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Experience with TachoSil in obstetric and gynecologic surgery
International Journal of Gynecology and Obstetrics 113 (2011) 112–115
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
CLINICAL ARTICLE
Experience with TachoSil in obstetric and gynecologic surgery Pietro Santulli, Louis Marcellin, Cyril Touboul, Marcos Ballester, Emile Darai, Roman Rouzier ⁎ Department of Obstetrics and Gynecology, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, CancerEst, Université Pierre et Marie Curie (UPMC), Paris, France
a r t i c l e
i n f o
Article history: Received 13 August 2010 Received in revised form 20 November 2010 Accepted 27 January 2011 Keywords: Hemostatic agents Surgical hemorrhage TachoSil
a b s t r a c t Objective: To evaluate the feasibility and effectiveness of using TachoSil during obstetric and gynecologic surgery. Methods: The retrospective cohort study, conducted at a French university hospital, included women who experienced perioperative bleeding requiring the use of TachoSil during 2007–2009. The following information was collected: patient age, indication for the use of TachoSil, need for a blood transfusion, type of surgery performed, postoperative course, and traceability of TachoSil. Results: TachoSil was used in 84 women. The main indications for the surgical interventions requiring TachoSil were ovarian malignancy (n = 18), fibroma (n = 17), breast cancer (n = 11), and endometrial cancer (n = 10). In 16 women, TachoSil was applied to the uterine serosa, particularly after cesarean delivery or polymyomectomy; in 7 women, it was applied to the major vascular axis. Red cell packs were infused in 24 women during surgery (average 3 packs per woman). Three women required repeat surgery. The use of TachoSil was not recorded in the operative reports of 43 (51%) women. Conclusion: The present findings confirm that the use of TachoSil in gynecologic and obstetric surgeries is effective and well tolerated. Measures to improve the traceability of TachoSil use are recommended. © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Rapid control of bleeding during surgery reduces blood loss and can help to decrease postoperative morbidity and mortality [1]. Uncontrollable bleeding in obstetric and gynecologic surgery is unusual but potentially life-threatening. In gynecologic surgery, such bleeding can occur during lymphadenectomy and debulking for advanced ovarian cancer. In obstetric surgery, uncontrollable uterine, vaginal, or pelvic hemorrhage is sometimes encountered after abdominal or vaginal delivery. Management of a major hemorrhage involves direct and selective vascular ligation with sutures or vascular clips or occlusion with electrocautery. When these measures fail, application of a topical hemostatic agent can help to control bleeding [2]. Since the early 1990s, a variety of hemostatic agents, such as fleeces of various origins, liquid fibrin sealants, an albumin–glutaraldehyde sealant, and synthetic glues, have been introduced as means to obtain satisfactory control of hemostasis during a range of surgical procedures. These agents have proved to be effective in improving surgical results, preventing early postoperative complications, reducing the duration of the intervention, and reducing the duration of postoperative hospitalization [3,4]. TachoSil (Nycomed, Zurich, Switzerland) is a sterile bioabsorbable hemostatic agent that consists of an equine collagen sponge coated on one side with human fibrinogen (5.5 mg/cm2) and human thrombin ⁎ Corresponding author at: Service de Gynécologie-Obstétrique, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France. Tel.: + 33 156016876; fax: + 33 156016062. E-mail address: [email protected] (R. Rouzier).
(2.0 IU/cm2). The yellow (active) side of the TachoSil patch is applied to a cleaned wound surface and the patch is pressed down with a moist surgical pad for 5 minutes to obtain complete hemostasis. On contact with the physiologic fluids at the wound site, the coating of the sponge dissolves and gradually releases the 2 active ingredients. A fibrinogen–thrombin reaction follows, mimicking the last phase of blood coagulation and leading to the conversion of fibrinogen to fibrin monomers. These monomers spontaneously polymerize to form a stable fibrin clot, holding the collagen tightly to the wound surface, and thus bleeding is prevented and the tissue is sealed. Unlike other fibrin sealants, which require preparation before use, TachoSil is a ready-to-use fixed-combination tissue sealant. It represents the third generation of surgical patches manufactured by Nycomed and is bioequivalent to its predecessor TachoComb [5] (Table 1). Because the coagulation factors in TachoSil are derived from human plasma and the collagen fleece is derived from horse tendons, its traceability requirements in France are defined by decree number 95–566 of the French Public Health Code, meaning that it must meet the same traceability standards as blood units. According to decree 95–566 and the manufacturer's recommendations, TachoSil use must be recorded in the pharmacy register, the operative theater register, and the operative report. Clinical studies have shown that TachoSil is effective in achieving hemostasis after kidney and liver resections [6,7], in preventing air leakage after lung surgery [8,9], and in reducing lymphatic fluid production from the mediastinum after mediastinal lymph node dissection [10]. However, data concerning the use of TachoSil in obstetric and gynecologic surgery are lacking. The aim of the present
0020-7292/$ – see front matter © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2010.11.019
P. Santulli et al. / International Journal of Gynecology and Obstetrics 113 (2011) 112–115 Table 1 Development process of surgical patches manufactured by Nycomed (Zurich, Switzerland). Name
Marketed
Collagen
Fibrinogen
Thrombin
Aprotinin
TachoComb TachoComb H TachoSil
1993 in Austria 2001 in Germany 2004 EU approval
Equine Equine Equine
Human Human Human
Bovine Human Human
Bovine Bovine –
observational study was to report the perioperative outcomes after the use of TachoSil in a French obstetric and gynecologic surgery center. The traceability of TachoSil used during obstetric and gynecologic surgery was also investigated. 2. Materials and methods The present observational study was performed in the obstetric and gynecologic surgery department of a tertiary care center (Hôpital Tenon) in Paris, France. Between January 1, 2007, and July 31, 2009, 13 908 surgical procedures in 7900 patients were performed at the study center. Women who received TachoSil for the control of a major hemorrhage were included in the present study. Information on the age of the patient, the type of surgery performed, the indication for TachoSil use, the need for a blood transfusion, the need for a repeat surgery to complete hemostasis, and the postoperative course was collected retrospectively by review of the operative reports. The surgical procedures were categorized as oncologic, benign gynecologic, or obstetric surgery. To evaluate the traceability of TachoSil, the registers of the hospital pharmacy and the operative theater were also searched for evidence of TachoSil use. In addition, the literature concerning the efficacy and safety of TachoSil was reviewed according to the methodology recommended by the Cochrane Collaboration. Studies were identified by searching CENTRAL, MEDLINE, the Nycomed commercial website, product monographs, and reference lists of published articles. The databases were searched using the following Medical Subject Headings (MeSH) and text words: “hemostatic agent;” “surgery;” and “TachoSil” (34 citations). The present study was approved by the local Institutional Review Board and Ethics Committee. Written informed consent—including consent regarding the use and disclosure of health care information for research purposes—was obtained from all patients. All statistical analyses were performed using the software package R (Free Software Foundation, Boston, MA, USA).
113
Table 2 Main indications for surgical intervention.a Type of surgery
No. (%) of surgeries performed
Oncologic surgery Ovarian cancer Breast cancer Endometrial cancer Cervical cancer Pelvic sarcoma Vulvar melanoma Benign gynecologic surgery Fibroma Severe endometriosis Total hysterectomy Obstetric surgery Cesarean delivery Hemostatic hysterectomy Ruptured cornual pregnancy Vascular (hypogastric artery) ligation Severe perineal tear Prepartum uterine rupture
50 (59.5) 18 (21.4) 11 (13.1) 10 (11.9) 6 (7.1) 4 (4.8) 1 (1.2) 21 (25.0) 17 (20.2) 2 (2.4) 2 (2.4) 13 (15.5) 6 (7.1) 3 (3.6) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2)
a
n = 84.
The use of TachoSil increased during the study period. While the annual incidence of TachoSil use in oncologic and benign gynecologic surgeries remained globally unchanged, the use in obstetric surgeries increased from 1 instance per year in 2007 to 10 instances per year in 2009 (Table 3). The most common sites of TachoSil application (Table 4) were the uterine serosa (16 [19.0%]), most often after cesarean delivery or polymyomectomy, and the major vascular axis after pelvic or para-aortic lymphadenectomy (7 [8.3%]) (Fig. 2). In total, 24 (28.6%) women required transfusions during surgery, with a mean number of 3 red blood cell units required per patient (Table 3). Three women needed to undergo a second surgical procedure within 24 hours for persistent active bleeding despite the
3. Results According to the pharmacy and operative room records, TachoSil was used in 84 women (100% concordance). The mean number of TachoSil patches used per surgery was 1.2. Of the surgeries, 50 (59.5%) were classified as oncologic, 21 (25.0%) as benign gynecologic, and 13 (15.5%) as obstetric (Table 2). The most common surgery indications were ovarian malignancy (18 [21.4%]), fibroma (17 [20.2%]), breast cancer (11 [13.1%]), and endometrial cancer (10 [11.9%]) (Table 2). Of the women with benign pathologies in whom TachoSil was used, 2 (2.4%) had severe endometriosis with persistent bleeding after laparoscopic colorectal resection (Table 2). The most common indication for TachoSil use during obstetric procedures was persistent uterine bleeding after a cesarean delivery (n = 6 [7.1%]). Three (3.6%) women with severe postpartum hemorrhage required TachoSil use to stop bleeding after hemostatic hysterectomy, and 1 woman (1.2%) required TachoSil use after vascular (hypogastric artery) ligation (Table 2). In 1 (1.2%) woman, TachoSil use was associated with placenta accreta. Finally, 1 (1.2%) woman with a first-trimester ruptured cornual pregnancy, treated by laparotomic resection, required complementary hemostasis with TachoSil (Fig. 1).
Fig. 1. TachoSil application after rupture of a cornual pregnancy. A. Right ruptured cornual pregnancy. B. Right cornual scar after resection. C. Application of TachoSil on right cornual scar.
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P. Santulli et al. / International Journal of Gynecology and Obstetrics 113 (2011) 112–115
Table 3 Evolution of the use of TachoSil. Year
2007
2008
2009
Total study period
Mean age of patients, y TachoSil use by type of surgery Oncologic surgery Benign gynecologic surgery Obstetric surgery All types of surgery Mean number of patches used per patient Number of transfusions required Mean number of red cell packs used per patient No mention of TachoSil in operative report
48.5
50.1
49.4
49.5
10 6 1 17 1.1 4 2.8
24 9 2 35 1.1 10 2.9
16 6 10 32 1.3 10 3.2
50 21 13 84 1.2 24 3.0
10 (58)
19 (54)
14 (43)
43 (51)
a
Values are given as number or number (percentage).
perioperative use of TachoSil: 1 patient after a para-aortic lymphadenectomy, 1 patient after a mastectomy, and 1 patient after debulking (splenectomy and caudal pancreatectomy; bleeding of partial pancreatectomy stump) for ovarian carcinoma. TachoSil use was not mentioned in the operative reports of 43 (51.2%) women, of whom 4 (4.8%) had obstetric surgery, 10 (11.9%) had an intervention for a benign condition, and 29 (34.5%) had oncologic surgery. 4. Discussion The present report focuses on the use of TachoSil in routine clinical obstetric and gynecologic practice, whereas most previous reports on the use of TachoSil in gynecologic surgery were single case reports. In the present series, the application of TachoSil resulted in complete hemostasis in a broad range of surgical procedures, with only 3 women requiring a repeat surgery. Surprisingly, TachoSil use was mentioned in half of the operative reports only, with records of TachoSil use lacking particularly after oncologic surgeries. The use of TachoSil has evolved with increased experience. TachoSil was first reported to be used in digestive and hepatobiliary surgeries before it was applied in patients with gynecologic and obstetric indications for surgery. In a continuous 14-year series [11] involving 1460 patients who underwent total laparoscopic hysterectomy for benign uterine pathologies, 19 (1.3%) patients had an intraoperative hemorrhage and 9 (0.6%) patients required a transfusion—highlighting the frequency of perioperative bleeding where TachoSil use might be required. Postoperative bleeding after a hysterectomy is not a rare event. In a 5-year retrospective study [12] involving 1167 women who underwent laparoscopic or vaginal hysterectomy, the overall incidence of bleeding after hysterectomy was 0.85% (n = 10). The authors reported that the hemorrhages could be successfully controlled using
Table 4 TachoSil application sites according to operative reports.a Application site
No. (%)
Axillary lymphadenectomy Mastectomy Uterine serosa Partial pancreatectomy stump Inferior vena cava Interaortocaval space Vaginal vault after hysterectomy Splenic capsule Pelvic lymphadenectomy Pelvectomy Perineal tear Not reported in operative report
4 2 16 3 3 1 4 1 3 3 1 43
a
n = 84.
(4.8) (2.4) (19.0) (3.6) (3.6) (1.2) (4.8) (1.2) (3.6) (3.6) (1.2) (51.2)
Fig. 2. TachoSil application on the major vascular axis after para-aortic lymphadenectomy. A. Before TachoSil application. B. After TachoSil application.
the laparoscope to apply TachoSil's predecessor, TachoComb [12]. Osada et al. [13] investigated the use of TachoComb for the control of oozing hemorrhages in 16 women who underwent surgery for myoma, cervical cancer, endometrial cancer, endometriosis, or pelvic adhesive disease. TachoComb was usually applied to the uterine serosa and adjacent areas. In 14 (87.5%) women, complete hemostasis of the oozing site was achieved; in the remaining 2 (12.5%) women, hemostasis was incomplete but adequate [13]. Ochiai et al. [14] evaluated the use of TachoComb in 45 women who had oozing hemorrhages during open gynecologic surgery. Primary hemostasis was achieved in 97.8% of these women [14]. The present results are in line with these reports. Other potential indications for the use of TachoSil include the reduction of postoperative adhesions after laparoscopic surgery and the prevention of heat-induced injuries to the uterine parenchyma (decline in fibrosis and inflammation), as indicated by findings in a rat model [15]. TachoComb was also capable of reducing adhesion reformation in a rabbit model [16]. Other authors [17] have proposed the application of TachoSil in the axillary area to reduce postoperative axillary drainage and seroma volume after axillar lymphadenectomy for breast cancer. TachoSil has also been used as a tissue barrier to prevent or treat air leakage following pulmonary resection [9], to prevent the development of biliary fistulas [18], and to treat recurrent vesicovaginal fistulas [19]. All of these indications must be investigated further in prospective studies.
P. Santulli et al. / International Journal of Gynecology and Obstetrics 113 (2011) 112–115
A prospective multicenter study [1] conducted in 12 European countries confirmed the safety of TachoSil; the study focused on the occurrence of thromboembolic events, major bleeding, and immunologic events (hypersensitivity including anaphylaxis) during the first 6 months after surgery. The authors reported 124 adverse events in 3098 patients receiving TachoSil. There were 46 (1.5%) thromboembolic events, 62 (2.0%) major bleeding events, and 8 (0.3%) immunologic events. In the group of patients who underwent gynecologic surgery, there were no thromboembolic or immunologic events and only 1 major bleeding event. The authors reported an overall incidence of thromboembolic events much lower than that reported elsewhere in the literature (10%–15%) [20], and they advised taking care when using TachoSil to avoid unintended intravascular application, which may result in life-threatening thromboembolic events. In the present series, no hypersensitivity or allergic reactions occurred, but 3 women had persistent bleeding. In the present study, the operative reports of 43 (51.2%) women contained no record of the use of TachoSil. According to the manufacturer, the possibility of infectious contamination cannot be excluded despite steps being taken during blood or plasma processing to inactivate or remove viruses and despite the careful selection of donors. Safety measures have proven effective against contamination with enveloped viruses, such as HIV and the hepatitis B and C viruses, and the nonenveloped hepatitis A virus, but less so against contamination with other nonenveloped viruses such as parvovirus B19. Contamination with unknown or emerging viruses and other types of infectious agents might also be possible. The manufacturer strongly recommends that hospitals maintain a record of the TachoSil batches used during surgery. The present study demonstrates that this recommendation was followed at the study center, but there is clearly room for improvement given that TachoSil use was not mentioned in half the operative reports. TachoSil can be used to halt perioperative bleeding in obstetric and gynecologic surgeries. The frequency of TachoSil use has increased during the past years and the indications for its use have become broader. However, in the present study, TachoSil was not traceable in 51.2% of cases. We recommend recording the product name and number in the operative report of each patient in whom TachoSil is used to achieve better traceability. Conflict of interest The authors have no conflicts of interest. References [1] Birth M, Figueras J, Bernardini S, Troen T, Gunther K, Mirza D, et al. Collagen fleecebound fibrin sealant is not associated with an increased risk of thromboembolic events or major bleeding after its use for haemostasis in surgery: a prospective multicentre surveillance study. Patient Saf Surg 2009;3(1):13.
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[2] Awonuga AO, Merhi ZO, Khulpateea N. Abdominal packing for intractable obstetrical and gynecologic hemorrhage. Int J Gynecol Obstet 2006;93(2):160–3. [3] Bechstein WO, Strey C. [Local and systemic hemostasis in surgery]. Chirurg 2007;78(2):95–96, 98–100. [4] Mankad PS, Codispoti M. The role of fibrin sealants in hemostasis. Am J Surg 2001;182(2 Suppl):21S–8S. [5] Erdogan D, van Gulik TM. Evolution of fibrinogen-coated collagen patch for use as a topical hemostatic agent. J Biomed Mater Res B Appl Biomater 2008;85(1): 272–8. [6] Frilling A, Stavrou GA, Mischinger HJ, de Hemptinne B, Rokkjaer M, Klempnauer J, et al. Effectiveness of a new carrier-bound fibrin sealant versus argon beamer as haemostatic agent during liver resection: a randomised prospective trial. Langenbecks Arch Surg 2005;390(2):114–20. [7] Siemer S, Lahme S, Altziebler S, Machtens S, Strohmaier W, Wechsel HW, et al. Efficacy and safety of TachoSil as haemostatic treatment versus standard suturing in kidney tumour resection: a randomised prospective study. Eur Urol Oct 2007;52(4): 1156–63. [8] Lang G, Csekeo A, Stamatis G, Lampl L, Hagman L, Marta GM, et al. Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy. Eur J Cardiothorac Surg 2004;25(2):160–6. [9] Anegg U, Lindenmann J, Matzi V, Smolle J, Maier A, Smolle-Juttner F. Efficiency of fleece-bound sealing (TachoSil) of air leaks in lung surgery: a prospective randomised trial. Eur J Cardiothorac Surg 2007;31(2):198–202. [10] Czerny M, Fleck T, Salat A, Zimpfer D, Klepetko W, Wolner E, et al. Sealing of the mediastinum with a local hemostyptic agent reduces chest tube duration after complete mediastinal lymph node dissection for stage I and II non-small cell lung carcinoma. Ann Thorac Surg 2004;77(3):1028–32. [11] Chopin N, Malaret JM, Lafay-Pillet MC, Fotso A, Foulot H, Chapron C. Total laparoscopic hysterectomy for benign uterine pathologies: obesity does not increase the risk of complications. Hum Reprod 2009;24(12):3057–62. [12] Holub Z, Kliment Jr L. Hemostasis using tissue glue in laparoscopy: discussion and review. Ceská Gynekol 2000;65(3):171–3. [13] Osada H, Tanaka H, Fujii TK, Tsunoda I, Yoshida T, Satoh K. Clinical evaluation of a haemostatic and anti-adhesion preparation used to prevent post-surgical adhesion. J Int Med Res 1999;27(5):247–52. [14] Ochiai K, Osada H, Terashima Y, Yokoyama S, Nakajima A, Ogawa T, et al. Utility of TO-193, a new sheet-form fibrin adhesive agent in obstetrics and gynaecologic surgery. Sanfujinka no Jissai (Obstetric Gynecol Pract) 1995;44:253–62. [15] Nohuz E, Darcha C, Moreno W, Tamburro S, Yanez M, Mulliez A, et al. Efficiency of TachoSil to prevent postsurgical adhesion development on laparoscopic rat model. Gynecol Surg 2009;6(4):323–9. [16] Osada H, Minai M, Yoshida T, Satoh K. Use of fibrin adhesive to reduce postsurgical adhesion reformation in rabbits. J Int Med Res 1999;27(5):242–6. [17] Barranger E, Morel O, Akerman G, Malartic C, Clement D. TachoSil to reduce the morbidity of axillary lymph node dissection in breast cancer. Breast Cancer Res 2007;9(Suppl 1):P21. [18] Frena A, Martin F. How to improve bilio-stasis in liver surgery. Chir Ital 2006;58(6): 793–5. [19] Erdogru T, Sanli A, Celik O, Baykara M. Laparoscopic transvesical repair of recurrent vesicovaginal fistula using with fleece-bound sealing system. Arch Gynecol Obstet 2008;277(5):461–4. [20] Committee on Practice Bulletins—Gynecology, American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 84: prevention of deep vein thrombosis and pulmonary embolism. Obstet Gynecol 2007;110(2 Pt 1):429–40.
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
CLINICAL ARTICLE
Experience with TachoSil in obstetric and gynecologic surgery Pietro Santulli, Louis Marcellin, Cyril Touboul, Marcos Ballester, Emile Darai, Roman Rouzier ⁎ Department of Obstetrics and Gynecology, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, CancerEst, Université Pierre et Marie Curie (UPMC), Paris, France
a r t i c l e
i n f o
Article history: Received 13 August 2010 Received in revised form 20 November 2010 Accepted 27 January 2011 Keywords: Hemostatic agents Surgical hemorrhage TachoSil
a b s t r a c t Objective: To evaluate the feasibility and effectiveness of using TachoSil during obstetric and gynecologic surgery. Methods: The retrospective cohort study, conducted at a French university hospital, included women who experienced perioperative bleeding requiring the use of TachoSil during 2007–2009. The following information was collected: patient age, indication for the use of TachoSil, need for a blood transfusion, type of surgery performed, postoperative course, and traceability of TachoSil. Results: TachoSil was used in 84 women. The main indications for the surgical interventions requiring TachoSil were ovarian malignancy (n = 18), fibroma (n = 17), breast cancer (n = 11), and endometrial cancer (n = 10). In 16 women, TachoSil was applied to the uterine serosa, particularly after cesarean delivery or polymyomectomy; in 7 women, it was applied to the major vascular axis. Red cell packs were infused in 24 women during surgery (average 3 packs per woman). Three women required repeat surgery. The use of TachoSil was not recorded in the operative reports of 43 (51%) women. Conclusion: The present findings confirm that the use of TachoSil in gynecologic and obstetric surgeries is effective and well tolerated. Measures to improve the traceability of TachoSil use are recommended. © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Rapid control of bleeding during surgery reduces blood loss and can help to decrease postoperative morbidity and mortality [1]. Uncontrollable bleeding in obstetric and gynecologic surgery is unusual but potentially life-threatening. In gynecologic surgery, such bleeding can occur during lymphadenectomy and debulking for advanced ovarian cancer. In obstetric surgery, uncontrollable uterine, vaginal, or pelvic hemorrhage is sometimes encountered after abdominal or vaginal delivery. Management of a major hemorrhage involves direct and selective vascular ligation with sutures or vascular clips or occlusion with electrocautery. When these measures fail, application of a topical hemostatic agent can help to control bleeding [2]. Since the early 1990s, a variety of hemostatic agents, such as fleeces of various origins, liquid fibrin sealants, an albumin–glutaraldehyde sealant, and synthetic glues, have been introduced as means to obtain satisfactory control of hemostasis during a range of surgical procedures. These agents have proved to be effective in improving surgical results, preventing early postoperative complications, reducing the duration of the intervention, and reducing the duration of postoperative hospitalization [3,4]. TachoSil (Nycomed, Zurich, Switzerland) is a sterile bioabsorbable hemostatic agent that consists of an equine collagen sponge coated on one side with human fibrinogen (5.5 mg/cm2) and human thrombin ⁎ Corresponding author at: Service de Gynécologie-Obstétrique, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France. Tel.: + 33 156016876; fax: + 33 156016062. E-mail address: [email protected] (R. Rouzier).
(2.0 IU/cm2). The yellow (active) side of the TachoSil patch is applied to a cleaned wound surface and the patch is pressed down with a moist surgical pad for 5 minutes to obtain complete hemostasis. On contact with the physiologic fluids at the wound site, the coating of the sponge dissolves and gradually releases the 2 active ingredients. A fibrinogen–thrombin reaction follows, mimicking the last phase of blood coagulation and leading to the conversion of fibrinogen to fibrin monomers. These monomers spontaneously polymerize to form a stable fibrin clot, holding the collagen tightly to the wound surface, and thus bleeding is prevented and the tissue is sealed. Unlike other fibrin sealants, which require preparation before use, TachoSil is a ready-to-use fixed-combination tissue sealant. It represents the third generation of surgical patches manufactured by Nycomed and is bioequivalent to its predecessor TachoComb [5] (Table 1). Because the coagulation factors in TachoSil are derived from human plasma and the collagen fleece is derived from horse tendons, its traceability requirements in France are defined by decree number 95–566 of the French Public Health Code, meaning that it must meet the same traceability standards as blood units. According to decree 95–566 and the manufacturer's recommendations, TachoSil use must be recorded in the pharmacy register, the operative theater register, and the operative report. Clinical studies have shown that TachoSil is effective in achieving hemostasis after kidney and liver resections [6,7], in preventing air leakage after lung surgery [8,9], and in reducing lymphatic fluid production from the mediastinum after mediastinal lymph node dissection [10]. However, data concerning the use of TachoSil in obstetric and gynecologic surgery are lacking. The aim of the present
0020-7292/$ – see front matter © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2010.11.019
P. Santulli et al. / International Journal of Gynecology and Obstetrics 113 (2011) 112–115 Table 1 Development process of surgical patches manufactured by Nycomed (Zurich, Switzerland). Name
Marketed
Collagen
Fibrinogen
Thrombin
Aprotinin
TachoComb TachoComb H TachoSil
1993 in Austria 2001 in Germany 2004 EU approval
Equine Equine Equine
Human Human Human
Bovine Human Human
Bovine Bovine –
observational study was to report the perioperative outcomes after the use of TachoSil in a French obstetric and gynecologic surgery center. The traceability of TachoSil used during obstetric and gynecologic surgery was also investigated. 2. Materials and methods The present observational study was performed in the obstetric and gynecologic surgery department of a tertiary care center (Hôpital Tenon) in Paris, France. Between January 1, 2007, and July 31, 2009, 13 908 surgical procedures in 7900 patients were performed at the study center. Women who received TachoSil for the control of a major hemorrhage were included in the present study. Information on the age of the patient, the type of surgery performed, the indication for TachoSil use, the need for a blood transfusion, the need for a repeat surgery to complete hemostasis, and the postoperative course was collected retrospectively by review of the operative reports. The surgical procedures were categorized as oncologic, benign gynecologic, or obstetric surgery. To evaluate the traceability of TachoSil, the registers of the hospital pharmacy and the operative theater were also searched for evidence of TachoSil use. In addition, the literature concerning the efficacy and safety of TachoSil was reviewed according to the methodology recommended by the Cochrane Collaboration. Studies were identified by searching CENTRAL, MEDLINE, the Nycomed commercial website, product monographs, and reference lists of published articles. The databases were searched using the following Medical Subject Headings (MeSH) and text words: “hemostatic agent;” “surgery;” and “TachoSil” (34 citations). The present study was approved by the local Institutional Review Board and Ethics Committee. Written informed consent—including consent regarding the use and disclosure of health care information for research purposes—was obtained from all patients. All statistical analyses were performed using the software package R (Free Software Foundation, Boston, MA, USA).
113
Table 2 Main indications for surgical intervention.a Type of surgery
No. (%) of surgeries performed
Oncologic surgery Ovarian cancer Breast cancer Endometrial cancer Cervical cancer Pelvic sarcoma Vulvar melanoma Benign gynecologic surgery Fibroma Severe endometriosis Total hysterectomy Obstetric surgery Cesarean delivery Hemostatic hysterectomy Ruptured cornual pregnancy Vascular (hypogastric artery) ligation Severe perineal tear Prepartum uterine rupture
50 (59.5) 18 (21.4) 11 (13.1) 10 (11.9) 6 (7.1) 4 (4.8) 1 (1.2) 21 (25.0) 17 (20.2) 2 (2.4) 2 (2.4) 13 (15.5) 6 (7.1) 3 (3.6) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2)
a
n = 84.
The use of TachoSil increased during the study period. While the annual incidence of TachoSil use in oncologic and benign gynecologic surgeries remained globally unchanged, the use in obstetric surgeries increased from 1 instance per year in 2007 to 10 instances per year in 2009 (Table 3). The most common sites of TachoSil application (Table 4) were the uterine serosa (16 [19.0%]), most often after cesarean delivery or polymyomectomy, and the major vascular axis after pelvic or para-aortic lymphadenectomy (7 [8.3%]) (Fig. 2). In total, 24 (28.6%) women required transfusions during surgery, with a mean number of 3 red blood cell units required per patient (Table 3). Three women needed to undergo a second surgical procedure within 24 hours for persistent active bleeding despite the
3. Results According to the pharmacy and operative room records, TachoSil was used in 84 women (100% concordance). The mean number of TachoSil patches used per surgery was 1.2. Of the surgeries, 50 (59.5%) were classified as oncologic, 21 (25.0%) as benign gynecologic, and 13 (15.5%) as obstetric (Table 2). The most common surgery indications were ovarian malignancy (18 [21.4%]), fibroma (17 [20.2%]), breast cancer (11 [13.1%]), and endometrial cancer (10 [11.9%]) (Table 2). Of the women with benign pathologies in whom TachoSil was used, 2 (2.4%) had severe endometriosis with persistent bleeding after laparoscopic colorectal resection (Table 2). The most common indication for TachoSil use during obstetric procedures was persistent uterine bleeding after a cesarean delivery (n = 6 [7.1%]). Three (3.6%) women with severe postpartum hemorrhage required TachoSil use to stop bleeding after hemostatic hysterectomy, and 1 woman (1.2%) required TachoSil use after vascular (hypogastric artery) ligation (Table 2). In 1 (1.2%) woman, TachoSil use was associated with placenta accreta. Finally, 1 (1.2%) woman with a first-trimester ruptured cornual pregnancy, treated by laparotomic resection, required complementary hemostasis with TachoSil (Fig. 1).
Fig. 1. TachoSil application after rupture of a cornual pregnancy. A. Right ruptured cornual pregnancy. B. Right cornual scar after resection. C. Application of TachoSil on right cornual scar.
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Table 3 Evolution of the use of TachoSil. Year
2007
2008
2009
Total study period
Mean age of patients, y TachoSil use by type of surgery Oncologic surgery Benign gynecologic surgery Obstetric surgery All types of surgery Mean number of patches used per patient Number of transfusions required Mean number of red cell packs used per patient No mention of TachoSil in operative report
48.5
50.1
49.4
49.5
10 6 1 17 1.1 4 2.8
24 9 2 35 1.1 10 2.9
16 6 10 32 1.3 10 3.2
50 21 13 84 1.2 24 3.0
10 (58)
19 (54)
14 (43)
43 (51)
a
Values are given as number or number (percentage).
perioperative use of TachoSil: 1 patient after a para-aortic lymphadenectomy, 1 patient after a mastectomy, and 1 patient after debulking (splenectomy and caudal pancreatectomy; bleeding of partial pancreatectomy stump) for ovarian carcinoma. TachoSil use was not mentioned in the operative reports of 43 (51.2%) women, of whom 4 (4.8%) had obstetric surgery, 10 (11.9%) had an intervention for a benign condition, and 29 (34.5%) had oncologic surgery. 4. Discussion The present report focuses on the use of TachoSil in routine clinical obstetric and gynecologic practice, whereas most previous reports on the use of TachoSil in gynecologic surgery were single case reports. In the present series, the application of TachoSil resulted in complete hemostasis in a broad range of surgical procedures, with only 3 women requiring a repeat surgery. Surprisingly, TachoSil use was mentioned in half of the operative reports only, with records of TachoSil use lacking particularly after oncologic surgeries. The use of TachoSil has evolved with increased experience. TachoSil was first reported to be used in digestive and hepatobiliary surgeries before it was applied in patients with gynecologic and obstetric indications for surgery. In a continuous 14-year series [11] involving 1460 patients who underwent total laparoscopic hysterectomy for benign uterine pathologies, 19 (1.3%) patients had an intraoperative hemorrhage and 9 (0.6%) patients required a transfusion—highlighting the frequency of perioperative bleeding where TachoSil use might be required. Postoperative bleeding after a hysterectomy is not a rare event. In a 5-year retrospective study [12] involving 1167 women who underwent laparoscopic or vaginal hysterectomy, the overall incidence of bleeding after hysterectomy was 0.85% (n = 10). The authors reported that the hemorrhages could be successfully controlled using
Table 4 TachoSil application sites according to operative reports.a Application site
No. (%)
Axillary lymphadenectomy Mastectomy Uterine serosa Partial pancreatectomy stump Inferior vena cava Interaortocaval space Vaginal vault after hysterectomy Splenic capsule Pelvic lymphadenectomy Pelvectomy Perineal tear Not reported in operative report
4 2 16 3 3 1 4 1 3 3 1 43
a
n = 84.
(4.8) (2.4) (19.0) (3.6) (3.6) (1.2) (4.8) (1.2) (3.6) (3.6) (1.2) (51.2)
Fig. 2. TachoSil application on the major vascular axis after para-aortic lymphadenectomy. A. Before TachoSil application. B. After TachoSil application.
the laparoscope to apply TachoSil's predecessor, TachoComb [12]. Osada et al. [13] investigated the use of TachoComb for the control of oozing hemorrhages in 16 women who underwent surgery for myoma, cervical cancer, endometrial cancer, endometriosis, or pelvic adhesive disease. TachoComb was usually applied to the uterine serosa and adjacent areas. In 14 (87.5%) women, complete hemostasis of the oozing site was achieved; in the remaining 2 (12.5%) women, hemostasis was incomplete but adequate [13]. Ochiai et al. [14] evaluated the use of TachoComb in 45 women who had oozing hemorrhages during open gynecologic surgery. Primary hemostasis was achieved in 97.8% of these women [14]. The present results are in line with these reports. Other potential indications for the use of TachoSil include the reduction of postoperative adhesions after laparoscopic surgery and the prevention of heat-induced injuries to the uterine parenchyma (decline in fibrosis and inflammation), as indicated by findings in a rat model [15]. TachoComb was also capable of reducing adhesion reformation in a rabbit model [16]. Other authors [17] have proposed the application of TachoSil in the axillary area to reduce postoperative axillary drainage and seroma volume after axillar lymphadenectomy for breast cancer. TachoSil has also been used as a tissue barrier to prevent or treat air leakage following pulmonary resection [9], to prevent the development of biliary fistulas [18], and to treat recurrent vesicovaginal fistulas [19]. All of these indications must be investigated further in prospective studies.
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A prospective multicenter study [1] conducted in 12 European countries confirmed the safety of TachoSil; the study focused on the occurrence of thromboembolic events, major bleeding, and immunologic events (hypersensitivity including anaphylaxis) during the first 6 months after surgery. The authors reported 124 adverse events in 3098 patients receiving TachoSil. There were 46 (1.5%) thromboembolic events, 62 (2.0%) major bleeding events, and 8 (0.3%) immunologic events. In the group of patients who underwent gynecologic surgery, there were no thromboembolic or immunologic events and only 1 major bleeding event. The authors reported an overall incidence of thromboembolic events much lower than that reported elsewhere in the literature (10%–15%) [20], and they advised taking care when using TachoSil to avoid unintended intravascular application, which may result in life-threatening thromboembolic events. In the present series, no hypersensitivity or allergic reactions occurred, but 3 women had persistent bleeding. In the present study, the operative reports of 43 (51.2%) women contained no record of the use of TachoSil. According to the manufacturer, the possibility of infectious contamination cannot be excluded despite steps being taken during blood or plasma processing to inactivate or remove viruses and despite the careful selection of donors. Safety measures have proven effective against contamination with enveloped viruses, such as HIV and the hepatitis B and C viruses, and the nonenveloped hepatitis A virus, but less so against contamination with other nonenveloped viruses such as parvovirus B19. Contamination with unknown or emerging viruses and other types of infectious agents might also be possible. The manufacturer strongly recommends that hospitals maintain a record of the TachoSil batches used during surgery. The present study demonstrates that this recommendation was followed at the study center, but there is clearly room for improvement given that TachoSil use was not mentioned in half the operative reports. TachoSil can be used to halt perioperative bleeding in obstetric and gynecologic surgeries. The frequency of TachoSil use has increased during the past years and the indications for its use have become broader. However, in the present study, TachoSil was not traceable in 51.2% of cases. We recommend recording the product name and number in the operative report of each patient in whom TachoSil is used to achieve better traceability. Conflict of interest The authors have no conflicts of interest. References [1] Birth M, Figueras J, Bernardini S, Troen T, Gunther K, Mirza D, et al. Collagen fleecebound fibrin sealant is not associated with an increased risk of thromboembolic events or major bleeding after its use for haemostasis in surgery: a prospective multicentre surveillance study. Patient Saf Surg 2009;3(1):13.
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