Abstract
Background
Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes.
Methods
A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min.
Results
Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality.
Conclusions
Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.
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References
Cauchy F, Aussilhou B, Dokmak S et al (2012) Reappraisal of the risks and benefits of major liver resection in patients with initially unresectable colorectal liver metastases. Ann Surg 256:746–752 discussion 752–4
Zimmitti G, Roses RE, Andreou A et al (2013) Greater complexity of liver surgery is not associated with an increased incidence of liver-related complications except for bile leak: an experience with 2,628 consecutive resections. J Gastrointest Surg 17:57–64 discussion pp. 64–5
Huntington JT, Royall NA, Schmidt CR (2014) Minimizing blood loss during hepatectomy: a literature review. J Surg Oncol 109:81–88
Kooby DA, Stockman J, Ben-Porat L et al (2003) Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases. Ann Surg 237:860–869 discussion 869–70
Katz SC, Shia J, Liau KH et al (2009) Operative blood loss independently predicts recurrence and survival after resection of hepatocellular carcinoma. Ann Surg 249:617–623
Hallet J, Kulyk I, Cheng ESW et al (2016) The impact of red blood cell transfusions on perioperative outcomes in the contemporary era of liver resection. Surgery 159:1591–1599
Smyrniotis V, Kostopanagiotou G, Theodoraki K et al (2004) The role of central venous pressure and type of vascular control in blood loss during major liver resections. Am J Surg 187:398–402
Alkozai EM, Lisman T, Porte RJ (2009) Bleeding in liver surgery: prevention and treatment. Clin Liver Dis 13:145–154
Boonstra EA, Molenaar IQ, Porte RJ, de Boer MT (2009) Topical haemostatic agents in liver surgery: do we need them? HPB 11:306–310
Nakajima Y, Shimamura T, Kamiyama T et al (2002) Control of intraoperative bleeding during liver resection: analysis of a questionnaire sent to 231 Japanese hospitals. Surg Today 32:48–52
Lochan R, Ansari I, Coates R et al (2013) Methods of haemostasis during liver resection–a UK national survey. Dig Surg 30:375–382
Wright JD, Ananth CV, Lewin SN et al (2014) Patterns of use of hemostatic agents in patients undergoing major surgery. J Surg Res 186:458–466
Brustia R, Granger B, Scatton O (2016) An update on topical haemostatic agents in liver surgery: systematic review and meta analysis. J Hepatobiliary Pancreat Sci 23:609–621
Ding H, Yuan J-Q, Zhou J-H et al (2013) Systematic review and meta-analysis of application of fibrin sealant after liver resection. Curr Med Res Opin 29:387–394
Sanjay P, Watt DG, Wigmore SJ (2013) Systematic review and meta-analysis of haemostatic and biliostatic efficacy of fibrin sealants in elective liver surgery. J Gastrointest Surg 17:829–836
Jansen JP, Fleurence R, Devine B et al (2011) Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. Value Health 14:417–428
Salanti G, Ades AE, Ioannidis JPA (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64:163–171
Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–e34
Hutton B, Salanti G, Caldwell DM et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162:777–784
Rohatgi A (2019) WebPlotDigitizer. Version 4.2. Austin, TX, USA. https://automeris.io/WebPlotDigitizer
Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14:135
Sterne JAC, Savovic J, Page M (2019) Others RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898
van Valkenhoef G, Lu G, de Brock B et al (2012) Automating network meta-analysis. Res Synth Methods 3:285–299
Sweeting MJ, Sutton AJ, Lambert PC (2004) What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 23:1351–1375
Kawasaki S, Origasa H, Tetens V, Kobayashi M (2017) Comparison of TachoSil and TachoComb in patients undergoing liver resection—a randomized, double-blind, non-inferiority trial. Langenbecks Arch Surg 402:591–598
Wang Z, Liao B-Y, Qiu S-J et al (2015) Oxidized regenerated cellulose reduces the amount of fluid drainage after liver resection: a randomized prospective clinical trial. Hepatogastroenterology 62:951–954
Minkowitz H, Navarro-Puerto J, Lakshman S, et al (2019) Prospective, randomized, phase II, non-Inferiority study to evaluate the safety and efficacy of topical thrombin (human) grifols as adjunct to hemostasis during vascular, hepatic, soft tissue, and spinal open surgery. J Am Coll Surg
Evaluation of Haemostatic Efficacy, Tolerability and Safety of Kedrion Fibrin Sealant in patients undergoing major or minor Liver Surgery. Multicenter, Controlled, Open Label Randomised Phase II/III study. https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011603-23/results. Accessed 25 Aug 2019
Bektas H, Nadalin S, Szabo I et al (2014) Hemostatic efficacy of latest-generation fibrin sealant after hepatic resection: a randomized controlled clinical study. Langenbecks Arch Surg 399:837–847
Bjelović M, Ayguasanosa J, Kim RD et al (2018) A prospective, randomized, phase III study to evaluate the efficacy and safety of fibrin sealant grifols as an adjunct to hemostasis as compared to cellulose sheets in hepatic surgery resections. J Gastrointest Surg 22:1939–1949
Bochicchio GV, Gupta N, Porte RJ et al (2015) The FINISH-3 trial: a phase 3, international, randomized, single-blind, controlled trial of topical fibrocaps in intraoperative surgical hemostasis. J Am Coll Surg 220:70–81
Chapman WC, Clavien PA, Fung J et al (2000) Effective control of hepatic bleeding with a novel collagen-based composite combined with autologous plasma: results of a randomized controlled trial. Arch Surg 135:1200–1204 discussion 1205
de Boer MT, Klaase JM, Verhoef C et al (2012) Fibrin sealant for prevention of resection surface-related complications after liver resection: a randomized controlled trial. Ann Surg 256:229
Figueras J, Llado L, Miro M et al (2007) Application of fibrin glue sealant after hepatectomy does not seem justified: results of a randomized study in 300 patients. Ann Surg 245:536–542
Genyk Y, Kato T, Pomposelli JJ et al (2016) Fibrin sealant patch (tachosil) vs oxidized regenerated cellulose patch (surgicel original) for the secondary treatment of local bleeding in patients undergoing hepatic resection: a randomized controlled trial. J Am Coll Surg 222:261–268
Kakaei F, Seyyed Sadeghi MS, Sanei B et al (2013) A randomized clinical trial comparing the effect of different haemostatic agents for haemostasis of the liver after hepatic resection. HPB Surg 2013:587608
Kobayashi S, Takeda Y, Nakahira S et al (2016) Fibrin sealant with polyglycolic acid felt vs fibrinogen-based collagen fleece at the liver cut surface for prevention of postoperative bile leakage and hemorrhage: a prospective, randomized, controlled study. J Am Coll Surg 222:59–64
Koea JB, Batiller J, Patel B et al (2013) A phase III, randomized, controlled, superiority trial evaluating the fibrin pad versus standard of care in controlling parenchymal bleeding during elective hepatic surgery. HPB 15:61–70
Koea JB, Batiller J, Aguirre N et al (2016) A multicentre, prospective, randomized, controlled trial comparing EVARREST™ fibrin sealant patch to standard of care in controlling bleeding following elective hepatectomy: anatomic versus non-anatomic resection. HPB 18:221–228
Kohno H, Nagasue N, Chang YC et al (1992) Comparison of topical hemostatic agents in elective hepatic resection: a clinical prospective randomized trial. World J Surg 16:966–969 discussion 970
Liu M, Lui WY (1993) The use of fibrin adhesive for hemostasis after liver resection. Zhonghua Yi Xue Za Zhi 51:19–22
Moench C, Mihaljevic AL, Hermanutz V et al (2014) Randomized controlled multicenter trial on the effectiveness of the collagen hemostat Sangustop® compared with a carrier-bound fibrin sealant during liver resection (ESSCALIVER study, NCT00918619). Langenbecks Arch Surg 399:725–733
Noun R, Elias D, Balladur P et al (1996) Fibrin glue effectiveness and tolerance after elective liver resection: a randomized trial. Hepatogastroenterology 43:221–224
Öllinger R, Mihaljevic AL, Schuhmacher C et al (2013) A multicentre, randomized clinical trial comparing the Veriset™ haemostatic patch with fibrin sealant for the management of bleeding during hepatic surgery. HPB 15:548–558
Rahbari NN, Birgin E, Sturm D et al (2019) Randomized clinical trial of BioFoam® Surgical Matrix to achieve hemostasis after liver resection. HPB. https://doi.org/10.1016/j.hpb.2019.10.1529
Schwartz M, Madariaga J, Hirose R et al (2004) Comparison of a new fibrin sealant with standard topical hemostatic agents. Arch Surg 139:1148–1154
Verhoef C, Singla N, Moneta G et al (2015) Fibrocaps for surgical hemostasis: two randomized, controlled phase II trials. J Surg Res 194:679–687
Corral M, Ferko N, Hollmann S et al (2016) Clinician reported ease of use for a novel fibrin sealant patch for hemostasis: results from four randomized controlled trials. Curr Med Res Opin 32:367–375
Probst P, Knebel P, Grummich K et al (2016) Industry bias in randomized controlled trials in general and abdominal surgery: an empirical study. Ann Surg 264:87–92
Wells CI, Ratnayake CBB, Perrin J, Pandanaboyana S (2019) Prophylactic negative pressure wound therapy in closed abdominal incisions: a meta-analysis of randomised controlled trials. World J Surg. https://doi.org/10.1007/s00268-019-05116-6
Pandanaboyana S, Bell R, Shah N et al (2017) A cost-effective analysis of fibrin sealants versus no sealant following open right hemihepatectomy for colorectal liver metastases. ANZ J Surg 87:E11–E14
Shander A (2007) Financial and clinical outcomes associated with surgical bleeding complications. Surgery 142:S20–S25
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Wells, C.I., Ratnayake, C.B.B., Mentor, K. et al. Haemostatic Efficacy of Topical Agents During Liver Resection: A Network Meta-Analysis of Randomised Trials. World J Surg 44, 3461–3469 (2020). https://doi.org/10.1007/s00268-020-05621-z
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DOI: https://doi.org/10.1007/s00268-020-05621-z