Department of Clinical Laboratory, Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, Chongqing, China.
Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Cochrane Database Syst Rev. 2023 Jun 19;6(6):CD009621. doi: 10.1002/14651858.CD009621.pub5.
Postoperative pancreatic fistula (POPF) is one of the most frequent and potentially life-threatening complications following pancreatic surgery. Fibrin sealants have been used in some centres to reduce POPF rate. However, the use of fibrin sealant during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2020.
To evaluate the benefits and harms of fibrin sealant use for the prevention of POPF (grade B or C) in people undergoing pancreatic surgery compared to no fibrin sealant use.
We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 09 March 2023, together with reference checking, citation searching, and contacting study authors to identify additional studies.
We included all randomised controlled trials (RCTs) that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery.
We used standard methodological procedures expected by Cochrane.
We included 14 RCTs, randomising 1989 participants, comparing fibrin sealant use versus no fibrin sealant use for different locations: stump closure reinforcement (eight trials), pancreatic anastomosis reinforcement (five trials), or main pancreatic duct occlusion (two trials). Six RCTs were carried out in single centres; two in dual centres; and six in multiple centres. One RCT was conducted in Australia; one in Austria; two in France; three in Italy; one in Japan; two in the Netherlands; two in South Korea; and two in the USA. The mean age of the participants ranged from 50.0 years to 66.5 years. All RCTs were at high risk of bias. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included eight RCTs involving 1119 participants: 559 were randomised to the fibrin sealant group and 560 to the control group after distal pancreatectomy. Fibrin sealant use may result in little to no difference in the rate of POPF (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.73 to 1.21; 5 studies, 1002 participants; low-certainty evidence) and overall postoperative morbidity (RR 1.20, 95% CI 0.98 to 1.48; 4 studies, 893 participants; low-certainty evidence). After fibrin sealant use, approximately 199 people (155 to 256 people) out of 1000 developed POPF compared with 212 people out of 1000 when no fibrin sealant was used. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto odds ratio (OR) 0.39, 95% CI 0.12 to 1.29; 7 studies, 1051 participants; very low-certainty evidence) and total length of hospital stay (mean difference (MD) 0.99 days, 95% CI -1.83 to 3.82; 2 studies, 371 participants; very low-certainty evidence). Fibrin sealant use may reduce the reoperation rate slightly (RR 0.40, 95% CI 0.18 to 0.90; 3 studies, 623 participants; low-certainty evidence). Serious adverse events were reported in five studies (732 participants), and there were no serious adverse events related to fibrin sealant use (low-certainty evidence). The studies did not report quality of life or cost-effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included five RCTs involving 519 participants: 248 were randomised to the fibrin sealant group and 271 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF (RR 1.34, 95% CI 0.72 to 2.48; 3 studies, 323 participants; very low-certainty evidence), postoperative mortality (Peto OR 0.24, 95% CI 0.05 to 1.06; 5 studies, 517 participants; very low-certainty evidence), reoperation rate (RR 0.74, 95% CI 0.33 to 1.66; 3 studies, 323 participants; very low-certainty evidence), and total hospital cost (MD -1489.00 US dollars, 95% CI -3256.08 to 278.08; 1 study, 124 participants; very low-certainty evidence). After fibrin sealant use, approximately 130 people (70 to 240 people) out of 1000 developed POPF compared with 97 people out of 1000 when no fibrin sealant was used. Fibrin sealant use may result in little to no difference both in overall postoperative morbidity (RR 1.02, 95% CI 0.87 to 1.19; 4 studies, 447 participants; low-certainty evidence) and in total length of hospital stay (MD -0.33 days, 95% CI -2.30 to 1.63; 4 studies, 447 participants; low-certainty evidence). Serious adverse events were reported in two studies (194 participants), and there were no serious adverse events related to fibrin sealant use (very low-certainty evidence). The studies did not report quality of life. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two RCTs involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto OR 1.41, 95% CI 0.63 to 3.13; 2 studies, 351 participants; very low-certainty evidence), overall postoperative morbidity (RR 1.16, 95% CI 0.67 to 2.02; 2 studies, 351 participants; very low-certainty evidence), and reoperation rate (RR 0.85, 95% CI 0.52 to 1.41; 2 studies, 351 participants; very low-certainty evidence). Fibrin sealant use may result in little to no difference in the total length of hospital stay (median 16 to 17 days versus 17 days; 2 studies, 351 participants; low-certainty evidence). Serious adverse events were reported in one study (169 participants; low-certainty evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report POPF, quality of life, or cost-effectiveness.
AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealant use may result in little to no difference in the rate of POPF in people undergoing distal pancreatectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF in people undergoing pancreaticoduodenectomy. The effect of fibrin sealant use on postoperative mortality is uncertain in people undergoing either distal pancreatectomy or pancreaticoduodenectomy.
术后胰腺瘘（POPF）是胰腺手术后最常见且潜在危及生命的并发症之一。纤维蛋白胶已在一些中心用于降低 POPF 发生率。然而，在胰腺手术中使用纤维蛋白胶存在争议。这是 2020 年发表的 Cochrane 综述的更新。
评估在接受胰腺手术的人群中，与不使用纤维蛋白胶相比，使用纤维蛋白胶预防（B 级或 C 级）POPF 的获益和危害。
我们于 2023 年 3 月 9 日检索了 Cochrane 图书馆、MEDLINE、Embase 以及另外两个数据库，并参考了参考文献、引用文献检索和与研究作者的联系，以确定其他研究。
我们纳入了所有比较纤维蛋白胶（纤维蛋白胶或纤维蛋白胶补丁）与对照（不使用纤维蛋白胶或安慰剂）在接受胰腺手术的人群中预防 POPF（B 级或 C 级）的随机对照试验（RCT）。
我们使用了 Cochrane 预期的标准方法学程序。
我们纳入了 14 项 RCT，涉及 1989 名参与者，比较了纤维蛋白胶在不同部位的使用：残端闭合加固（8 项研究）、胰腺吻合加固（5 项研究）或主胰管闭塞（2 项研究）。6 项 RCT 在单中心进行；2 项在双中心进行；6 项在多中心进行。1 项 RCT 在澳大利亚进行；1 项在奥地利进行；2 项在法国进行；3 项在意大利进行；1 项在日本进行；2 项在荷兰进行；2 项在韩国进行；2 项在美国进行。参与者的平均年龄范围从 50.0 岁到 66.5 岁。所有 RCT 均存在高偏倚风险。
我们纳入了 8 项 RCT，涉及 1119 名参与者：559 名随机分配到纤维蛋白胶组，560 名分配到对照组。在胰头十二指肠切除术后，纤维蛋白胶的使用可能对 POPF 发生率（风险比（RR）0.94，95%置信区间（CI）0.73 至 1.21；5 项研究，1002 名参与者；低质量证据）和总体术后发病率（RR 1.20，95%CI 0.98 至 1.48；4 项研究，893 名参与者；低质量证据）没有显著影响。在使用纤维蛋白胶后，与对照组相比，大约每 1000 人中会有 199 人（155 至 256 人）发生 POPF，而每 1000 人中会有 212 人（7 项研究，1051 名参与者；极低质量证据）发生。关于纤维蛋白胶使用对术后死亡率（Peto 比值比（OR）0.39，95%CI 0.12 至 1.29；7 项研究，1051 名参与者；极低质量证据）和总住院时间（平均差值（MD）0.99 天，95%CI -1.83 至 3.82；2 项研究，371 名参与者；极低质量证据）的影响，证据非常不确定。纤维蛋白胶的使用可能会略微降低再手术率（RR 0.40，95%CI 0.18 至 0.90；3 项研究，623 名参与者；低质量证据）。五项研究（732 名参与者）报告了严重不良事件，但没有与纤维蛋白胶使用相关的严重不良事件（低质量证据）。这些研究没有报告生活质量或成本效益。
我们纳入了 5 项 RCT，涉及 519 名参与者：248 名随机分配到纤维蛋白胶组，271 名分配到对照组。在胰腺头十二指肠切除术后，纤维蛋白胶使用对 POPF 发生率（RR 1.34，95%CI 0.72 至 2.48；3 项研究，323 名参与者；极低质量证据）、术后死亡率（Peto OR 0.24，95%CI 0.05 至 1.06；5 项研究，517 名参与者；极低质量证据）、再手术率（RR 0.74，95%CI 0.33 至 1.66；3 项研究，323 名参与者；极低质量证据）和总住院费用（MD -1489.00 美元，95%CI -3256.08 至 278.08；1 项研究，124 名参与者；极低质量证据）的影响的证据非常不确定。在使用纤维蛋白胶后，与对照组相比，大约每 1000 人中会有 130 人（70 至 240 人）发生 POPF，而每 1000 人中会有 97 人（4 项研究，447 名参与者；低质量证据）发生。纤维蛋白胶的使用可能会对总体术后发病率（RR 1.02，95%CI 0.87 至 1.19；4 项研究，447 名参与者；低质量证据）和总住院时间（MD -0.33 天，95%CI -2.30 至 1.63；4 项研究，447 名参与者；低质量证据）没有显著影响。两项研究（194 名参与者）报告了严重不良事件，但没有与纤维蛋白胶使用相关的严重不良事件（极低质量证据）。这些研究没有报告生活质量。
我们纳入了 2 项 RCT，涉及 351 名参与者：188 名随机分配到纤维蛋白胶组，163 名分配到对照组。在胰腺头十二指肠切除术后，纤维蛋白胶使用对术后死亡率（Peto OR 1.41，95%CI 0.63 至 3.13；2 项研究，351 名参与者；极低质量证据）、总体术后发病率（RR 1.16，95%CI 0.67 至 2.02；2 项研究，351 名参与者；极低质量证据）和再手术率（RR 0.85，95%CI 0.52 至 1.41；2 项研究，351 名参与者；极低质量证据）的影响的证据非常不确定。纤维蛋白胶的使用可能会对总住院时间（中位数 16 至 17 天与 17 天；2 项研究，351 名参与者；低质量证据）没有显著影响。一项研究（169 名参与者；低质量证据）报告了严重不良事件：与对照组相比，应用纤维蛋白胶封闭主胰管后，更多的参与者在三个月（33.7%纤维蛋白胶组与 10.8%对照组；29 名参与者与 9 名参与者）和 12 个月（33.7%纤维蛋白胶组与 14.5%对照组；29 名参与者与 12 名参与者）时发生糖尿病。这些研究没有报告 POPF、生活质量或成本效益。
根据目前的证据，在接受胰头十二指肠切除术的人群中，纤维蛋白胶的使用可能对 POPF 的发生率没有显著影响。在接受胰头十二指肠切除术的人群中，纤维蛋白胶使用对 POPF 发生率的影响的证据非常不确定。在接受胰头十二指肠切除术或胰腺切除术的人群中，纤维蛋白胶使用对术后死亡率的影响不确定。
