页，共五十一页。,Immunologic Effects of lipid emulsions in ARDS,n-3 lipids may have beneficial effects in ARDS in contrast to n-6 lipids.SCCM+Canadian Guidelin
9、es:N-3+ARDS:Grade A recommendation,第十七页，共五十一页。,N-3 lipids and bacterial translocation/bacterial killing?,Endo/Exotoxin,Focus,Bacterialtranslocation,nosocomialPneumonia,1.barrier dysfunction,Gut,2.barrier dysfunction,第十八页，共五十一页。,Improvement of blood flow in the intestine in endotoxic rats by n-3 lipi
10、ds,L=SBOL-M=SBO+MCTFO-20=L-M+FO(20%)FO-40=L-M+FO(40%),Pscheidl,E et al,第十九页，共五十一页。,Improvement of bacterial killing in the liver in endotoxic rats by n-3 lipids,L=SBOL-M=SBO+MCTFO-20=L-M+FO(20%)FO-40=L-M+FO(40%),Pscheidl,E et al,第二十页，共五十一页。,Impact of Fish Oil on LPS-induced Response in Volunteers,8
11、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):789-97,第二十一页，共五十一页。,Fish Oil reduces LPS-induced fever-response in volunteers,第二十二页，共五十一页。,Effect of SBO-based lipids,Increased in
12、flammatory responseReduced bacterial killing/clearanceIncreased primary/seconday organ damageMay translate into clinical effects,第二十三页，共五十一页。,SIRS,CARS,Biphasic reaction of leukocytes in septic patients,Hyper,Hypo,Effective Response,Mayer,Curr Opin Clin Nutr Metab Care 1998,SIRS:systemic inflammator
13、y response syndromeCARS:compensatory anti-inflammatory response syndrome,第二十四页，共五十一页。,Design: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
14、:LCT 10%2)FO 10%Parameters:FFA,Leukotrienes,PAF,Thromboxane,.,Mayer,K et al,第二十五页，共五十一页。,Free Fatty Acids:Lipid Emulsions and Intensive Care,Free Fatty Acids,LPL,第二十六页，共五十一页。,J Am Acad Dermatol 1998Intensive Care Med 2003,Impact of Sepsis and Infusion of Lipid Emulsions on Free Fatty Acids,*,*,第二十七页
15、，共五十一页。,5-Lipoxygenase Metabolism in PMN,*availability of free fatty acid(AA/EPA)*Eicosapentaenoic acid is the preferred substrate,第二十八页，共五十一页。,Design:controlled,randomised studySetting:Intensive Care UnitPatients:21 septic shock patients,6 healthy controlsNutrition:Parenteral nutrition over 5 days,
16、total lipid intake 0.5 g/kg b.w./d Groups:1)Control:LCT 10%2)FO 10%Parameters:FFA,Cytokines,Mayer,K et al,第二十九页，共五十一页。,Mayer 2003,Am J Resp Crit Care Med,第三十页，共五十一页。,Mayer,Curr Opin Clin Nutr 2006,第三十一页，共五十一页。,Biochemical Background,第三十二页，共五十一页。,Use of RvE1 in a Colitis-ModelRead-out:Letality,weight,histologyinflammatory genes,第三十三页，共五十一页。,Mayer,Curr Opin Clin Nutr 2006,第三十四页，共五十一页。,Impact of n-3 Lipids on Immunity,第三十五页，共五十一页。,Case History 07.11.2006,Female patient,*1939,Arterial hypertension,S
