N-3脂肪酸在急重癥的應(yīng)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兒童常見(jiàn)癥狀的鑒別與處理發(fā)熱 驚厥嘔吐 腹痛頭痛 腿痛兒童常見(jiàn)癥狀發(fā)熱是最常見(jiàn)的癥狀，見(jiàn)于各種全身性和（或）局部性感染，以及許多非感染性疾病它是小兒很多疾病中的一種癥狀，是對(duì)疾病的反射性反應(yīng)人在安靜狀態(tài)下，體溫一般恒定，呈明顯晝夜變化，清晨最低，晚上最高，但一日之差不超過(guò)1飲食、劇烈運(yùn)動(dòng)、哭鬧、情緒激動(dòng)等都可

25、使體溫暫時(shí)性升高，這不屬于病理性發(fā)熱發(fā) 熱正常體溫3637.4低熱37.5 38中度發(fā)熱38.1 39高熱39.1 41超高熱41發(fā) 熱發(fā)熱的觀察精神狀態(tài)；面色；呼吸；伴隨癥狀如嘔吐、頭痛處理措施 通風(fēng)散熱，解開衣服多飲水、吃清淡易消化的食物 物理降溫：冷毛巾濕敷、洗溫水浴 體溫超過(guò)39時(shí)給退熱劑或洗溫水澡發(fā) 熱驚厥是常見(jiàn)的一類不隨意運(yùn)動(dòng)，表現(xiàn)為全身或局部肌群突然發(fā)生不自主收縮現(xiàn)象，常伴有意識(shí)障礙癥狀驚厥下列臨床征象的任何一項(xiàng)應(yīng)警惕驚厥的發(fā)作極度煩躁或不時(shí)“驚跳”，精神緊張神情驚恐，四肢肌張力突然增加呼吸突然急促，暫?；虿灰?guī)律體溫驟升，面色劇變驚厥驚厥先兆多數(shù)為驟然發(fā)作，典型者為突然意識(shí)喪失或

26、跌倒，兩眼上翻或凝視、斜視，頭向后仰或轉(zhuǎn)向一側(cè)，口吐白沫，牙關(guān)禁閉，面部、四肢呈強(qiáng)直性或陣攣性抽搐，伴有呼吸屏氣，面色紫紺，大小便失禁，經(jīng)數(shù)秒、數(shù)分或數(shù)十分鐘后驚厥停止，進(jìn)入昏睡狀態(tài)。發(fā)作停止后不久意識(shí)恢復(fù)驚厥臨床癥狀驚 厥高熱引起的驚厥發(fā)生率很高，占兒童期的30%特點(diǎn)多發(fā)年齡為6個(gè)月至3歲上感引起者占60%全身性抽搐并伴有意識(shí)障礙癥狀，停止后，意識(shí)很快恢復(fù)一次發(fā)熱性疾病中，一般只發(fā)作1次，很少發(fā)作2次以上抽搐時(shí)間短暫可追尋到高熱驚厥史和家族遺傳史預(yù)后良好，少數(shù)可轉(zhuǎn)變?yōu)榘d癇（1%3%）處理措施保持呼吸道通暢，防止窒息：平臥；清除口、鼻、喉內(nèi)的分泌物或嘔吐物；人工呼吸驚厥發(fā)作時(shí)，應(yīng)進(jìn)行緊急止驚，

27、觀察抽搐情況防止意外損傷控制驚厥：首選藥物安定或用水化氫醛灌腸法止驚針刺取穴人中、合谷穴或用拇指指壓人中、印堂、合谷等穴位驚厥護(hù)理專人守護(hù)，防止意外損傷注意監(jiān)護(hù)，詳細(xì)記錄呼吸、脈搏、血壓、體溫、精神、神志以及瞳孔變化和驚厥發(fā)作情況高熱者應(yīng)及時(shí)松解衣褲以利散熱，并采用物理法降溫供給充足的熱量與水分，觀察排泄物性狀，注意留取標(biāo)本，并及時(shí)送檢驚厥嘔吐嘔吐是小兒常見(jiàn)癥狀之一，多由消化系統(tǒng)疾病引起，也可由全身各系統(tǒng)和器官的多種疾病引起神經(jīng)性嘔吐咽食過(guò)急過(guò)快，條件發(fā)射；心理障礙，厭食消化系統(tǒng)疾病動(dòng)力性、感染性、消化道畸形消化道外疾病顱內(nèi)疾?。焊鞣N腦膜炎、腦炎、腦外傷等呼吸道消化道疾?。荷细?、支氣管炎、肺炎等其他：喂養(yǎng)不當(dāng)、各種食物或藥物中毒 嘔吐病因嘔吐處 理一般處理：嘔吐后飲適量開水、避免劇烈運(yùn)動(dòng)頻繁嘔吐：及時(shí)給予口服補(bǔ)鹽液或送醫(yī)院給予輸液長(zhǎng)期