Sudan Medical Journal

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1 Sudan Medical Journal ا غ ا طج ١ ا غ دا ١ :61-66 Original Article Controlling blood loss at open myomectomy by local Ergometrine injection: interventional study Kaima A Frass, MD *, Abdelrahman H Al Harazi, MD **, Alia A Shoib, MD, MD **, Faculty of Medicine, Sana a University *,***, Faculty of Medicine, Thamar University ** انس طشة عهى ان ز ف اث بء انع ه ت ان فت حت الستئصبل ان سو انه ف بحق االسج يتش : دساست تذخه د. لبئ خ ػجذ هللا فشاص د. ػجذ ا شؽ ا ؾشاص د. ػ ١ خ ػجذ هللا شؼ ١ ت األ ذاف: ذفذ ز ا ذساعخ ؼشفخ رأص ١ ش ؽم ػمبس االسع زش ٠ ثذاخ ا شؽ أص بء اعشاء ػ ١ خ اعزئظبي ا س ا ١ ف ػ ؽش ٠ ك ا جط ف ا غ ١ طشح ػ ا ض ٠ ف ا ظبؽت ؼ ١ خ ا زم ١ ا ؾبعخ ئ م د ش ٠ ؼبد. انطش قت: دساعخ اعزجبل ١ خ اعش ٠ ذ ف غزشف ا ض سح ا ؼب ثظ ؼبء خالي فزشح ٣۰ ش شا ١ ٠( 2013 ؽز د ٠ غ جش.)2015 ان تبئج: أظ شد ا ذساعخ أ ؼذي ا ض ٠ ف اص بء ا ؼ ١ خ وب 110.8±68.9 ١ زش ف غ ػخ ا ذساعخ مبث 490.6±86.4 ١ زش ف غ ػخ ا شب ذح (0.001>P) م ا ذ أص بء ا ؼ ١ خ ر االؽز ١ بط ذ )17.9%( غ ػخ ا شب ذح فمؾ وب ؼذي ا مض ف ا ١ ع ث ١ ذ غ ػخ ا شب ذح ب اؽظبئ ١ ب مبس خ ث غ ػخ ا ذساعخ. أ ٠ ؼب ى س ا ش ٠ ؼبد ف ا غزشف غ ػخ ا ذساعخ وب لظ ١ شا مبس خ ث غ ػخ ا شب ذح وب ا فشق ث ١ ا غ ػز ١ ب اؽظبئ ١ ب )0.001>P(. انخالصت:ئػطبء اال ٠ شع زش ٠ اص بء ػ ١ خ اعزئظبي ا س ا ١ ف وب رأص ١ ش ل ف ا زم ١ ا ض ٠ ف أ ا زم ١ ا ؾبعخ م ا ذ. رمظ ١ ش فزشح ا ؼ ١ خ فزشح ا جمبء ف ا غزشف. Abstract Background: To assess the haemostatic efficacy and safety of Ergometrine Maleate injection intramyometrium during abdominal myomectomy in controlling blood loss and reducing the need for blood transfusion. Materials and Methods: This was a prospective, case-control study carried out at AL-Thawra General Hospital, Sana'a, Yemen over a 30 months period (from July 1 st, 2013 to Dec 30 th, 2015). We included 79 patients who had abdominal myomectomy for symptomatic myomas. They were randomly divided into 2 groups, either to receive Ergometrine (n=40), or as a control ( n=39). The amount of intraoperative blood loss, operative time, blood transfusion and the change in hemoglobin levels were assessed. Results: The average blood loss during surgery was 110.8±68.9 ml for the Corresponding author Kaima A Frass kaimafrass@hotmail.com Mob: Ergometrine treated group and 490.6±86.4 ml for the control group (P<0.001). Intraoperative blood transfusion was necessary for 7 patients (17.9%) of the control group. The mean decline of hemoglobin level was 1 ± for the treated group vs 1.9 ± for the control group. Length of the postoperative hospital stay was 2.7 ± 1.1 days for the Ergometrine group and 4.1 ± 1.3 days for the control group (P< 0.001). Conclusions: Injection of Ergometrine intramyometrium during open myomectomy provides a bloodless operative field, reduces significantly intraoperative blood loss, operative time and the need for blood transfusion. Keywords: Abdominal myomectomy, bleeding, Ergometrine. Introduction Uterine myomas (fibroids) are the most common benign tumors of the female genital tract. They are clinically apparent in about 25% of women, but if asymptomatic fibroids are included the true clinical prevalence is higher. Careful pathological examination of surgical specimens suggests that the 61

2 prevalence is as high as 77% (1). Fibroids may cause significant morbidity. Symptoms include prolonged or heavy menstrual bleeding, pelvic pressure or pain and reproductive dysfunction. Symptoms are usually dependent on the location, number and size of the fibroids (1). Myomectomy, which like hysterectomy has been available for over 150 years, limits surgery to removal of the fibroids alone and thus preserves fertility. Myomectomy is generally performed via hysteroscopy, laparoscopy or via laparotomy (2). Laparotomy, abdominal myomectomy is useful for treating subserosal or intramural fibroids (3), while the hysteroscopic route is more appropriate for submucosal fibroids (4). Laparoscopic myomectomy is useful for treating easily accessible tumors such as superficial or pedunculated fibroids (4). However, myomectomy, especially open abdominal procedures can result in considerable intraoperative bleeding from uterine incision and myoma beds therefore controlling of blood loss during myomectomy is a cardinal step to the success of patients recovery and to avoid blood transfusion hazards (5,6). The aim of this study was to evaluate the haemostatic efficacy and safety of Ergometrine injection intramyometrially during abdominal myomectomy in controlling blood loss and reducing the need for blood transfusion. Materials and Methods We included 79 women in this study who were admitted to Al-Thawra General Hospital, Sana'a over a period of 30 months (From July 1st 2013 to 30 th Dec 2015). The study was conducted according to the Helsinki declaration and was approved by the ethics committee of the hospital. A written consent was obtained from each participant. The inclusion criteria were symptomatic intramural myomas requesting myomectomy and hemoglobin concentration > 11.5 g/dl. We excluded all women with bleeding tendency, taking anticoagulant therapy, hypertensive, or have cardiac, liver or kidney diseases. After admission, detailed history, general and gynecology examination were performed. The investigation included complete blood counts (CBC), white blood cells (WBCs), platelet counts, urea, creatinine, liver function tests, blood sugar, coagulation profile, urinalysis and virology screening. Abdomino-pelvic ultrasound was performed. A pre-study questionnaire was prepared and involved age, demographic information, marital status, parity, infertility, menstrual cycle regularity, duration and amount of flow, feeling of swelling, infertility, pressure symptoms, medication and other relevant information. The purpose of the study was explained to all patients. The patients were divided into 2 groups, study group (n= 40) and control group (n= 39), based on simple randomization. They were matched according to the age, size and number of fibroids. All patients underwent preoperative preparation according to the hospital protocol which includes two to four units of packed RBCs, bowel preparation and administration of 1gram ceftriaxone at the time of operation. In the operative theatre, Foley catheters were inserted, the patients were scrubbed and draped as standard, and general anesthesia was used. A suprapubic transverse skin incision was made. After the peritoneal cavity has entered, the abdomens were inspected and the bowels were held up by two moist packs in each side. The uterus was exteriorized and the largest myoma was identified. Two ampules of Methergine, (Ergometrine Maleate, Novartis India Ltd) each ampule is 1 ml containing 0.2 mg Methergine were infiltrated around the base of myoma avoiding direct injection into vascular area. A single anterior vertical or elliptical incision close to the midline as possible was used. The myoma was removed as usual and the other myomas, if present, were removed through this incision whenever feasible. If another large myoma was met, the same injection was repeated one time only. The rest of the procedure was completed as standard with the placement of surgical drainage for all patients. All myomectomies were performed by the 62

3 authors (KAF, AHAH). The blood loss was estimated as the difference in weight between the dry and soaked swabs plus the amount of blood collected in the suction bottle. The specimens were routinely submitted for histopathologic study and the results were consistent with myomas. The outcome measures were the amount of intraoperative blood loss and postoperative bleeding assessed by surgical drains, change in the hemoglobin level, and blood transfusion rate. The standard postoperative care was followed, the drainage was removed when there was no active bleeding and the Foley's catheter removed 24 hours postoperative. The gathered data were analyzed using the statistical package for social sciences (SPSS. lnc. Chicago, IL, USA) IBM version 21. The results were expressed as mean ± standard deviation or proportion as appropriate. Chi-square test (X 2 ) was used for qualitative variable and Student-t-test for quantitative variables. A P value of < 0.05 was considered statistically significant. Results A total of 79 patients were included in this study. Study group (n= 40) and control group (n=39). The clinical characteristics were presented in Table 1. Table 1: Patients' characteristics Variable Study group (n=40) Control group (n= 39) P-value Age (y) 37.7 ± ± BMI (kg/in2) 23.6 ± ± Parity, n(%) Nullipara 24 (60) 22 (56.4) 0.37 Multipara 16 (40) 17 (43.6) 0.37 Previous surgery, n(%) 6 (15) 5 (12.8) 0.38 Symptoms, n(%) Menorrhagia 25 (62.5) 24 (61.5) 0.46 Compression 7 (17.5) 9 (23) 0.26 Infertility 8 (20) 6 (15.3) 0.29 Location of myoma, n(%) Anterior 22 (55) 21 (53.8) 0.45 Posterior 14 (35) 12 (30.8) 0.34 Lateral or fundal 4 (10) 6 (15.4) 0.23 Preoperative Hb (g/dl) 12.8 ± ± The data expressed as mean ± SD or n(%). BMI: Body mass index. There were no statistically significant differences between the two groups with regard to the age, parity, BMI, symptoms and preoperative hemoglobin level (P >0.05). Both groups were comparable regarding the number, location, and size of the main fibroid per patient. Pelvic adhesion was found in 2 patients of the study group versus 3 patients of the control group. The difference was statistically insignificant (P > 0.05). The mean intra-operative blood loss was significantly greater in the control group compared with the study group (490.6 ± 86.4 ml versus ± 68.9 ml, (P< 0.001). The mean operative time was significantly shorter in the study group than the control group (P< 0.001). None of the study group received blood transfusion while the blood transfusion was needed for 7 cases (17.9%) of the control group. The difference was statistically significant (P< 0.05). The mean hospital stay was 2.7 ± 1.1 days for the study group and 4.1 ± 1.3 day for the control group (P< 0.001). Table 2 shows the outcome of the study. Control group had a significant decrease in Hb level 24 hours after operation compared with the study group (P< 0.005). The side effects related to Ergometrine 63

4 injection were not observed apart from febrile morbidity which was noted in 3 cases of the study group versus 3 cases in the control group. Table 2: Outcome of the study. Variable Study group (n=40) Control group (n= 39) P-value Diameter of main fibroid (cm) 5.8 ± ± No. of myoma per patient 4.7 ± ± Intraoperative blood loss (ml) ± ± Operative time (min) 67.4 ± ± Blood transfusion, n(%) - 7 (17.9) Postoperative Hb (g/dl) 11.8 ± ± Hospital stay (day) 2.7 ± ± Febrile morbidity, n(%) 3 (7.5) 3 (7.69) The data expressed as mean ± SD or n(%). :Extremely significant Discussion The main finding of this study is that, with the use of Ergometrine the blood loss during open myomectomy was significantly reduced compared with untreated group (P < 0.001). Ergometrine is an amine ergot alkaloid which increases the amplitude and frequency of uterine contractions and uterine tone that in turn impedes uterine blood flow. It produces arterial vasoconstriction by stimulation of alpha-adrenergic and serotonin receptors and inhibition of endothelial-derived relaxation factors release (7). After intramuscular injection, uterine contractions initiated within 2-3 minutes and persists for 3 hours or longer (8). Ergometrine is a known uterotonic drug and the first line treatment of postpartum hemorrhage particularly when atonic uterus is the suspected cause (7). The extended duration of Ergometrine action (> 3 hours) is the main advantage over that of vasopressin (17-35 min) (9) because it eliminates the concern raised about other substances that increase uterine tone at myomectomy including Ergometrine as they simply delay bleeding and may give false sense security (10). We found in this study that after intramyometrial Ergometrine injection, myometrium was strongly contracted and pale which provided a bloodless operative field and much easily surgical procedures. The occult bleeding after the drug's clearance was not observed in this study as supported by the absence of postoperative bleeding monitored by drainage and the need for blood transfusion. Shokeir T and colleagues (2013) evaluated the effect of 64 prostaglandin analogue type 2 (Dinoprostone) on the blood loss at abdominal myomectomy in a double blind placebo randomized controlled trial (11). They found that administration of 20 mg (Prostin E2) vaginal suppository 1 hour before operation resulted in a statistically significant reduction of blood loss (364.1 ± ml versus ± ml, P=0.02) in the treated and control groups respectively. However, compared with marked reduction of blood loss noted in our study, it appears that Ergometrine is superior to Dinoprostone because Ergometrine has more potent action on the uterine contractility as well as on the blood vessels supplying myomas. In the present study, the duration of operation was significantly shorter among the study group compared with the control (P<0.001). It has been concluded that the operative time is a significant predictor of blood loss, and is a surrogate marker for other factors that may increase the operative duration, such as anatomical variations, the extent of resection and underlying pelvic adhesion from previous surgery (11). We suggest that the Ergometrine could probably be suitable when large and multiple myoma are encountered and for those patients with previous pelvic surgery due to its long lasting action. However, larger studies are required to examine the effect of Ergometrine on this subgroup of patients. In our study, none of the patients in the study group received blood transfusion which further supports our hypothesis that Ergometrine can cause a considerable improvement in

5 intraoperative blood loss. However, the need for blood transfusion can be lessened by optimizing hemoglobin level preoperatively particularly when menorrhagia is the clinical symptom of fibroids. A number of drugs have been introduced to control hemorrhage during myomectomy but the fibroid characteristics (number, size, position, etc.) make the comparison of efficacy difficult (6). The effectiveness of oxytocin at open myomectomy has been evaluated at a dosage of 15u dissolved in 125ml normal saline, but the results showed no significant beneficial effects (12). In contrast to oxytocin, misoprostol, a prostaglandin E1 analogue has been evaluated at a dosage of 400mg vaginally, showing a promising results (13). Vasopressin, a potent vasoconstrictor agent, is the most widely used at myomectomy with favorable hemostatic effect but is not without risks. The use of vasopressin is prohibited in France and Italy due to its potential adverse effects on the cardiovascular system (13,14). GnRH agonists are another option to prevent blood loss during myomectomy or to correct anemia prior to surgery. The use of GnRH agonists for a maximum of 6 months has been shown to reduce blood loss, improve pre and post operative hemoglobin levels as well as reduce the size of the uterus and myomas (12). However, it might make the operation more difficult due to loss of the plane of dissection and also has serious adverse effects such as menopausal symptoms, loss of bone mineral density, and hot flushes (3). A pericervical mechanical tourniquet use at abdominal myomectomy for decreasing blood loss has been shown to have accepted results without any irreversible adverse effect on uterine perfusion and ovarian function (12). However, the various strategies proposed to control blood loss at myomectomy cannot substitute for good surgical techniques. Adherence to basic principles is essential for good results (10). In the current study, there were no observed side effects related to Ergometrine. It is likely that as the total dosage used was not more than that used to arrest postpartum hemorrhage, thus severe side effects were not expected. Ergometrine should not be used in patients with peripheral vascular disease or heart disease and in patients with hypertension (15). This highlights the importance of selecting patients based on carefully screening before operation. This study had a few limitations. First, we used the convenient sample size recruited during 30 months. Second, the study was performed at a single hospital; hence additional larger studies are required to confirm this data. In conclusion, injection of Ergometrine intramyometrium during open myomectomy provides a bloodless operative field, reduces significantly intraoperative blood loss, operative time and the need for blood transfusion. Ergometrine seems to be safe and worthy of clinical application at myomectomy in women with myomas, who have no coexisting systemic vascular disease or hypertension. Conflict of interest The authors have no conflict of interest and the work was not supported or funded by any company. Acknowledgement The authors thank Dr Nataliya Bosa, PhD a Russian Principal Anaesthesiologist who has a highly experienced and helped with excellent cooperation in preoperative preparation, conduction of anaesthesia and postoperative care for the majority of patients mentions in this study. Authors contribution Author * Concept, design, surgeon of the cases, literature review, critical review, processing, Author ** Concept, surgeon of the cases, data collection, interpretation, others. Author *** Statistical analysis, data collection, writing of draft. 65

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