液體復(fù)蘇-膠體的地位-管向東.ppt

液體復(fù)蘇-膠體的地位,中山大學(xué) 附屬第一醫(yī)院 重癥醫(yī)學(xué)科 管向東,-170多年前（1832年）， 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,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)缀醣椴荚谡麄€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(xì)胞 內(nèi)液,細(xì)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(yuǎn)遠(yuǎn)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%),2019/7/9,Frank-Starling 定律,(Multi-) Organ Failure,Microcirculatory dysfunction,What else besides volume restriction and expansion?,Fluid resuscitation,Tissue oxygenation,Capillary 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. 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 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; 34:13331337,Acutely ill patients frequently require fluid repletion Hypovolemia: external loss & internal loss Relative Hypovolemia: increases venous capacitance Volume repletion may be essential Restore critical levels of cardiac output and arterial pressure More 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 assessed Benefits of delayed resuscitation Large volume of fluid red cell deficit oxygen deficit Persistent 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,Distinguished from conventional fluid administration Usually to critical patients with cardiorespiratory failure The fluid challenge 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,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(kuò)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(xì)胞壓積 血液攜氧能力下降，降低組織氧合,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 from changes in intravascular space. The end point,.peripheral or pulmonary edema”,Twigley 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(yán)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(dá)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 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(xì)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 膠體液有助于恢復(fù)膠體滲透壓和減少晶體負(fù)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 Hg,Hydrostatic Pressure 靜水壓12 mm Hg,Tissue 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(xì)胞氧供 非容量作用： 改善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 consecutively major trauma patients,William C. Shoemaker Outcome Prediction of Emergency Patients by Noninvasive Hemodynamic Monitoring Chest. 2001;120:528-537,William C. Shoemaker Outcome Prediction of Emergency Patients by Noninvasive Hemodynamic Monitoring Chest. 2001;120:528-537,Hemodynamcs（ crystalloid ）: 151 consecutively major 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,白蛋白增加血漿中抗氧化劑硫醇含量,Gregory J. etc. Crit Care Med. 2004;32:755-759,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 failures ICU LOS Hospital LOS Ventilator duration RRT Conclusion: Outcome with albumin in ICU no different from Saline,Q: 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 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 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 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）,Objectives To 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. 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 allocation 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 RR was 0.91 (95% CI 0.49 to 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 1.05).,Perel P, Roberts I, Colloids versus crystalloids for fluid resuscitation 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（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, Colloids 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Archie Cochrane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 PAOP and reduce speed/volume accordingly,Grade 1D,Surviving Sepsis Campaign: 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 oxygen tension (ptio2) in the two volume groups,Katrin Lang, Joachim Boldt, Stefan 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. Wilkes, 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 , 911,Survivors,HEA or gelatine for Severe Sepsis ?,Resuscitation:selection of Fluid,Crystalloids 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 concentrations Balanced salt solutions (Ringers lactate / Hartmanns solution) Mildly hypotonic, may exacerbate cerebral edema,Jean-Louis Vincent, Max Harry Weil, Crit Care Med 2006; 34:13331337,Resuscitation: 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 complications in critically ill patients SAFE trial: Improved survival with albumin in patients with sepsis who are hypoalbuminemia