Tourniquet with Intravenous Tranexamic Acid versus Tourniquet with Vaginal Misoprostol for Blood Loss Reduction during Open Myomectomy: A Double-Blind Randomised Trial.

The study participants' randomisation, allocation, follow-up and analysis are displayed in the CONSORT flow chart. CONSORT flow diagram of study participants The socio-demographic characteristics of the study participants are shown in Table 1 . There were no statistically significant differences between the two groups regarding the socio-demographic variables. Socio-Demographic Characteristics Of Participants Menorrhagia was the most common presentation identified by the study participants and was followed by the feeling of a pelvic mass. There was, however, no statistically significant difference between the two groups with regard to the presenting symptoms of the study participants in this study, as shown in Table 2 . SYMPTOMS OF PARTICIPANTS There was no statistically significant difference in the mean pre-operative haemoglobin of the two groups of women studied. The post-operative haemoglobin level was, however, noted to be higher in the tourniquet with tranexamic acid group (Group I), and this was statistically significant, p < 0.001, as shown in Table 3 . Mean Pre-Operative Haemoglobin (Hb) And Mean Post-Operative Haemoglobin (Hb) The mean intraoperative blood loss, mean estimated blood loss per 100g of fibroids removed and the need for blood transfusion were all reduced in the tourniquet with tranexamic acid group. These findings were significant (p < 0.001, p < 0.001, and p = 0.0321, respectively) as shown in Table 4 . Outcome Variables Mean Intra-Operative Blood Loss, Mean Estimated Blood Loss Per 100g Of Fibroid Removed And Need For Blood Transfusion

As the debate as to which agent is best in addressing the most feared complication of myomectomy - bleeding rages on, the findings from this study showed that peri-cervical intra-operative tourniquet application, along with intravenous tranexamic acid administration, was associated with a lower blood loss compared with tourniquet plus vaginal misoprostol in this study population. Further multi-centre, multi-country trials may be needed to make more generalizable statements.

This was a randomised interventional comparative study on the efficacy of a tourniquet with intravenous tranexamic acid versus a tourniquet with vaginal misoprostol in reducing blood loss during open abdominal myomectomy. A total of 78 participants with symptomatic uterine fibroids who had open myomectomy were recruited and randomised into two groups. Group I received 1g intravenous Tranexamic acid intra-operatively following incision on the uterus and before enucleation of the uterine fibroids after tourniquet application. While Group II received 400 micrograms of vaginal misoprostol inserted into the posterior vaginal fornix one hour before the myomectomy, and also had tourniquet application. The socio-demographic characteristics of both arms of the study showed that there was no statistically significant difference between them. This suggests that the randomisation process was effective in ensuring that both groups had a similar distribution of probable confounders. Effective randomisation of study participants into the comparison groups is the most effective method of eliminating the effect of confounding variables in studies involving human subjects, which is critical to the validity of the study's findings.[ 21 ] Various measures have been recognised to reduce blood loss during open myomectomy, such as uterine and/or ovarian artery ligation and the use of drugs such as misoprostol, intravenous tranexamic acid, oxytocin, etc. However, the best intervention to reduce blood loss during myomectomy is still debatable.[ 15 ] At present, there is moderate-quality evidence that misoprostol may reduce bleeding during myomectomy and low-quality evidence that tranexamic acid may reduce bleeding during myomectomy.[ 11 ] Among patients undergoing myomectomy, Baradwan et al., in a systematic review and meta-analysis of randomised controlled trials, found that prophylactic tranexamic acid was largely safe and linked to a substantial reduction in perioperative blood loss and related morbidities.[ 22 ] Also, Nnagbo et al in Enugu, Nigeria, observed that among women undergoing myomectomy, the additional use of vaginal misoprostol alongside tourniquet application significantly reduced intraoperative blood loss as compared to those who had tourniquet application alone.[ 13 ] This study showed that there was a significant difference in the mean postoperative haemoglobin levels of the two groups studied in favour of those who received tourniquet application and intraoperative tranexamic acid administration (p < 0.001). The application of a tourniquet with tranexamic acid also had a lesser intra-operative blood loss when compared to the tourniquet with vaginal misoprostol. This was also statistically significant (p < 0.001). In addition, with regard to the need for blood transfusion during and immediately after myomectomy, the tourniquet with tranexamic acid group also had a better outcome, which was also statistically significant (p = 0.032). It is best to state from the onset that, to the best of the authors' knowledge, there are limited studies that have compared the use of a tourniquet with either intravenous tranexamic acid or vaginal misoprostol in the reduction of blood loss during open abdominal myomectomy. In a related study by Shafqat et al, [ 16 ] comparing intravenous tranexamic acid to vaginal misoprostol for the reduction of blood loss during open myomectomy, they found a significant difference in the reduction of blood loss in the misoprostol group. However, their study noted no significant difference in fall in haemoglobin levels, duration of surgery and need for blood transfusion between the two groups. The authors did not apply a tourniquet for their study; they also enrolled only women with intramural fibroids (participants with submucous and subserous fibroids were excluded), and had uterine sizes above 16 weeks excluded from their study. These may have accounted for the difference in results obtained. In the study by Gouda et al in Egypt [ 15 ] that compared intravenous tranexamic acid to rectal misoprostol in reducing blood loss during open myomectomy, the authors observed no statistically significant difference in the intraoperative blood transfusion rate and intraoperative blood loss between the two groups of women studied. The tranexamic group, however, recorded a higher post-operative blood transfusion rate. The authors in this study used rectal misoprostol, as opposed to vaginal misoprostol used in our study, and had preoperative administration of tranexamic acid, as opposed to intraoperative administration of tranexamic acid used in our study. They also only recruited patients with fewer than five myomas and excluded those with subserous myomas, as opposed to our study, which did not consider the number, site and size of fibroid masses during patient selection. The authors also did not mention whether they had tourniquets applied to their patients. Could these have accounted for the slight differences experienced in their findings? Overall, there were no adverse effects recorded with the use of any of these pharmacological agents for reducing blood loss during myomectomy.

This study used a double-blind randomised trial (parallel design) and followed the Consolidated Standards of Reporting Trials (CONSORT).[ 17 ] This study was registered with the Pan African Clinical Trial Registry, with RCT registration number PACTR202406615201194. FMC Asaba is a 350-bedded tertiary hospital located in Asaba, the capital of the oil-rich Delta State in Nigeria. It receives referrals from primary, secondary, and even tertiary hospitals in Delta State and neighbouring Anambra and Edo states, too. This included all consenting women of reproductive age who had open myomectomy for symptomatic uterine fibroids at the Federal Medical Centre, Asaba, over seven months between 5 th September 2023 and 10 th April 2024. Patients who had open myomectomy with pre-operative haemoglobin ≥ 10g/dl, patients who were willing to receive blood transfusion during open myomectomy and those who were willing to receive the proposed intervention (intravenous tranexamic acid or vaginal misoprostol). Prospective participants with prior pelvic surgeries and risk of adhesions with prolonged surgery and increased bleeding, those with co-existing endometriosis or adenomyosis from clinical history or findings from investigations, those with co-morbidities such as renal or cardiac disease, those with disorders like thrombocytopenia with increased risk of bleeding and any known allergy to Tranexamic acid or Misoprostol. The primary outcome measure was the amount of blood loss during open myomectomy in both groups, while the secondary outcome measures included the need for blood transfusion as well as any adverse drug reactions noted in any of the participants. There is no statistically significant difference in blood loss during open myomectomy using a tourniquet with 1g intravenous tranexamic acid versus a tourniquet with 400mcg of vaginal misoprostol. There is a statistically significant difference in blood loss during open myomectomy using a tourniquet with 1g intravenous tranexamic acid versus a tourniquet with 400mcg of vaginal misoprostol. The sample size for this study was calculated using the formula below.[ 18 ] n = 2 ( Z α / 2 + Z p ) 2 P ( 1 - P ) ( P 1 - P 2 ) 2 Where Zα/2 = 1.96 at type 1 error of 5%, Zp = 0.842 at 80% power, P1 = Prevalence of uterine fibroids in a previous study- Group 1, P2 = Prevalence of uterine fibroids in another study - Group 2, P = Prevalence in Group 1 + Prevalence in Group 2 / 2 P1 = 33.9%[ 19 ] and P2 = 6.83%[ 20 ] (from previous studies). A total of 39 participants were recruited in each arm, resulting in a total of 78 participants after accounting for a 10% loss to follow-up. Randomisation numbers were generated using a computer-generated random number generator. These computer-generated numbers were placed in sealed envelopes and stored in a container. Following counselling and recruitment of prospective participants, they were allowed to pick from the container containing the sealed envelopes. The number inside the envelope was also placed in the patient's folder. Neither the study participants nor the researcher/research assistant were aware of the group each participant belonged to. Each participant was allotted to either the tranexamic acid group or the vaginal misoprostol group, depending on the random number the participant picked from the sealed envelope. There were a total of 78 sealed envelopes. Blinding was maintained by ensuring that both participants and the researcher were unaware of treatment allocation. One hour before surgery, women in the misoprostol group received 400 µg vaginal misoprostol, while those in the tranexamic acid group received 5 mg vaginal folic acid as placebo. Thus, all participants underwent identical vaginal drug administration procedures. During surgery, the tranexamic acid group received 1 g intravenous tranexamic acid after uterine incision and before fibroid enucleation, administered by an independent anaesthetist who also assessed outcomes. Research assistants administered preoperative vaginal medications, while the researcher neither administered interventions nor performed surgeries. Both groups underwent uterine artery occlusion using isthmic tourniquets, followed by standard abdominal myomectomy performed by consultants according to established surgical techniques. Intra-operative blood loss was calculated mainly using the difference in the pre-operative (twenty-four hours before surgery) and post-operative (forty-eight hours after surgery) haemoglobin, the gravimetric method using the number and weight of surgical pads, blood in a suction canister, and volume of blood in the abdominal drain. A study proforma was used to collect the required data for the study. The patients were all admitted and followed up till discharge. At the end of their hospital stay, the proforma for each patient was checked for completion and entered into a spreadsheet. Data were subsequently analysed using Statistical Product for Service Solutions (SPSS) version 26. Categorical variables were expressed in frequencies and percentages, while continuous variables were expressed as means and standard deviations. The Chi-square test was used for the test of association between categorical variables, while the Student's t-test was used to test for continuous variables, and a P-value < 0.05 was considered to be statistically significant. Ethical approval was obtained from the Hospital Health Research and Ethical Committee (HREC) with approval number FMC/ASB/A81 VOL. XII359 before the commencement of the study in conformity with the Helsinki Declaration, with emphasis on the core ethical principles of autonomy, beneficence, non-maleficence and justice.

Uterine fibroids (leiomyoma) remain the most common benign tumour of the female genital tract found in women of reproductive age.[ 1 ] Fibroids can develop within three anatomical parts of the uterus and are classified as subserous, intramural and submucous fibroids.[ 2 ] Although fibroids are a global burden impacting 80% of premenopausal women, they are more prevalent among blacks than among other races. The estimated cumulative incidence of fibroids in women ≤ 50 years old is significantly higher in blacks (>80%) compared with white women (approximately 70%).[ 3 ] The global burden of uterine fibroids is becoming more serious in the middle socio-demographic index (SDI), low-middle SDI and low SDI quintiles.[ 4 ] Fibroids originate from uterine smooth muscle cells (myometrium) whose growth primarily depends on circulating estrogen levels.[ 5 ] The clinical presentation in a woman with uterine fibroids may be asymptomatic or may comprise a variety of symptoms such as heavy menstrual bleeding, dysmenorrhea, pelvic pressure symptoms, including urinary frequency or retention, hydronephrosis, constipation or tenesmus. A pelvic mass, pelvic pain and dyspareunia are other symptoms. Women with uterine fibroids or symptoms suggestive of fibroids experience significant distress that reduces quality of life, particularly among racial minorities and women in lower-income brackets.[ 6 ] Also, a national survey in France showed that 64% of the women surveyed reported moderate to very important impacts of fibroids on their quality of life.[ 7 ] The current treatment options for symptomatic fibroid treatment include expectant, medical, surgical and interventional radiology procedures.[ 8 ] While open myomectomy is the most adopted surgical strategy in the conservative treatment of uterine fibroids, it is a complicated surgery in terms of blood loss and the need for transfusion and haemorrhage remains the most important concern with open myomectomy.[ 9 ] To overcome this, various methods such as mechanical clamps, intraoperative intravenous tranexamic acid or topical tranexamic acid, pre-operative vaginal or rectal misoprostol, intramyometrial bupivacaine with epinephrine, intramyometrial vasopressin and haemostatic sealing agent have been utilised. Analysis of a large multicenter database suggests that the overall risk of blood transfusion during myomectomy is 10% and is associated with increased postoperative morbidity.[ 10 ] In practical settings, some patients may be averse to blood transfusion either on religious grounds or due to personal wishes. Also, blood transfusion is associated with its risks. To avert complications relating to blood loss and blood transfusion, two methods are compared in this study to ascertain which will result in less blood loss. There is moderate-quality evidence that misoprostol may reduce bleeding during myomectomy and low-quality evidence that tranexamic acid may reduce bleeding during myomectomy.[ 11 ] Tranexamic acid is an antifibrinolytic agent and has been reported in various studies to be a proven agent to reduce blood loss when used as an adjunct to a tourniquet during open myomectomy.[ 12 ] Misoprostol, on the other hand, is a prostaglandin E1 analogue that causes uterine contraction. It has also been reported in various studies to be a proven agent in reducing blood loss during open myomectomy.[ 13 , 14 ] The basis of using these two agents is for a comparison of efficacy between these pharmacological agents in reducing blood loss during open abdominal myomectomy, and hence help make recommendations to Gynaecologists based on the findings. Gouda et al[ 15 ] in a randomised controlled trial in Egypt found no difference between women who had intravenous tranexamic acid and rectal misoprostol during myomectomy with regards mean blood loss, while Shafqat et al[ 16 ] in Pakistan found a significant difference in blood loss in favour of women who received misoprostol during abdominal myomectomy. This study aimed to compare the amount of blood loss during open myomectomy using a tourniquet with tranexamic acid and a tourniquet with vaginal misoprostol by employing a double-blind randomised controlled trial study design.