Use of Nitrous Oxide for Pain Alleviation in Women Undergoing Osmotic Dilator Insertion for Dilatation and Evacuation

Study Overview
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Brief Summary
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A randomised control study aiming to examine whether inhaled N2O/O2 during cervical preparation for second trimester dilatation and evacuation with osmotic dilators (laminaria) alleviates pain and is superior to placebo.

Detailed Description
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Introduction: Women undergoing second trimester abortion often undergo preparation of the cervix prior to the Dilatation and Evacuation (D&E). Women may undergo preparation with osmotic dilators (laminaria) or prostaglandins, both methods are effective and safe for cervical preparation(1). In our institution, the protocol for cervical preparation in the second trimester with osmotic dilator insertion takes place 24 hours before the procedure in the gynecologic emergency room/clinic. Currently, the protocol does not include any method of pain relief during the cervix preparation procedure. At this time, besides general anesthesia, there are no satisfactory evidence-based methods for pain alleviation for osmotic dilators insertion. For example, a recent randomized controlled trial showed topical application of lidocaine spray to the cervix before insertion did not result in lower reported pain as compared with placebo(2). Inhaled nitrous oxide administered with oxygen (N2O/O2) is an acceptable, effective and widely used method for pain relief in short painful pediatric ,dental and urologic procedures(3-5), as well as in the labor room and in the emergency room(6, 7). N2O/O2 has analgesic, anxiolytic and amnestic properties. N2O/O2 has rapid onset and reversal with minimal side effects and few contraindications. Side effects of N2O/O2 are relatively minor and include nausea, dizziness, drowsiness, light-headedness, and diaphoresis. Contraindications include congenital heart defects, pulmonary hypertension, megaloblastic anemia and relatively low blood O2 saturation (<95%)(8, 9). A recent randomized controlled trial showed inhaled N2O/O2 is associated with less pain compared to oral sedation for pain management during in-office hysteroscopic sterilization(9) To the best of our knowledge, there is no literature regarding the efficacy of use of nitrous oxide for pain alleviation in women undergoing osmotic dilator insertion for second trimester Dilatation and Evacuation. Goal: To examine whether inhaled N2O/O2 during cervical preparation for second trimester dilatation and evacuation alleviates pain and is superior to placebo. Methods: A prospective randomized placebo-controlled trial consisting of two groups: Inhaled N2O/O2 (group 1) Placebo group (O2 only) (group 2) Women undergoing dilatation and evacuation in the second trimester and are about to undergo cervical dilatation with osmotic dilators (laminaria) will be invited to participate in a randomized placebo control trial comparing Inhaled N2O/O2 or placebo (O2 only). The recruitment and trial will take place in the emergency room/clinic where the women come a day before the D&E for cervical preparation. This procedure is routinely performed in a gynecologic chair without any sedation thus assessing pain scores is possible. Informed consent will be obtained from each participant. Randomization will be performed using a computer randomization generator. After enrollment, patients will be randomized into one of the two study arms. allocation to the two treatment groups will be concealed in sequentially numbered opaque envelopes that will be opened only by the nurse actually administering the gas (either inhaled N2O/O2 or inhaled oxygen). The participant and physician will be completely blinded to the intervention. Participants will be asked about their most severe pain during menses and asked to rate it from 0 to 10. The patient will be placed in the lithotomy position. Group1: Patients will receive inhaled N2O/O2 (70% N2O and 30% O2). A sterile bivalve speculum will be placed. Laminaria will be inserted. Inhaled N2O/O2 will be stopped after speculum removal. Group2: Patients will receive inhaled O2 (100% O2). A sterile bivalve speculum will be placed. Laminaria will be inserted. Inhaled O2 will be stopped after speculum removal. Patients will receive inhaled O2 (100% O2) throughout the procedure until speculum removal. Pain will be assessed at 7-time intervals using a visual analog pain scale 0 (no pain) to 100 (worst possible pain) - 1.Prior to mask application, 2. Before speculum insertion, 3. Immediately after speculum insertion, 4. Immediately after insertion of first laminaria, 5. Immediately after insertion of last laminaria, 6. After speculum removal (including actual VAS and recall of maximal VAS during the procedure), 7. Before the D&E the next day. Satisfaction with the procedure will be collected as well- overall satisfaction (0-100) and satisfaction with pain control (0-100). Data regarding adverse events will be collected as well. Primary outcome: Self-report of pain score immediately following speculum removal. Secondary outcome: Self-report of maximal pain during the procedure. The protocol will not be repeated if a participant is to return for further laminaria insertion.

Official Title
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Use of Nitrous Oxide for Pain Alleviation in Women Undergoing Osmotic Dilator Insertion for Second Trimester Dilatation and Evacuation

Conditions
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Pain Alleviation, Dilatation and Evacuation, Laminaria Placement, Nitrous Oxide

Intervention / Treatment
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* Drug: Nitrous oxide (N2O/O2)
* Drug: Oxygen (O2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Exclusion Criteria: D&E due to PPROM or infection. Known N2O allergy. Contraindication to N2O use - Congenital heart defects, pulmonary hypertension, megaloblastic anemia, O2 blood saturation <95%

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Arm<br>Patients will receive inhaled N2O/O2 (70% N2O and 30% O2). A sterile bivalve speculum will be placed. Laminaria will be inserted. Inhaled N2O/O2 will be stopped after speculum removal. | Drug: Nitrous oxide (N2O/O2)<br>* Nitrous oxide (N2O/O2) for pain alleviation<br>|
| Placebo Comparator: Control Arm<br>Patients will receive inhaled O2 (100% O2). A sterile bivalve speculum will be placed. Laminaria will be inserted. Inhaled O2 will be stopped after speculum removal. Patients will receive inhaled O2 (100% O2) throughout the procedure until speculum removal. | Drug: Oxygen (O2)<br>* Oxygen (O2) as placebo for control group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-report of change in pain score immediately following speculum removal | Pain will be assessed at 7-time intervals using a visual analog pain scale 0 (no pain) to 100 (worst possible pain) - 1.Prior to mask application, 2. Before speculum insertion, 3. Immediately after speculum insertion, 4. Immediately after insertion of first laminaria, 5. Immediately after insertion of last laminaria, 6. After speculum removal (including actual VAS and recall of maximal VAS during the procedure), 7. Before the D&E the next day. | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-report of change in maximal pain during the procedure | Pain will be assessed at 7-time intervals using a visual analog pain scale 0 (no pain) to 100 (worst possible pain) - 1.Prior to mask application, 2. Before speculum insertion, 3. Immediately after speculum insertion, 4. Immediately after insertion of first laminaria, 5. Immediately after insertion of last laminaria, 6. After speculum removal (including actual VAS and recall of maximal VAS during the procedure), 7. Before the D&E the next day. | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain Alleviation, Dilatation and Evacuation, Laminaria Placement, Nitrous Oxide