1、临床输血:我们如何做得更好?ICU人类输血史 1656年，血液输入血管成功。1667年，人体尝试接受输入动物血。1817-1818年，人体间开始真正输血，其中8例中3例输入成功。1900年Landsteiner首先发现了红细胞血型，这一划时代的发现，使输血变得安全、有效，从此输血真正在临床上使用，成为许多危重疾病的抢救手段。Pope Innocent VIII“a Jewish daring innovator,whose name has not come down to us in memory of his deed,proposed to find the pontiff a foun
2、tain of jouvenance in the blood of three youths who died as martyrs to their own devotion and the practitioners zeal.”Drinkard,18701492年罗马教皇八世患脑卒中，群医束手无策，有一名医生提出饮用人血来治疗，结果病未治好，有三位年轻人因放血过多白白送了命。血液循环的发现血液循环的发现：William Harvey(1578 1657)1616:Harvey calculated that blood flows at the rate of 8640 oz/hr a
3、nd discovered that blood circulates throughout the bodyWrote Exercitatio anatomica de motu cordis et sanguinis in animalibus in which he reported his findingsThe Paris Faculty of Medicine 目前公认英国Lower开创了动物输血的先河，法国Denys是第一个在人体上输血的成功者。Richard Lower(1631-1691)早期输血:动物 人Early lamb blood transfusion浓厚的宗教或迷
4、信的色彩浓厚的宗教或迷信的色彩 早期输血不是建立在理性基础上，也不是用于失血或贫血的治疗，而是带有浓厚的宗教或迷信的色彩，以为输血可能改变行为或使人返老还童。James BlundellIn 1818,James Blundell attempted human-to human transfusion of a man suffering from gastric carcinoma.“What is to be done in such an emergency?A dog might come when you whistled,but the animal is small;a cal
5、f might have appeared better suited for the purpose,but then it has not been taught to walk properly up the stairs.”人人Blundells transfusion devices included the impellor(A),which consisted of a cup,tube,and syringe;and the gravitator(B),consisting of a receptacle held high above the patient with an
6、attached tube through which the blood was injected into the patient.Karl Landsteiner1930 Nobel Prize LaureateIn 1900,Landsteinershowed that serum fromsome individuals couldagglutinate or hemolyzethe red blood cells of certain,but not all,other individuals.The serum ofthe latter would likewiseaggluti
7、nate the red bloodcells of the former.Still other individuals red cells were unaffected by the serum from either of these.He named these threedifferent types A,B,andC.Today these are typesA,B,and O.发现血型如何更长时间保存血液？How to store blood longer?Is there any suitable Blood Blood SubstitutesSubstitutes输血指征
8、血红蛋白下降到多少才需要输血？研究背景研究背景 虽然每年全球范围内输RBC血量达8500万单位，但是输血实践却有很大的不同；AABB制定了这个指南，推荐血流动力学稳定成人和儿童临床输RBC的血红蛋白阈值和其他临床指标。最佳使用是足够的红细胞能最大限度地提高临床效果，同时避免不必要的输血导致费用增加或潜在的感染性或非感染性风险。1950-2011.2：RCT，不限语言 Cochrane Injuries Group Specialized Register,CENTRAL(Cochrane Central Register of Controlled Trials),MEDLINE from 1
9、950 to the second week of August 2009,EMBASE from 1980 to the fourth week of 2011,SCI-EXPANDED(Science Citation Index Expanded)from 1970 to February 2011,CPCI-S(Conference Proceedings Citation Index-Science)from 1990 to February 2011 Grade分级系统评估指标评估指标 总体死亡率总体死亡率 非致命心肌梗死非致命心肌梗死心血管事件 肺水肿卒中 血栓形成肾功能衰竭 感
10、染出血 精神异常 功能康复 住院时间主要依据：3项大型RCT TRICC(Transfusion Requirements in Critical Care)TRIPICU(Transfusion Strategies for Patients in Pediatric Intensive Care Units)FOCUS(Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair)trialQ1.对于血流动力学稳定的住院
11、患者，Hb水平处于什么范围时，应考虑输注红细胞？推荐：遵循限制性输注策略。对于ICU成人和儿童患者，当Hb水平70 g/L时，应该考虑输注红细胞。对于术后患者，当Hb水平80 g/L或出现贫血症状（如胸痛、直立性低血压、或心动过速且对液体复苏无效或充血性心力衰竭）可考虑输注红细胞。推荐依据：该推荐基于限制性输注策略很安全，且血液使用量较少。证据质量：高；推荐强度：强。AABB guidelineQ2.对于既往患心血管疾病、血流动力学稳定的住院患者，Hb水平处于什么范围时，应考虑输注红细胞？推荐：遵循限制性输注策略。当Hb水平80 g/L或出现如胸痛、直立性低血压、心动过速且液体复苏无效、充血性
12、心力衰竭症状时，考虑输注红细胞。推荐依据：该推荐依据为红细胞输注后总体死亡率不受负面影响，较少红细胞输注可降低花费及输注所致不良反应的发生危险。证据质量：中等；推荐强度：弱。AABB guideline Q3.对于血流动力学稳定的急性冠脉综合征住院患者，Hb处于什么水平时应考虑输注红细胞？推荐：不推荐支持或反对开放性或限制性红细胞输注策略。需要进一步研究以确定最佳阈值。不推荐支持或反对的依据：缺少随机对照试验的临床资料。证据质量：非常低；推荐强度：不确定。AABB guidelineQ4.对于血流动力学稳定的住院患者，红细胞输注应以贫血症状而不是Hb水平为指导吗？推荐：患者的贫血症状与Hb水平
13、均可影响是否输注红细胞的决定推荐依据：FOCUS试验结果支持当Hb水平80g/L时，基于贫血症状决定是否输注红细胞的观点。证据质量：低；推荐强度：弱。AABB guidelineFOCUS 研究背景：术后RBC输注阈值一直存在争议。探讨更高的阈值对骨盘骨折手术病人的恢复是否有益。方法：2016例骨盘骨折，50岁，有心血管病史或高危因素，术后Hb10g/dL。随机分成2组：开放输血组（阈值Hb10g/dL），限制输血组（Hb8g/dL，贫血症状或医师判断）。判断标准：60天死亡率及室内自行行走。FOCUS 结果：院内急性冠脉综合症：4.3%vs 5.2%60天死亡率：7.6%vs 6.6%其他并
14、发症发生率也相似 结论：开放输血策略并未改善预后FOCUSTRICC 研究背景：开放或限制输血策略是否与重症病人的预后有关。比较30天全因死亡率及器官功能障碍严重程度。方法：838例收入ICU病人，72h内Hb9.0g/dL限制组：418例，Hb 79g/dL（7.0，输血）开放组：420例，Hb 1012g/dL（10，输血）TRICC 结果：限制 vs 开放 30天死亡率18.7%vs 23.3%,P=0.11 院内死亡率22.2%vs 28.1%，P=0.05 APACHEII20、年龄限制组 其他并发症无差异 结论：对于重症病人，限制输血策略至少与开放策略同样有效，可能优于开放策略（除
15、外急性心梗和不稳定性心绞痛）TRICCTRIPICU 研究背景：儿科重症输注RBC的最佳阈值未明确。假设通过MODS评分，认为限制性输血策略与开放性输血策略同样安全。方法：637例儿科重症病人，病情相对稳定，收入ICU后7天内Hb9.5g/dL 限制性输血（Hb7.0g/dL），开放性输血（Hb9.5g/dL）结果：限制vs开放：8.70.4 vs 10.80.5g/dL,P0.001,平均低2.10.2 g/dLTRIPICU患者情况及结果：均无差异！死亡率、感染率、机械通气时间等均无差异输血：给我们带来哪些危险？3项大型国际研究，24,112 例急性冠脉综合征（ACS）病人 输血与预后之间
16、相关性 Cox 比例风险模型 主要观察点：30天死亡率RaoSVetal.JAMA.2004;292:1555-1562Relationship of Blood Transfusion and Clinical Outcomes in Patients With Acute Coronary SyndromesRaoSVetal.JAMA.2004;292:1555-1562TransfusionNo TransfusionAdjusted hazard ratio 3.94(3.26-4.75)观察性研究的荟萃分析45项研究-272,596 例病人对年龄及疾病严重程度进行多因素方差分析校正
17、 观察指标:死亡率 感染率 多器官功能障碍 ARDSCritCareMed2008;36(9):2667-74结果：输血与死亡、感染并发症风险密切相关CritCareMed2008;36(9):2667-74Association between blood transfusion and the risk of death(OR&95%CI).Pooled OR 1.7(95%CI 1.4-1.9)Association between blood transfusion and the risk of infectious complications(OR&95%CI).Pooled OR
18、 1.8(95%CI 1.5-2.2)输血与ARDS发生密切相关CritCareMed2008;36(9):2667-74Association between blood transfusion and the risk of ARDS(OR&95%CI).Pooled OR 2.5(95%CI 1.6-3.3)输血的风险输血的风险 病毒传播 急性输血反应 免疫抑制 急性炎症反应Noninfectious HazardsImmunosuppressionInfectionDecline in HIV,HBV,HCV Risks of Transmission via Blood TxBusc
19、h MP,et al.JAMA.2003;289:959-62.1:1001:10001:10,0001:100,0001:1,000,0001:10,000,000198319851987198919911993199519971999 2001Revised DonorDeferral CriteriaNon-A,Non-B Hepatitis Surrogate TestingHIV AntibodyScreeningHCV AntibodyScreeningp24 AntigenTestingHCV and HIVNucleic AcidTestingHIVHCVHBV输血风险：感染性
20、疾病输血风险：感染性疾病HIV =1 in 1.8 millionHCV=1 in 1.6 millionHBV=1 in 220,000HIV=human immunodeficiency virus.HCV=hepatitis C virus.HBV=hepatitis B virus.Busch MP,et al.JAMA.2003;289:959-62.Williamson LM,et al.BMJ.1999;319:16-9.Serious Hazards of Transfusion8%2%14%15%53%输血的危险性输血的危险性Minor allergic reactionsB
21、acterial infection(platelets)Viral hepatitisHemolytic transfusion reactionHTLV I/II infectionAcute lung injuryAnaphylactic shockFatal hemolytic reactionGraft-vs-host diseaseImmunosuppression1:1001:2,5001:5,0001:6,0001:200,0001:500,0001:500,0001:600,000RareUnknownHTLV=human T-cell leukemia-lymphoma v
22、irus.Klein HG.Am J Surg.1995.170;6A(suppl):21S-26S.输血增加术后细菌感染的危险输血增加术后细菌感染的危险 20项研究,1986-2000 N=13,152(输血 5215例,No-Tx 7937例)输血相关感染：输血相关感染：Common OR 3.45(range 1.43-15.15)17 of 20 studies with p 0.05 创伤亚组：创伤亚组：Common OR 5.26(range 5.03-5.43)All studies with p 0.05(0.005 0.0001)Blood Tx associated wit
23、h greater risk in trauma ptsHill GE,Minei JP et al.J Trauma 2003;54:908-914Prospective cohort study,n=2085Project Impact Nosocomial Infections:14.3%vs.5.8%,p 0.001Taylor RW et al.Crit Care Med 2006;34:23022308 15,592 例心血管手术病人 观察指标：菌血症、皮肤及软组织感染 55%病人接受浓缩RBC,21%血小板,13%纤维蛋白原,3%冷沉淀 增加输注RBC与感染发生率增加有关(p 0
24、.0001)J Am Coll Surg 2006;202:131-138ReedW,etal.Semin Hematol 2007:44:24-31Utter G et al.Transfusion 2006 Nov;46(11):1863-9Leukoreduction does not diminish tx-associated MicrochimerismGould S et al.Am J Crit Care;Jan 2007;16(1):39-48输血为什么不能改变输血为什么不能改变病人的预后？病人的预后？库存红细胞 RBC可塑性降低 2,3,DPG减少 代谢性酸中毒 携氧能力降
25、低 随时间延长，RBC死亡增加(30%dead)不能改变组织的氧利用l 全血（Whole Blood）4，35天血小板及凝血因子35天后无活性l 浓缩红细胞（pRBC）储存：4，42天l 血小板 储存：20-24条件下5天 指征：血小板减少症,15,000出血 50,000有创操作 15 days lose deformability and ATP Altered capillary lumen size(decreased cross-sectional diameter)in critically ill patients Increased“stickiness”(adherence)
26、of RBCs to altered endothelium in the microcirculation of critically ill pts.Distribution of Transfused Units by Age of Blood CRIT StudyPercentage of PatientsOldest Age of Blood in Days0-10 10-20 20-30 30-40 4060%of Blood transfused is 20 days oldIn Trauma Subset,68%of blood is 20 days oldThe median
27、 duration of storage was 11 days for newer blood and 20 days for older blood.Patients who were given older units had higher rates of in-hospital mortality(2.8%vs.1.7%,P=0.004),intubation beyond 72 hours(9.7%vs.5.6%,P0.001),renal failure(2.7%vs.1.6%,P=0.003),and sepsis or septicemia(4.0%vs.2.8%,P=0.0
28、1).A composite of complications was more common in patients given older blood(25.9%vs.22.4%,P=0.001).Similarly,older blood was associated with an increase in the risk-adjusted rate of the composite outcome(P=0.03).At 1 year,mortality was significantly less in patients given newer blood(7.4%vs.11.0%,
29、P0.001).Composite Outcome:In-hospital mortalityAnd Complications(STS)Blood Transfusion and ClinicalStudies on RBC transfusion and outcome in ischemic heart disease.YearStudyDesignnPatientsPrimary ResultsHebert1997RetrospectiveCritically ill patients with cardiac disease,as part of a retrospective as
30、sessment of transfusion practices in Canadian ICUsIncreased survival with transfusion when Hb 8g/dL Decreased mortality in patients with nadir Hb 30%Decreased mortality in patients with nadir Hematocrit 24%Adapted in part from:Gerber DR.Crit Care Med 2008;36(4):1068-1074.Effect of Blood Transfusion
31、on Long-Term Survival After Cardiac Operation1915 CABG ptsAfter correction for comorbidities and other factors,tx was still associated with a 70%increase in mortality(RR 1.7;95%CI 1.4 to 2.0;p 0.001).Engoren MC et al.(MCO,Toledo)Ann Thorac Surg 2002;74:1180610,289 CABG pts,1995 2002Perioperative RBC
32、 tx is associated with adverse outcome.Attention should be directed toward blood conservation methods and a more judicious use of PRBC.Ann Thorac Surg 2006;81:1650 70123-5 6Cleveland Clinic,OHSummary 贫血在重症病人中是常见的贫血在重症病人中是常见的 没有证据表明输血可以改变重症病人的预后没有证据表明输血可以改变重症病人的预后 重症病人可以耐受的重症病人可以耐受的HbHb下限：下限：7 mg/dL
33、7 mg/dL 应当根据病人的生理情况决定是否输血应当根据病人的生理情况决定是否输血是否输注RBC？临床医师：Hb水平（阈值）指南：不仅仅是Hb水平，更强调贫血症状中中 国国 1999年1月，卫生部颁布的医疗机构临床用血管理办法中明确规定，病人血红蛋白低于100g/L和血球压积低于30的属于输血适应证。1997年3月修订的新刑法第334条和第335条：在输血工作中，对不依照规定进行血液检测或者违背其他操作规程，造成危害他人身体健康后果的，对单位判处罚金，并对其直接负责的主管人员和其他直接负责人员，处五年以下有期徒刑或者拘役。医务人员由于严重不负责任，造成就诊人死亡或者严重损害就诊人身体健康的，
34、处三年以下有期徒刑.其他输血指南American Society of AnesthesiologistsBritish Committee for Standards in Haematology Australian and New Zealand Society of Blood Transfusion European Society of CardiologyACS8g/dL SCCM/EASTadult trauma and critical care 7g/dL （排除心肌缺血）67g/dL比利时鲁汶大学Vincent评论（1）应更关注输血及其相关问题，而不是贫血相关问题。任何输
35、血决定必须权衡输血相关的风险和收益，以及限制输血引起的贫血。尽管输血与不良转归相关，但贫血也可以增加死亡率。评估开放性与限制输血策略的研究常强调输注数量问题，而未考虑到纳入患者人群的特殊特征（特别是冠状动脉疾病和患者年龄）。AABB推荐的具体输注阈值有助于使输注实践标准化，但是该方法过于简单,仅基于Hb水平决定是否输注理由不充分 根据典型的贫血症状，如疲乏、心动过速和呼吸困难（或机械通气），做出输血决定不够合理，因为这些是反映疾病严重程度的常见指标。输注决策需要考虑到患者个体因素，如年龄和是否存在冠状动脉疾病，以评估特殊患者从输注中获益的可能性。临床上输血决策是一个复杂的过程，需要进行全面考虑，不能仅靠单一数值做出决定。比利时鲁汶大学Vincent评论（2）有时很无奈有时也很纠结请指教，谢谢!
