Preoperative Levator Ani Muscle Injection and Pudendal Nerve Block for Pain Control After Vaginal Reconstructive Surgery

Phase 1

Completed

• Conditions: Surgery; Pelvic Organ Prolapse; Postoperative Pain
• Interventions: Drug: Bupivacaine; Drug: Dexamethasone; Procedure: Bilateral Levator Ani Muscle Injection; Procedure: Bilateral Pudendal Nerve Block; Drug: Saline

• Registration Number: NCT03040011
• Lead Sponsor: Lauren Giugale, MD

Brief Summary

To test the hypothesis that preoperative injections along the levator ani muscles and pudendal nerve with bupivacaine and dexamethasone improve pain control after vaginal apical reconstructive surgery. A three-arm, double-blinded, randomized controlled trial of a total of 75 women will be performed.

The study population will be adult women (\>18 years of age) with uterovaginal or vaginal vault prolapse who have been scheduled for native tissue vaginal reconstructive surgery which includes an apical support procedure. Participants will be enrolled prior to surgery. The procedure will involved four injection sites: the bilateral levator ani muscles via a transobturator approach and bilateral pudendal nerves via a transvaginal approach. Random assignment will occur to one of three study arms: combined arm (20 milliliters bupivacaine/dexamethasone solution divided between the 4 injection sites), bupivacaine arm (20 milliliters bupivacaine divided between the 4 injection sites), or placebo arm (20 milliliters saline divided between the 4 injection sites).

Detailed Description

The primary purpose of this three arm, randomized clinical trial is to test the hypothesis that preoperative injections along the levator ani muscles and pudendal nerve with bupivacaine and dexamethasone improve pain control after vaginal native tissue apical reconstructive surgery.

Hypothesis: concurrent bilateral transobturator levator ani muscle injections and transvaginal pudendal nerve blocks with bupivacaine and dexamethasone performed prior to vaginal apical support procedures will result in improved pain scores at 24 hours postoperatively.

Participants will be randomized to three arms: bupivacaine/dexamethasone group, bupivacaine group, and placebo group. Block randomization will occur and will be stratified by surgery type to ensure that similar numbers of each procedure are randomized to each study arm.

All 3 groups will receive pudendal nerve blocks and transobturator levator ani muscle injections as outlined in detail below (with either bupivacaine/dexamethasone, bupivacaine alone or saline depending on randomization). The interventions will be performed after the participant is positioned in lithotomy position and after sterile preparation of the vagina and perineum per standard protocol. These injections will be performed at the start of the procedure prior to any vaginal repair and be administered by either the attending surgeon or the urogynecology fellow. After the interventions below, the vaginal reconstructive procedures will be performed as usual by the attending surgeon and surgical team. There are both fellows and residents who participate in these vaginal reconstructive surgeries, however for study purposes, resident physicians will not be permitted to administer either the pudendal nerve block or the transobturator injections. There are four attending surgeons and four fellow physicians who will be administering the injections. While all surgeons are familiar with the anatomy and have performed these procedures, each physician will be instructed on the intended procedures and additionally will be directly observed in the operating room for at least one procedure to ensure consistency in technique. All participants will undergo a standardized general anesthesia regimen.

After the study intervention, all participants will then undergo the scheduled vaginal reconstructive procedure as standard. Infiltration of the vaginal epithelium with lidocaine is common in vaginal repairs. The maximum doses of lidocaine and bupivacaine are additive. The amount of local infiltration to 50 milliliters of 0.5% lidocaine with epinephrine. This dose is equal to 250mg of lidocaine which, when also taking into account the 50mg of bupivacaine, is within a safe dosing range for a participant weighing 50kg.

Administration of all four injections involved in the study protocol and described above take approximately 5 additional minutes in total at the start of the case. After the injections are performed, there will be no further interventions.

Other assessments that will be performed as part of the study protocol are outlined below:

Baseline assessments: Pain assessment, assessment of presence of any baseline nausea or vomiting, baseline activities assessment will all be performed in preoperative area on the day of surgery prior to randomization.

Postoperative pain score assessment: 3 hours, 24 hours, 48 hours, 72 hours, and 1 week postoperatively. Postoperative pain measured by the numerical rating scale (NRS). The NRS is a publicly available pain assessment tool that consists of an eleven point scale ranging from 0 to 10 (0 = no pain and 10 = worst possible pain) presented visually on a horizontal line. Participants are asked to report a number or mark on the scale. Previous studies have demonstrated its reliability, validity and ease of administration. The NRS was chosen because a systematic review article demonstrated higher compliance rates, better responsiveness and ease of use relative to visual analog scales. Additionally, the NRS has been shown to have strong validity and low error rates when used in an elderly (\>60 years) postoperative patient population.

Postoperative nausea and vomiting assessment: 3 hours postoperatively The intensity of postoperative nausea and vomiting (PONV) using the PONV Intensity scale. The PONV scale is a four question assessment designed to measure clinically significant nausea and vomiting. It was initially validated in a general surgery population and has been validated in early postoperative gynecology patients. Clinically important nausea and vomiting is defined as a score greater than or equal to 50. This scale takes approximately 1 minute to complete and is publicly available. The amount of inpatient anti-emetic consumption will also be assessed. Any anti-emetic administered from surgery end time will be recorded as well as the dosage. Anti-emetic type and dosage will be recorded until the time of discharge.

Voiding status at time of foley catheter removal. All patients routinely have some assessment of voiding function prior to discharge. Whether each participant passed or failed a voiding trial after surgery will be recorded in the database. If a participant fails, the standard of care is do be discharged to home after learning self-catheterization or with a foley catheter. In the event that a participant fails a postoperative voiding trial, whether participants receive a foley catheter or were performing self-catheterization will be recorded. As this is a routine part of postoperative care, the research protocol will not interfere with the performance or outcomes of a voiding trial. Results will be documented, however no specific assessment tool will be used.

Time to resume normal activities measured by the activities assessment scale (AAS): 1 week, 2 weeks, 6 weeks and 12 weeks postoperatively The AAS was initially designed to assess functional activity in the perioperative period in the general surgery population. It has since been deemed a valid and reliable measure to assess postoperative activity level in a Female Pelvic Medicine and Reconstructive Surgery patient population. It has the ability to measure perioperative function and takes approximately 3-5 minutes to complete. It consists of a 13 item questionnaire assessing various types of physical activity and the degree of difficulty associated with each activity. The types of activities assessed fall into three subscales: sedentary activities (questions 1-4), ambulatory activities (questions 6-8), and work or exercise activities (questions 11-13). Respondents also have the option to indicate that these activities were not performed for another indication (this item is not scored). The time frame for all questions is the previous 24 hours. Given that many patients are instructed to avoid strenuous work or exercise activity in the postoperative period, the subscales of sedentary activities and ambulatory activities, which patients are encouraged to perform as tolerated in the postoperative period, will be of most interest.

Consumption of analgesic medications: during inpatient hospital stay and for first 72 hours postoperatively Narcotic consumption will be measured in morphine equivalents. The amount of narcotics will be obtained from the inpatient hospital record. All narcotics received from the surgery end time to the time of discharge will be included. Morphine equivalents will be calculated with online calculator available at http://www.agencymeddirectors.wa.gov/Calculator/DoseCalculator.htm. Similarly, the amount of NSAIDs will be obtained from the inpatient hospital record. All NSAIDs received from the surgery end time to the time of discharge will be included. To assess both the amount of narcotic and NSAID consumption after discharge, the participant will be provided with a diary form to record how many daily tablets of narcotic and NSAIDs are taken. This form will be completed from postoperative days 1-3.

For all forms, the participants will be instructed to mail the forms back to the office once completed (in a pre-address envelope provided as part of the study). Participants will also have the option of brining the forms in to the office at the time of a participant's postoperative visit.

Participants, physicians and any nursing personnel involved in patient care will remain masked until 12 weeks postoperatively.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-01-25
• Study First Submitted QC: 2017-01-31
• Study First Posted: 2017-02-01
• Study Start: 2017-06-01
• Primary Completion: 2019-04-11
• Study Completion: 2019-08-05
• Results First Submitted: 2020-02-07
• Status Verified: 2020-03
• Results First Submitted QC: 2020-03-06
• Last Update Submitted: 2020-03-06
• Results First Posted: 2020-03-09
• Last Update Posted: 2020-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 79

Inclusion Criteria

1. Women ages 18 or older who are scheduled for a vaginal native tissue repair with apical support procedure including uterosacral ligament suspension, sacrospinous ligament fixation, or colpectomy and colpocleisis with or without levator myorrhaphy
2. Concomitant procedures including hysterectomy, anterior and posterior colporrhaphies , perineorrhaphies and midurethral sling placements are acceptable and do not result in exclusion
3. Available for at least 12 weeks of follow-up
4. Able to undergoing general anesthesia

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Exclusion Criteria

1. Planned mesh-augmented apical support procedure (placement of synthetic midurethral sling is acceptable and not considered an exclusion criteria)
2. Planned mesh excision
3. Laparoscopic, robotic or abdominal surgery
4. Known adverse reaction or allergy to intervention medication
5. Evidence of fistula or known infection (vulvovaginal cellulitis, abscess, abdominopelvic infection, or systemic fungal infection)
6. Chronic pelvic pain as an active issue
7. Daily opiate consumption for any indication
8. History of pelvic radiation
9. Chronic steroid use
10. Diabetes mellitus
11. Known HIV/AIDS or immunosuppression secondary to transplant related medications
12. Planned surgery under regional anesthesia
13. Non-English speaking or inability to complete questionnaires
14. Bleeding disorders that would impair a patient's clotting ability
15. Weight less than 50kg

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bupivacaine Arm	Bilateral Levator Ani Muscle Injection	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of 20 milliliters 0.25% bupivacaine (2.5mg/milliliter). The total amount will be divided equally between the four injection sites.
Bupivacaine/Dexamethasone Arm	Bilateral Pudendal Nerve Block	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of a mixture of 20 milliliters of 0.25% bupivacaine (2.5mg/milliliter ) and 2 milliliters of dexamethasone (4mg/milliliter). The total amount of the bupivacaine/dexamethasone solution will be divided equally between the four injection sites.
Bupivacaine/Dexamethasone Arm	Bilateral Levator Ani Muscle Injection	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of a mixture of 20 milliliters of 0.25% bupivacaine (2.5mg/milliliter ) and 2 milliliters of dexamethasone (4mg/milliliter). The total amount of the bupivacaine/dexamethasone solution will be divided equally between the four injection sites.
Bupivacaine Arm	Bupivacaine	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of 20 milliliters 0.25% bupivacaine (2.5mg/milliliter). The total amount will be divided equally between the four injection sites.
Bupivacaine Arm	Bilateral Pudendal Nerve Block	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of 20 milliliters 0.25% bupivacaine (2.5mg/milliliter). The total amount will be divided equally between the four injection sites.
Placebo Arm	Bilateral Levator Ani Muscle Injection	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of 20 milliliters 0.9% saline (normal saline). The total amount will be divided equally between the four injection sites.
Placebo Arm	Bilateral Pudendal Nerve Block	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of 20 milliliters 0.9% saline (normal saline). The total amount will be divided equally between the four injection sites.
Placebo Arm	Saline	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of 20 milliliters 0.9% saline (normal saline). The total amount will be divided equally between the four injection sites.
Bupivacaine/Dexamethasone Arm	Dexamethasone	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of a mixture of 20 milliliters of 0.25% bupivacaine (2.5mg/milliliter ) and 2 milliliters of dexamethasone (4mg/milliliter). The total amount of the bupivacaine/dexamethasone solution will be divided equally between the four injection sites.
Bupivacaine/Dexamethasone Arm	Bupivacaine	After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of a mixture of 20 milliliters of 0.25% bupivacaine (2.5mg/milliliter ) and 2 milliliters of dexamethasone (4mg/milliliter). The total amount of the bupivacaine/dexamethasone solution will be divided equally between the four injection sites.

Primary Outcome Measures

Name	Time	Method
Primary Postoperative Pain Measured by the Numerical Rating Scale (NRS)	24 hours postoperatively	Postoperative pain measured by the numerical rating scale (NRS) at 24 hours postoperatively. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.

Secondary Outcome Measures

Name	Time	Method
POD 2 Postoperative Pain Measured by the NRS	2 days after surgery	Postoperative Pain Measured by the NRS 2 days after surgery. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.
Proportion of Patients With Same Day Discharge	Day of surgery	Same day discharge was defined as a patient being discharged on the same day as surgery and did not require an admission after surgery. The proportion of patients who were discharged on the day of surgery was compared between groups.
POD 3 Narcotic Consumption	Postoperative day 3	The total amount of narcotic pain medication used on postoperative day 3 was calculated and measured in oral morphine equivalents.
Nausea and Vomiting Measured by the PONV Scale	6 hours postoperatively	Intensity of postoperative nausea and vomiting (PONV) measured by the PONV scale prior to discharge. The Postoperative Nausea and Vomiting Intensity Scale is a four-question assessment to measure clinically significant nausea and vomiting with a range from 0-7 with higher scores signifying more clinically significant nausea and vomiting.
1 Week Postoperative Pain Measured by the NRS	1 week after surgery	Postoperative Pain Measured by the Numeric Rating Scale 1 week after surgery. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.
POD 3 Postoperative Pain Measured by the NRS	3 days after surgery	Postoperative Pain Measured by the NRS 3 days after surgery. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.
6 Hour Postoperative Pain Measured by the NRS	6 hours postoperatively	Postoperative pain as measured by the NRS at 6 hours after surgery. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.; Of note, there is a typographical error in the protocol section and refers to this outcome as a NRS score at 3 hours postoperatively. The final IRB approved protocol is a 6 hour postoperative timepoint and this is the correct outcome reported here in the results section.
Postoperative Urinary Retention	0-24 hours postoperatively	Urinary retention was defined as the need to perform self-catheterization or have an indwelling catheter placed postoperatively. The proportion of patients with urinary retention was compared between groups.
Adverse Events	0-12 weeks postoperatively	The number of adverse events in each study group was assessed and compared between study groups. An adverse event was described as any medical or surgical complication that occurred either intraoperatively or postoperatively.
Anti-emetic Consumption	3 hours postoperatively	The amount of inpatient anti-emetic consumption, recorded in number of doses of nausea medication
POD 2 Narcotic Consumption	Postoperative day 2	The total amount of narcotic pain medication used on postoperative day 2 was calculated and measured in oral morphine equivalents.
POD 1 Ibuprofen Consumption	Postoperative day 1	The total amount of ibuprofen medication used on postoperative day 1.
Return to Baseline Activities Using the Activities Assessment Scale	12 weeks postoperative	Resumed normal daily activities using the Activities Assessment Scale (AAS) by 12 weeks after surgery. The AAS is a 13-point scale on which patients rate their difficulty performing a range of activities from "No difficulty" to "Not able to do it." A final score ranging from 0-100 is transformed, with higher numbers reflecting less difficulty with activities.; We defined return to normal as when a patient's postoperative AAS scores was at or greater than the baseline AAS score. We report the proportion of patients in each study arm who returned to baseline activity at each timepoint.
POD 1 Narcotic Consumption	Postoperative day 1	The total amount of narcotic pain medication used on postoperative day 1 was calculated and measured in oral morphine equivalents.
POD 3 Ibuprofen Consumption	Postoperative day 3	The total amount of ibuprofen medication used on postoperative day 3.
POD 2 Ibuprofen Consumption	Postoperative day 2	The total amount of ibuprofen medication used on postoperative day 2.

Trial Locations

Locations (1)

Magee-Womens Hospital of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States