背景:由于手术止血不足,血管手术后可能会发生内出血,异常凝血,或手术并发症。出血范围从轻微开始,没有输血要求,到巨大的,需要多次输血。有很多药物,系统给定或局部应用,这可能会减少输血的需要。
目的:评估抗纤维蛋白溶解和止血药物和药物在减少出血和需要输血方面的有效性和安全性。
方法:我们搜索:Cochrane中央对照试验登记册;MEDLINE;Embase;CINAHL,输血证据库。我们还检索了WHOICTRP和ClinicalTrials.gov试验登记处的正在进行的和未发表的试验。从数据库开始到2022年3月31日,搜索使用MeSH和自由文本术语的组合,没有语言或出版状态的限制。
方法:我们纳入了成人药物治疗的随机对照试验(RCT),以减少由于大血管手术或有中度或重度失血风险的血管手术引起的出血。使用安慰剂,常规护理或其他药物方案作为对照。
方法:我们使用标准Cochrane方法。我们的主要结果是红细胞输注单位和全因死亡率。我们的次要结果包括接受同种异体血液制品的风险,因出血而再次手术或重复手术的风险,血栓栓塞事件的风险,严重不良事件的风险和住院时间。我们使用等级来评估证据的确定性。
结果:我们纳入了22项RCT,分析了3393名参与者,其中有69名参与者的一项RCT仅以抽象形式报告,没有可用的数据。七个RCT评估了全身药物治疗(三个抑肽酶,两种去氨加压素,两种氨甲环酸)和15种RCT评估了局部药物治疗(含药物的生物可吸收敷料或胶水),包括纤维蛋白,凝血酶,胶原蛋白,明胶,合成密封剂和一种研究性新剂。大多数试验是在高收入国家进行的,大多数试验仅包括接受选择性手术的参与者。我们还确定了两个正在进行的RCT。由于与本综述相关的结果报告很少,我们无法进行计划的网络荟萃分析。系统性药物治疗我们确定了三种系统性药物的七项试验:抑肽酶,去氨加压素和氨甲环酸,所有的安慰剂对照。抑肽酶和去氨加压素的试验规模很小,我们所有结果的确定性证据都很低。氨甲环酸与安慰剂是与参与者数量最多的全身性药物比较(2项试验;1460名参与者),两者的偏见风险都很低。其中最大的包括总共9535名接受不同的高风险手术的个体,并报告了关于血管亚组的有限信息(1399名参与者)。两项试验均未报告每位参与者在30天内输注的红细胞单位数。三个结果与非常低的确定性证据相关,这是由于研究规模小和事件数量少导致的非常宽的置信区间(CI)。这些是:全因死亡率长达30天;需要同种异体输血长达30天的参与者人数;以及由于出血而需要重复手术或手术的风险。氨甲环酸可能对30天内血栓栓塞事件的风险没有影响(风险比(RR)1.10,95%CI0.88至1.36;1项试验,1360名参与者;由于不精确而导致的低确定性证据)。有一项正在进行的大型试验(8320名参与者)比较氨甲环酸与安慰剂在接受非心脏手术的人中需要输注红细胞的高风险。计划在2023年4月完成招聘。该试验的主要结果是输注红细胞的参与者比例和静脉血栓栓塞(DVT或PE)的发生率。局部药物治疗由于其开放标签设计,大多数局部药物治疗试验存在较高的偏倚风险(与常规治疗相比,或将液体与海绵进行比较)。所有的试验都很小,大多数都很小,并且在术后期间很少报道临床相关结果。纤维蛋白密封剂与常规治疗是与参与者数量最多的局部药物比较(5项试验,784名参与者)。将纤维蛋白密封剂与常规护理进行比较的五项试验都存在较高的偏倚风险,由于开放标签试验设计,没有采取措施将报告偏差降至最低。所有的试验都是由制药公司资助的。五项试验均未报告每位参与者在30天内输注的红细胞数量或在30天内需要进行同种异体输血的参与者数量。由于样本量小和事件数量少,其他三个结果与具有宽置信区间的极低确定性证据相关。这些因素包括:长达30天的全因死亡率;因出血而需要重复手术的风险;以及长达30天的血栓栓塞性疾病风险.我们确定了一项大型试验(500名参与者),比较了接受腹主动脉瘤修复术的参与者的纤维蛋白密封剂与常规治疗。尚未开始招聘。该试验将动脉疾病导致的死亡和再干预率列为主要结果。
结论:由于缺乏数据,我们不确定任何用于减少大血管手术所致出血的全身或局部治疗是否对以下方面有影响:长达30天的全因死亡率;因出血需要重复手术或手术的风险;每位参与者长达30天的红细胞输注数或需要同种异体输血长达30天的参与者数量.氨甲环酸可能对血栓栓塞事件的风险没有影响,直到30天。这很重要,因为有人担心这种风险可能会增加。需要针对数千名参与者的样本量目标和临床相关结果的试验,我们期待着在未来看到正在进行的试验的结果。
Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion.
To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss.
We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status.
We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control.
We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence.
We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this
review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants). The five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies. None of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. The other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days. We identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes.
Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.