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成人髋部骨折手术中减少红细胞输血的干预措施:系统评价概述。

Interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews.

机构信息

Bone and Joint Health, Blizard Institute, Queen Mary University of London, London, UK.

Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, UK.

出版信息

Cochrane Database Syst Rev. 2023 Jun 8;6(6):CD013737. doi: 10.1002/14651858.CD013737.pub2.


DOI:10.1002/14651858.CD013737.pub2
PMID:37294864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10249061/
Abstract

BACKGROUND: Following hip fracture, people sustain an acute blood loss caused by the injury and subsequent surgery. Because the majority of hip fractures occur in older adults, blood loss may be compounded by pre-existing anaemia. Allogenic blood transfusions (ABT) may be given before, during, and after surgery to correct chronic anaemia or acute blood loss. However, there is uncertainty about the benefit-risk ratio for ABT. This is a potentially scarce resource, with availability of blood products sometimes uncertain. Other strategies from Patient Blood Management may prevent or minimise blood loss and avoid administration of ABT. OBJECTIVES: To summarise the evidence from Cochrane Reviews and other systematic reviews of randomised or quasi-randomised trials evaluating the effects of pharmacological and non-pharmacological interventions, administered perioperatively, on reducing blood loss, anaemia, and the need for ABT in adults undergoing hip fracture surgery. METHODS: In January 2022, we searched the Cochrane Library, MEDLINE, Embase, and five other databases for systematic reviews of randomised controlled trials (RCTs) of interventions given to prevent or minimise blood loss, treat the effects of anaemia, and reduce the need for ABT, in adults undergoing hip fracture surgery. We searched for pharmacological interventions (fibrinogen, factor VIIa and factor XIII, desmopressin, antifibrinolytics, fibrin and non-fibrin sealants and glue, agents to reverse the effects of anticoagulants, erythropoiesis agents, iron, vitamin B12, and folate replacement therapy) and non-pharmacological interventions (surgical approaches to reduce or manage blood loss, intraoperative cell salvage and autologous blood transfusion, temperature management, and oxygen therapy). We used Cochrane methodology, and assessed the methodological quality of included reviews using AMSTAR 2. We assessed the degree of overlap of RCTs between reviews. Because overlap was very high, we used a hierarchical approach to select reviews from which to report data; we compared the findings of selected reviews with findings from the other reviews. Outcomes were: number of people requiring ABT, volume of transfused blood (measured as units of packed red blood cells (PRC)), postoperative delirium, adverse events, activities of daily living (ADL), health-related quality of life (HRQoL), and mortality. MAIN RESULTS: We found 26 systematic reviews including 36 RCTs (3923 participants), which only evaluated tranexamic acid and iron. We found no reviews of other pharmacological interventions or any non-pharmacological interventions. Tranexamic acid (17 reviews, 29 eligible RCTs) We selected reviews with the most recent search date, and which included data for the most outcomes. The methodological quality of these reviews was low. However, the findings were largely consistent across reviews. One review included 24 RCTs, with participants who had internal fixation or arthroplasty for different types of hip fracture. Tranexamic acid was given intravenously or topically during the perioperative period. In this review, based on a control group risk of 451 people per 1000, 194 fewer people per 1000 probably require ABT after receiving tranexamic acid (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.46 to 0.68; 21 studies, 2148 participants; moderate-certainty evidence). We downgraded the certainty for possible publication bias. Review authors found that there was probably little or no difference in the risks of adverse events, reported as deep vein thrombosis (RR 1.16, 95% CI 0.74 to 1.81; 22 studies), pulmonary embolism (RR 1.01, 95% CI 0.36 to 2.86; 9 studies), myocardial infarction (RR 1.00, 95% CI 0.23 to 4.33; 8 studies), cerebrovascular accident (RR 1.45, 95% CI 0.56 to 3.70; 8 studies), or death (RR 1.01, 95% CI 0.70 to 1.46; 10 studies). We judged evidence from these outcomes to be moderate certainty, downgraded for imprecision. Another review, with a similarly broad inclusion criteria, included 10 studies, and found that tranexamic acid probably reduces the volume of transfused PRC (0.53 fewer units, 95% CI 0.27 to 0.80; 7 studies, 813 participants; moderate-certainty evidence). We downgraded the certainty because of unexplained high levels of statistical heterogeneity. No reviews reported outcomes of postoperative delirium, ADL, or HRQoL. Iron (9 reviews, 7 eligible RCTs) Whilst all reviews included studies in hip fracture populations, most also included other surgical populations. The most current, direct evidence was reported in two RCTs, with 403 participants with hip fracture; iron was given intravenously, starting preoperatively. This review did not include evidence for iron with erythropoietin. The methodological quality of this review was low. In this review, there was low-certainty evidence from two studies (403 participants) that there may be little or no difference according to whether intravenous iron was given in: the number of people who required ABT (RR 0.90, 95% CI 0.73 to 1.11), the volume of transfused blood (MD -0.07 units of PRC, 95% CI -0.31 to 0.17), infection (RR 0.99, 95% CI 0.55 to 1.80), or mortality within 30 days (RR 1.06, 95% CI 0.53 to 2.13). There may be little or no difference in delirium (25 events in the iron group compared to 26 events in control group; 1 study, 303 participants; low-certainty evidence). We are very unsure whether there was any difference in HRQoL, since it was reported without an effect estimate. The findings were largely consistent across reviews. We downgraded the evidence for imprecision, because studies included few participants, and the wide CIs indicated possible benefit and harm. No reviews reported outcomes of cognitive dysfunction, ADL, or HRQoL. AUTHORS' CONCLUSIONS: Tranexamic acid probably reduces the need for ABT in adults undergoing hip fracture surgery, and there is probably little or no difference in adverse events. For iron, there may be little or no difference in overall clinical effects, but this finding is limited by evidence from only a few small studies. Reviews of these treatments did not adequately include patient-reported outcome measures (PROMS), and evidence for their effectiveness remains incomplete. We were unable to effectively explore the impact of timing and route of administration between reviews. A lack of systematic reviews for other types of pharmacological or any non-pharmacological interventions to reduce the need for ABT indicates a need for further evidence syntheses to explore this. Methodologically sound evidence syntheses should include PROMS within four months of surgery.

摘要

背景:髋部骨折后,由于受伤和随后的手术,患者会急性失血。由于大多数髋部骨折发生在老年人中,失血可能因先前存在的贫血而加重。异体输血(allogenic blood transfusion,ABT)可能在手术前、手术中和手术后给予,以纠正慢性贫血或急性失血。然而,ABT 的获益风险比尚不确定。这是一种潜在的稀缺资源,有时血液制品的供应不确定。患者血液管理中的其他策略可以预防或减少失血,并避免给予 ABT。

目的:总结 Cochrane 评价和其他系统评价的证据,这些评价评估了围手术期给予的药理学和非药理学干预措施对减少成年人髋部骨折手术中失血、贫血和 ABT 需求的影响。

方法:2022 年 1 月,我们在 Cochrane 图书馆、MEDLINE、Embase 和其他五个数据库中搜索了随机对照试验(randomised controlled trials,RCTs)的系统评价,这些 RCTs 评估了预防或减少失血、治疗贫血影响和减少 ABT 需求的干预措施,这些干预措施在接受髋部骨折手术的成年人中使用。我们搜索了药理学干预措施(纤维蛋白原、因子 VIIa 和因子 XIII、去氨加压素、抗纤维蛋白溶解剂和非纤维蛋白密封剂和胶、逆转抗凝剂作用的药物、促红细胞生成素、铁、维生素 B12 和叶酸替代治疗)和非药理学干预措施(减少或管理失血的手术方法、术中细胞回收和自体输血、体温管理和氧疗)。我们使用了 Cochrane 方法,并使用 AMSTAR 2 评估了纳入评价的方法学质量。我们评估了评价之间的 RCT 重叠程度。由于重叠程度非常高,我们使用分层方法从报告数据的评价中选择,我们比较了选定的评价与其他评价的发现。结局为:需要 ABT 的人数、输注的红细胞单位数(以单位的浓缩红细胞(packed red blood cells,PRC)表示)、术后谵妄、不良事件、日常生活活动(activities of daily living,ADL)、健康相关生活质量(health-related quality of life,HRQoL)和死亡率。

主要结果:我们发现了 26 项系统评价,其中包括 36 项 RCT(3923 名参与者),这些评价仅评估了氨甲环酸和铁。我们没有发现其他药理学干预措施或任何非药理学干预措施的评价。氨甲环酸(17 项评价,29 项合格 RCT)我们选择了最近搜索日期的评价,并纳入了最多结局的数据。这些评价的方法学质量较低。然而,这些发现基本上在评价之间是一致的。一项评价纳入了 24 项 RCT,参与者为不同类型髋部骨折的内固定或关节置换术。氨甲环酸在围手术期静脉内或局部给予。在这项评价中,基于对照组每 1000 人中有 451 人需要 ABT 的风险,接受氨甲环酸治疗后,每 1000 人中可能有 194 人不需要 ABT(风险比(risk ratio,RR)0.56,95%置信区间(confidence interval,CI)0.46 至 0.68;21 项研究,2148 名参与者;中等确定性证据)。我们降低了可能存在发表偏倚的确定性。评价作者发现,在不良事件的风险方面,可能差异很小或没有差异,报告的不良事件包括深静脉血栓形成(RR 1.16,95%CI 0.74 至 1.81;22 项研究)、肺栓塞(RR 1.01,95%CI 0.36 至 2.86;9 项研究)、心肌梗死(RR 1.00,95%CI 0.23 至 4.33;8 项研究)、脑血管意外(RR 1.45,95%CI 0.56 至 3.70;8 项研究)或死亡(RR 1.01,95%CI 0.70 至 1.46;10 项研究)。我们对这些结局的证据评价为中等确定性,由于不精确而降低了确定性。另一项具有类似广泛纳入标准的评价纳入了 10 项研究,发现氨甲环酸可能减少输注的 PRC 单位数(减少 0.53 个单位,95%CI 0.27 至 0.80;7 项研究,813 名参与者;中等确定性证据)。我们降低了确定性,因为存在无法解释的高度统计学异质性。没有评价报告术后谵妄、ADL 或 HRQoL 的结局。铁(9 项评价,7 项合格 RCT)虽然所有评价都包括髋部骨折人群的研究,但大多数还包括其他手术人群。最近的直接证据在两项 RCT 中报告,其中 403 名参与者患有髋部骨折;铁静脉内给予,术前开始。该评价未包括与促红细胞生成素联合使用铁的证据。该评价的方法学质量较低。在这项评价中,有两项研究(403 名参与者)的低确定性证据表明,根据是否给予静脉内铁,可能差异很小或没有差异:需要 ABT 的人数(RR 0.90,95%CI 0.73 至 1.11)、输注的 PRC 单位数(MD -0.07 个单位,95%CI -0.31 至 0.17)、感染(RR 0.99,95%CI 0.55 至 1.80)或 30 天内死亡率(RR 1.06,95%CI 0.53 至 2.13)。在谵妄方面可能差异很小或没有差异(铁组 25 例事件,对照组 26 例事件;1 项研究,303 名参与者;低确定性证据)。我们非常不确定铁对 HRQoL 是否有任何影响,因为它没有报告效应估计值。这些发现基本上在评价之间是一致的。我们降低了精确度的证据,因为研究纳入的参与者较少,并且宽置信区间表明可能有获益和危害。没有评价报告认知功能、ADL 或 HRQoL 的结局。

结论:氨甲环酸可能减少成年人髋部骨折手术中 ABT 的需求,而且在不良事件方面可能差异很小或没有差异。对于铁,在总体临床效果方面可能差异很小或没有差异,但这一发现受到仅有少数小研究的证据的限制。这些治疗方法的评价没有充分纳入患者报告的结局测量指标(patient-reported outcome measures,PROMs),其有效性仍不完整。我们无法有效地探讨评价之间的给药时间和途径的影响。缺乏其他类型的药理学或任何非药理学干预措施来减少 ABT 的系统评价表明需要进一步的证据综合。方法学上合理的证据综合应在手术后四个月内纳入 PROMs。

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本文引用的文献

[1]
The Use of Tranexamic Acid in Hip Fracture Surgery-A Systematic Review and Meta-analysis.

J Orthop Trauma. 2022-12-1

[2]
Update on the efficacy and safety of intravenous tranexamic acid in hip fracture surgery: a systematic review and meta-analysis.

Eur J Orthop Surg Traumatol. 2023-7

[3]
Randomised controlled trial comparing intraoperative cell salvage and autotransfusion with standard care in the treatment of hip fractures: a protocol for the WHITE 9 study.

BMJ Open. 2022-6-8

[4]
Arthroplasties for hip fracture in adults.

Cochrane Database Syst Rev. 2022-2-14

[5]
Surgical interventions for treating intracapsular hip fractures in older adults: a network meta-analysis.

Cochrane Database Syst Rev. 2022-2-14

[6]
Surgical interventions for treating extracapsular hip fractures in older adults: a network meta-analysis.

Cochrane Database Syst Rev. 2022-2-10

[7]
Cephalomedullary nails versus extramedullary implants for extracapsular hip fractures in older adults.

Cochrane Database Syst Rev. 2022-1-26

[8]
Perioperative Hypothermia Is Associated With Increased 30-Day Mortality in Hip Fracture Patients in the United Kingdom: Α Systematic Review and Meta-analysis.

J Orthop Trauma. 2022-7-1

[9]
Transfusion thresholds for guiding red blood cell transfusion.

Cochrane Database Syst Rev. 2021-12-21

[10]
Tranexamic acid usage in hip fracture surgery: a meta-analysis and meta-regression analysis of current practice.

Arch Orthop Trauma Surg. 2022-10

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