N-3脂肪酸在急重症的应用.ppt

Titelmasterformat durch Klicken bearbeiten,Textmasterformate durch Klicken bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,*,N-3,Lipids,in,Critical,Care,Medicine,Dr.Konstantin Mayer,University of Giessen,Lung,Center,Pulmonary,and,Critical,Care,Medicine,University Hospital Giessen and Marburg,Lipid,Mediator Synthesis,Impact of n-3 vs.n-6,Fatty,Acids,on Inflammation,Key Features of Acute Lung Injury,pulmonary hypertension,VQ-mismatch/Shunt,vasomotor dysfunction,vascular leakage,gas exchange,secundary,bacterial invasion,Q,O,2,O,2,O,2,leukocyte invasion,Capillary sequestration,Alveolar invasion,N-3,Lipids,Randomized,controlled,study,21,Pts,with,septic,ARDS,LCT,or,LCT/MCT 12g/h,Pulmonary,hemodynamics,/Ventilation,parameter,Results,LCT(n-6),Increase,in,Pulmonary,Artery,Pressure,(MPAP),Decrease,in,Oxygenation-Index,(PaO2/FiO2),Grimminger,Mayer et al.J,Pharm,Exp,Ther,1993,Am J,Physiol,1995,Am J,Resp,Cell,Mol,Biol,1997,Am J,Resp,Crit,Care,Med,1997,Am J,Physiol,2000,Protective impact of n-3 fatty acids,on edema-formation in a model of septic lung failure,LTB,4,+,LTB,4,+,LTB,4,+,LTB,5,+,Effects of Parenteral Application of,Fish Oil versus Soy Bean Oil Emulsions,on Bacterial Clearance Functions,I.,Kelbel,T.Koch,A.,Prechtl,A.Heller,E.,Schlotzer,H.G.,Schiefer,H.,Neuhof,Infusion Therapy&Transfusion Medicine:26,226-232,1999,Experimental Protocol,(,Kelbel,et al.,1999),Design:36 rabbits,randomly assigned to 6 groups,Treatment: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 10,8,CFU),Sacrifice of animals 3 or 6 h after bact.injection,Parameters:Bacterial counts in lung,liver,spleen&kidney,Number of bacterial colonies in the lung,Kelbel,et al.1999,Long-term,lipid-infusion,in,mice,Leukocyte,Invasion in a Model of,Acute,Lung,Injury,Impact of n-3,Lipids,LPS,*,Crit,Care,Med,2007,BAL,Broncho,alveolar,lavage,LPS,lipopolysaccharide,Enteral n-3,lipids,+,anti-oxidants,:N-3,Lipids,&ARDS,RCT of 146 critically ill patients,acute lung injury and positive,bronchoalveolar,lavage for leukocytes,Double-blinded,Enteral:N-3 Lipids vs.high fat diet,Gadek,Crit,Care Med 1999;27:1409,ARDS Enteral n-3,Lipids,Adapted,from,:,Gadek,JE.et al.,Crit,Care,Med,1999;27:1409-20,p=.011,p=.016,Do lipids modulate acute lung injury?Should we have faith in fat?,Key Features of ARDS,pulmonary hypertension,VQ-mismatch/Shunt,vasomotor dysfunction,vascular leakage,gas exchange,secundary,bacterial invasion,Q,O,2,O,2,O,2,leukocyte invasion,Capillary sequestration,Alveolar invasion,Lipid emulsions are a mainstay of parenteral nutrition,used in many ventilated patients with acute lung injury,Immunologic,Effects,of,lipid,emulsions,in ARDS,n-3,lipids,may,have,beneficial,effects,in ARDS in,contrast,to n-6,lipids,.,SCCM+Canadian,Guidelines,:,N-3+ARDS:Grade A,recommendation,N-3,lipids,and,bacterial,translocation,/,bacterial,killing,?,Endo/,Exotoxin,Focus,Bacterial,translocation,nosocomial,Pneumonia,1.barrier dysfunction,Gut,2.barrier,dysfunction,Improvement,of,blood,flow,in,the,intestine,in,endotoxic,rats,by,n-3,lipids,L=SBO,L-M=SBO+MCT,FO-20=L-M+FO(20%),FO-40=L-M+FO(40%),Pscheidl,E et al,Improvement,of,bacterial,killing,in,the,liver,in,endotoxic,rats,by,n-3,lipids,L=SBO,L-M=SBO+MCT,FO-20L-M+FO(20%),FO-40=L-M+FO(40%),Pscheidl,E et al,Impact of,Fish,Oil on,LPS-induced,Response in,Volunteers,8,volunteers,0.5 g/kg/d FO,for,2 d,8,volunteers,no,infusion,LPS 2 ng/kg,intravenous,readout,:,cytokines,hormones,RR,HF,temperature,Pluess,T et al.,Intensive,Care,Med.2007;33(5):789-97,Fish,Oil,reduces,LPS-induced,fever-response,in,volunteers,Effect,of,SBO-based,lipids,Increased,inflammatory,response,Reduced,bacterial,killing,/,clearance,Increased,primary,/,seconday,organ,damage,May,translate,into,clinical,effects,SIRS,CARS,Biphasic,reaction,of,leukocytes,in,septic,patients,Hyper,Hypo,Effective,Response,Mayer,Curr,Opin,Clin,Nutr,Metab,Care,1998,SIRS:,systemic,inflammatory,response,syndrome,CARS:,compensatory,anti-inflammatory,response,syndrome,Design:,open label,randomized,pilot study,Setting:,Intensive Care Unit,Patients:,10 septic shock patients,8 healthy controls,Nutrition:,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 al,Infection,Sepsis,Free,Fatty,Acids,:,Lipid,Emulsions,and Intensive,Care,Free,Fatty,Acids,Triglycerides,LPL,Heparin,Lipid,Mediatores,J Am,Acad,Dermatol,1998,Intensive,Care,Med,2003,Impact of Sepsis and Infusion of,Lipid,Emulsions,on Free,Fatty,Acids,*,*,5-Lipoxygenase Metabolism in PMN,*availability of free fatty acid(AA/EPA),*Eicosapentaenoic acid is the preferred substrate,Design:,controlled,randomised,study,Setting:,Intensive Care Unit,Patients:,21 septic shock patients,6 healthy controls,Nutrition:,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,Cytokines,Mayer,K et al,Mayer 2003,Am J,Resp,Crit,Care,Med,Mayer,Curr,Opin,Clin,Nutr,2006,Biochemical,Background,Use,of RvE1 in a,Colitis-Model,Read-out,:,Letality,weight,histology,inflammatory,genes,Mayer,Curr,Opin,Clin,Nutr,2006,Impact of n-3,Lipids,on,Immunity,Case,History,07.11.2006,Female patient,*1939,Arterial hypertension,Smoker,Multiple,herniates,disks lower back,Presented with acute abdomen,Bowel sounds present,Pain,Tender Abdomen,Case History 07.11.2006,CT thorax+abdomen,Exsudative,pancreatitis,Lung edema,Case History 07.11.2006,transferred to medical intensive care unit,Clinical Course,Upon improvement transfer to step-down unit 3 days later,After 2 days development of acute,dyspnoea,Low blood pressure,Clinical Course,Re-Transfer to intensive care unit,Beginning ARDS,Severe,necrotising,pancreatitis(CT),Clinical Course,Intubation,Difficult respiratory situation,FiO2 0,7-1,0;,PaO2 50 70 mm Hg;,Acute renal failure,MODS,Clinical,Course,Septic,course,Addition 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,installed,Clinical,Course,Slow,improvement,of,the,patient,Improvement,of ARDS,Sucessful,weaning,and,extubation,Discharge,of,the,patient,to a,rehabilitation,facility,Second,case,Patient,male,*14.12.1961,Travel to,Italy,a,week,before,admittance,Presented,with,fever,and,cough,to,another,hospital,Clinical,course,Intubation,01.07.2007,Development,of ARDS,Difficult,ventilation,situation,Transfer to,our,facility,02.07.2007,Clinical,course,02.07.2007,PaO2/Fi02=60,mmHg,further,detoriation,Installation of,ECMO-therapy,Received,diagnosis,of,legionella,pneumonia,due,to positive,urine,test in,other,hospital,Addition of FO on,top,of TPN and EN,Clinical,course,07.2007,Gradual,improvement,with,therapy,Weaning,from,ECMO,Weaning,from,ventilation,Discharge,to,rehabilitation,center,Conclusion:Sepsis+n-3 lipids,Beneficial actions of n-3 FA containing lipid emulsions in models of acute lung injury and sepsis,Improved organ function/integrity,Improved bacterial killing,Improved outcome due to n-3 FA containing diets in patients with acute lung injury and sepsis,Possible benefits of n-3 containing lipid emulsions in septic patients,Thank,you,for,your,attention,