1、液体复苏-胶体的地位中山大学 附属第一医院 重症医学科管向东明胶明胶GELATINGELATIN白蛋白白蛋白ALBUMINALBUMIN19151915World World War IWar I19451945World War IIWorld War II19601960War In Vietnam War In Vietnam 右旋糖苷右旋糖苷DEXTRANDEXTRAN羟乙基淀粉羟乙基淀粉19431943World War IIWorld War II为什么要开发出这些胶体为什么要开发出这些胶体?重症液体复苏的重要性 胶体及其作用 目前的争论 总结什么是胶体?胶体（colloid）又称
2、胶状分散体（colloidal dispersion）是一种均匀混合物，在胶体中含有两种不同相态的物质，一种分散，另一种连续。分散的一部分是由微小的粒子或液滴所组成，大小介于1到100纳米之间，且几乎遍布在整个连续相态中。按分散剂的不同可分为：气溶胶(雾、烟、云)；固溶胶(水晶、有色玻璃)液溶胶（蛋白溶液，淀粉溶液，肥皂水，人体血液）细胞内液细胞外液体液-约占人体体重60%40%组织间液15%血浆5%蛋白质在血浆中含量远远高于组织间液血浆总蛋白含量约为60-80g/L其中，白蛋白含量约为35-50g/L（占血浆总蛋白的60%)2023-2-7Frank-Starling 定律定律 COWhat
3、 else besides volume restriction and expansion?Fluid resuscitationTissue oxygenationCapillary leak ameliorationHemodynamicsClinical outocmeRisk of AnaphylaxisEffect on coagulationEffect on Renal functionJean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337Introduction Acutely ill patients
4、 frequently require fluid repletion.Hypovolemia External loss:bleeding,gastrointestinal,urinary tracts,skin Internal loss:extravasation of blood,exudation/transudation of fluids Relative Hypovolemia:increases venous capacitance Sepsis,drugs Volume repletion may be essential to restore critical level
5、s 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;34:13331337 Acutely ill patients frequently require fluid repletion Hypovolemia:external loss&internal loss Relative Hypovolemia:increases ven
6、ous capacitance Volume repletion may be essential Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337Introduction:Benefit/risk of fluid repletion must be assessed Benefits of delayed resuscitation Large volume of fluid red cell deficit oxygen deficit Persistent hypovolemia will result i
7、n MODSJean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337Distinguished from conventional fluid administrationUsually to critical patients with cardiorespiratory failureThe fluid challenge is reserved for patients and offers
8、 three major advantages:重症液体复苏的重要性 胶体及其作用 目前的争论 总结复苏液体种类复苏液体种类白蛋白白蛋白血浆血浆?明胶明胶胶体液胶体液晶体液晶体液林格氏液林格氏液生理盐水生理盐水 右旋糖苷右旋糖苷羟乙基淀粉羟乙基淀粉改良明胶改良明胶HES200/0.5HES130/0.4尿联明胶尿联明胶聚明胶肽聚明胶肽天然胶体天然胶体人工胶体人工胶体高渗盐高渗盐液液7.5%盐水盐水+低右低右晶体液复苏？z赞成使用晶体液的理由：z费用低，容易得到z对肾功能保持较好z很少产生不良反应。这几种液体都能纠正脱水z可纠正低钠血症z高渗盐水（HS）扩容效率高z反对使用晶体液的理由：z平均留
9、驻时间短（只有45min）z液体输入量大z造成血清白蛋白的稀释，血渗透压降低，间质水肿、肺水肿z稀释血中凝血因子z降低血小板计数和血红细胞压积z血液携氧能力下降，降低组织氧合Koustova E,Stanton K,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 The edema problem of crystalloi
10、ds is well knownis well knownu“Fluid is poured into the“Fluid is poured into the interstitial space on clinical interstitial space on clinical information gained from changes information gained from changes in intravascular space.in intravascular space.uThe endThe end point,.peripheral point,.periph
11、eral or pulmonary edema”or pulmonary edema”Twigley&Hillman,Twigley&Hillman,Anesthesia Anesthesia 1985;40:860-871 1985;40:860-871因生存率下降NHLBI 终止高张盐水治疗休克的研究NIH所属的国立心肺血液研究所(NHLBI)已经终止了一项有关严重出血导致休克的创伤患者的临床液体复苏干预试验该试验旨在研究高张盐水溶液治疗此类患者疗效及安全性试验终止的原因：观察到高张盐水治疗组患者在到达医院或急诊科前病死率显著升高，尽管高张盐水组及生理盐水组患者28天病死率（研究终点）相似
12、 NHLBI Halts Study of Concentrated Saline for Shock Due to Lack of Survival Benefit.American Academy of Emergency Medicine 2009-16(3),MedScape Today Colloids help to restore COP and reduce Crystalloid load胶体液有助于恢复胶体渗透压和减少晶体负荷胶体液有助于恢复胶体渗透压和减少晶体负荷 Artery(Arteriole)动脉,小动脉Vein(Venule)静脉,小静脉Plasma Protei
13、n Colloid Osmotic Pressure胶体渗透压22 mm Hg简化简化Starling定律定律Hydrostatic Pressure静水压32 mm HgHydrostatic Pressure静水压12 mm HgTissue Fluid组织液Hypovolemia Edema,organ damage低低血容量血容量 水肿水肿,器官损伤器官损伤胶体渗透压胶体液的作用(colloid)151 consecutivelymajor trauma patients William C.ShoemakerOutcome Prediction of Emergency Patien
14、ts by Noninvasive Hemodynamic Monitoring Chest.2001;120:528-537 William C.ShoemakerOutcome Prediction of Emergency Patients by Noninvasive Hemodynamic Monitoring Chest.2001;120:528-537 Hemodynamcs（crystalloid）:151 consecutivelymajor trauma patientsNormalSubstance P-1 min laterStudy of Capillary Leak
15、Crit Care Med 2006;34:17751782白蛋白增加血浆中抗氧化剂硫醇含量Gregory J.etc.Crit Care Med.2004;32:755-759 白蛋白增加血浆中抗氧化剂含量Gregory J.etc.Crit Care Med.2004;32:755-759 The SAFE Study Alb:saline deaths 726:729(RR 0.99)Similar new organ failures ICU LOS Hospital LOS Ventilator duration RRT Conclusion:Outcome with albumin
16、 in ICU no different from SalineQ:Does this mean crystalloids and colloids are the same?Does this mean all colloids are same?Finfer et al,NEJM 2004;350:2247-56 重症液体复苏的重要性 胶体及其作用 目前的讨论 总结胶体液复苏并无优势-荟萃分析 Objective:the effect on mortality of resuscitation with colloid compared with crystalloids.Design:S
17、ystematic review of randomised controlled trials of resuscitation with colloids compared 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 hyp
18、ertonic crystalloid with isotonic crystalloid(n=1422)and one trial that compared 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
19、1998;316:9614.Conclusions:This systematic review does not support the continued 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:
20、identified 63 eligible trials,55 of these presented mortality data.Colloids 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 alloc
21、ation concealment was excluded,pooled RR was 1.00(95%CI 0.91 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
22、 RR was 0.91(95%CI 0.49to 1.72).Dextran-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
23、 1.05).Perel P,Roberts I,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,i
24、n patients with trauma,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,Robe
25、rts I,Colloids versus crystalloids for fluid resuscitation in criticallyill patients(Review).The Cochrane Library 2008,Issue 3注：Cochrane是国际最大的循证医学试验的协作网，以已故英国内科医师和著名流行病学家Archie Cochrane的名字命名胶体，ICU用，还是不用？Fluid Challengep 500-100 ml cristalloidsp 300-500 ml colloidsp over 30 minp control CVP or PAOPan
26、d reduce speed/volume accordingly Grade 1DSurviving Sepsis Campaign: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 Bol
27、dt,Stefan Suttner,et al.Colloids VersusCrystalloids and Tissue Oxygen Tension in Patients Undergoing Major Abdominal Surgery.Anesth Analg 2001;93:4059白蛋白对于重症患者接受白蛋白治疗的重症患者的并发症接受白蛋白治疗的重症患者的并发症:一项荟萃分析一项荟萃分析(Albumin-B-004)Vincent,Jean-Louis,Navickis,Roberta J.Wilkes,Mahlon M.Morbidity in hospitalized p
28、atients receiving human albumin:A meta-analysis of randomized,controlled trials*Crit Care Med 2004;32(10):2029-2038胶体：我们关心的组织氧代谢？SHOCK,2006 Vol.25,No.2,pp.103Y116 Schortgen et coll Lancet 2001,357,911SurvivorsHEA or gelatine for Severe Sepsis?Resuscitation:selection of Fluid Crystalloids or Colloids
29、 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 concentrations Balanced salt solutions(Ringers lactate/Hartmanns solution)Mildly hypotonic,may exacerbate cerebral edemaJean-Louis Vi
30、ncent,Max Harry Weil,Crit Care Med 2006;34:13331337Resuscitation:selection of Fluid SAFE study:albumin vs crystalloid solution Mortality rate was identical Hypoalbuminemia is associated with higher morbidity Vincent JL et al,Ann Surg 2003;237:319334:meta-analysis Albumin administration may reduce co
31、mplications in critically ill patients SAFE trial:Improved survival with albumin in patients with sepsis who are hypoalbuminemia(relative risk of death,0.87;95%CI,0.74 1.02;p 0.06)Albumin may be beneficial in this subset of critically ill patientsJean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;
32、34:13331337Resuscitation:selection of Fluid Synthetic colloid solution:Hydroxyethyl starch solutions:Less expensive,adverse effects on blood clotting Gelatins:Smaller MW,less effective plasma expanders,low costJean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337Resuscitation:selection of
33、 Fluid No intravenous fluid solution that is ideal in all clinical settings No secure data support a preference for one over another The choice is best made contingent on:the underlying disease the type of fluid that has been lost the severity of circulatory failure the serum albumin concentration of the patient the risk of bleeding.Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337 重症液体复苏的重要性 胶体及其作用 目前的争论 总结总 结 重症病人的液体复苏，是最重要/最早的复苏手段之一 容量替代、血流动力学稳定、组织氧合均是临床液体复苏的重要目标 液体选择种类很多，无论何种液体（晶胶体），从使用开始，需要考虑不良作用 胶体液的使用，要同时考虑容量以外问题 目前，晶体或胶体复苏孰优孰劣，需要更有说服力的循证医学证据支持谢谢！
