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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,-170多年前（1832年），一位苏格兰医师，发现了这种通过静脉血管把药液送入人体的治疗手段,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
2、体血液）,人体白蛋白的含量与分布,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%),2023/1/21,Frank-Starling 定律,(Multi-)Organ Failure,Microcirculatorydysfunction,What else besides volume restriction and expansion?,Fluid resuscitation,Tissue oxygenation,Capillary
3、 leak amelioration,Hemodynamics,Clinical outocme,Risk of Anaphylaxis,Effect on coagulation,Effect on Renal function,Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337,Introduction,Acutely ill patients frequently require fluid repletion.HypovolemiaExternal loss:bleeding,gastrointestinal
4、,urinary tracts,skinInternal loss:extravasation of blood,exudation/transudation of fluidsRelative Hypovolemia:increases venous capacitanceSepsis,drugsVolume repletion may be essential to restore critical levels of cardiac output and arterial pressure,resulting in more normal perfusion of vital organ
5、s and tissues.,Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337,Acutely ill patients frequently require fluid repletionHypovolemia:external loss&internal lossRelative Hypovolemia:increases venous capacitanceVolume repletion may be essential Restore critical levels of cardiac output a
6、nd arterial pressureMore normal perfusion of vital organs and tissues,Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337,Introduction,Hemorrhage:Benefit/risk of fluid repletion must be assessedBenefits of delayed resuscitationLarge volume of fluid red cell deficit oxygen deficitPersist
7、ent hypovolemia will result in MODS,Fluid repletion is typically more effective during hypovolemic states but is less effective 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;34:13331337,Disting
8、uished from conventional fluid administrationUsually to critical patients with cardiorespiratory failureThe fluid challenge is reserved for hemodynamically unstable patients and offers three major advantages:Quantitation of the cardiovascular response during volume infusion.Prompt correction of flui
9、d deficits.Minimizing the risk of fluid overload and its potentially adverse effects,especially on the lungs.,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,高渗盐液7.5%盐水+低右,晶体液复苏？,赞成使用晶体液的理由：费用低，容易得到对肾功能保持较好很少产生不良反应。这几种液体都能纠正脱水可纠正低钠血症高渗盐水（HS）扩容效率高反对使用晶体液的理由：平均留驻时间短（只有45min）液体输入量大造成血清白蛋白的稀释，血渗透压降低，间质水肿、肺水肿稀释血中凝血因子降低血小
10、板计数和血红细胞压积血液携氧能力下降，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 is well known,“Fluid is poured into the interstitial space on clinical information gained f
11、rom changes in intravascular space.The end point,.peripheral or pulmonary edema”,Twigley 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,NHLBI Halts Study of Conce
12、ntrated Saline for 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 胶体渗透压的平衡是毛细血管的交换的基本因素Crystalloids cannot impact COP Edema 单独使用晶体无法维持胶体渗透压水肿,Colloids help to restore COP and reduce Cryst
13、alloid load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 Protein Colloid Osmotic Pressure胶体渗透压22 mm Hg,简化Starling定律,Hydrostatic Pressure静水压32 mm Hg,Hydrostatic Pressure静水压12 mm Hg,Tissue Fluid组织液,Hypovolemia Edema,organ damage低血容量 水肿,器官损伤,胶体渗透压,胶体液的作用,容量作用：维持血流动力学稳定维持血浆胶体渗透压
14、改善微循环改善组织细胞氧供 非容量作用：改善CLS改善炎性反应物质结合和转运抗氧化作用,(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
15、Monitoring Chest.2001;120:528-537,Hemodynamcs（crystalloid）:151 consecutivelymajor trauma patients,Normal,Substance P-1 min later,Study of Capillary Leak,Direct:Scanning EM:normal endothelial cell junction Donald McDonald 1999,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 Me
16、d.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 failuresICU LOSHospital LOSVentilator durationRRTConclusion:Outcome with albumin in ICU no different from Saline,Q:Does this mean crystalloids and colloids
17、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:Systematic review of randomised controlled trials of resuscitation with collo
18、ids 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 hypertonic crystalloid with isotonic crystalloid(n=1422)and one trial that comp
19、ared 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 cont
20、inued 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.Collo
21、ids 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 0.91 to 1.09).Hy
22、droxyethyl 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-nine trials compared dextran wit
23、h 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,Colloids versus crystalloids for fluid resusci
24、tation in criticallyill patients(Review).The Cochrane Library 2008,Issue 3,Authors conclusions：There is no evidence from RCTs that resuscitation with colloids reduces the risk of death,compared to resuscitation with crystalloids,in patients with trauma,burns or following surgery.,Cochrane Report（200
25、8）,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,Colloids versus crystalloids for fluid resuscitation in criti
26、callyill 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ArchieCochrane的名字命名,胶体，ICU用，还是不用？,Fluid Challenge,500-100 ml cristalloids 300-500 ml colloids over 30 min control CVP or PAOPand reduce speed/volume accordingly,Grade 1D,Surviving Sepsis Campaign:
27、International guidelines for management of severe sepsis and septic shock:2008Crit Care Med 2008 Vol.36,No.1,Figure.Differences(in percentage from baseline)of tissue oxygentension(ptio2)in the two volume groups,Katrin Lang,Joachim Boldt,Stefan Suttner,et al.Colloids VersusCrystalloids and Tissue Oxy
28、gen Tension in Patients Undergoing Major Abdominal Surgery.Anesth Analg 2001;93:4059,白蛋白对于重症患者,结论：白蛋白可以显著降低重症病例整体并发症的发生（危险比:0.92;可信区间:0.86-0.98)；且并发症的发生率与白蛋白的使用剂量显著相关（p=0.002),(Albumin-B-004),Vincent,Jean-Louis,Navickis,Roberta J.Wilkes,Mahlon M.Morbidity in hospitalized patients receiving human alb
29、umin: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 2001,357,911,Survivors,HEA or gelatine for Severe Sepsis?,Resuscitation:selection of Fluid,Crystalloids or Colloids can be used Fluid cha
30、llenges 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 solution)Mildly hypotonic,may exacerbate cerebral edema,Jean-Louis Vincent,Max Harry Weil,C
31、rit Care Med 2006;34:13331337,Resuscitation:selection of Fluid,SAFE 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 criticall
32、y ill patientsSAFE 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 patients,Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337,Resuscitatio
33、n:selection of Fluid,Synthetic colloid solution:Hydroxyethyl starch solutions:Less expensive,adverse effects on blood clottingGelatins:Smaller MW,less effective plasma expanders,low cost,Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337,Resuscitation:selection of Fluid,No intravenous
34、fluid solution that is ideal in all clinical settingsNo secure data support a preference for one over anotherThe choice is best made contingent on:the underlying diseasethe type of fluid that has been lostthe severity of circulatory failurethe serum albumin concentration of the patientthe 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！,
