Preoperative Misoprostol in Reducing Blood Loss in Total Abdominal Hysterectomy (TAH)

Study Overview
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Brief Summary
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Total abdominal hysterectomy is known to be associated with operative blood loss, which can lead to patients' morbidity. Misoprostol, a prostaglandin, has been shown to be effective in reducing operative blood loss during myomectomy. It is the first study to investigate if preoperative misoprostol is effective in reducing operative blood loss during total abdominal hysterectomy.

Detailed Description
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Uterine leiomyoma is the commonest benign tumour affecting women in their reproductive age. Around 20-50% can cause symptoms that warrant treatment. Different medical therapies, including gonadotrophin releasing hormone analogues, mifepristone, progestins and androgens have been tried. However, most of the medical therapy have significant side-effects that would only allow a short-term treatment. Total abdominal hysterectomy is the definitive treatment for large, symptomatic fibroids. Operative mortality of total abdominal hysterectomy is rare. However, the operation may be associated with significant morbidities. Significant operative blood loss that required blood transfusion and oral iron supplement is not uncommonly encountered after total abdominal hysterectomy. Various methods have been tried to reduce the operative blood loss during total abdominal hysterectomy. A course of hormonal therapy for a few months before operation aiming to shrink the size of fibroid(s) and reduce the vascularity is the commonest approach. Although it is effective, there are significant side effects and the cost of gonadotrophin releasing hormone analogues is high. Intramyometrial vasopressin injection has been reported, but serious complications have been reported. Misoprostol, a prostaglandin E1 analogue, has been widely used in clinical practice in obstetrics and gynaecology. It stimulates uterine contractions and this increase in myometrial contraction will lead to contraction of the vessels supplying blood to the leiomyomas. Misoprostol has also been shown to increase the uterine artery resistance and reduce the blood flow to the leiomyomas. Study by Celik et al has shown that pre-operative misoprostol can reduce intra-operative blood loss and need for post-operative blood transfusion after abdominal myomectomy. Chang et al investigated the use of misoprostol and oxytocin in laparoscopy-assisted vaginal hysterectomy and found that the combination of pre-operative misoprostol and intra-operative oxytocin can reduce blood loss by 200 ml. As misoprostol can stimulate uterine contraction and reduce uterine blood flow, based on the hypothesis that pre-operative misoprostol may redistribute the blood from the diseased uterus back to the circulation hence reducing operative blood loss during total abdominal hysterectomy, we use a double-blind randomized controlled trial to investigate whether a single dose of sublingual misoprostol before total abdominal hysterectomy +/- salpingo-oophorectomy for symptomatic uterine leiomyomas can reduce operative blood loss and need for post-operative blood transfusion.

Official Title
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A Pilot Study of the Preoperative Misoprostol in Reducing Operative Blood Loss During Hysterectomy

Conditions
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Hysterectomy

Intervention / Treatment
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* Drug: Misoprostol
* Drug: Vitamin B 6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: symptomatic women undergoing total abdominal hysterectomy for various benign gynaecological diseases in Queen Mary Hospital Exclusion Criteria: any contraindication to misoprostol, including mitral stenosis, glaucoma, sickle cell anaemia, diastolic pressure over 100mmHg, severe asthma, or known allergy to prostaglandin; a known history of pelvic/ovarian endometriosis; a known history of or active medical disease; a known history of previous myomectomy; women who had pre-operative mifepristone or gonadotrophin releasing hormone analogues treatment; women with mental impairment or incompetent in giving consent.
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: preoperative misoprostol<br>400mcg misoprostol given preoperatively | Drug: Misoprostol<br>* 400mcg misoprostol given sublingually 30 minutes before total abdominal hysterectomy<br>|
| Placebo Comparator: Placebo<br> | Drug: Vitamin B 6<br>* 20mg vitamin B6 given sublingually 30 minutes before total abdominal hysterectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| operative blood loss | The total volume of blood loss was estimated by measuring the amount of blood accumulated in the aspiration equipment and the amount of blood on the surgical gauze using a alkaline haematin method. | duration of operation, up to 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the requirement of blood transfusion |  | from intra-operation to hospital discharge, up to 7 days | 
| the change in haemoglobin level after operation |  | preoperative to 30 hours postoperative | 
| the incidence of side effects |  | 30 minutes after misoprostol/placebo was given | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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misoprostol, hysterectomy, operative blood loss, total abdominal hysterectomy