A Preliminary Study on the Use of Cyanoacrylate Glue for the Closure of Fetal Membranes

This article was downloaded by: [Trinity College Dublin] On: 8 November 2009 Access details: Access Details: [subscription number 785045690] Publisher Informa Healthcare Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Minimally Invasive Therapy and Allied Technologies Publication details, including instructions for authors and subscription information: http://www.informaworld.com/smpp/title~content=t713683124 A preliminary study on the use of cyanoacrylate glue for the closure of fetal membranes Mustafa Basaran a; Mehmet Vural a; Bulent Ekmekci b; Oktay Irkorucu c a Faculty of Medicine, Department of Obstetrics and Gynecology, Zonguldak Karaelmas University, Zonguldak, Turkey b Faculty of Engineering, Department of Mechanical Engineering, Zonguldak Karaelmas University, Zonguldak, Turkey c Faculty of Medicine, Department of Surgery, Zonguldak Karaelmas University, Zonguldak, Turkey First Published:2009 To cite this Article Basaran, Mustafa, Vural, Mehmet, Ekmekci, Bulent and Irkorucu, Oktay(2009)'A preliminary study on the use of cyanoacrylate glue for the closure of fetal membranes',Minimally Invasive Therapy and Allied Technologies,18:5,302 — 305 To link to this Article: DOI: 10.1080/13645700903201548 URL: http://dx.doi.org/10.1080/13645700903201548 PLEASE SCROLL DOWN FOR ARTICLE Full terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. 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The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Minimally Invasive Therapy. 2009;18:302–305 SHORT REPORT A preliminary study on the use of cyanoacrylate glue for the closure of fetal membranes Mustafa Basaran1, Mehmet Vural1, Bulent Ekmekci2, Oktay Irkorucu3 1Faculty of Medicine, Department of Obstetrics and Gynecology, Zonguldak Karaelmas University, Zonguldak, Turkey, of Engineering, Department of Mechanical Engineering, Zonguldak Karaelmas University, Zonguldak,Turkey and 3Faculty of Medicine, Department of Surgery, Zonguldak Karaelmas University, Zonguldak, Turkey Downloaded By: [Trinity College Dublin] At: 19:36 8 November 2009 2Faculty Abstract Amnion leakage, infection and inflammation are the most important problems of intrauterine fetal surgery. This study aimed to determine the shear strength characteristics of fetal membranes attached with cyanoacrylate glue. Fresh amniochorionic membrane stripes (40×30 mm) were prepared after ten term elective cesarean section patients. Two stripes were attached with 5 mm overlapping and an increasing weight was applied until separation. Shear strength of the attached segment and resultant normal stresses developed in the membrane were calculated. Finally, corresponding intraluminal pressure that shear strength could resist without rupture was estimated by assuming two perfect semi-spherical membranes that are glued together with 5 mm overlapping to form a perfect sphere with a diameter of 200 mm. Mean total weight until rupture was 156 ± 72 gr. Shear strength of the glued 5 mm segment was calculated as 10199 ± 4696 Pa (104 ± 48 cmH20) that resulted in 101989 ± 46963 Pa (1040 ± 479 cmH20) mean tensile normal stress within the membrane. Assuming a perfect sphere with a diameter of 200 mm, the maximum intraluminal pressure that attached membrane stripes could resist without rupture was calculated as 1020 ± 470 Pa (10.4 ± 4.79 cmH2O). This preliminary basic study showed that the shear strength of cyanoacrylate was strong even in small tissue segments. Considering antibacterial properties, immediate action in the presence of tissue fluids, and water impermeability of the attachment sites, this agent should be considered for closure of amniochorionic membranes after fetal surgery. Key words: Fetal surgery, shear strength, fetal membranes, amniochorionic membrane, cyanoacrylate Introduction Fetal surgery has steadily increased in recent years (1). However, amniotic leakage, infection and inflammation still are most important problems in intrauterine fetal surgery and have prevented widespread use. These complications are considered as the ‘Achilles heel’ of intrauterine surgery (2). Cyanoacrylates are a group of molecules first described in 1949 and rapidly accepted as industrial adhesives (3). Their mechanism of action involves anionic polymerization of hydroxyl residues in which water itself acts as catalyzer. This effect is strong enough for tissue grafting. Water molecules act as catalyzer in the adhesive action of cyanoacrylates. Therefore, contrary to other adhesive materials, tissue fluids and blood facilitate adhesion with cyanoacrylates. Moreover, cyanoacrylates have bacteriostatic and hemostatic effects (4). In this preliminary basic study, we aimed to determine the basic shearing characteristics of fresh amniochorionic membrane segments attached with cyanoacrylate glue and to discuss its role in intrauterine fetal surgery. Material and methods Patient selection and setting During the study period, ten term pregnancies in 20 to 30-year-old women were recruited for the study Correspondence: M. Basaran, Zonguldak Karaelmas University Faculty of Medicine, Department of Obstetrics and Gynecology, Esenkoy, Kozlu 67600, Zonguldak, Turkey, Fax: +90 372 2610264, E-mail: mustafabasaran@ymail.com, mbasaran@med.karaelmas.edu.tr ISSN 1364-5706 print/ISSN 1365-2931 online © 2009 Informa UK Ltd DOI: 10.1080/13645700903201548  according to eligibility criteria (nonsmoker, primiparous, uncomplicated follow-up, posterior location of placenta, gestational age confirmed with first trimester ultrasonography, elective cesarean section at 38-39 wk of gestational age) (Figure 1). All participants were evaluated in the Obstetric Clinic of Zonguldak Karaelmas University Hospital. Informed consent for the use of placentas was obtained from parents. This study was approved by the Ethics Committee of Zonguldak Karaelmas University Hospital (2008-05, 10.4.2008). Downloaded By: [Trinity College Dublin] At: 19:36 8 November 2009 Tissue preparation Placenta and membranes were carefully delivered and prepared in all patients. Two amniochorionic membrane stripes, 40×30 mm in size, were prepared from each patient. These stripes were attached with n-butyl cyanoacrylate (Histoacryl®, Tissue Seal LLC, Ann Arbor, MI, USA) at short edge with 5  mm overlap (Figure 1A). The amnion of one stripe was attached to the chorion of other stripe so that one surface of attached segment was chorion while the other side was amnion (Figure 1B). Testing All measurements were performed within 30 minutes of placental delivery at 22-24ºC. Simple weightbearing self-developed testing equipment was used for measurements. Five minutes after application of cyanoacrylate, gradually increasing weight was applied with 10 gr increments at three-minute intervals (Figure 1B). Each specimen was stressed to its point of breaking strength. The maximum load was recorded in grams. Cyanoacrylates for the closure of fetal membranes 303 5 mm 30 mm 75 mm 5 mm ~1 mm A. B. Weight Figure 1. Preparation of fetal membrane stripes and testing tensile strength. (A) Each part of fetal membrane with 30 mm width was glued with a 5 mm overlapping. (B) After gluing 75 mm stripe attached to weight-bearing apparatus with gradually increasing weight. resist without rupture was calculated by using the following formula: p= 4st d p: Intraluminal pressure s: Resultant normal stress in the membrane d: Diameter of sphere t: Thickness of amniotic membrane. Microsoft Office Excel 2003 for Windows (Microsoft Corp., Redmond, WA, USA) was used for database and calculations. Kolmogorov-Smirnov test was used to test normal distribution. One sample student’s t test was used to compare maximum intraluminal pressure with known 8 cmH2O intraluminal pressure. SPSS for Windows 11.5 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. All values were expressed as mean ± standard deviation (minimum-maximum). The statistical significance level was set to 0.05. Results Calculations and analysis The following formula was used to convert the maximum load in grams to Newtons: Max. Load (grams) /1000 × 9.80665 = Newtons.The shear strength of a glued segment was calculated by dividing the maximum load to the area of the glued segment, which was 30 mm × 5 mm. The thickness of all amniochorionic membrane stripes was assumed as 0.5 mm. Resultant normal stress was calculated by dividing the maximum load to the cross sectional area of the stripes, which was 30 mm × 0.5 mm. Assuming two perfect semi-spherical membranes that are glued together with 5 mm overlapping to form a perfect sphere with a diameter of 200 mm, the maximum intraluminal pressure that the shear strength of an attached membrane stripe could The mean age of patients was 24.6 ± 2.9 (21-29) years. Calculated stress characteristics of stripes are presented in Table I. All samples ruptured at the attachment site. The maximum intraluminal pressure that could be withstood without rupture (10.40 ± 4.79 cmH2O) did not significantly differ when compared with intrauterine pressure which was assumed as 8 cmH2O (p=0.15). Discussion Cyanoacrylates Cyanoacrylates are a group of molecules that are widely used as industrial adhesives (3). Today they are also widely used in medicine (Table II). 304 M. Basaran et al. Table I. Membrane characteristics. Characteristic Measurements* Total weight (gr) 156 ± 71.8 (60-270) Shear strength (Pascal) 10199 ± 4696 (3923 - 17652) Shear strength (cmH2O) 104 ± 47.9 (40 - 180) Shear strength (mmHg) 76.5 ± 35.2 (29.4- 132.4) Resultant tensile stress in the membrane (Pascal) 101989 ± 46963 (39227 - 176520) Maximum intraluminal pressure (cmH2O) 10.40 ± 4.79 (4-18) Total time (sec) 2749 ± 1312 (934-4883) * Mean ± standard deviation (minimum-maximum). Toxicity reported with cyanoacrylates includes inflammation and tissue necrosis, thrombotic events, calcifications, release of formaldehyde in tissue (minimal but detectable). Development of sarcoma was reported in rat peritoneum for isobutyl form (6). Moreover, most of the metabolic processes are still not known. However, toxicity is inversely related with the alkyl side chain of cyanoacrylate and currently used molecules in medicine have a long side chain (n-butyl-2cyanoacrylate, octyl-2-cyanoacrylate) (7). In parallel with the current use of cyanoacrylates in medicine, we used long side chain form n-butyl-2-cyanoacrylate in this study. Downloaded By: [Trinity College Dublin] At: 19:36 8 November 2009 Fetal surgery Table II. Use of cyanoacrylates in medicine. Specialty Usage General surgery Surgical wound closure, hemostasis Emergency medicine Traumatic wound closure Endoscopic surgery Treatment of esophageal varices Ophthalmology Repair of corneal perforations Thoracic surgery Sealing of pulmonary leaks Neurosurgery Repair of peripheral nerves, treatment of intracranial aneurysms Otologic surgery Reconstruction of ossicular chain Interventional radiology and cardiology Embolization of vascular abnormalities Pediatrics Superficial wound closure in children Pediatric endoscopic surgery Tissue approximation and hemostasis Urology Hemostasis and preventing of urinary leakage after nephrectomy Vascular surgery Sealing anastomoses of vascular grafts Colorectal surgery Sutureless colonic anastomosis Obstetrics and gynecology Tubal sterilization Pharmacotherapy Drug carriers * Modified from Leggat et al. (3). The mechanism of action of cyanoacrylates involves polymerization of hydroxyl groups on the surface being glued. Water acts as a catalyst for the action of cyanoacrylates. Therefore, the presence of tissue fluids (ie. amniotic fluid and blood) augments the adhesive action. Numerous base residues of proteinaceous substances make them a perfect material for the adhesive action of cyanoacrylates. As a result, cyanoacrylates are extremely adhesive to biological tissue (3). Cyanoacrylates also have antimicrobial and hemostatic properties (5). Fetal surgical procedures have increased in recent years (1). Especially considering the advances in the understanding of the pathophysiological processes of some congenital malformations such as meningomyeloceles, intrauterine fetal interventions may be the only hope for effective treatment (8). However, complication rates in these procedures are still high and most of these complications are related to the closure of the uterus and fetal membranes, not the fetal part of the surgical procedure. Amniotic leakage, amniochorionic separation and related complications are considered as the most important drawback of intrauterine fetal surgery (2). Chorioamnionic separation is an important complication reported in 47% of the patients (1). Cyanoacrylates could also help to reduce the incidence of chorioamnionic separation by tightly attaching amnion to chorion at the closure site. The presence of oligohydramnios causes a decrease of amniotic pressure (9). Low pressure closure of fetal membranes may yield better results than our calculations in this study. Moreover, closure of fetal membranes with surrounding myometrium with cyanoacrylates might provide greater strength at the attachment site. Most of the fetal surgical procedures were performed in second trimester (1). Characteristics of second trimester fetal membranes might be different compared to third trimester changes in the ultrastructural characteristics. However, considering the ultrastructural changes that cause weakness of membranes in the last trimester (10), higher shearing strength characteristics might be possible. Additionally, normal stresses on the membranes may be lower due to the lower level of uterine volume and mass, lower frequency of Braxton-Hicks contractions in early pregnancy. In this study, we assumed a perfect sphere of 20  cm for better correlation with second trimester pregnancy. Cyanoacrylates for the closure of fetal membranes Proposed use of cyanoacrylates in fetal surgery Downloaded By: [Trinity College Dublin] At: 19:36 8 November 2009 References The mean maximum intraluminal pressure that the membrane stripes were able to bear was calculated as 10.40 ± 4.79 cmH2O. In this study, only 5  mm width of membranes was attached together. Even with this small width, the shear strength of attached segments was remarkable. This width could be increased to 10 mm or more for better results. Inflammation and release of prostaglandins due to cyanoacrylates may cause problems. However, these effects were shown to be reduced by the use of indomethacin, which also could be used as a tocolytic after fetal surgery (3, 11). Use of indomethacin could also help to reduce the intrauterine pressure by tocolytic action and by keeping amniotic fluid volume at low levels. Handling of cyanoacrylates is difficult. Therefore, special instruments that enable precise control of the amount and the surface applied are required in clinical use. Furthermore, layered closure of myometrium to chorionic external surface of membranes might further increase the strength of adhesion. In conclusion, this in vitro study has demonstrated that fresh and wet amniochorionic membranes could be glued easily and rapidly using cyanoacrylates. Cyanoacrylates are excellent candidates for the closure of fetal membranes after open intrauterine surgery or fetoscopic access sites. 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[Induction of sarcomas by the tissue-binding substance Histoacryl-blau in the rat]. Z Exp Chir Transplant Kunstliche Organe 1987;20:55–60. 7. Montanaro L, Arciola CR, Cenni E, et al. Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use. Biomaterials 2001;22:59–66. 8. Bruner JP, Tulipan N, Paschall RL, et  al. Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus. Jama 1999;282:1819–25. 9. Fisk NM, Tannirandorn Y, Nicolini U, Talbert DG, et  al. Amniotic pressure in disorders of amniotic fluid volume. Obstet Gynecol. 1990;76:210–4. 10. Uchide K, Ueno H, Inoue M, Sakai A, et al. Matrix metalloproteinase-9 and tensile strength of fetal membranes in uncomplicated labor. Obstet Gynecol. 2000;95:851–5. 11. Papatheofanis FJ. Cytotoxicity of alkyl-2-cyanoacrylate adhesives. J Biomed Mater Res. 1989;23:661–8. 305