THE EFFICACY OF MISOPROSTOL PLUS VASOPRESSIN VERSUS VASOPRESSIN ALONE ON SURGICAL OUTCOMES THROUGH MINIMALLY INVASIVE MYOMECTOMY: A DOUBLE BLIND RANDOMIZED CLINICAL TRIAL

Author Name(s): Zohreh Tavana MD, *Parnian Kordjamshidi MD, Saeed Alborzi MD
Author Email: parnian.jamshidi@yahoo.com

Abstract

To determine the efficacy of rectal misoprostol combined with intra myometrial injection of vasopressin on surgical outcomes of minimally invasive myomectomy compared with the vasopressin alone. Methods: In a parallel double blind randomized clinical trial, the 1855 year-old women referred to two laparoscopy clinics as candidates of minimally invasive myomectomy for symptomatic uterine fibroids were investigated. A total of 80 patients were assigned in two equal groups of 40 to receive either vasopressin alone or vasopressin plus rectal misoprostol administration. The primary outcomes of the study included; blood loss during surgery and hemoglobin (Hb) drop after surgery extracting the baseline and 6-hour postsurgery serum hemoglobin levels. Results: Mean age of the participants was 35.2(SD: 5.7) years. Mean blood loss was 424 cc (95% CI: 228.7-619.3) in control group versus 268 cc (95% CI: 100.9-312.6) in intervention group(p-value for superiority hypothesis was 0.03).Mean hemoglobin drop after the surgery in control group was 1.68 mg/dl (95% CI: 1.31-2.1) vs. 1.1mg/dl (95% CI: 0.63-1.6) in trial group (p<0.05).Mean length of operation time was 116(SD=35.9) minutes in control group versus 79(SD=26.5) minutes in trial group(P<0.001).Mean drain volume was 155.8 cc in control group versus 99.5 cc in trial group (P<0.05).Seven patients in control group compared with five patients in trial group developed at least one type of complications either through the operation or postoperatively. Conclusion: Rectal misoprostol plus vasopressin appears to have higher efficacy than vasopressin alone for controlling blood loss related complications and surgical outcomes in minimally invasive myomectomy.

Keywords

Myomectomy; Misoprostol; Vasopressin; Clinical Trial

Introduction

Benign smooth muscle tumors of the uterus, known as fibroids ormyomas, are often symptomless. However, about one-third of women with fibroids will present with symptoms that are severe enough to warrant
treatment[1]. The standard treatment of symptomatic fibroids is hysterectomy for women who have completed childbearing, and myomectomy for women who desire future childbearing or simply want to preserve their uterus[2]. Myomectomy, the surgical removal of myomas, can be associated with lifethreatening bleeding. Laparoscopic myomectomy is gaining popularity due to its minimally invasive nature. The bleeding risk is increased during laparoscopic myomectomy because it is performed without first controlling the blood flow to the uterus[3]. Various treatment modalities have been used to reduce the amount of blood loss after myomectomy. These include both pharmacologic and non-pharmacologic interventions[4]. Both vasopressin and misoprostol affect blood loss during myomectomy through different mechanisms and are shown to reduce the blood loss to some extent but not fully satisfactorily [4, 5]. Only a small sized study has compared combined misoprostol and vasopressin treatment with vasopressin when administered alone finding promising results. In a larger randomized clinical trial study investigated whether rectal misoprostol combined with intramyometrial injection of vasopressin can provide higher efficacy on surgical outcomes of minimally invasive myomectomy than the vasopressin alone.

Conclusion

The results of current study support the efficacy of an additive effect for misoprostol When added to vasopressin on primary and most secondary outcomes of the study. Reducing blood loss at the time of myomectomy. Various pharmacologic interventions have been investigated to manage reduce haemorrhage during myomectomy for fibroids. These include intravenous administrations such as intravenous tranexamic acid and intravenous ascorbic acid [7-12] as well as local administration of drug such as vaginal misoprostol, intramyometrial vasopressin, intramyometrial bupivacaine plus epinephrine and vaginal dinoprostone and rectal misoprostol[13, 14]. Based on the most recent systematic review, at present there is moderate-quality evidence that misoprostol alone may reduce bleeding during myomectomy[4]. Its additive effect on vasopressin has been investigated in a study from Jamaica on 50 women with symptomatic uterine fibroids, comparing 25 receiving misoprostol plus vasopressin and 25 receiving vasopressin alone before myomectomy found that the combined treatment had higher efficacy than vasopressin alone in reducing the blood loss after abdominal treatment[15]. Both the misoprostol and vasopressin affect by reducing myometrial blood flow, however, this happens for misoprostol mainly by restricting the vascular supply through inducing myometrial contractions while vasopressin affects through vasoconstriction. A direct vasoconstrictive effect of misoprostol on uterine artery has also be attributed in literature, but no invivo study was retrieved for this[15, 16]. Wing et al. also showed that misoprostol administration does not appear to have an effect on OTR and V1aR mRNA receptor expression [17]. The study by Frederic et al. was the only study retrieved from the literature that , similarly with present study, has compared the combined effect of misoprostol and vasopressin with vasopressin alone on blood loss related complications in myomectomy [15]. There were minor differences between the two studies in that current study was conducted on minimally invasive myomectomy, however, the dosing pattern of trial were highly similar and quite comparable. In both studies, several outcomes in each study were found to be significantly different between the combined treatment and vasopressin in favor of the combined treatment. These included mean blood loss during surgery, mean hemoglobin drop, Mean length of surgery time, Mean length of stay, and Mean drain volume for current study. The outcomes statistically significant in favor of combined treatment in study by Frederic et al. included mean blood loss during surgery, mean hemoglobin drop and need for transfusion. Neither of the studies were able to assess potential drug interaction between the misoprostol and vasopressin due to design limitations. A factorial clinical trial design will be needed to achieve such an aim. The treatment modalities in both studies were not found to be different with respect to potential side effects investigated. Conclusion: Rectal misoprostol plus vasopressin appears to have higher efficacy than vasopressin alone for controlling blood loss related complications and surgical outcomes in minimally invasive myomectomy.

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