The role of topic vaginal products in posthysterectomy
vaginal atrophy
DAN RUICAN1), ANA-MARIA PETRESCU1), ROXANA DRĂGUȘIN1)2), LUCIAN-GEORGE ZORILĂ1)2), DOMINIC-GABRIEL ILIESCU1,2)
- Emergency County Clinical Hospital Craiova, Department of Obstetrics-Gynaecology
- University of Medicine and Pharmacy Craiova, Department of Mother and Child
Increased sensitivity of available modern diagnostic procedures for cervical neoplasia screening, such as liquid-based cytology, videocolposcopy or HPV genotyping, allows early diagnosis and with a better rate of cervical preinvasive lesions. The high number of women of childbearing age who have such lesions incurs the need for a conservative approach. Preneoplastic lesions (CIN), vaginal and cervical condyloma, complicated nabothian cysts, and cervical fibromas benefit of the same conservative cervico-vaginal surgical procedures: loop excisions, excision of the transformation zone (LEEP / LLETZ), conization. Such surgical techniques performed predominantly via electroresection are considered the standard of care for these pathologies. Although this surgical approach is widely used, it is affected by a series of morbidities, and the most common postoperative complications are represented by haemorrhages, infection and cervical stenosis.
Thus, haemostasis is very important during and after surgery. Haemostasis is the act of restricting or blocking the blood flow from an injured vessel or organ. The adjunctive haemostatic techniques are important during invasive operations and procedures when normal coagulation processes do not achieve their goal. Maintaining of haemostasis intraoperatively is essential for preserving the physiological functions of the patient and of the surgical field. Also this decreases the operative time, decreases patient morbidity and mortality, offering a better postoperative prognosis and a superior control of the injured area.
Bleeding incidence can be decreased with electrocauterization, application of surgical sutures or local pressure with or without association of topic agents with vasoconstrictive effect or other haemostatic solutions. Pastes containing ferric subsulfate (Monsel) or bismuth subgallate and epinephrine are successfully used to prevent primary bleeding. The advantages of these mixtures are low price, negligible side effects and the possibility to decrease postoperative bleeding.
Bismuth subgallate (BS) is an amorphous light yellow powder, without smell and taste, insoluble, stable in air, but sensitive to light, used in the treatment of pathologies such as Vincent angina and syphilis, for reducing the unpleasant odour caused by colostomy or cleaning open wounds. BS has haemostatic properties, acting on coagulation factor XII (Hageman factor), activating the coagulation cascade and favouring the early formation of a fibrin clot.
There is a large amount of evidence regarding the efficacy of BS in oral surgery. Haemostasis is essential in these situations, particularly in case of interventions resulting in open wounds which expose connective tissue. It is also important for correcting haemostasis during surgery in patients with coagulation disorders, when usual manoeuvres have failed.
Maniglia et al. (2) reported the usefulness of bismuth subgallate in ENT. They noticed the decrease of the number of post-interventional bleeding cases in patients in whom they applied BS. Other authors also confirmed this property (2-4), demonstrating its efficacy in stopping bleeding from small calibre vessels and capillaries. In a randomised trial (3) which compared the BS paste with a control group, the BS group had an operative time decreased by 18% (9.9 ± 3.0 vs. 11.5 ± 4.1 min; p<0.005), used fewer sterile tampons (3.7 ± 1.3 vs. 4.5 ± 1.8; p<0.005), and used fewer surgical sutures (2.1 ± 1.4 vs. 3.4 ± 1.8; p<0.005). In a similar study (4), the operative time was decreased by 25% in patients in whom BS paste was applied (16.8 ± 6.1 vs. 22.6 ± 10.6 min; p<0.003). However, there are no blind clinical studies. Regarding published studies, there are many variables which can interfere with the effect of the treatment, such as different surgical techniques, the experience of the surgeon, the association of tonsillectomy with adenoidectomy, the age of the patients, the different formulation of the mixture, and different definitions of haemorrhage.
Kim et al. (5) compared two different haemostasis methods in palate incisions in 20 patients. Application of bismuth subgallate paste on these wounds demonstrated significant benefits in obtaining haemostasis compared to methods which use only local pressure. The average time of achieving haemostasis was significantly shorter in the group in which bismuth subgallate paste was used compared to the group in which only local tampons were used. The difference between these groups had an important statistical significance.
Rey et al. (4) reported the usefulness of BS in haemophilic patients.
The healing process involves multiple reactions which take place simultaneously; therefore it is not possible to delimit each stage. In theory, this process can be divided in: coagulation, inflammation, contraction, and remodelling; their goal is to repair the injured tissue.
Coagulation starts a few seconds after the occurrence of the lesion. The thrombus is formed and also the extracellular matrix containing growth factors and inflammatory mediators (cytokines) which contribute to re-epithelisation and the processes of limiting the lesion.
The inflammatory process is characterised by haemostasis, cell migration, and formation of a provisional matrix. Platelets are essential in the formation of the haemostatic plug and in the same time – via the degranulation process – they secrete many mediators and growth factors which are released in the affected area. Macrophages are the most important cells in the healing process. These secrete chemotactic factors which attract other inflammatory cells in the lesion, produce prostaglandins with vasodilator effect, and prepare the lesion area for the proliferative phase. This consists of angiogenesis, migration and proliferation of fibroblasts, deposition of extracellular matrix via collagen synthesis, maturation, and connective remodelling.
Histology studies conducted in the immediate time period of tooth extractions demonstrated that the dental alveoli used as control (without application of BS) were filled with blood clots and detritus from the periodontal membrane attached to the periodontal cortical. Alveoli treated with BS had an increased number of BS particles in these blood clots and in the periodontal membrane remnants. At 7 days post-intervention, an active osteogenesis process was demonstrated in the apical part of both alveoli groups. In the residual alveoli parts an intense granulation process was noticed. Isolated BS particles surrounded by macrophages were identified in the granulation tissue of alveoli treated with BS. At 14 days after the dental surgery, both alveoli types had active osteoblasts which were filling the entire alveolus, completely covered by epithelium. No BS particles were evident after 30 days, as both alveoli types were filled with lamellar bone tissue and covered with a well-differentiated keratinized stratified epithelium. Results demonstrate that the application of BS in dental alveoli immediately after tooth extraction does not interfere with the bone regeneration process.
Bismuth subgallate is an astringent agent which can promote precipitation of some proteins and the formation of a protective film which lines the biopsied area in the time period immediate to the surgery. This film can represent a physical protection, reducing bacterial colonisation and preventing the excessive formation of granulation tissue. No side effects were reported in the clinical studies regarding the application of BS paste. Wound superinfection is a concern for clinicians, and none of the listed studies reported any infections related to the application of BS paste.
There are many similarities between the oral and the vaginal mucous membranes. Both are lined by a non-keratinized stratified squamous epithelium, which has a tendency to parakeratinization in the vagina at the middle of the menstrual cycle. The epithelium is supported by the lamina propria, an elastic connective tissue placed on a layer of smooth muscle. Both types of mucous membrane are richly vascularized, and their permeability is similar. Thus, although research regarding the effects of BS on the cervico-vaginal mucous membrane and stroma is limited, we can assume an equivalence of the effects. Cerviron, as vaginal tablets, can be used as adjunctive treatment after excisions in the vagina. Due to its content of bismuth subgallate, a compound which had proved its usefulness in ENT and dental surgery, these vaginal tablets can limit bleeding and can have a protective effect on the vaginal mucous membrane, following surgery.
Healing quality. An experimental study which used bismuth subgallate on laboratory animals, on induced skin wounds, demonstrated that the qualitative evolution of the granulation tissue did not show any differences compared to the control group in which saline solution was used. The number of macrophages was initially higher in the group treated with BS due to the physical presence of particles in the wounds, bot the absence of giant cells or of any foreign body reaction was noticed. After 7 days, the ulcerations in the test group and also in the control group had normal epithelization, as bismuth subgallate had no negative effects on healing.
Side effects. Bismuth salts are commonly used in other pathologies (gastrointestinal diseases, syphilis), and these patients report various adverse reactions (dermatological reactions, etc.). (10). However, the doses used in these cases are high and are administered over a long time period, days or even weeks. When used for haemostatic purposes, exposure to bismuth is minimal.
Conclusions
In conclusion we can assume some advantages of BS use, such as decrease of operative time in cervico-vaginal surgeries, but also reduction of incidence of post-interventional haemorrhage, and also promoting a high quality scar formation, very important in women of childbearing age. These effects can generate important cost savings for the healthcare system. BS has a high haemostatic activity, can be easily sterilized using conventional methods, and is relatively cheap, is easy to use, even as vaginal tablets, therefore its efficiency in the gynaecological-surgical area in the area of the lower reproductive tract certainly deserves the continuation and diversification of research in this area.
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