张循善输血治疗传统观念的变革与更新XXXX省医学会.ppt

1、输血治疗传统观念的变革与更新,主要内容,询证输血医学新观念 现代输血疗法的临床应用,询证输血医学新观念,输血作为重症患者的支持疗法没有询证依据 同种输血能够导致外科患者及重症患者不良转归 输血不能促进伤口愈合 “失多少血，补多少血”是过时、错误观念,Crit Care Med 2009 Vol. 37, No. 12. 3124,Crit Care Med 2004; 32Suppl.:S542S547,意大利国家指南 Blood Transfus 2009; 7: 49-64,Annals of Internal Medicine 2012 ； 157（1）：50,输血作为支持疗法不再是现代

2、红细胞输注指征,败血症患者要求较高Hb水平的适应证不包括支持目的,Conditions in septic patients that may require a higher hemoglobin Acute instability Cardiovascular disease Coronary artery disease Low cardiac output Pulmonary disease Severe arterial hypoxemia Organ or tissue ischemia Severe mixed venous desaturation（混合静脉血氧饱和度，过低表明

3、组织氧合障碍） Elevated lactate level Use of blood products in sepsis: An evidence-based review. Crit Care Med 2004; 32(Suppl):S542S547.,FFP适应证不包括抗感染输注FFP不能作为支持疗法,Fresh-Frozen Plasma Transfusion Question: When should FFP be transfused in patients with severe sepsis? Recommendation: Routine use of FFP to co

4、rrect laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures is not recommended. FFP is indicated for coagulopathy due to documented deficiency of coagulation factors (increased PT APTT) in the presence of active bleeding or before surgical or invasive procedures

5、. Use of blood products in sepsis: An evidence-based review. Crit Care Med 2004; 32(Suppl):S542S547.,重症患者输注红细胞导致的不良转归,From 571 articles screened, 45 met inclusion criteria In 42 of the 45 studies the risks of RBC transfusion outweighed the benefits; Seventeen of 18 studies, demonstrated that RBC tra

6、nsfusions were an independent predictor of death; Twenty-two studies examined the association between RBC transfusion and nosocomial infection; in all these studies blood transfusion was an independent risk factor for infection. RBC transfusions similarly increased the risk of developing multi-organ

7、 dysfunction syndrome (three studies) and acute respiratory distress syndrome (six studies). Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literatureJ. Crit Care Med. 2008;36(9):2667-2674,相对危险度,腹腔间隙综合征,Prospective, multiple center, obse

8、rvational cohort study（观测队列研究） of 4,892 ICU pts in the US Propensity score（倾向指数） matched Designed to examine the relationship of anemia and RBC transfusion with clinical outcomes Almost 95% of patients admitted to the ICU have a Hb level below “normal” by day 3 In total, 11,391 RBC units were transf

9、used. Overall, 44% of pts admitted to the ICU received one or more RBC units while in the ICU,Crit Care Med. 2004 Jan;32(1):39-52,The mean pre-transfusion Hb was 8.6 1.7 g/dL,RBC transfusion was independently associated with higher mortality (OR 1.65 CI 1.35-2.03). OR 2.62 if 3-4 units transfused p

10、0.0001,35% of Blood transfused in patients with Hgb 9,Crit Care Med. 2004 Jan;32(1):39-52,Analysis of 24,112 enrollees in 3 large international trials of patients with acute coronary syndromes Association between transfusion and outcome Cox proportional hazards modeling Main outcome = 30 day mortali

11、ty,Rao SV et al. JAMA. 2004;292:1555-1562,Blood Transfusion and Clinical Outcome in Acute Coronary Syndrome,Rao SV et al. JAMA. 2004;292:1555-1562,Transfusion,No Transfusion,Adjusted hazard ratio 3.94 (3.26-4.75),研究对象,研究结论,老年退伍军人局,15,592 Cardiovascular operations Infection endpoints bacteremia, SSI

12、55% of pts received PRBCs, 21% plts, 13% FFP, 3% cryoprecipitate Increased RBC tx associated with increased infection (p 0.0001), confirmed by logistic regression analysis.,J Am Coll Surg 2006;202:131-138,Effect of Blood Transfusion on Long-Term SurvivalAfter Cardiac Operation,1915 CABG pts After co

13、rrection 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;74:11806,患者输注红细胞导致的不良转归机制,Storage lesion 库存红细胞2.3-DPG含量下降 Metabolic acidosis Altered oxygen carrying capac

14、ity 库存红细胞变形能力下降 库存红细胞携带NO能力减弱 Increased red cell death with increased age of blood (30% dead) No improvement in oxygen utilization at the tissue level 同种输血的免疫负向调节作用,研究结果,The median duration of storage was 11 days for newer blood and 20 days for older blood. Patients who were given older units had hi

15、gher 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 = 0.01). A composite of complications was more common in patients given older blood (25.9% vs. 22.4

16、%, 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%, P0.001).,Immune Effects of Blood,Immunologic effects of allogenic blood Tx D

17、ecreased T-cell proliferation Decreased CD3, CD4, CD8 T-cells Increased soluble cytokine receptor sTNF-R, sIL-2R Increased suppressor T-cell activity Reduced natural killer cell activity,McAlister FA et al, Br J Surg 1998;85:171-8. Innerhofer P et al, Transfusion 1999;39:1089-96.,输血不能促进伤口愈合,手术切口愈合紊乱

18、诊断标准,结果和机制,underwent laparotomy（剖腹术） underwent gastrectomy （胃切除） underwent gastroduodenostomy（胃十二指肠吻合术） CONCLUSIONS: Blood transfusions increased the incidence of anastomotic abscess（脓肿） and impaired anastomotic wound healing.,2001 and June 2005 we have performed a prospective observational study in

19、 1553 elective and emergency patients who underwent median sternotomy for heart surgery. CONCLUSIONS: According to our results, the total amount of allogeneic blood transfused is a major factor contributing to sternal dehiscence （胸骨裂开）regardless of other risk preconditions. European Journal of Anaes

20、thesiology: May 2006 - Volume 23 - Issue - p 1-2,Colorectal Dis.2007V9N4:362-7,“缺多少血，补多少血”与“失多少血，补多少血”是否合理？,英国输血一般原则,RBCs should be administered as single units for most operative and inpatient indications (transfuse and reassess strategy) except for ongoing blood loss with hemodynamic instability.

21、Tx decisions are clinical judgments that should be based on the overall clinical assessment of the individual patient. Transfusion decisions should not be based on laboratory parameters alone. Routine premedication is not advised unless the patient has a history of previous transfusion reactions. Pr

22、emedication has not been shown to reduce the risk of transfusion reactions.,Guidelines for Blood Transfusion: PRBCs,现代红细胞输注适应症和输注指征一 、慢性贫血,贫血时机体的反应* 慢性贫血的输血目的 提高血红蛋白水平，以保证组织供氧。因此应当输注红细胞即可，不应输注全血。 慢性贫血的输血原则 临床上输注红细胞主要是消除或减轻缺氧症状，只要将Hb水平提高到能保证足够的组织供氧即可，不需要通过输血将患者的Hb水平恢复到正常水平。.红细胞保存输血到HB正常水平不能改变患者的转归.PD

23、F,人类耐受低Hb的能力,英国红细胞输注指南（2002年）,Red Blood Cell Transfusion: A Clinical Practice GuidelineFrom the AABB,Ann Intern Med.2012V157N1:49-58,直立,Methods We enrolled 838 critically ill patients who had hemglobin concentrations of less than 9.0 g /dl and randomly assigned 418 patients to a restrictive strategy

24、 of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g /dl and hemoglobin concentrations were maintained at 7.0 to 9.0 g /dl, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g

25、/dl and hemoglobin concentrations were maintained at 10.0 to 12.0 g /dl. Results Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P=0.11). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.2 percent vs. 28.1

26、 percent, P=0.05).,输红细胞指征 一般认为Hb降低到正常值的 50以下，才需要输注红细胞；Hb降低不到上述水平但是患者伴有心、肺功能受损或心、脑等重要脏器的血管硬化，使组织得不到足够的氧时，也需要输注红细胞。 贫血病因的确定和治疗,二、急性贫血,由于手术、创伤和其它疾病引起的急性贫血，临床医生在输血指征掌握、血液成分品种的选择、输注剂量的确定时，应当根据患者的临床具体情况，才能做出正确的决定，才能安全、有效、及时的进行输血治疗。值得注意的是临床医生应当严格掌握输血指征，减少不必要的输血。,临床医生对急性失血的输血指征把握仍然存在问题,英国20072008年国家输血审核发现，3

27、8%患者缺少夜间输血临床指征；消化道出血患者输血 澳大利亚学者发现某教学医院blood product use was inappropriate for 16% of red cell, 13% of platelet and 31% of fresh frozen plasma (FFP) transfusion episodes. 国外学者研究结肠、直肠癌围手术期输血存在输血指征掌握不严现象。 国内部分外科医生输血指征掌握仍然不严 美国的临床输血管理,急性贫血输血和血液成分选择的依据 失血量 临床情况,失血量与输血指征关系,患者丢失20（新生儿10%）的血容量以下，或成人失血量在1000

28、毫升以内，不必输注红细胞； 失血量在2025时，及时补液和输注红细胞2单位即可； 失血量在25时，除了及时补液和输注红细胞外，可根据患者具体情况加输全血、FFP或血小板。,英国红细胞输注指南（2002年）,临床情况,心肺功能受损或伴有心脑血管病变的患者，由于心肺功能状况可直接影响机体耐受和代偿因急性失血引起的组织供氧不足，因此应当适当放宽输血指征； 患者失血前有无贫血及贫血程度： 患者骨髓和肝脏功能状况等也是在急性出血后是否输血，选择血液制品种类及输血剂量的重要因素。,血小板输注,血小板输注原则 预防性血小板输注 治疗性血小板输注 外科患者的血小板输注 血小板输注后的疗效评价,血小板输注原则,

29、血小板输血疗法主要应用在防止患者出血或治疗活动性出血。在临床上决定是否需要输注血小板以及输注剂量主要取决于患者临床情况、血小板减少的原因、血小板计数、患者血小板的功能。,预防性血小板输注的有关问题,血小板输注剂量 一般预防性血小板输注剂量为每10Kg体重输注2单位血小板/d或1个治疗量的机采血小板。目前尚无证据表明此类患者需要输注更大剂量的血小板。 计算公式预计达到的Plt（mm3）患者原有的Plt（mm3） 1.42 5000 注：国外每单位血小板是由400ml全血中制备，国内是从200ml全血中制备；国外血小板每单位是70109；国内24109。,预防性血小板输注的有关问题,血小板输注指征

30、 Plt 510109/L； 长期输注血小板者 难以达到疗效时，应当应用CCI来判断血小板的输注效果； 患者血小板功能异常 例如服用阿司匹林和尿毒症，临床医生应当根据临床具体情况决定是否需要输注血小板，不要机械的根据PLT； ITP患者血小板输注问题,输注血小板治疗活动性出血,患者PLT50109/L并伴有活动性出血时，应当进行血小板输注。,外科血小板输注,较大的外科手术患者术前PLT最好维持在50109/L以上。 血小板减少的患者术后应当维持PLT50109/L，以利于损伤愈合及防止出血。,血小板输注的疗效评估,对长期反复输注血小板者应当进行血小板疗效评估，确定下次血小板输注时间和剂量。,血

31、小板纠正指数corrected count increment （CCI）,（输注后血小板计数输注前血小板计数）体表面积(m2) 血小板纠正指数（CCI） 输注的血小板总数(1011) 血小板计数单位是109/L，输注后血小板计数 为输注后1小时Plt。 CCI710表示血小板输注无效,FFP的输注问题,不应做为营养剂、扩容剂 严格掌握适应征* 输注剂量 1015ml/kg,可提高凝血因子到正常水平的25 足量,FFP输注适应症,1. TTP; 2. 大量输血或术间急性出血，疑凝血因子缺乏； 3. 华法林过量的及时纠正（出血或即将手术）； 4. PT/APTT1.5对照，伴急性出血或侵入性手术

32、前出现下列情况： 单个凝血因子缺乏（不包括血友病A/B）； DIC; 肝衰竭。,Guidelines for the use of fresh-frozen plasma British Journal of Haematology 2004; 126:11,Single inherited clotting factor deficiencies for which no virus-safe fractionated product is available. ex. Factor V Multi-factor deficiencies associated with severe ble

33、eding (ex.DIC with bleeding) Fresh-frozen plasma is not indicated in DIC with no evidence of bleeding. Hypofibrinogenemia: Cryoprecipitate may be indicated if the plasma fibrinogen is less than 1 g/l, TTP: Single volume daily plasma exchange should ideally be begun at presentation (gradeA recommenda

34、tion, levelIb evidence),Guidelines for FFP,Surgical bleeding: Should be guided by timely tests of coagulation FFP should never be used as a simple volume relacement in adults or children (grade B recommendation, level IIb evidence). Massive transfusion: If bleeding continues after large volumes of c

35、rystalloid, red cells and platelets have been transfused, FFP and cryoprecipitate may be given so that the PT and APTT ratios are shortened to within 1.5, and a fibrinogen concentration of at least 1.0 g/l in plasma obtained.,British Journal of Haematology 2004; 126:11,Guidelines for FFP,DIC Treating the underlying cause is the cornerstone of managing DIC. If the patient is bleeding, a co