Background
Methods
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Liquid fibrin adhesives
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Fibrin patch
1A. Strong recommendation, high-quality evidence | Benefits clearly outweigh risks and burdens, or vice versa | RCTs without important limitations or overwhelming evidence from observational studies | Strong recommendation, applies to most patients in most circumstances without reservation |
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1B. Strong recommendation, moderate-quality evidence | Benefits clearly outweigh risk and burdens, or vice versa | RCTs with important limitations (inconsistent results, methodological flaws, indirect analyses or imprecise conclusions) or exceptionally strong evidence from observational studies | Strong recommendation, applies to most patients in most circumstances without reservation |
1C. Strong recommendation, low-quality or very low-quality evidence | Benefits clearly outweigh risk and burdens, and vice versa | Observational studies or case series | Strong recommendation but subject to change when higher-quality evidence becomes available |
2A. Weak recommendation, moderate-quality evidence | Benefits closely balanced with risks and burdens | RCTs without important limitations or overwhelming evidence from observational studies | Weak recommendation, best action may differ depending on the patient, treatment circumstances, or social values |
2B. Weak recommendation, moderate-quality evidence | Benefits closely balanced with risks and burdens | RCTs with important limitations (inconsistent results, methodological flaws, indirect analyses or imprecise conclusions) or exceptionally strong evidence from observational studies | Weak recommendation, best action may differ depending on the patient, treatment circumstances, or social values |
2C. Weak recommendation, low-quality or very low-quality evidence | Uncertainty in the estimates of benefits, risks, and burdens; benefits, risks, and burdens may be closely balanced | Observational studies or case series | Very weak recommendation, alternative treatments may be equally reasonable and merit consideration |
Results
General considerations
Scientific foundation
Category | Commercial name | Action | When to use | Cautions |
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Liquid adhesives |
Fibrinogen + thrombin:
Tisseel, Evicel, Beriplast, Vitagel, Cryoseal, Evarrest, Crosseal, Quixil
Human Thrombin:
Evithromb, Thrombin-JMI, Rechothromb
+ Bovine gelatin
Floseal
+ Porcine gelatin
Surgiflo | Fibrinogen and thrombin mixed at the site of application to form clot. | Adjunctive measure to control residual mild or moderate bleeding (oozing and/or spurting). Effective irrespective of patient’s coagulation status. Weak sealant effect | Do not use in individuals known to react to human blood products. Increased risk of thrombosis with bovine thrombin. Avoid intravascular administration because of thromboembolic risk. Avoid tranexamic acid containing products if CSF leak because of neurotoxicity. Gelatine granules can swell up to 20% |
Adhesives with mechanical support |
Fibrinogen + thrombin + equine collagen patch
TachoSil | The patch facilitates compression on bleeding site | Adjunctive measure to control residual severe bleeding because the patch prevents the streaming effect of blood. Weak sealant effect | |
Mechanical hemostats | -Oxidized Cellulose Surgicel (fibrillar, original) Nu-Knit (fibrillar, original)
-Collagen (microfibrillar- MFC)
Avitene, Helistat/Helitene, Instat/Ultrafoam
-Porcine gelatin
Gelfoam (flour, sponge, plus) Surgifoam -Polysaccharides spheres Arista AH | These agents can be used only in patients with normal coagulation system. They form a tri-dimensional matrix at the site of bleeding, which allows clotting to occur. Provides physical matrix for clotting initiation; low pH contributes to platelet activation Platelet adherence and activation Concentrates platelets and clotting factors | Very good handling characteristics; does not stick to instruments; typically dissolves in 2–6 weeks; low pH has antimicrobial effect; effective on residual oozing No significant swelling Effective despite heparinization Nonantigenic; neutral pH allows use with biological agents; effective on oozing and bleeding from bone Rapidly absorbed; effective on residual mild bleeding if conventional method impractical | Not effective in coagulation disorders It inhibits thrombin because of low pH; may induce inflammation for foreign body reaction; caution if used in narrowed spaces because it can swell. Less effective if thrombocytopenia; may bind to neural structures; avoid if blood-saving device used as MFC can pass through the filters Caution if used in confined spaces as it swells; remove the excess after obtained hemostasis; may embolize in intravascular compartments Caution in diabetic patients; Risk of embolism if accidentally injected or placed within a blood vessel. |
Hemostatic dressings |
Zeolite
QuickClot ACS+
Smectite
WoundStat
Kaolin
Quick Clot Combat Gauze (CG)
Chitin/chitosan
HemCon Celox (CE) (granules, gauze) | Molecular sieves absorb water at site of wound and increase concentration of clotting factors, platelets, RBCs. Procoagulant agents which enhances coagulation by providing a high local concentration of coagulation factors. Muco-adhesive agent with direct electrostatic interaction between negatively charged cell membranes of the erythrocytes and positively charged chitosan | Control of significant hemorrhage in anatomic areas where tourniquets cannot be applied and where sustained direct pressure alone is not feasible (neck, groin, axilla) Bleeding wounds on the field Bleeding wounds on the field. Can be poured into wound and conform to it. Easily portable Removal much easier than other granules/powder agents | Exothermic reaction with risk of burn at the site of application for both the products Not biodegradable, must be completely removed before definitive repair Allergy to crustaceans. Eccessive stiffness |
Adhesives
Liquid fibrin adhesives
Scientific foundation
Fibrin patch
Scientific foundation
Year | Design | Comments | GoR-LoE | |
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Annegg U et al. [31]. | 2007 | Ranzomized, single-center | The use of TachoSil® after pulmonary resection resulted in reduction of air leak with significant shortening of time of tube removal and of hospital length of stay | 1C |
Belda-Sanchis et al. [32] | 2010 | Cochrane review | Surgical sealants have some beneficial effects in reducing postoperative air leaks, but their systematic use cannot be recommended at the moment | 1A |
Briceno et al. [24] | 2010 | Prospective controlled | The fibrin sealant after major liver resection was effective for decreasing drainage volume; postoperative blood transfusion requirements; moderate to severe postoperative complications and mean hospital stay | 1C |
Chalmers et al. [3] | 2010 | Prospective randomized | Tranexamic acid-free fibrin sealant is safe, and significantly shortened the time to haemostasis in vascular procedures using PTFE | 1B |
Chapman et al. [4] | 2007 | Phase 3, randomized, double-blind | Recombinant thrombin has comparable efficacy, a similar safety profile, and is considerably less immunogenic than bovine thrombin when used for surgical hemostasis | 1C |
Cheng et al. [29] | 2016 | Cochrane review | Considering the lack of effect on prevention of POPF, high costs, and the potential harms for endocrine pancreatic function, fibrin sealants should not be recommended routinely for people undergoing pancreatic surgery | 1A |
Colombo et al. [14] | 2014 | Systematic review | TachoSil® has a role as a supportive measure to improve hemostasis and promote tissue sealing when standard techniques are insufficient | 1B |
Cormio et al. [33] | 2012 | Prospective randomized | TachoSil sealed tubeless PCNL does not reduce pain and analgesic requirements, but it significantly reduces urinary leakage and postoperative hospital stay | 2A |
De Boer et al. [19] | 2012 | Systematic review | Fibrin sealants can be effective as an adjunct to achieve hemostasis during liver resections. However, considering lack of evidence on the efficacy of fibrin sealants in reducing postoperative resection surface-related complications, routine use of fibrin sealants in liver surgery cannot be recommended. | 1B |
Dhillon et al. [1] | 2011 | Systematic review | Liquid fibrin sealants are effective as adjunctive measure to improve hemostasis | 1B |
Echave et al. [2] | 2014 | Systematic review | Floseal® showed improvement over other hemostatics agents in achieving hemostatis and reducing blood loss | 1B |
Erdogan et al. [16] | 2007 | Systematic review | There is no clear proof of the biliostatic efficacy of topical hemostatic agents used after liver resection on the resection surface | 1B |
Esposito et al. [23]. | 2016 | Systematic review | Fibrin sealants provide a higher rate of intraoperative watertight closure of dura suture line and they may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile | 1B |
Figueras et al. [17] | 2007 | Prospective randomized | Application of fibrin sealants in the raw surface after hepatectomy does not seem justified | 1C |
Filosso et al. [30] | 2013 | Prospective randomized | TachoSil® was superior to standard stapling and suturing aerostatic techniques in reducing postoperative air leaks in patients undergoing redo thoracic surgery. | 1B |
Fisher et al. [5] | 2011 | Randomized, multicenter | Tranexamic acid- and aprotinin-free fibrin sealant is safe and effective for achieving hemostasis in soft tissue during elective retroperitoneal or intra-abdominal surgery. | 1B |
Fisher et al. [10] | 2013 | Prospective randomized | Fibrin pad is superior to absorbable hemostat in soft-tissue bleeding control and is safe and effective for rapidly and reliably achieving hemostasis | 1B |
Genyk et al. [12] | 2016 | Multicenter randomized open-lable | The FSP (TachoSil®) was safe and superior to ORCG (Surgicel Original) for achieving hemostasis in patients undergoing hepatic resection | 1B |
Green et al. [22] | 2015 | Multicenter, prospective randomized | Fibrin sealant is effective as an adjunct to dural sutures to provide watertight closure of the dura mater in neurosurgery | 1C |
Jankowitz et al. [21] | 2009 | Retrospective | The use of fibrin glue for dural repair did not significantly decrease the incidence of a persistent cerebrospinal fluid leak | 2A |
Kobayashi et al. [18] | 2016 | Multicenter randomized | Fibrin sealant with polyglicolic acid compared with collagen fleece did not reduce biliary leakage and hemorrhage | 1C |
Koea et al. [11] | 2015 | Randomized controlled | The FP is safe and superior to SoC for controlling challenging severe soft-tissue bleeding encountered during intra-abdominal and thoracic surgical procedures | 1C |
Maisano et al. [13] | 2009 | Randomized controlled | TachoSil® was significantly superior to standard haemostatic fleece material in obtaining effective and fast intra-operative haemostasis in cardiovascular surgical procedures. TachoSil was safe and well tolerated. | 1B |
Montorsi et al. [27] | 2012 | Multicenter randomized controlled | TachoSil® had no significant effect on the rate of POPF, although there was a significant reduction of amylase level in drainage fluid on postoperative day 1. | 1B |
Marangos et al. [26] | 2011 | Retrospective | The application of the TachoSil® patch did not affect either occurrence of POPF or duration of postoperative hospital stay. Routine use of TachoSil® patch to prevent pancreatic fistulas does not provide clinically significant benefit. | 1C |
Perussi Biscola et al. [20] | 2017 | Systematic review | The new heterologous fibrin sealant from snake venom represents a consistent alternative to biological sealants, since they may avoid transmission of infectious diseases | 1C |
Pommergaard et al. [26] | 2013 | Systematic review | Liquid fibrin adhesive should be beneficial to prevent leak of ileal anastomoses in gastric and bariatric surgery | 1C |
Saha et al. [9] | 2012 | Prospective randomized | Fibrin sealant is safe and its efficacy is superior to manual compression for hemostasis in patients with vascular ePTFE graft | 1C |
Schwartz et al. [6] | 2004 | Prospective randomized controlled | Crosseal fibrin sealant significantly reduces the time of hemostasis following liver resection in comparison with the standard topical hemostatic agents | 1C |
Simo et al. [15] | 2012 | Systematic review | Application of TachoSil® in hepatobiliary and pancreatic surgery has proven effectiveness in hemostasis and as tissue sealant | 1C |
Spotniz et al. [7] | 2012 | Systematic review | Fibrin sealants have multiple new uses that should result in further improvement in patient care | 1C |
Taylor et al.[8] | 2003 | Randomized prospective multicenter | Fibrin sealants are more effective than thrombin-soaked gelatin sponge for achieving hemostasis of needle or suture hole bleeding from PTFE femoral artery grafts. | 1B |
Vakalopoulos et al. [25] | 2012 | Systematic review | Fibrin sealant seem not be necessary as external coating of colonic anastomoses to prevent leakage | 1C |
Mechanical hemostats
Scientific foundation
Year | Design | Comments | GoR-LoE | |
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Agarwal et al. [68] | 2010 | Case series | Excessive amount of oxidized cellulose may induce granuloma | 2C |
Broadbelt et al. [39] | 2002 | Case series | Excessive amount of cellulose in confined space like foramina may induce compression of spinal cord because of swelling | 2C |
Bruckner et al. [41] | 2014 | Retrospective | The use of polysaccharide hemospheres absorbable hemostat in complex cardiothoracic surgery resulted in significant reduction in hemostasis time, postoperative chest tube output, and need for postoperative blood transfusion | 2A |
Emmez et al. [38] | 2010 | Experimental in vivo | Microporous polysaccharides spheres may be used for hemostasis in neurosurgical setting, without inducing granuloma | 2A |
Lewis et al. [36] | 2013 | Experimental in vivo-in vitro preclinical | Oxidized non-regenerated cellulose provides superior hemostasis and equivalent bactericidal effectiveness relative to oxidized regenerated cellulose | 2C |
Menovsky et al. [69] | 2011 | Case reports | Removal of Surgicel® Fibrillar™ is advised after hemostasis has been achieved to avoid the development of complications due to a mass effect | 2C |
Ragusa et al. [34] | 2007 | Randomized prospective | Absorbable gelatin in association with antibiotic is effective in reduce bleeding and infectious complications after cardiac surgery | 2A |
Sabino et al. [37] | 2007 | Retrospective | 2B | |
Wagenhauser et al. [35] | 2016 | Experimental preclinical | Stronger inhibition of essential cellular processes of wound healing were observed for Oxidized non-regenerated cellulose when compared with oxidized regenerated cellulose | 2C |
Xu et al. [40] | 2016 | Randomized controlled | Hemostatic collagen sponge demonstrated better hemostasis effects than gelatin sponge with lower volume of postoperative drainage volume and blood loss in posterior spinal fusion | 2A |
Sealants
Scientific foundation
Year | Design | Comments | GoR-LoE | |
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Allen et al. [49] | 2004 | Prospective randomized | Polymeric sealants may reduce air leak after pulmonary resection | 2A |
Belletrutti et al. [50] | 2008 | Retrospective | N-butyl-2-cyanoacrylate is effective and safe for bleeding control from gastric varices | 2A |
Coselli et al. [52] | 2003 | Prospective randomized | The bovine serum albumin and glutaraldehyde sealant is a safe and effective adjunct to reduce the occurrence of anastomotic site bleeding in cardiovascular surgery | 2A |
Dumville et al. [42] | 2014 | Cochrane review | There is some evidence that dehiscence rates may be higher in wound closed with tissue adhesives than with sutures; there was no evidence of any difference between sutures and tissue adhesive for outcomes such as cosmetic appearance and satisfaction | 1A |
Imkamp et al. [47] | 2015 | Prospective | Hemopatch® is effective to improve hemostasis in nephron-sparing surgery | 2B |
Kim et al. [45] | 2011 | Prospective randomized | Polyethylene glycol hydrogel spinal sealant is effective as adjunctive measure to improve watertight closure of dura mater in spine surgery | 2A |
Lewis et al. [43] | 2016 | Systematic review | Hemopatch® is an effective, easy-to-use hemostatic agent in open and minimally invasive surgery of patients with thrombin- or platelet-induced coagulopathies | 1C |
Miscusi et al. [53] | 2014 | Prospective | Sealants are useful for dural watertight closure | 2A |
Ollinger et al. [48] | 2013 | Prospective multicenter | Polyethylene glycol patch is useful in control of bleeding from hepatic cut surface | 2A |
Parildar et al. [51] | 2003 | Prospective | N-butyl cyanoacrylate is an useful tool for angioembolization of visceral psuedoaneurism | 2A |
Selli et al. [43] | 2013 | Case reports | N-butyl-2-cyanoacrylate represent a valid first line treatment to control urinary fistula when the output is not excessive and there is a favourable ratio between length and diameter of fistula tract | 2C |
Wright et al. [44] | 2015 | Prospective, randomized controlled, multicenter | Polyethylene glycol hydrogel sealant has been proven safe and effective for provide a watertight closure as an adjunct to sutured closure of durotomies | 2A |
Hemostatic dressings (mineral and polysaccharides)
Scientific foundation
Year | Design | Comments | GoR-LoE | |
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Bulger et al. [55] | 2014 | Guidelines | Topical hemostatic agent in combination with direct pressure are effective for bleeding control in pre-hospital settings in anatomical areas where tourniquet cannot be applied | 1A |
Cox et al. [64] | 2009 | Retrospective cohort study | HemCon appears to be safe, while QuickClot may produce superficial burns. These products should be taken into account to assist in controlling internal hemorrhage, especially during damage control surgery | 2C |
Jacobs et al. [56] | 2013 | Guidelines | Wider civilian use of tourniquet should be encouraged for the control of significant extremity hemorrhage when direct manual compression is ineffective or impractical | 1A |
Kheirabadi et al. [62] | 2009 | Experimental, animal | The hemostatic agents are more effective and safe than the currently deployed devices in controlling arterial hemorrhage | 2A |
Leonard et al. [54] | 2016 | Retrospective, multicenter | QuickClot is an effective and safe adjunct to control hemorrhage in prehospital setting | 2A |
McManus [57] | 2007 | Case series | Zeolite, despite potential complication of thermal injuries, has shown to be a valuable hemostatic agent if used under appropriated circumstances | 2C |
Rhee et al. [58] | 2008 | Case series | QuickClot has been proven safe and effective to control prehospital non compressible hemorrhage | 2A |
Shina et al. [59] | 2015 | Retrospective | Hemostatic dressing seem to be an effective tool for junctional hemorrhage control and should be considered as second-line treatment for extremity hemorrhage control at the point of injury | 1C |
Te Grotenhuis et al. [63] | 2016 | Prospective | Chitogauze is an effective and safe adjunct in the prehospital traatment of massive external traumatic hemorrhage | 1C |
Waibel et al. [61] | 2011 | Prospective | Chitosan bandage is safe even in shellfish allergic patients | 2C |
Wedmore et al. [60] | 2006 | Retrospective | Chitosan-based hemostatic dressing is useful for prehospital combat casualties | 2C |