Brunskill Susan J, Millette Sarah L, Shokoohi Ali, Pulford E C, Doree Carolyn, Murphy Michael F, Stanworth Simon
Systematic Review Initiative, NHS Blood and Transplant, Level 2, John Radcliffe Hospital, Headington, Oxford, Oxon, UK, OX3 9BQ.
Cochrane Database Syst Rev. 2015 Apr 21;2015(4):CD009699. doi: 10.1002/14651858.CD009699.pub2.
The incidence of hip fracture is increasing and it is more common with increasing age. Surgery is used for almost all hip fractures. Blood loss occurs as a consequence of both the fracture and the surgery and thus red blood cell transfusion is frequently used. However, red blood cell transfusion is not without risks. Therefore, it is important to identify the evidence for the effective and safe use of red blood cell transfusion in people with hip fracture.
To assess the effects (benefits and harms) of red blood cell transfusion in people undergoing surgery for hip fracture.
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (31 October 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 10), MEDLINE (January 1946 to 20 November 2014), EMBASE (January 1974 to 20 November 2014), CINAHL (January 1982 to 20 November 2014), British Nursing Index Database (January 1992 to 20 November 2014), the Systematic Review Initiative's Transfusion Evidence Library, PubMed for e-publications, various other databases and ongoing trial registers.
Randomised controlled trials comparing red blood cell transfusion versus no transfusion or an alternative to transfusion, different transfusion protocols or different transfusion thresholds in people undergoing surgery for hip fracture.
Three review authors independently assessed each study's risk of bias and extracted data using a study-specific form. We pooled data where there was homogeneity in the trial comparisons and the timing of outcome measurement. We used GRADE criteria to assess the quality (low, moderate or high) of the evidence for each outcome.
We included six trials (2722 participants): all compared two thresholds for red blood cell transfusion: a 'liberal' strategy to maintain a haemoglobin concentration of usually 10 g/dL versus a more 'restrictive' strategy based on symptoms of anaemia or a lower haemoglobin concentration, usually 8 g/dL. The exact nature of the transfusion interventions, types of surgery and participants varied between trials. The mean age of participants ranged from 81 to 87 years and approximately 24% of participants were men. The largest trial enrolled 2016 participants, over 60% of whom had a history of cardiovascular disease. The percentage of participants receiving a red blood cell transfusion ranged from 74% to 100% in the liberal transfusion threshold group and from 11% to 45% in the restrictive transfusion threshold group. There were no results available for the smallest trial (18 participants). All studies were at some risk of bias, in particular performance bias relating to the absence of blinding of personnel. We judged the evidence for all outcomes, except myocardial infarction, was low quality reflecting risk of bias primarily from imbalances in protocol violations in the largest trial and imprecision, often because of insufficient events. Thus, further research is likely to have an important impact on these results.There was no evidence of a difference between a liberal versus restricted threshold transfusion in mortality, at 30 days post hip fracture surgery (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.67 to 1.26; five trials; 2683 participants; low quality evidence) or at 60 days post surgery (RR 1.08, 95% CI 0.80 to 1.44; three trials; 2283 participants; low quality evidence). Assuming an illustrative baseline risk of 50 deaths per 1000 participants in the restricted threshold group at 30 days, these data equate to four fewer (95% CI 17 fewer to 14 more) deaths per 1000 in the liberal threshold group at 30 days.There was no evidence of a difference between a liberal versus restricted threshold transfusion in functional recovery at 60 days, assessed in terms of the inability to walk 10 feet (3 m) without human assistance (RR 1.00, 95% CI 0.87 to 1.15; two trials; 2083 participants; low quality evidence).There was low quality evidence of no difference between the transfusion thresholds in postoperative morbidity for the following complications: thromboembolism (RR 1.15 favouring a restrictive threshold, 95% CI 0.56 to 2.37; four trials; 2416 participants), stroke (RR 2.40 favouring a restrictive threshold, 95% CI 0.85 to 6.79; four trials; 2416 participants), wound infection (RR 1.61 favouring a restrictive threshold, 95% CI 0.77 to 3.35; three trials; 2332 participants), respiratory infection (pneumonia) (RR 1.35 favouring a restrictive threshold, 95% CI 0.95 to 1.92; four trials; 2416 participants) and new diagnosis of congestive heart failure (RR 0.77 favouring a liberal threshold, 95% CI 0.48 to 1.23; three trials; 2332 participants). There was very low quality evidence of a lower risk of myocardial infarction in the liberal compared with the restrictive transfusion threshold group (RR 0.59, 95% CI 0.36 to 0.96; three trials; 2217 participants). Assuming an illustrative baseline risk of myocardial infarction of 24 per 1000 participants in the restricted threshold group, this result was compatible with between one and 15 fewer myocardial infarctions in the liberal threshold group.
AUTHORS' CONCLUSIONS: We found low quality evidence of no difference in mortality, functional recovery or postoperative morbidity between 'liberal' versus 'restrictive' thresholds for red blood cell transfusion in people undergoing surgery for hip fracture. Although further research may change the estimates of effect, the currently available evidence does not support the use of liberal red blood cell transfusion thresholds based on a 10 g/dL haemoglobin trigger in preference to more restrictive transfusion thresholds based on lower haemoglobin levels or symptoms of anaemia in these people. Future research needs to address the effectiveness of red blood cell transfusions at different time points in the surgical pathway, whether pre-operative, peri-operative or postoperative. In particular, such research would need to consider people who are symptomatic or haemodynamically unstable who were excluded from most of these trials.
髋部骨折的发病率正在上升,且随着年龄增长更为常见。几乎所有髋部骨折都采用手术治疗。骨折和手术都会导致失血,因此经常需要输注红细胞。然而,输注红细胞并非没有风险。因此,确定髋部骨折患者有效且安全使用红细胞输注的证据很重要。
评估红细胞输注对接受髋部骨折手术患者的影响(益处和危害)。
我们检索了Cochrane骨、关节和肌肉创伤小组专业注册库(2014年10月31日)、Cochrane对照试验中心注册库(Cochrane图书馆,2014年第10期)、MEDLINE(1946年1月至2014年11月20日)、EMBASE(1974年1月至2014年11月20日)、CINAHL(1982年1月至2014年11月20日)、英国护理索引数据库(1992年1月至2014年11月20日)、系统评价倡议的输血证据库、PubMed电子出版物、各种其他数据库以及正在进行的试验注册库。
比较红细胞输注与不输血或输血替代方案、不同输血方案或不同输血阈值的随机对照试验,研究对象为接受髋部骨折手术的患者。
三位综述作者独立评估每项研究的偏倚风险,并使用特定研究表格提取数据。我们在试验比较和结局测量时间一致的情况下汇总数据。我们使用GRADE标准评估每个结局的证据质量(低、中或高)。
我们纳入了六项试验(2722名参与者):所有试验均比较了两个红细胞输注阈值:一种“宽松”策略,通常维持血红蛋白浓度为10 g/dL,另一种更“严格”的策略,基于贫血症状或更低的血红蛋白浓度,通常为8 g/dL。不同试验中输血干预的确切性质、手术类型和参与者各不相同。参与者的平均年龄在81至87岁之间,约24%的参与者为男性。最大的试验纳入了2016名参与者,其中超过60%有心血管疾病史。在宽松输血阈值组中,接受红细胞输注的参与者比例为74%至100%,在严格输血阈值组中为11%至45%。最小的试验(18名参与者)没有结果。所有研究都存在一定的偏倚风险,特别是与人员未设盲有关的实施偏倚。我们判断,除心肌梗死外,所有结局的证据质量都很低,这主要反映了最大试验中方案违反不平衡导致的偏倚风险以及不精确性,通常是因为事件数量不足。因此,进一步的研究可能会对这些结果产生重要影响。在髋部骨折手术后30天,宽松与严格阈值输血在死亡率方面没有差异的证据(风险比(RR)0.92,95%置信区间(CI)0.67至1.26;五项试验;2683名参与者;低质量证据),或在手术后60天(RR 1.08,95%CI 0.80至1.44;三项试验;2283名参与者;低质量证据)。假设在30天时严格阈值组每1000名参与者中有50人死亡的基线风险为例,这些数据相当于在30天时宽松阈值组每1000人中死亡人数减少4人(95%CI减少17人至增加14人)。在60天时,以无法在无人协助下行走10英尺(3米)来评估,宽松与严格阈值输血在功能恢复方面没有差异的证据(RR 1.00,95%CI 0.87至1.15;两项试验;2083名参与者;低质量证据)。对于以下并发症,输血阈值在术后发病率方面没有差异的证据质量很低:血栓栓塞(RR 1.15,倾向于严格阈值,95%CI 0.56至2.37;四项试验;2416名参与者)、中风(RR 2.40,倾向于严格阈值,95%CI 0.85至6.79;四项试验;2416名参与者)、伤口感染(RR 1.61,倾向于严格阈值,95%CI 0.77至3.35;三项试验;2332名参与者)、呼吸道感染(肺炎)(RR 1.35,倾向于严格阈值,95%CI 0.95至1.92;四项试验;2416名参与者)和充血性心力衰竭新诊断(RR 0.77,倾向于宽松阈值,95%CI 0.48至1.23;三项试验;2332名参与者)。与严格输血阈值组相比,宽松输血阈值组心肌梗死风险较低的证据质量非常低(RR 0.59,95%CI 0.36至0.96;三项试验;2217名参与者)。假设在严格阈值组中每1000名参与者中心肌梗死的基线风险为例为24例,这一结果与宽松阈值组中心肌梗死减少1至15例相符。
我们发现低质量证据表明,在接受髋部骨折手术的患者中,红细胞输注的“宽松”与“严格”阈值在死亡率、功能恢复或术后发病率方面没有差异。尽管进一步的研究可能会改变效应估计,但目前可得的证据不支持在这些患者中使用基于血红蛋白浓度10 g/dL触发的宽松红细胞输注阈值,而更倾向于基于更低血红蛋白水平或贫血症状的更严格输血阈值。未来的研究需要探讨在手术过程中不同时间点(术前、术中和术后)红细胞输注的有效性。特别是,此类研究需要考虑那些有症状或血流动力学不稳定的患者,而这些患者在大多数试验中被排除在外。