Effect of Misoprostol on Fluid Deficit Volume in Hysteroscopic Myomectomy: A Double-Blinded Randomized Controlled Trial

Summary

The goal of this double blinded randomized control trial is to evaluate the impact of misoprostol on fluid deficit during hysteroscopic myomectomies. The main questions it aims to answer are: Is there is difference in fluid deficit in patients who receive misoprostol vs placebo pre operatively for hysteroscopic myomectomies? Participants will be randomized to received 800 mcg of either rectal misoprostol prior to their hysteroscopic myomectomy or 4 tablets of placebo (ZEEBO) prior to their hysteroscopic myomectomy.

Detailed description

Misoprostol is a synthetic analogue of prostaglandin E1 originally developed for the prevention and treatment of NSAID-induced peptic ulcers. Over time, it has become widely used in obstetrics and gynecology due to its uterotonic properties. It is FDA-approved as part of the regimen, paired with mifepristone, for medical abortion and is commonly used off-label for cervical ripening, management of postpartum hemorrhage, and preoperative preparation for gynecologic procedures. In non-pregnant women, misoprostol is frequently administered prior to procedures such as hysteroscopy, intrauterine device insertion, and endometrial biopsy to facilitate cervical dilation. It can be delivered via multiple routes, including oral, sublingual, buccal, vaginal, and rectal. Rectal administration typically results in onset of action within 10-20 minutes, peak plasma concentrations at 60-80 minutes, and a duration of action of approximately 3-4 hours due to its short half-life (20-40 minutes). Its uterotonic effects are mediated by increased intracellular calcium, which activates myosin light-chain kinase. Reported side effects include cramping, bleeding, fever, shivering, nausea, vomiting, and diarrhea, though these are generally mild and dose dependent. Previous studies have evaluated misoprostol's ability to reduce intraoperative blood loss during abdominal and laparoscopic myomectomy, typically using a single preoperative administered vaginally or rectally. These studies demonstrated significant reductions in blood loss. In gynecologic practice, doses ranging from 400 to 1000 mcg are commonly used and well tolerated. Our study focuses on hysteroscopic myomectomy, a minimally invasive procedure performed via the cervix using a hysteroscope to visualize and resect submucosal fibroids within the uterine cavity. Unlike abdominal or laparoscopic approaches, hysteroscopic procedures are not associated with significant blood loss. Instead, the primary intraoperative concern is fluid overload. This can occur when the distension medium, typically normal saline (NS), is absorbed systemically through exposed vascular channels. Although NS is isotonic and does not disrupt electrolyte balance, excessive absorption can lead to complications such as pulmonary edema, cardiac strain, and peripheral edema. To mitigate this risk, national and institutional guidelines recommend terminating the procedure when the fluid deficit (the difference between the volume instilled and the volume recovered) reaches 2.5 liters. Misoprostol's uterotonic properties may help reduce fluid absorption by promoting uterine contractions and limiting vascular exposure, potentially allowing the procedure to be more complete without exceeding fluid safety thresholds. This potential benefit is biologically plausible and clinically relevant. We have selected a dose of 800 mcg rectally, which is within the established safe and commonly used range in gynecologic practice. This dose is expected to be well tolerated and does not increase risk to participants.To maintain blinding, participants in the placebo arm will receive four Zeebo-branded tablets, each containing 250 milligrams, in weight, of microcrystalline cellulose, administered rectally to match the appearance and administration of the active drug. Zeebo is an inert placebo with no pharmacologic activity, and additional risks are minor. STUDY ENDPOINTS: Primary endpoint: • Difference in intraoperative fluid deficit (in milliliters) as measured by the automated fluid management system, between the misoprostol and placebo groups. Secondary endpoints: * Difference in total fluid volume used (in milliliters) between groups. * Difference in total procedure time (in minutes) between groups. * Frequency of repeat hysteroscopic myomectomy due to incomplete fibroid resection caused by early termination of the initial procedure. * Total specimen weight.

Arms & interventions

• DrugMisoprostol Tabets

  800 mcg of misoprostol will be administered per rectum to intervention group prior to their scheduled hysteroscopic myomectomy.

• DrugPlacebo

  4 tablets of Zeebo (Microcsrystalline cellulose) placebo tablets will be placed per rectum to prior to undergoing a hysteroscopic myomectomy, for patients assigned to the placebo arm.

Outcome measures

Eligibility criteria