N-3脂肪酸在急重症的应用课件

1、N-3 Lipids in Critical Care MedicineDr. Konstantin MayerUniversity of Giessen Lung CenterPulmonary and Critical Care MedicineUniversity Hospital Giessen and MarburgLipid Mediator SynthesisImpact of n-3 vs. n-6 Fatty Acids on InflammationKey Features of Acute Lung Injury pulmonary hypertension VQ-mis

2、match / Shuntvasomotor dysfunction vascular leakagegas exchange secundary bacterial invasionQO2O2O2 leukocyte invasionCapillary sequestrationAlveolar invasionN-3 LipidsRandomized, controlled study21 Pts with septic ARDS LCT or LCT/MCT 12g/hPulmonary hemodynamics / Ventilation parameterResultsLCT (n-

3、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 1995Am 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 s

4、eptic lung failureLTB4 +LTB4 +LTB4 +LTB5 +Effects 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, 1999Experimental

5、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.

6、 injectionParameters: Bacterial counts in lung, liver, spleen & kidneyNumber of bacterial colonies in the lungKelbel et al. 1999Long-term lipid-infusion in miceLeukocyte Invasion in a Model of Acute Lung Injury Impact of n-3 LipidsLPS*Crit Care Med 2007BALBroncho alveolar lavageLPSlipopolysaccharide

7、Enteral 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;27:1409ARDS Enteral n-3 LipidsAdapted from: Gadek JE. et al., Crit C

8、are Med 1999; 27:1409-20p = .011p = .016Do 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 sequestrationAlve

9、olar invasionLipid emulsions are a mainstay of parenteral nutritionused in many ventilated patients with acute lung injuryImmunologic 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 recommenda

10、tionN-3 lipids and bacterial translocation / bacterial killing?Endo/ExotoxinFocusBacterialtranslocationnosocomialPneumonia1. barrier dysfunctionGut2. barrier dysfunctionImprovement 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

11、 (40%)Pscheidl, E et alImprovement 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 alImpact of Fish Oil on LPS-induced Response in Volunteers8 volunteers 0.5 g/kg/d FO for 2 d8 volunteers no infusionLPS 2

12、ng/kg intravenousreadout: cytokines, hormones, RR, HF, temperature, Pluess T et al., Intensive Care Med. 2007; 33(5):789-97Fish Oil reduces LPS-induced fever-response in volunteersEffect of SBO-based lipidsIncreased inflammatory responseReduced bacterial killing / clearanceIncreased primary / second

13、ay organ damageMay translate into clinical effectsSIRSCARSBiphasic reaction of leukocytes in septic patientsHyperHypoEffective ResponseMayer, Curr Opin Clin Nutr Metab Care 1998 SIRS: systemic inflammatory response syndromeCARS: compensatory anti-inflammatory response syndromeDesign: open label, ran

14、domized, 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 alInfectionSepsisFree F

15、atty Acids: Lipid Emulsions and Intensive CareFree Fatty AcidsTriglyceridesLPLHeparinLipid MediatoresJ Am Acad Dermatol 1998Intensive Care Med 2003Impact of Sepsis and Infusion of Lipid Emulsions on Free Fatty Acids*5-Lipoxygenase Metabolism in PMN* availability of free fatty acid (AA / EPA)* Eicosa

16、pentaenoic acid is the preferred substrateDesign: 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, CytokinesMa

17、yer, K et alMayer 2003, Am J Resp Crit Care MedMayer, Curr Opin Clin Nutr 2006Biochemical BackgroundUse of RvE1 in a Colitis-ModelRead-out: Letality, weight, histologyinflammatory genesMayer, Curr Opin Clin Nutr 2006Impact of n-3 Lipids on ImmunityCase History 07.11.2006Female patient, *1939, Arteri

18、al hypertension, Smoker, Multiple herniates disks lower backPresented with acute abdomenBowel sounds presentPainTender AbdomenCase History 07.11.2006CT thorax + abdomen Exsudative pancreatitis Lung edemaCase History 07.11.2006transferred to medical intensive care unitClinical CourseUpon improvement

19、transfer to step-down unit 3 days laterAfter 2 days development of acute dyspnoeaLow blood pressureClinical CourseRe-Transfer to intensive care unitBeginning ARDSSevere necrotising pancreatitis (CT)Clinical CourseIntubationDifficult respiratory situation FiO2 0,7 - 1,0; PaO2 50 70 mm Hg; Acute renal

20、 failureMODSClinical 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 CourseSlow improvement of the patientImprovement of ARDSSucessful wean

21、ing and extubationDischarge of the patient to a rehabilitation facilitySecond casePatient, male, *14.12.1961Travel to Italy a week before admittancePresented with fever and cough to another hospitalClinical courseIntubation 01.07.2007Development of ARDSDifficult ventilation situationTransfer to our facility 02.07.2007Clinical course 02.07.