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1、N-3 Lipids in Critical Care Medicine,Dr. Konstantin MayerUniversity of Giessen Lung CenterPulmonary and Critical Care MedicineUniversity Hospital Giessen and Marburg,Lipid Mediator Synthesis,Impact of n-3 vs. n-6 Fatty Acids on Inflammation,Key Features of Acute Lung Injury,Randomized, controlled st
2、udy21 Pts with septic ARDS LCT or LCT/MCT 12g/hPulmonary 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 1997Am J R
3、esp 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 +,Effects of Parenteral Application ofFish Oil versus Soy Bean Oil Emulsionson Bacterial Clearance FunctionsI. Kelbel, T. Koch, A. Prechtl, A. H
4、eller,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 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 r
5、ich) 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,Number of bacterial colonies in the lung,Kelbel et al. 1999,Long-term lipid-infusion in mice,Leukocyte Invasion
6、 in a Model of Acute Lung Injury Impact of n-3 Lipids,LPS,*,Crit Care Med 2007,BALBroncho alveolar lavageLPSlipopolysaccharide,Enteral n-3 lipids + anti-oxidants:N-3 Lipids & ARDS,RCT of 146 critically ill patients acute lung injury and positive bronchoalveolar lavage for leukocytesDouble-blindedEnt
7、eral: N-3 Lipids vs. high fat dietGadek, 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?,Lipid emulsions are a mainstay of parenteral nutritionused in
8、 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/Ex
9、otoxin,Focus,Bacterialtranslocation,nosocomialPneumonia,1. barrier dysfunction,Gut,2. barrier dysfunction,Improvement of blood flow in the intestine 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,Improvement of bacterial killing in t
10、he 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,Impact of Fish Oil on LPS-induced Response in Volunteers,8 volunteers 0.5 g/kg/d FO for 2 d8 volunteers no infusionLPS 2 ng/kg intravenousreadout: cytokines, hormones, RR, HF, t
11、emperature, ,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 responseReduced bacterial killing / clearanceIncreased primary / seconday organ damageMay translate into clinical effects,S
12、IRS,CARS,Biphasic reaction of leukocytes in septic patients,Hyper,Hypo,Effective Response,Mayer, Curr Opin Clin Nutr Metab Care 1998,SIRS: systemic inflammatory response syndromeCARS: compensatory anti-inflammatory response syndrome,Design: open label, randomized, pilot studySetting:Intensive Care U
13、nitPatients: 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 al,Free Fatty Acids: Lipid Emulsions and Intensive Care,Free Fatty
14、 Acids,LPL,Heparin,J Am Acad Dermatol 1998Intensive 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 st
15、udySetting: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, Cytokines,Mayer, K et al,Mayer 2003, Am J Resp Crit Care Med,Mayer, Curr Opin Clin Nut
16、r 2006,Biochemical Background,Use of RvE1 in a Colitis-ModelRead-out: Letality, weight, histologyinflammatory 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 backPresen
17、ted with acute abdomenBowel sounds presentPainTender 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 laterAfter 2 days developm
18、ent of acute dyspnoeaLow blood pressure,Clinical Course,Re-Transfer to intensive care unitBeginning ARDSSevere necrotising pancreatitis (CT),Clinical Course,IntubationDifficult respiratory situation FiO2 0,7 - 1,0; PaO2 50 70 mm Hg; Acute renal failureMODS,Clinical Course,Septic courseAddition of FO
19、 (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 patientImprovement of ARDSSucessful weaning and extubationDischarge of the patient to a reha
20、bilitation facility,Second case,Patient, male, *14.12.1961Travel to Italy a week before admittancePresented with fever and cough to another hospital,Clinical course,Intubation 01.07.2007Development of ARDSDifficult ventilation situationTransfer to our facility 02.07.2007,Clinical course 02.07.2007,P
21、aO2/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 EN,Clinical course 07.2007,Gradual improvement with therapyWeaning from ECMOWeaning from ventilationDischarge to
22、rehabilitation center,Conclusion: Sepsis + n-3 lipids,Beneficial 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 patients,Thank you for your attention,
