Blood Transfusion in Elderly Xinli NI, MD, PhD Department of Anesthesiology General Hospital of Ningxia Medical University, China xinlini6@nyfy.com.cn Good afternoon ,every one. I am xinli Ni from China ,general hospital of ningxia medical univisity It is my great hornor to stand here and commicate with you. Today I am going to talk about blood transfuasion in elderly

Blood donation in China in 2011 YinChuan Ningxia This is my hometown, Yinchuan,Ningxia located in notherwest of Chinese map TRANSFUSION 2015;55;2523–2530

of Ningxia Medical University General Hospital of Ningxia Medical University

Department of Anesthesiology Surgical Cases：42000 per year Doctors：103 Nurses：26 OR：52 Surgical Cases：42000 per year

How much blood is needed? Over 143 million operations are needed annually 28% of these will require transfusion support Using an average of 3 units RBCs 116 million total units In HICs, 76% go to those over 65 Louis M. Katz, et al. Transfusion, 2018;58(5);1299–1306 Based on a report of Third International Blood Safety Forum, globally …totally 116 units of RBC were transfused Date from report 2017, USA Third International Blood Safety Forum

Patients receiving transfusions increased with age In the surgical group, patients older than 65 years made up 41% of the group but accounted for 67.1% of patients receiving transfusions. Patients in the 70–80 age group receive eight times more RBCs units than patients aged 20–40 Patients over 65 years old received 86% more units of RBCs than patients less than 65 --Ali A, Auvinen. Transfusion 2010; 50(3):584–588 --Simone M, et al.Transfusion, 2010, 40(9):1140-1146 1、Finnish transfusion registry data demonstrated 2、And same study from France also shown

A 20-fold increase in RBC transfusion in patients older than 65 compared with patients younger than 40 years old This date from a Germany hospital also indicated older patients recieved more blood products They showed a 20-fold increase in the probability of receiving a RBC transfusion in any year during the observation period in patients older than 65 compared with the group of patients younger than 40 years old.

RBCs usage per capita by age in Finland 2002 to 2006 This is a Finland report, RBC usage was increasing with age

Simulation of clinical use of RBCs units per 1000 population (based on age-distributed variation in blood usage [as RBC units] in Finland between 2002 and 2006) based on age-distributed variation in blood usage, This trend is likely to similar in different country

Management of blood transfusion Why：Hemorrhage Anemia How：Transfusion thresholds Temperature What: Clinical outcomes Immediate and delayed complications Management of anemia and blood transfusion in older adults is controversial. We have to focus on the following three key points The most common indication for transfusion is Anemia, second reason is. haemorrhage Red blood cells not only increase oxygen carrying capacity, but they also play a role in providing hemostasis Elderly patients with their decline in physiological reserve and different responses to blood loss and anaemia are at increased risk from anaemia generally, as well as in the postoperative period.

Additional medical factors influencing blood product consumption Cardiovascular disease: coronary syndrome Coagulation disorders: hepatic function thrombocytopenia   Chronic renal disease: erythropoietin deficiency Hypoxia: pulmonary dysfunction Core body temperature: fever Additionally , we have to conside if patients have a pre-existing medicine disease, such as

Treatment in hemorrhage Maintain perfusion pressure Maintain oxygen delivery to organs Stop surgical bleeding Treat any coagulopathy Massive transfusion remains one of the greatest challenges for the anesthesiologist. It is most commonly seen in acute trauma, complex cardiac surgery, obstetric hemorrhage, and coagulopathic patients, but it may also occur with any intraoperative event.

The bloody vicious circle 布拉迪 微社 If a severe trauma patient was unable to be treated timely, the condition will develop into a bloody vicious circle

This date from Florida It shows Elderly patients had lower admission Hb levels (10.2 versus 11.3 g/dL), received more RBC transfusions

Aging may have a negative impact on postinjury anemia Even these elderly trauma patients receiving more transfusions , still had persistently lower Hb levels at discharge

AE is mostly mild, that is, with Hb around 11 to 12 g/dL HemaSphere2(3):e40, June 2018. Anemia in Elderly (AE) WHO estimates that the number of people aged >60 years will rise from 900 million in 2015 to 2 billion in 2050, moving from 12% to 22% of the global population WHO estimates that the number of people aged >60 years will rise from 900 million in 2015 to 2 billion in 2050 According to epidemiological studies, AE is a public problem ,mostly with mild Anemia ,Hb around 11 to 12 g/dL According to epidemiological studies, AE is mostly mild, that is, with Hb around 11 to 12 g/dL

The etiologies of AE are multifactorial and complex Mahmoudi R. 2017;24(3):200-208. A possible mechanism might be chronic suboptimal oxygen delivery to aged and possibly already damaged organs, including the heart.

Hb values between 13 to 15 g/dL for women and 14 to 17 g/dL for men shown the lowest risk for mortality HemaSphere2(3):e40, June 2018

Which one is more better Restrictive or liberal transfusion So for restrictive or liberal transfusion which one is better, the discussion has been for two dacades.

In this study from USA and Canada, they analysed the long-term mortality of patients assigned to the two transfusion strategies

Total around 1000 patients was analyzed in each group

Interpretation Long-term mortality did not differ significantly between the liberal transfusion strategy (432 deaths) and the restrictive transfusion strategy (409 deaths) (hazard ratio 1·09 [95% CI 0·95–1·25]; p=0·21). Liberal blood transfusion did not affect mortality compared with a restrictive transfusion strategy in a high- risk group of elderly patients with underlying cardiovascular disease or risk factors.

AABB(formerlyknownastheAmericanAssociation ofBloodBanks) JAMA. 2016;316(19):2025-2035.

JAMA. 2016;316(19):2025-2035.

Simon G I, Lancet Haematology, 2017 Review from Australia’s National Blood Authority. 14 Simon G I, Lancet Haematology, 2017

Older patients who followed a liberal transfusion strategy had a significantly lower risk of 30 and 90-day mortality than did those who followed a restrictive transfusion strategy

The Journal of Thoracic and Cardiovascular Surgery. November 2015 From Brazil, Hct 30% vs Hct 24% 心脏手术病人更推荐自由输血策略 The aim of this study was to compare outcomes in patients undergoing cardiac surgery who are aged 60 years or more or less than 60 years after implementation of a restrictive or a liberal transfusion strategy. Alternatively, a more liberal transfusion strategy might reduce cardiac complications by reducing short-term clinical or subclinical myocardial damage by increasing oxygen delivery to the heart, which could have long-term health implications. The Journal of Thoracic and Cardiovascular Surgery. November 2015

Transfusion in older adults with hip fracture Study from France. In this retrospective study of older adults admitted with hip fracture, a restrictive transfusion strategy was associated with fewer in-hospital cardiovascular complications, fewer packed RBC units used, and fewer transfusions than a more liberal strategy, without a significant difference in long-term mortality. JAGS 2018

Blood Transfusion in Elderly Patients with Acute Myocardial Infarction: Data from the RICO Survey

Paper From Tulane University USA

Long-term debate Transfusion could possibly increase the rate of long-term mortality by increasing the frequency of two of the most common causes of death: infections and cancer. A more liberal transfusion strategy might reduce cardiac complications by reducing short-term clinical or subclinical myocardial damage by increasing oxygen delivery to the heart, which could have long-term health implications. Cardiovascular risk of anemia may be more harmful than the risk of blood transfusion in older patients The decision to give a transfusion to an elderly patient is deemed complex, sometimes guided by the patient’s family.

Moncharmont P, et al. Blood Transfus, 2017, 15(3):1-5. RBC alloimmunisation after transfusion 老年患者作为一个庞大的用血群体，输血不良反应的发生率也高，那么老年患者应该如何输血？ 此文章可粗读，主要是法国的一份输血后不良反应的回顾性研究，在2008-2013 年间法国发生的所有输血不良反应中，80岁以上患者占约1/3比例。讨论：老年患 者虽然器官功能退化，但免疫功能仍保持活跃，作为主要的输血群体，因此输血不 良反应发生也多。From 1 January 2008 to 31 December 2013, there were 40,570 notifications of adverse reactions in transfused patients Among which 11,625 reports (28.7%) were of RBC alloimmunisation Of these 11,625 cases of RBC alloimmunisation, 3,617 (31.1%) involved transfused patients of 80 years old or more. Moncharmont P, et al. Blood Transfus, 2017, 15(3):1-5.

Research from Singapore General Hospital。Red cell distribution width (RDW) is an automated measure of the heterogeneity in erythrocyte sizes and is routinely performed as part of a Full Blood Count。 Anaemia was defined by the World Health Organisation (WHO)’s gender-based classification of anaemia severity. Mild anaemia is defined as haemoglobin (Hb) 11–12.9 g/dL in males and 11–11.9 g/dL in females; moderate anaemia Hb 8–10.9 g/dL and severe anaemia Hb <8.0 g/dL. RDW is reported as a coefficient of variation (percentage) of red blood cell volume with the normal reference range for RDW in this hospital laboratory to be 10.9% to 15.7%.

Temperature regulation 正常情况下，体内的热量并不是平均分配的。持续性的温度调节性血管收缩维持机体核心和外周的温度梯度在2℃～4℃之间。全麻降低血管收缩阈值到正常体温以下水平才开放动静脉短路。这样，在全麻期间的第1小时，由于热量的重新分布使核心温度降低1℃～1．5℃。全麻1小时后，核心温度降低速度减慢，这种降低接近线性，降低的原因是因为热量的散失超过了代谢产热。约90％的热量是从皮肤散失的。

Dtsch Arztebl Int. 2015 Mar 6;112(10):166-72. 全麻降低血管收缩阈值到正常体温以下水平才开放动静脉短路。这样，在全麻期间的第1小时，由于热量的重新分布使核心温度降低1℃～1．5℃。全麻1小时后，核心温度降低速度减慢，这种降低接近线性，降低的原因是因为热量的散失超过了代谢产热。约90％的热量是从皮肤散失的。全麻后3～4小时，核心体温通常会停止降低，形成温度平台。该温度平台可能反应了机体产热和散热处于平衡状态。当病人温度降低到一定程度时，温度调节性血管收缩被激活，从而减少皮肤散热，保留机体内部代谢热。因此，术中的血管收缩通过抑制代谢所产生热量从核心向外发散，重新建立正常的核心至外周温度梯度。在全麻恢复的过程中，未作有效加温的病人，寒战发生率约为40％。 Dtsch Arztebl Int. 2015 Mar 6;112(10):166-72.

斯堪的那文雅麻醉学报 丹麦

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J Orthop Surg Res. 2014 Feb; 10;9:8. Impact of warming blood transfusion and infusion toward cerebral oxygen metabolism and cognitive recovery in the perioperative period of elderly knee replacement J Orthop Surg Res. 2014 Feb; 10;9:8. 单中心、前瞻性、随机、单盲、对照试验，课题来源：宁夏科技攻关项目（2012）。 42

Post-operative quality of recovery scores PQRS参数包括六大类，生理功能主要在拔管后即刻以及早期时段进行评估，监测苏醒期生理安全性。伤害性刺激包括疼痛和恶心。情感包括焦虑以及抑郁。日常时候活动能力包括行走、站立、饮食和着装的能力。认知功能主要评估定向力、口头记忆力、执行能力、注意力和集中力。这些指标从有效且经典的神经认知测试中筛选的指标。通过前期的预实验，表明此量表方法较简单，病人易接受 ，因此我们认为PQRS量表可以用于评估全麻术后早期的认知功能评估。PQRS适用于全麻术后患者认知功能恢复的评估，但修订过的评估方法对术后早期轻度认知功能障碍的检出率可能不及原始方法高。 43 Royse CF. Anesthesiology. 2010;113:892-905 43

Chang in HR、MAP 两组患者在输血后各时间点MAP、HR组内及组间相比无明显统计学差异，说明加温输血输液对患者平均动脉压及心率无明显影响。 45

两组患者鼻咽温在输血后各个时间点较术前均出现明显的下降，两组患者在输血后各时间点比较均有显著统计学差异（P﹤0 WBI组患者在输血后1小时体温恢复至术前水平，而CON组患者直至输血后2小时恢复至术前水平，说明我们采用加温输血输液能够明显降低老年患者围术期低体温的发生，缩短低体温的持续时间。 46

两组患者在输血后即刻、输血后30min大脑中动脉收缩期峰流速率（WBI: 84. 55±7. 95, 82. 90±8 两组患者在输血后即刻、输血后30min大脑中动脉收缩期峰流速率（WBI: 84.55±7.95, 82.90±8.83, CON: 85.01±7.97, 83.69±7.43），较输血前明显降低，组内比较有统计学差异（P﹤0.05, P﹤0.01），组间比较无明显差异。CON组患者在输血后即刻出现阻力指数（0.54±0.04）较输血前增加，但组间比较无明显差异（P＞0.05)。 47

两组患者在输血后30min CERO2分别为：(48. 32±10. 37, 49. 16±14. 53)%，较输血前(38. 60±13 两组患者在输血后30min CERO2分别为：(48.32±10.37, 49.16±14.53)%，较输血前(38.60±13.68，40.60±16.17)%明显增高（P﹤0.01），但组间比较无明显差异（P＞0.05)。 48

两组患者SjvO2在T3时间点分别为：（WBI：48. 05±10. 98，CON：46. 85±7. 42）较T1(WBI：62 两组患者SjvO2在T3时间点分别为：（WBI：48.05±10.98，CON：46.85±7.42）较T1(WBI：62.62±11.67，CON：60.02±13.43）明显降低（P﹤0.01），但组间比较无明显差异（P＞0.05)。我们考虑输血后早期出现的CERO2增加及SjvO2降低可能是由于患者术后短时间内急性出血引起的脑组织供血相对不足引起的。两组之间比较无明显差异，说明加温输血输液对老年患者围术期脑氧代谢无明显影响。 49

两组患者颈静脉球部血乳酸值在输血后即刻、输血后30min、输血后1h分别为：（WBI：1. 678±0. 363，1. 770±0 两组患者颈静脉球部血乳酸值在输血后即刻、输血后30min、输血后1h分别为：（WBI：1.678±0.363，1.770±0.443，1.695±0.581；CON: 1.625±0.378，1.735±0.409，1.640±0.052）较T1明显增高（P﹤0.05），但组间比较无明显差异（P＞0.05)。我们考虑可能是一方面由于术中使用止血带，止血带释放后，大量炎性因子、炎性介质及酸性产物的入血，使得两组患者血乳酸升高；其次由于炎性因子及炎性介质的释放导致血管扩张，组织出现相对灌注不足，而引起血乳酸的升高。 50

Intraoperative warming blood transfusion contribute little to post-operative recovery quality in patients undergoing arthroplasty 两组患者在拔管后15min、40min、术后1d、3d均存在不同程度的整体及认知功能恢复不良，但组间比较无明显差异(P＞0.05)。 WBI组患者在术后15min存在31例认知功能为未完全恢复，CON组患者存在35例；WBI组患者在术后40min存在24例认知功能为未完全恢复，CON组患者存在25例；WBI组患者在术后1d存在18例认知功能为未完全恢复，CON组患者存在21例；WBI组患者在术后3d存在14例认知功能为未完全恢复，CON组患者存在16例；但组间比较无明显差异(P＞0.05)。 52

Blood loss in primary total knee arthroplasty J Orthop Surg Res. 2015; 10: 97. Blood loss in primary total knee arthroplasty -body temperature is not a significant risk factor -a prospective, consecutive, observational cohort study Orthopaedic Department, John Hunter Hospital, Australia RESULTS: No relationship between peri-operative patient temperature and blood loss was found within the recorded patient temperature range of 34.7-37.8°C. As long as patient temperature is maintained within a reasonable range during the intra-operative and post-operative periods, strategies other than rigid temperature control above 36.5 °C may be more effective in reducing blood loss following TKA. during the intra-operative and post-operative periods 53

Cochrane Database Syst Rev Cochrane Database Syst Rev. 2015 Apr 13;4: Warming of intravenous and irrigation fluids for preventing inadvertent perioperative hypothermia. OBJECTIVES: To estimate the effectiveness of preoperative or intraoperative warming, or both, of intravenous and irrigation fluids in preventing perioperative hypothermia and its complications during surgery in adults. SEARCH METHODS: We searched the Literature 1950 to 4 February 2014, and reference lists of identified articles. We also searched the Current Controlled Trials website and ClinicalTrials.gov. 英国科克伦系统评价数据库于2015年对1950年到2014年公开发表的临床研究文献再次做系统分析。以评价围术期液体加温、冲洗液加温或者两个同时加温对预防围术期低体温及其并发症的有效性。 54

MAIN RESULTS: AUTHORS' CONCLUSIONS: We included in this review 24 studies with a total of 1250 participants. Investigators used a range of methods to warm fluids to temperatures between 37°C and 41°C. Our protocol specified the risk of hypothermia as the primary outcome; The only secondary outcome reported in the trials that provided useable data was shivering. Evidence was unclear regarding the effects of fluid warming on bleeding. No data were reported on our other specified outcomes of cardiovascular complications, infection, pressure ulcers, bleeding, mortality, length of stay, unplanned intensive care admission and adverse events. AUTHORS' CONCLUSIONS: Warm intravenous fluids appear to keep patients warmer during surgery than room temperature fluids. It is unclear whether the actual differences in temperature are clinically meaningful, or if other benefits or harms are associated with the use of warmed fluids. It is also unclear if using fluid warming in addition to other warming methods confers any benefit, as a ceiling effect is likely when multiple methods of warming are used 研究人员集中分析了24项临床对照研究共纳入1250例患者，指定低温的风险作为主要观察指标，寒战作为次要观察指标，发现液体加温、冲洗液加温或者两者同时加温影响心血管并发症、感染、应激性溃疡、出血、死亡率、ICU停留时间以及不良事件的发生证据不足。最后，作者的结论是，与输注室温液体相比，加温输液有利于患者在手术期间保暖，但这样的温度差异究竟是否具有真正的临床意义并不清楚。而且，如果使用液体加温附加其他保暖方式是否能提供更多好处目前也不清楚。因为多种方式联合保温可能有封顶效应。 55

Nature. 2015 Feb 12;518(7538):236-9 Cooling induces loss of synaptic contacts, which are reformed on rewarming, a form of structural plasticity. Cooling and hibernation induce a number of cold-shock proteins（RBM3） in the brain Enhancing cold-shock pathways as potential protective therapies in neurodegenerative disorders. 56

Synapse numbers decline on cooling and recover on rewarming in wild-type mice counted in both 3D and 2D. yellow, presynaptic; green, postsynaptic compartments 57

Tradeoffs between risks and benefits Specific attention and careful assessment should be given when giving transfusion to the elderly Transfusion practices for RBCs should be designed to optimize clinical outcomes Several questions about optimal blood transfusion thresholds remain to be answered Further geriatric-specific studies are needed to guide the development and revision of blood management and transfusion guidelines for older adults. Emphasized that the hemoglobin level alone should not dictate transfusion but that it should also be based on clinical statu.

“Our own blood is still the best thing to have in our veins” Summary “Our own blood is still the best thing to have in our veins” --- Frenzel et al., 2008 Blood transfusion is often a marker for greater severity of illness

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