N-3脂肪酸在急重症的应用

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

22、facility 02.07.2007Clinical course 02.07.2007PaO2/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 ENClinical course 07.2007Gradual improvement with therapyWeaning fr

23、om ECMOWeaning from ventilationDischarge to rehabilitation centerConclusion: 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 diet

24、s in patients with acute lung injury and sepsisPossible benefits of n-3 containing lipid emulsions in septic patientsThank you for your attention儿童常见症状的鉴别与处理发热 惊厥呕吐 腹痛头痛 腿痛儿童常见症状发热是最常见的症状，见于各种全身性和（或）局部性感染，以及许多非感染性疾病它是小儿很多疾病中的一种症状，是对疾病的反射性反应人在安静状态下，体温一般恒定，呈明显昼夜变化，清晨最低，晚上最高，但一日之差不超过1饮食、剧烈运动、哭闹、情绪激动等都可

25、使体温暂时性升高，这不属于病理性发热发 热正常体温3637.4低热37.5 38中度发热38.1 39高热39.1 41超高热41发 热发热的观察精神状态；面色；呼吸；伴随症状如呕吐、头痛处理措施 通风散热，解开衣服多饮水、吃清淡易消化的食物 物理降温：冷毛巾湿敷、洗温水浴 体温超过39时给退热剂或洗温水澡发 热惊厥是常见的一类不随意运动，表现为全身或局部肌群突然发生不自主收缩现象，常伴有意识障碍症状惊厥下列临床征象的任何一项应警惕惊厥的发作极度烦躁或不时“惊跳”，精神紧张神情惊恐，四肢肌张力突然增加呼吸突然急促，暂停或不规律体温骤升，面色剧变惊厥惊厥先兆多数为骤然发作，典型者为突然意识丧失或

26、跌倒，两眼上翻或凝视、斜视，头向后仰或转向一侧，口吐白沫，牙关禁闭，面部、四肢呈强直性或阵挛性抽搐，伴有呼吸屏气，面色紫绀，大小便失禁，经数秒、数分或数十分钟后惊厥停止，进入昏睡状态。发作停止后不久意识恢复惊厥临床症状惊 厥高热引起的惊厥发生率很高，占儿童期的30%特点多发年龄为6个月至3岁上感引起者占60%全身性抽搐并伴有意识障碍症状，停止后，意识很快恢复一次发热性疾病中，一般只发作1次，很少发作2次以上抽搐时间短暂可追寻到高热惊厥史和家族遗传史预后良好，少数可转变为癫痫（1%3%）处理措施保持呼吸道通畅，防止窒息：平卧；清除口、鼻、喉内的分泌物或呕吐物；人工呼吸惊厥发作时，应进行紧急止惊，

27、观察抽搐情况防止意外损伤控制惊厥：首选药物安定或用水化氢醛灌肠法止惊针刺取穴人中、合谷穴或用拇指指压人中、印堂、合谷等穴位惊厥护理专人守护，防止意外损伤注意监护，详细记录呼吸、脉搏、血压、体温、精神、神志以及瞳孔变化和惊厥发作情况高热者应及时松解衣裤以利散热，并采用物理法降温供给充足的热量与水分，观察排泄物性状，注意留取标本，并及时送检惊厥呕吐呕吐是小儿常见症状之一，多由消化系统疾病引起，也可由全身各系统和器官的多种疾病引起神经性呕吐咽食过急过快，条件发射；心理障碍，厌食消化系统疾病动力性、感染性、消化道畸形消化道外疾病颅内疾病：各种脑膜炎、脑炎、脑外伤等呼吸道消化道疾病：上感、支气管炎、肺炎等其他：喂养不当、各种食物或药物中毒 呕吐病因呕吐处 理一般处理：呕吐后饮适量开水、避免剧烈运动频繁呕吐：及时给予口服补盐液或送医院给予输液长期