Edwards Steven J, Crawford Fay, van Velthoven Michelle Helena, Berardi Andrea, Osei-Assibey George, Bacelar Mariana, Salih Fatima, Wakefield Victoria
Health Technol Assess. 2016 Dec;20(94):1-224. doi: 10.3310/hta20940.
Fibrin sealants are used in different types of surgery to prevent the accumulation of post-operative fluid (seroma) or blood (haematoma) or to arrest haemorrhage (bleeding). However, there is uncertainty around the benefits and harms of fibrin sealant use.
To systematically review the evidence on the benefits and harms of fibrin sealants in non-emergency surgery in adults.
Electronic databases [MEDLINE, EMBASE and The Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and the Cochrane Central Register of Controlled Trials)] were searched from inception to May 2015. The websites of regulatory bodies (the Medicines and Healthcare products Regulatory Agency, the European Medicines Agency and the Food and Drug Administration) were also searched to identify evidence of harms.
This review included randomised controlled trials (RCTs) and observational studies using any type of fibrin sealant compared with standard care in non-emergency surgery in adults. The primary outcome was risk of developing seroma and haematoma. Only RCTs were used to inform clinical effectiveness and both RCTs and observational studies were used for the assessment of harms related to the use of fibrin sealant. Two reviewers independently screened all titles and abstracts to identify potentially relevant studies. Data extraction was undertaken by one reviewer and validated by a second. The quality of included studies was assessed independently by two reviewers using the Cochrane Collaboration risk-of-bias tool for RCTs and the Centre for Reviews and Dissemination guidance for adverse events for observational studies. A fixed-effects model was used for meta-analysis.
We included 186 RCTs and eight observational studies across 14 surgical specialties and five reports from the regulatory bodies. Most RCTs were judged to be at an unclear risk of bias. Adverse events were inappropriately reported in observational studies. Meta-analysis across non-emergency surgical specialties did not show a statistically significant difference in the risk of seroma for fibrin sealants versus standard care in 32 RCTs analysed [ = 3472, odds ratio (OR) 0.84, 95% confidence interval (CI) 0.68 to 1.04; = 0.13; = 12.7%], but a statistically significant benefit was found on haematoma development in 24 RCTs ( = 2403, OR 0.62, 95% CI 0.44 to 0.86; = 0.01; = 0%). Adverse events related to fibrin sealant use were reported in 10 RCTs and eight observational studies across surgical specialties, and 22 RCTs explicitly stated that there were no adverse events. One RCT reported a single death but no other study reported mortality or any serious adverse events. Five regulatory body reports noted death from air emboli associated with fibrin sprays.
It was not possible to provide a detailed evaluation of individual RCTs in their specific contexts because of the limited resources that were available for this research. In addition, the number of RCTs that were identified made it impractical to conduct independent data extraction by two reviewers in the time available.
The effectiveness of fibrin sealants does not appear to vary according to surgical procedures with regard to reducing the risk of seroma or haematoma. Surgeons should note the potential risk of gas embolism if spray application of fibrin sealants is used and not to exceed the recommended pressure and spraying distance. Future research should be carried out in surgery specialties for which only limited data were found, including neurological, gynaecological, oral and maxillofacial, urology, colorectal and orthopaedics surgery (for any outcome); breast surgery and upper gastrointestinal (development of haematoma); and cardiothoracic heart or lung surgery (reoperation rates). In addition, studies need to use adequate sample sizes, to blind participants and outcome assessors, and to follow reporting guidelines.
This study is registered as PROSPERO CRD42015020710.
The National Institute for Health Research Health Technology Assessment programme.
纤维蛋白密封剂用于不同类型的手术，以防止术后液体（血清肿）或血液（血肿）积聚，或止血。然而，使用纤维蛋白密封剂的益处和危害尚不确定。
系统评价纤维蛋白密封剂在成人非急诊手术中使用的益处和危害的证据。
检索电子数据库[医学主题词表（MEDLINE）、荷兰医学文摘数据库（EMBASE）和考克兰图书馆（包括考克兰系统评价数据库、效果评价文摘数据库、卫生技术评估数据库和考克兰对照试验中心注册库）]，检索时间从建库至2015年5月。还检索了监管机构网站[药品和保健产品监管局、欧洲药品管理局和美国食品药品监督管理局]，以确定危害证据。
本综述纳入了随机对照试验（RCT）和观察性研究，这些研究将任何类型的纤维蛋白密封剂与成人非急诊手术中的标准治疗进行比较。主要结局是发生血清肿和血肿的风险。仅使用RCT来提供临床有效性信息，RCT和观察性研究均用于评估与使用纤维蛋白密封剂相关的危害。两名综述作者独立筛选所有标题和摘要，以识别潜在相关研究。由一名综述作者进行数据提取，并由另一名作者进行验证。两名综述作者分别使用考克兰协作网偏倚风险工具对RCT进行质量评估，使用综述与传播中心关于观察性研究不良事件的指南对观察性研究进行质量评估。采用固定效应模型进行荟萃分析。
我们纳入了14个外科专业的186项RCT和8项观察性研究，以及监管机构的5份报告。大多数RCT被判定存在偏倚风险不明确的情况。观察性研究中不良事件报告不当。在纳入分析的32项RCT中，对非急诊外科专业进行的荟萃分析未显示纤维蛋白密封剂与标准治疗相比在血清肿风险方面存在统计学显著差异[样本量=3472，比值比（OR）0.84，95%置信区间（CI）0.68至1.04；P=0.13；I²=12.7%]，但在24项RCT中发现纤维蛋白密封剂在血肿形成方面有统计学显著益处（样本量=2403，OR 0.62，95%CI 0.44至0.86；P=0.01；I²=0%）。10项RCT和8项各外科专业的观察性研究报告了与使用纤维蛋白密封剂相关的不良事件，22项RCT明确表示无不良事件。1项RCT报告了1例死亡，但其他研究均未报告死亡率或任何严重不良事件。5份监管机构报告指出有因与纤维蛋白喷雾相关的空气栓塞导致死亡的情况。
由于本研究可用资源有限，无法在其特定背景下对各个RCT进行详细评估。此外，已识别的RCT数量使得两名综述作者在可用时间内进行独立数据提取不切实际。
就降低血清肿或血肿风险而言，纤维蛋白密封剂的有效性似乎不会因手术程序而异。外科医生应注意，如果使用纤维蛋白密封剂喷雾，存在气体栓塞的潜在风险，且不要超过推荐压力和喷雾距离。未来研究应在仅发现有限数据的外科专业中开展，包括神经外科、妇科、口腔颌面外科、泌尿外科、结直肠外科和骨科手术（针对任何结局）；乳腺外科和上消化道手术（血肿形成）；以及心胸心脏或肺部手术（再次手术率）。此外，研究需要使用足够的样本量，对参与者和结局评估者进行盲法处理，并遵循报告指南。
本研究注册为PROSPERO CRD42015020710。
英国国家卫生研究院卫生技术评估项目。
