液體復(fù)蘇-膠體的地位

1、-170多年前（1832一位蘇格蘭醫(yī)師，發(fā)現(xiàn)了這種通過靜脈血管把藥液送入人體的治療手段明膠GELATIN白蛋白ALBUMIN1915World War I1945World War II1960War In Vietnam 右旋糖苷DEXTRAN羥乙基淀粉1943World War II為什么要開發(fā)出這些膠體?重癥液體復(fù)蘇的重要性膠體及其作用目前的爭論總結(jié)什么是膠體?膠體（colloid）又稱膠狀分散體（colloidal dispersion） 是一種均勻混合物，在膠體中含有兩種不同相態(tài)的物質(zhì)，一種分散，另一種連續(xù)。分散的一部分是由微小的粒子或液滴所組成，大小介于1到100納米之間，且?guī)缀醣?/p>

2、布在整個連續(xù)相態(tài)中。按分散劑的不同可分為： 氣溶膠(霧、煙、云)； 固溶膠(水晶、有色玻璃) 液溶膠（蛋白溶液，淀粉溶液，肥皂水，人體血液）人體白蛋白的含量與分布細胞內(nèi)液細胞外液體液-約占人體體重60%40%組織間液15%血漿5%蛋白質(zhì)在血漿中含量遠遠高于組織間液血漿總蛋白含量約為60-80g/L其中，白蛋白含量約為35-50g/L（占血漿總蛋白的60%)Frank-Starling 定律2022/10/5(Multi-) Organ FailureCell dystructionby imbalance between O2 - supply andO2 - consumptionO2und

3、ersupportO2debtMacrocirculatorydysfunction COMicrocirculatorydysfunctionWhat else besides volume restriction and expansion?Fluid resuscitationTissue oxygenationCapillary leak ameliorationHemodynamicsClinical outocmeRisk of AnaphylaxisEffect on coagulationEffect on Renal functionJean-Louis Vincent, M

4、ax Harry Weil, Crit Care Med 2006; 34:13331337IntroductionAcutely ill patients frequently require fluid repletion.HypovolemiaExternal loss: bleeding, gastrointestinal, urinary tracts, skinInternal loss: extravasation of blood, exudation / transudation of fluidsRelative Hypovolemia: increases venous

5、capacitanceSepsis, drugsVolume repletion may be essential to restore critical levels of cardiac output and arterial pressure, resulting in more normal perfusion of vital organs and tissues.Jean-Louis Vincent, Max Harry Weil, Crit Care Med 2006; 34:13331337Acutely ill patients frequently require flui

6、d repletionHypovolemia: external loss & internal lossRelative Hypovolemia: increases venous capacitanceVolume repletion may be essential Restore critical levels of cardiac output and arterial pressureMore normal perfusion of vital organs and tissuesJean-Louis Vincent, Max Harry Weil, Crit Care Med 2

7、006; 34:13331337IntroductionHemorrhage:Benefit / risk of fluid repletion must be assessedBenefits of delayed resuscitationLarge volume of fluid red cell deficit oxygen deficitPersistent hypovolemia will result in MODSFluid repletion is typically more effective during hypovolemic states but is less e

8、ffective in later stages.Jean-Louis Vincent, Max Harry Weil, Crit Care Med 2006; 34:13331337“fluid challenge”Jean-Louis Vincent, Max Harry Weil, Crit Care Med 2006; 34:13331337Distinguished from conventional fluid administrationUsually to critical patients with cardiorespiratory failureThe fluid cha

9、llenge is reserved for hemodynamically unstable patients and offers three major advantages:Quantitation of the cardiovascular response during volume infusion.Prompt correction of fluid deficits. Minimizing the risk of fluid overload and its potentially adverse effects, especially on the lungs.重癥液體復(fù)蘇

10、的重要性膠體及其作用目前的爭論總結(jié)復(fù)蘇液體種類白蛋白血漿?明膠膠體液晶體液林格氏液生理鹽水 右旋糖苷羥乙基淀粉改良明膠HES200/0.5HES130/0.4尿聯(lián)明膠聚明膠肽天然膠體人工膠體高滲鹽液7.5%鹽水+低右晶體液復(fù)蘇？贊成使用晶體液的理由：費用低，容易得到對腎功能保持較好很少產(chǎn)生不良反應(yīng)。這幾種液體都能糾正脫水可糾正低鈉血癥高滲鹽水（HS）擴容效率高反對使用晶體液的理由：平均留駐時間短（只有45min）液體輸入量大造成血清白蛋白的稀釋，血滲透壓降低，間質(zhì)水腫、肺水腫稀釋血中凝血因子降低血小板計數(shù)和血紅細胞壓積血液攜氧能力下降，降低組織氧合Koustova E, Stanton K,

11、Gushchin V, et al. Trauma 2002;52:872-878.Rotstein OD. Trauma 2000;49:580-83.Lang K, Boldt J, Suttner S, et al. Analg.2001.93:405-409.The edema problem of crystalloids is well known“Fluid is poured into the interstitial space on clinical information gained from changes in intravascular space.The end

12、 point,.peripheral or pulmonary edema”Twigley & Hillman, Anesthesia 1985;40:860-871因生存率下降NHLBI 終止高張鹽水治療休克的研究NIH所屬的國立心肺血液研究所(NHLBI)已經(jīng)終止了一項有關(guān)嚴重出血導(dǎo)致休克的創(chuàng)傷患者的臨床液體復(fù)蘇干預(yù)試驗該試驗旨在研究高張鹽水溶液治療此類患者療效及安全性試驗終止的原因：觀察到高張鹽水治療組患者在到達醫(yī)院或急診科前病死率顯著升高，盡管高張鹽水組及生理鹽水組患者28天病死率（研究終點）相似 NHLBI Halts Study of Concentrated Saline for

13、 Shock Due to Lack of Survival Benefit.American Academy of Emergency Medicine 2009 - 16 (3),MedScape Today COP balance essential for balanced flow across capillary 膠體滲透壓的平衡是毛細血管的交換的基本因素Crystalloids cannot impact COP Edema 單獨使用晶體無法維持膠體滲透壓水腫Colloids help to restore COP and reduce Crystalloid load膠體液有助

14、于恢復(fù)膠體滲透壓和減少晶體負荷 Artery (Arteriole)動脈,小動脈Vein (Venule)靜脈,小靜脈Plasma Protein Colloid Osmotic Pressure膠體滲透壓22 mm Hg簡化Starling定律Hydrostatic Pressure靜水壓32 mm HgHydrostatic Pressure靜水壓12 mm HgTissue Fluid組織液Hypovolemia Edema, organ damage低血容量 水腫, 器官損傷膠體滲透壓膠體液的作用容量作用：維持血流動力學(xué)穩(wěn)定維持血漿膠體滲透壓改善微循環(huán)改善組織細胞氧供 非容量作用：改善

15、CLS改善炎性反應(yīng)物質(zhì)結(jié)合和轉(zhuǎn)運抗氧化作用(colloid)151 consecutivelymajor trauma patients William C. ShoemakerOutcome Prediction of Emergency Patients by Noninvasive Hemodynamic Monitoring Chest. 2001;120:528-537 William C. ShoemakerOutcome Prediction of Emergency Patients by Noninvasive Hemodynamic Monitoring Chest. 20

16、01;120:528-537 Hemodynamcs（ crystalloid ）: 151 consecutivelymajor trauma patientsNormalSubstance P- 1 min laterStudy of Capillary LeakDirect: Scanning EM: normal endothelial cell junction Donald McDonald 1999Crit Care Med 2006; 34:17751782白蛋白增加血漿中抗氧化劑硫醇含量Gregory J. etc. Crit Care Med. 2004;32:755-75

17、9 白蛋白增加血漿中抗氧化劑含量Gregory J. etc. Crit Care Med. 2004;32:755-759 The SAFE Study Alb: saline deaths 726:729 (RR 0.99)Similar new organ failuresICU LOSHospital LOSVentilator durationRRTConclusion: Outcome with albumin in ICU no different from SalineQ: Does this mean crystalloids and colloids are the sam

18、e? Does this mean all colloids are same?Finfer et al, NEJM 2004;350:2247-56重癥液體復(fù)蘇的重要性膠體及其作用目前的討論總結(jié)膠體液復(fù)蘇并無優(yōu)勢-薈萃分析Objective: the effect on mortality of resuscitation with colloid compared with crystalloids. Design: Systematic review of randomised controlled trials of resuscitation with colloids compar

19、ed with crystalloids for critically ill patients; Subjects: 37 randomised controlled trials were eligible: 26 uncompounded trials that compared colloids with crystalloids (n=1622), 10 trials that compared colloid in hypertonic crystalloid with isotonic crystalloid (n=1422) and one trial that compare

20、d colloid in isotonic crystalloid with hypertonic crystalloid (n=38).Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials. BMJ 1998;316:9614.Conclusions: This systematic review does not support the con

21、tinued use of colloids for volume replacement in critically ill patients.Cochrane Report（2008）ObjectivesTo assess the effects of colloids compared to crystalloids for fluid resuscitation in critically ill patients.Main results: identified 63 eligible trials, 55 of these presented mortality data.Coll

22、oids compared to crystalloids Albumin - 23 trials reported data on mortality, including a total of 7,754 patients. The pooled relative risk (RR) was 1.01 (95% confidence interval 95% CI 0.92 to 1.10). When the trial with poor quality allocation concealment was excluded, pooled RR was 1.00 (95% CI 0.

23、91 to 1.09). Hydroxyethyl starch - 16 trials compared hydroxyethyl starch with crystalloids, n = 637 patients. The pooled RR was 1.05 (95% CI 0.63 to 1.75). Modified gelatin - 11 trials compared modified gelatin with crystalloid, n = 506 patients. The pooled RR was 0.91 (95% CI 0.49to 1.72). Dextran

24、 - nine trials compared dextran with a crystalloid, n = 834 patients. The pooled RR was 1.24 (95% CI 0.94 to 1.65). Eight trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1,283 randomised participants. Pooled RR was 0.88 (95% CI 0.74 to 1.05).Perel P, Roberts I,

25、 Colloids versus crystalloids for fluid resuscitation in criticallyill patients (Review). The Cochrane Library 2008, Issue 3Authors conclusions：There is no evidence from RCTs that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with tra

26、uma, burns or following surgery. Cochrane Report（2008）As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patients can be justified outside the context of RCTs.Perel P, Roberts I, Colloid

27、s versus crystalloids for fluid resuscitation in criticallyill patients (Review). The Cochrane Library 2008, Issue 3注：Cochrane是國際最大的循證醫(yī)學(xué)試驗的協(xié)作網(wǎng)，以已故英國內(nèi)科醫(yī)師和著名流行病學(xué)家ArchieCochrane的名字命名膠體，ICU用，還是不用？Fluid Challenge 500-100 ml cristalloids 300-500 ml colloids over 30 min control CVP or PAOPand reduce speed/

28、volume accordingly Grade 1DSurviving Sepsis Caign: International guidelines for management of severe sepsis and septic shock: 2008Crit Care Med 2008 Vol. 36, No. 1Figure. Differences (in percentage from baseline) of tissue oxygentension (ptio2) in the two volume groupsKatrin Lang, Joachim Boldt, Ste

29、fan Suttner, et al. Colloids VersusCrystalloids and Tissue Oxygen Tension in Patients Undergoing Major Abdominal Surgery. Anesth Analg 2001;93:4059白蛋白對于重癥患者結(jié)論：白蛋白可以顯著降低重癥病例整體并發(fā)癥的發(fā)生（危險比:0.92;可信區(qū)間:0.86-0.98)；且并發(fā)癥的發(fā)生率與白蛋白的使用劑量顯著相關(guān)（p=0.002)( Albumin-B-004) Vincent, Jean-Louis, Navickis, Roberta J. Wilke

30、s, Mahlon M. Morbidity in hospitalized patients receiving human albumin: A meta-analysis of randomized, controlled trials * Crit Care Med 2004;32(10):2029-2038膠體：我們關(guān)心的組織氧代謝？SHOCK, 2006 Vol. 25, No. 2, pp. 103Y116 Schortgen et coll Lancet 2001 , 357 , 911SurvivorsHEA or gelatine for Severe Sepsis ?Re

31、suscitation:selection of FluidCrystalloids or Colloids can be used Fluid challenges with colloids allow for more rapid completion of challenge. Crystalloid:Physiologic (0.9%) salt solution (saline) May increase serum chloride concentrationsBalanced salt solutions (Ringers lactate / Hartmanns solutio

32、n)Mildly hypotonic, may exacerbate cerebral edemaJean-Louis Vincent, Max Harry Weil, Crit Care Med 2006; 34:13331337Resuscitation: selection of FluidSAFE study: albumin vs crystalloid solutionMortality rate was identical Hypoalbuminemia is associated with higher morbidityVincent JL et al, Ann Surg 2003; 237:319334: meta-analysisAlbumin administration may reduce complications in critically ill patientsSAFE trial:Improved survival with albumin in patients wi