Clinical trial NCT03040011
Conditions: Pelvic Organ Prolapse Surgery Postoperative Pain
Keywords: Vaginal Surgery Pelvic Organ Prolapse Postoperative Pain
Sponsor: Lauren Giugale, MD
Start date: 2017-06-01; Completion date: 2019-08-05
Enrollment: 79 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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. arm 3: 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.
Interventions: intervention 1: Dexamethasone intervention 2: Bupivacaine intervention 3: Bilateral Pudendal Nerve Block intervention 4: Bilateral Levator Ani Muscle Injection intervention 5: Saline
Intervention descriptions: intervention 1: Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description. intervention 2: Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description. intervention 3: Performed transvaginally. The ischial spines will be palpated transvaginally and the sacrospinous ligament identified as a firm band running medially and posteriorly from the ischial spine to the sacrum. The needle guide will be inserted and positioned against the vaginal mucosa on the sacrospinous ligament approximately 1 cm medial and inferior to the ischial spine. When the needle guide is properly positioned, the spinal needle is advanced approximately 1cm through the vaginal mucosa into the sacrospinous ligament. The needle will be aspirated to ensure no intravascular needle placement. With a negative aspirate, 5 milliliters of solution are injected. This same procedure will be performed on the contralateral side. intervention 4: Performed transperineally. With thumb, superomedial aspect of obturator foramen is palpated 2-3 cm lateral to the clitoris. The index and middle finger are in the vagina to confirm obturator foramen. A spinal needle is inserted through the the obturator foramen into the obturator internus muscle. The needle is angled slightly posteriorly towards the ischial spine, parallel to the arcus tendineus levator ani and arcus tendineus fascia pelvis. The needle is advanced to the level of the ischial spine, the vaginal hand ensuring that the needle has not perforated the vaginal wall. Once the needle tip is at a depth of the ischial spine, aspiration is performed to ensure no intravascular needle placement. 5 milliliters of solution is injected along the length of the needle tract. intervention 5: Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description.

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 6 
 
Study Protocol  
 
 
 
 
 
 
Official Title: Preoperative Levator Ani Muscle Injection and Pudendal Nerve Block 
With Bupivacaine and Dexamethasone for Improved Pain Control After Vaginal 
Reconstructive Surgery: A Three-Arm Randomized Controlled Trial   
  
 
 
ClinicalTrials.gov ID (NCT number): NCT03040011 
 
 
 
Protocol Date: 10/24/2019 
 
 
 
 


Page 2 of 6 
 
Scientific Background 
Many major gynecologic surgeries are increasingly becoming outpatient procedures (1-
3). One criterion for same-day discharge is adequate pain control. Despite this, many 
women report suboptimal pain control after discharge following vaginal surgery (4). 
Furthermore, at 6 weeks postoperatively, only 50% of patients felt that they had fully 
recovered from surgery (4). Thus, even though a minimally invasive approach, there are 
areas for improvement in postoperative recovery after vaginal surgery. 
 
Various local anesthetic techniques, including pudendal nerve blocks, have been 
studied as forms of preemptive analgesia to improve pain associated with vaginal 
surgery.  While the methodologies vary making direct comparison difficult, the studies 
assessing preemptive analgesia at the time of vaginal surgery have yielded mixed 
results, particularly for apical support procedures (5-9) and an effective and 
generalizable way to reduce postoperative pain in a population of Female Pelvic 
Medicine and Reconstructive Surgery patients undergoing vaginal reconstructive 
surgery with apical suspension procedures has not been defined. 
 
We utilize a novel injection technique in which we inject the study medication via a 
transobturator approach into the levator ani muscles directly.  We utilized this approach 
in addition to the pudendal nerve blockade to deliver study medication to the levator ani 
muscles themselves and any distal nerve branches of the levator ani nerve, with the 
idea that this would decrease pain and edema at the operative site and improve 
postoperative pain control. We add dexamethasone to bupivacaine for the intervention 
group because of its known anti-inflammatory qualities (10). These anti-inflammatory 
properties have been translated to the surgical realm and the addition of perioperative 
dexamethasone has been demonstrated to be a safe and effective way to improve 
perioperative recovery in multiple disciplines, including gynecology (11-15).  
 
Study Objectives 
 
Our primary aim is to determine if bilateral transobturator levator ani muscle injections 
and transvaginal pudendal nerve blocks with bupivacaine and dexamethasone improve 
postoperative pain measured by the numerical rating scale (NRS) on postoperative day 
1 after vaginal reconstructive apical support procedures.  
 
Our secondary aims include postoperative nausea and vomiting (measured by the 
postoperative nausea and vomiting score), analgesic consumption (measured in 
morphine equivalents), same-day discharge, postoperative pain at 6 hours, 48 hours, 72 
hours and 1 week (measured by the NRS), need for either self-catheterization or 
indwelling catheter, safety and adverse events, and time to resume normal activity 
(measured by the activities assessment scale at 1,2,6 and 12 weeks postoperatively). 
 
Study Design & Methods 
 
We performed a 3-arm, double-blind, randomized, placebo-controlled trial of bilateral 
transobturator levator ani muscle injections and transvaginal pudendal nerve blocks 


Page 3 of 6 
 
prior to native tissue vaginal apical support procedures for pelvic organ prolapse. 
Women were randomized to one of three study medication groups distributed over 4 
injection sites: 22mL of 0.9% saline (placebo group), 22 mL of 0.25% bupivacaine 
(bupivacaine group), or 20 mL of 0.25% bupivacaine with 4mg (2mL) of dexamethasone 
(combined group).  
 
Recruitment occurred and written informed consent was obtained during regularly 
scheduled preoperative office visits. If no preoperative visit was scheduled, informed 
consent was performed by telephone and the consent form was either mailed to the 
patient or signed on the morning of surgery. Block randomization occurred 1-2 days 
prior to scheduled surgery in a 1:1:1 ratio by a research coordinator not involved in 
study intervention or outcome assessment. The randomization scheme was stored in a 
password protected, secure location and only accessed by this research coordinator. 
We also took additional steps to ensure a double-blinded design. After randomization 
but before the start of the prolapse procedure, pharmacy personnel delivered the study 
medication to the operating room in a single, clear syringe labeled “Study Medication” 
and the corresponding study identification number. All syringes were identical. 
Additionally, normal saline, bupivacaine and dexamethasone are all clear solutions, 
which allowed us to blind physicians to the study medication being administered. 
Patients were also blinded to the study intervention until 12 weeks of follow-up. 
 
All 3 study groups received transobturator levator ani muscle injections and pudendal 
nerve blocks with either saline, bupivacaine alone or bupivacaine and dexamethasone 
according to randomization. The study intervention was performed after the induction of 
general anesthesia and prior to the start of the prolapse repair. After the patient was 
placed in dorsal lithotomy position, sterile preparation occurred, and a urethral catheter 
was inserted. The bilateral transobturator levator muscle injections were performed first. 
The superior medial aspect of the obturator foramen was identified by palpation 
approximately 2-3 cm lateral and 2-3 cm inferior to the clitoris. With the thumb palpating 
the superior medial aspect of the obturator foramen, the index and middle finger were 
inserted into the vagina to confirm identification of the obturator foramen. A spinal 
needle was then inserted through the superior medial aspect of the obturator foramen 
through the obturator internus muscle. The trajectory of the needle at this point was 
angled slightly posteriorly towards the ischial spine, traveling parallel to the arcus 
tendineus levator ani and arcus tendineus fascia pelvis. The spinal needle was 
advanced to the level of the ischial spine, maintaining the same trajectory and with the 
vaginal hand ensuring that the spinal needle did not perforate the vaginal wall. Once the 
tip of the needle was at a depth where it had reached the ischial spine, aspiration was 
performed to ensure no intravascular needle placement and the study medication was 
injected. Bilateral pudendal nerve blocks were performed transvaginally after the 
transobturator injections. The pudendal nerve blocks were performed according to 
previously described technique (21,22). Five milliliters of study medication were injected 
at each of the four injection sites for a total of 20 mL of study medication. The 
intervention was performed by one of five attending surgeons or one of four 
urogynecology fellows. After the interventions, the vaginal reconstructive procedures 
were performed as usual by the attending surgeon and surgical team. Both fellows and 


Page 4 of 6 
 
residents participated in these vaginal reconstructive surgeries, however for study 
purposes, resident physicians were not permitted to administer either the study 
injections. 
 
To standardize care, all study participants received the same institutional induction and 
intraoperative enhanced recovery after surgery general anesthesia protocol, full details 
of which have been previously published (23). In summary, patients received 
intravenous propofol, ketamine, lidocaine, muscle relaxant and dexamethasone for 
induction and intravenous ketamine and lidocaine for maintenance (23). The 
intravenous dexamethasone given upon induction is part of the protocol to prevent 
postoperative nausea and vomiting. To standardize intraoperative local anesthetic, the 
amount of additional local infiltration was limited to 50ml of 0.5% lidocaine with 
epinephrine. According to our ERAS protocol, all surgeries were planned to be same-
day surgeries. Any deviations from protocol were documented. 
 
Our primary outcome was a numeric rating scale (NRS) pain score on postoperative 
day (POD) one. The NRS is an eleven-point scale ranging from 0 to 10 presented 
visually on a horizontal line. Higher scores represent more postoperative pain. 
 
Secondary outcomes included pain scores at additional timepoints (6 hours after 
surgery, POD 2, POD 3 and 1 week after surgery), same day discharge rates, voiding 
status at time of discharge, postoperative narcotic consumption measured in oral 
morphine equivalents, postoperative ibuprofen consumption, postoperative nausea and 
vomiting (PONV), postoperative activities assessment, and adverse events.  PONV was 
assessed using the PONV Intensity scale, a four-question assessment to measure 
clinically significant nausea and vomiting with higher scores signifying more clinically 
significant PONV (26). Time to resume normal activities was measured by the activities 
assessment scale (AAS), 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 (27). Assessments were completed by the patient at home and mailed to 
research staff upon completion. Women were followed for 12 weeks postoperatively and 
no additional office visits were required as part of the research protocol. 
 
Eligibility Criteria  
 
Women were eligible for inclusion if they were ≥18 years old and scheduled for a 
vaginal native tissue repair with apical support procedure (uterosacral ligament 
suspension, sacrospinous ligament fixation, levator myorrhaphy or colpocleisis) and 
able to undergo general anesthesia. Concomitant procedures including hysterectomy, 
anterior and posterior colporrhaphies, perineorrhaphies and midurethral sling 
placements were permitted. All patients needed to be available for at least 12 weeks of 
follow-up.  Women were excluded for any of the following reasons: planned mesh-
augmented apical support procedure or mesh excision, laparoscopic, robotic or 
abdominal surgery, known adverse reaction or allergy to intervention medication, 
evidence of fistula or infection, chronic pelvic pain as an active issue, daily opiate 


Page 5 of 6 
 
consumption, history of pelvic radiation, daily steroid use, diabetes mellitus, 
immunosuppression, planned surgery under regional anesthesia, non-English speaking 
or inability to complete questionnaires, bleeding diatheses, or weight less than 50kg. 
We incorporated a weight less than 50kg as an exclusion criterion to ensure that the 
bupivacaine dosage was below the weight-based maximum dose, as recommended by 
our anesthesia colleagues (16). 
 
Statistical Analysis Plan 
 
All results will be analyzed by intention-to-treat based upon the study group to which 
subjects were randomized. One-way ANOVA, Kruskal Wallis, Chi-square, and Fisher’s 
Exact will be used to compare continuous and categorical variables, respectively. Based 
upon prior studies demonstrating that pain after vaginal surgery ranges from a 2 to 5 on 
numeric scales (range 0-10) and literature suggesting that a 33% decrease in pain is 
clinically significant, we elected to assess a 2-point change in NRS scores between 
treatment groups (5,7,9,28). Based upon an ANOVA evaluated at the 2-sided 0.05 
significance level and a standard deviation of 17.5, a sample size of 21 patients per arm 
provided 90% power to detect a 2-point change in NRS scores. To account for 20% 
attrition, we increased to 25 patients per arm for a total of 75 women. 
 
We hypothesized that concurrent bilateral transobturator levator ani muscle injections 
and transvaginal pudendal nerve blocks with bupivacaine and dexamethasone 
performed prior to vaginal native tissue apical prolapse repair would result in statistically 
significant improved pain scores on postoperative day one. 
 
References 
1. 
Alton K, Sullivan S, Udaltsova N, Yamamoto M, Zaritsky E. Same-Day Discharge 
After Minimally Invasive Myomectomy. Obstet Gynecol. 2016;127(3):539-544. 
2. 
Perron-Burdick M, Yamamoto M, Zaritsky E. Same-day discharge after 
laparoscopic hysterectomy. Obstet Gynecol. 2011;117(5):1136-1141. 
3. 
Zakaria MA, Levy BS. Outpatient vaginal hysterectomy: optimizing perioperative 
management for same-day discharge. Obstet Gynecol. 2012;120(6):1355-1361. 
4. 
Evenson M, Payne D, Nygaard I. Recovery at home after major gynecologic 
surgery: how do our patients fare? Obstet Gynecol. 2012;119(4):780-784. 
5. 
Abramov Y, Sand PK, Gandhi S, et al. The effect of preemptive pudendal nerve 
blockade on pain after transvaginal pelvic reconstructive surgery. Obstet 
Gynecol. 2005;106(4):782-788. 
6. 
Imbelloni LE, Vieira EM, Gouveia MA, Netinho JG, Spirandelli LD, Cordeiro JA. 
Pudendal block with bupivacaine for postoperative pain relief. Dis Colon Rectum. 
2007;50(10):1656-1661. 
7. 
Ismail MT, Elshmaa NS. Pre-emptive analgesia by nerve stimulator guided 
pudendal nerve block for posterior colpoperineorrhaphy. Eur J Obstet Gynecol 
Reprod Biol. 2012;163(2):200-203. 
8. 
Rouholamin S, Jabalameli M, Mostafa A. The effect of preemptive pudendal 
nerve block on pain after anterior and posterior vaginal repair. Adv Biomed Res. 
2015;4:153. 


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9. 
Unger C, Walters MD. A Randomized Double-Blind Placebo-Controlled Trial on 
the Effect of Local Analgesia on Postoperative Gluteal Pain in Patients 
Undergoing Sacrospinous Ligament Colpopexy. Female Pelvic Med Reconstr 
Surg. 2016;22(5, Supplement 1):S2. 
10. 
Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. 
Clin Sci (Lond). 1998;94(6):557-572. 
11. 
Albrecht E, Kern C, Kirkham KR. A systematic review and meta-analysis of 
perineural dexamethasone for peripheral nerve blocks. Anaesthesia. 
2015;70(1):71-83. 
12. 
Antunes AA, Avelar RL, Martins Neto EC, Frota R, Dias E. Effect of two routes of 
administration of dexamethasone on pain, edema, and trismus in impacted lower 
third molar surgery. Oral Maxillofac Surg. 2011;15(4):217-223. 
13. 
Gao W, Zhang QR, Jiang L, Geng JY. Comparison of local and intravenous 
dexamethasone for postoperative pain and recovery after tonsillectomy. 
Otolaryngol Head Neck Surg. 2015;152(3):530-535. 
14. 
Huynh TM, Marret E, Bonnet F. Combination of dexamethasone and local 
anaesthetic solution in peripheral nerve blocks: A meta-analysis of randomised 
controlled trials. Eur J Anaesthesiol. 2015;32(11):751-758. 
15. 
Pauls RN, Crisp CC, Oakley SH, et al. Effects of dexamethasone on quality of 
recovery following vaginal surgery: a randomized trial. Am J Obstet Gynecol. 
2015;213(5):718 e711-717. 
16. 
Dexamethasone (systemic): Drug information. UpToDate; 2016. Accessed 
November 9, 2016. 
21. 
Cunningham FG. Williams obstetrics. 24th edition. ed. New York: McGraw-Hill 
Medical; 2014. 
22. 
Vidaeff A. Pudendal and paracervical block. In: Ramin S, Eckler K, eds. 
UpToDate. Waltham, MA: UpToDate; 2016. Accessed November 8, 2016. 
23. 
Carter-Brooks CM, Du AL, Ruppert KM, Romanova AL, Zyczynski HM. 
Implementation of a urogynecology-specific enhanced recovery after surgery 
(ERAS) pathway. Am J Obstet Gynecol. 2018;219(5):495 e491-495 e410. 
26. 
Allen ML, Leslie K, Jansen N. Validation of the postoperative nausea and 
vomiting intensity score in gynaecological patients. Anaesth Intensive Care. 
2011;39(1):73-78. 
27. 
Barber MD, Kenton K, Janz NK, et al. Validation of the activities assessment 
scale in women undergoing pelvic reconstructive surgery. Female Pelvic Med 
Reconstr Surg. 2012;18(4):205-210. 
28. 
Jensen MP, Chen C, Brugger AM. Interpretation of visual analog scale ratings 
and change scores: a reanalysis of two clinical trials of postoperative pain. J 
Pain. 2003;4(7):407-414. 
 

ICF_001.pdf: 
                                                                          Page 1 of 8                                           
           
   University Of Pittsburgh          
     Institutional Review Board    
 
Approval Date: 11/6/2018 
Renewal Date:  11/5/2019 
 
IRB #:   PRO16110378 
 
 
 
 
 
University of Pittsburgh 
Department of OB/GYN  
300 Halket Street 
Pittsburgh, PA 15213 
412.641.1403 
 
CONSENT TO ACT AS A SUBJECT IN A RESEARCH STUDY 
 
TITLE:   
Preoperative pudendal nerve block and levator ani 
muscle injection for improved pain control after vaginal 
reconstructive surgery: a three-arm, randomized, 
double-blind, placebo-controlled trial 
 
PRINCIPAL INVESTIGATOR:   Lauren Giugale, MD 
 
 
 
 
 
Department of Obstetrics, Gynecology and Reproductive 
Sciences 
Division of Urogynecology 
Magee Womens Hospital 
 
 
 
 
 
412-270-1046 
 
STUDY COORDINATOR:  
Judy Gruss, RN 
 
 
 
 
 
412-641-7850 
 
SOURCES OF SUPPORT 
Magee-Womens Research Institute - Clinical Trainee 
Research Award 
 
Why is this study being done? 
Pain control is an important part of care after surgery for pelvic organ prolapse. Pelvic organ 
prolapse is the dropping or sagging of the pelvic organs (like the bladder or uterus). This study is 
being done to find a method that will improve pain control after vaginal prolapse surgery. One 
approach to pain control is injecting local anesthesia near the site of surgery. We are looking at 
the injection of local anesthesia and a small dose of steroid in the muscles of the pelvis during 
surgery to see if we can lessen postoperative pain after vaginal surgery.  
 
The local anesthetics bupivacaine and short-acting steroid dexamethasone have both been used in 
other areas of surgery with safe results and improvement in recovery after surgery. However, 
there is less information available on the effects of these medications during vaginal prolapse 
surgery. In this study, these medications will be injected by your surgeon after you are already 
asleep for surgery with the goal of decreasing the overall response to pain. This study will help 
doctors understand if this is an effective way to potentially decrease the pain that patients 
experience after prolapse surgery.  
 


                                                                          Page 2 of 8                                           
           
   University Of Pittsburgh          
     Institutional Review Board    
 
Approval Date: 11/6/2018 
Renewal Date:  11/5/2019 
 
IRB #:   PRO16110378 
 
 
Who is being asked to take part in this study? 
Approximately 75 women from the Magee-Womens Hospital of UPMC who are at least 18 years 
old and undergoing vaginal surgery for pelvic organ prolapse will be asked to participate in this 
study.  
 
 What are the procedures of this study? 
1.  If you agree to participate in this study, research staff will review your record to make sure 
you are eligible for the study.  They will record some information from your record on study 
forms that do not contain your name or any other identifying information. Things that they will 
record include your age, race/ethnicity, body mass index, smoking status, medical and surgical 
history, and postoperative care.  You may be asked to confirm or provide information that is 
missing or incomplete. 
 
2. You will be randomly assigned to receive pelvic injections with either a placebo (saline 
solution, but no active medication), bupivacaine local anesthetic alone, or a solution containing 
both bupivacaine and dexamethasone. You will have a 1 in 3 chance of receiving the placebo 
medication and a 2 in 3 chance of receiving an active medication.  Neither you nor your surgeon 
will know if you receive the drug or the placebo. Bupivacaine is approved by the FDA (US Food 
and Drug Administration) for local anesthesia and dexamethasone is approved by the FDA as an 
anti-inflammatory agent.  The combination of bupivacaine and dexamethasone is not FDA-
approved for use in vaginal prolapse surgery. The procedures to inject these solutions are 
performed after you are already asleep, but before the surgery for prolapse has started. Your 
surgeon will perform these injections. The injections do not affect the rest of your prolapse 
surgery. You will receive two injections within the vagina and two injections outside of the 
vagina. The medication is injection into the small muscles that surround the vagina. Additionally, 
each surgeon is familiar with the procedures for injecting the medication and has performed 
similar procedures previously. Your care after this surgery will not be changed based on which 
of the three injections you receive. Your care after surgery will be the same as it would be if you 
did not enroll in this research study. 
 
3. You will be asked to fill out 3 short surveys before surgery for a baseline assessment (this will 
take approximately 7 minutes). After surgery, we are interested in your pain, any nausea or 
vomiting, and your bladder function. You will be asked to rate your pain on a score of 0-10 and 
also be asked questions regarding the amount of nausea and vomiting you had after surgery (this 
will take approximately 3 minutes and you will complete these forms before you leave the 
hospital).  As part of normal postoperative care, your bladder will be tested after surgery to 
assess whether you can void on your own.  This study will not interfere with whether or not you 
have a bladder test, but we will record the results of your bladder function.  
 
4. We are also interested in understanding your pain and how many pain medications you are 
taking once you are at home after surgery. At home, you will be asked about your pain level and 
asked to record how many pain pills you take during the first 3 days after surgery and record a 
final pain level 1 week after surgery. Lastly, we are interested in knowing when you are “back to 
normal” after surgery, and you will be asked questions about when you are able to do certain 
activities (like cleaning and cooking) after surgery. You will answer these questions at 1 week, 2 


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   University Of Pittsburgh          
     Institutional Review Board    
 
Approval Date: 11/6/2018 
Renewal Date:  11/5/2019 
 
IRB #:   PRO16110378 
 
 
weeks, 6 weeks and 12 weeks after surgery to tell us how you are doing. The forms completed at 
home should take you approximately 5 minutes to complete. After you have completed all of the 
forms, you will send these forms to our office in an envelope provided. You may also bring these 
forms with you to your follow-up visit.  
 
5. Study staff will contact you to remind you to schedule your follow-up visit and return the 
survey forms, as well as answer any study related questions you may have. 
 
6 Because we want to follow our study patients closely, we ask that if you seek treatment for any 
possible postoperative problem, that you are treated by your surgeon whenever possible.  You 
will also be asked to alert the study team if you have any problems after surgery.  In case you 
need to seek treatment from another care provider, we ask that you contact the study team after 
receiving that care to provide us with an update. We will provide a card with our contact 
information. 
 
7. The study team will contact you periodically over the 12 weeks after surgery to answer any 
questions you have and remind you to fill out your study surveys.  They will also remind you to 
return the forms and to follow-up with your doctor 6 weeks after surgery.  
 
8 At your routine 6-week postoperative visit, the research team may collect any completed 
surveys that you have, in the event that you have brought them with you instead of mailing them 
in to the office.  
 
9. At 12 weeks after your surgery, you will complete the last survey and mail the completed form 
into the office. This will mark the end of the research study.  
 
What is the duration of participation in this study? 
If you agree to participate and are eligible, your participation will be requested from the day of 
your surgery through 12 weeks following your surgery.  You will only receive medication in the 
operating room on the day of surgery. The remainder of the study duration involves follow-up 
after surgery.  
 
What are the possible risks and discomforts of this study? 
Risks of transobturator and transvaginal injections: Many of the risks associated with the study 
injections are similar to the risks associated with prolapse surgery itself. These include bleeding, 
infection, damage to nearby structures (bladder and bowel), and need for further surgery. 
Hematomas (blood collections) may form at the injection sites, which usually resolve 
spontaneously. Rarely, a hematoma will need further surgical management.  
 
Risks of bupivacaine: If either too much medication is used or if the medication enters the blood 
stream, there can be toxicity related to injection of local anesthesia. Minor symptoms of toxicity 
include ringing in the ears or a metallic taste in the mouth, however severe symptoms of toxicity 
could include heart problems. Precautions are taken to limit the dose of bupivacaine that you 
receive and to make sure the injection is going into a muscle and not into a blood vessel. 
Numbness and tingling and occasional pain in the groin, buttock and leg can occur with 


                                                                          Page 4 of 8                                           
           
   University Of Pittsburgh          
     Institutional Review Board    
 
Approval Date: 11/6/2018 
Renewal Date:  11/5/2019 
 
IRB #:   PRO16110378 
 
 
injections of local anesthesia. These symptoms are usually temporary and related to the 
anesthetic effect of the bupivacaine. While uncommon, if you are having difficulty walking after 
the procedure, we will have you evaluated by physical therapy prior to discharge from the 
hospital to ensure safety. Lastly, although rare, allergic reaction to bupivacaine can occur. You 
will be monitored by anesthesiology closely while receiving any study medications and any 
adverse reaction to study medication will be managed immediately. 
 
Risks of dexamethasone: While other studies looking at the use of dexamethasone during surgery 
have not demonstrated any increased risk of infection or delayed wound healing, this is a 
theoretical risk. You receive antibiotics at the time of surgery to minimize the risk of infection. 
Additionally, the effects of dexamethasone are short compared to other steroid medications. 
Upon discharge after surgery, you should watch for warning signs of infection including vaginal 
bleeding, discharge, fevers or chills and call the research team (number provided) and 
Urogynecology office for any concerns. An increase in blood glucose levels has been 
demonstrated following the administration of steroids. However, the increase in serum glucose 
levels is small and temporary. For this reason, we are not allowing anyone with diabetes to 
participate in this study.   
 
Risks of survey completion: You will be asked to complete a number if surveys within 12 weeks 
after your surgery to assess your postoperative recovery. The answers to your questions will 
remain confidential and do not impact the care you will receive from your doctor. You do not 
have to complete survey questions that make you uncomfortable.  
 
Risks of study data collection: There is the possibility of loss of confidentiality. In very rare 
cases, people not associated with this research study may inadvertently see your identifiable 
research results. We will do everything in our power to prevent this from happening by keeping 
all research records in locked files, and filing medical information by a research record number, 
rather than by your name or social security number. The codebook containing your name and 
number will be kept by the Study Coordinator in a separate secure location. 
 
Will I benefit from taking part in this study? 
If you receive bupivacaine or bupivacaine and dexamethasone as part of the study, you may 
experience decreased pain after surgery.  If you receive a placebo injection, you may benefit 
from decreased exposure to medications.  The information obtained from this study will give us 
an understanding of whether or not these injections should be used routinely to decrease pain 
after prolapse surgery.  
 
Will anyone know that I am taking part in this study? 
All records pertaining to your involvement in this study are kept strictly confidential (private) 
and any data that includes your identity will be stored in locked files. Your identity will not be 
revealed in any description or publications of this research. Medical records will not be shared 
with anyone not directly involved in your medical care.  Safeguards will be used to minimize 
breach of confidentiality.  This will include labeling all data with a study number rather than 
your name or other direct identifiers.   
 


                                                                          Page 5 of 8                                           
           
   University Of Pittsburgh          
     Institutional Review Board    
 
Approval Date: 11/6/2018 
Renewal Date:  11/5/2019 
 
IRB #:   PRO16110378 
 
 
What treatments or procedures are available if I decide not to take part in this research study? 
You do not have to participate in this study. If you do not participate in this study, you will have 
your vaginal prolapse surgery performed by your doctor as scheduled without any changes. You 
will receive all other care provided to patients receiving pelvic reconstructive surgery. 
 
If I agree to take part in this research study, will I be told of any new risks that may be found 
during the course of the study? 
You will be promptly notified if, during the conduct of this research study, any new information 
develops which may cause you to change your mind about continuing to participate. 
 
Will my insurance provider or I be charged for the costs of any procedures performed as part 
of this research study? 
You and/or your insurance will be charged, in the standard manner, for the surgery, hospital stay, 
office visits, and procedures performed for your routine medical care. This includes any visits to 
your doctor for postoperative care or postoperative complications. You will be responsible for 
any co-pays, coinsurances, or deductibles associated with your clinical visits.   
 
Neither you, nor your insurance provider, will be charged for the costs of any of the procedures 
performed for the purpose of this research study. These procedures include the levator muscle 
injections, pudendal nerve blocks, survey completion and medical record abstraction.  You will 
not be charged for the bupivacaine, dexamethasone or placebo medications administered as part 
of this study. 
 
Will I be paid if I take part in this research study? 
You do not receive any payment as part of the research study.    
 
Who will pay if I am injured as a result of taking part in this study? 
University of Pittsburgh researchers and their associates who provide services at the University 
of Pittsburgh Medical Center (UPMC) recognize the importance of your voluntary participation 
in their research studies.  These individuals and their staff will make reasonable efforts to 
minimize, control, and treat any injuries that may arise as a result of this research.  If you believe 
that the research procedures have resulted in an injury to you, immediately contact Dr. Giugale at 
the number listed on the first page. Emergency medical treatment for injuries solely and directly 
related to your participation in this research study will be provided to you by the hospitals of 
UPMC. Your insurance provider may be billed for the costs of this emergency treatment, but 
none of those costs will be charged directly to you. If your research-related injury requires 
medical care beyond this emergency treatment, you will be responsible for the costs of this 
follow-up care. At this time, there is no plan for any additional financial compensation. 
 
Will this research study involve the use or disclosure of my identifiable medical information? 
This research study will involve the recording of past, current and/or future identifiable medical 
information from your hospital and/or other health care provider (for example, your physician’s 
office records).  This information that will be recorded will be limited to information concerning 
the surgical procedure (for example, diagnostic information, lab and scanned results, 
medications, medical history).  This information will be used to determine your eligibility for 


                                                                          Page 6 of 8                                           
           
   University Of Pittsburgh          
     Institutional Review Board    
 
Approval Date: 11/6/2018 
Renewal Date:  11/5/2019 
 
IRB #:   PRO16110378 
 
 
this study and to follow your response once you are enrolled in the study.  
 
Who will have access to identifiable information related to my participation in this research 
study? 
In addition to the investigators listed on the first page of this authorization (consent) form and 
their research staff, the following individuals will or may have access to identifiable information 
(which may include your identifiable medical information) related to your participation in this 
research study:  
 
Authorized representatives of the UPMC hospitals or other affiliated health care providers may 
have access to identifiable information (which may include your identifiable medical 
information) related to your participation in this research study for the purpose of (1) fulfilling 
orders, made by the investigators, for hospital and health care services (e.g., laboratory tests, 
diagnostic procedures) associated with research study participation; (2) addressing correct 
payment for tests and procedures ordered by the investigators; and/or (3) for internal hospital 
operations (i.e. quality assurance). 
 
Authorized representatives of the University of Pittsburgh Research Conduct and Compliance 
Office may review your identifiable research information (which may include your identifiable 
medical information) for the purpose of monitoring the appropriate conduct of this research 
study.  
 
In unusual cases, the investigators may be required to release identifiable information (which 
may include your identifiable medical information) related to your participation in this research 
study in response to an order from a court of law.  If the investigators learn that you or someone 
with whom you are involved is in serious danger or potential harm, they will need to inform, as 
required by Pennsylvania law, the appropriate agencies. 
 
For how long will the investigators be permitted to use and disclose identifiable information 
related to my participation in this research study? 
The investigators may continue to use and disclose, for the purposes described above, 
identifiable information (which may include your identifiable medical information) related to 
your participation in this research study for a minimum of seven years after final reporting or 
publication of a project.  
 
Is my participation in this research study voluntary? 
Your participation in this research study, to include the use and disclosure of your identifiable 
information for the purposes described above, is completely voluntary.  (Note, however, that if 
you do not provide your consent for the use and disclosure of your identifiable information for 
the purposes described above, you will not be allowed to participate in the research study.)  
Whether or not you provide your consent for participation in this research study will have no 
effect on your current or future relationship with the University of Pittsburgh.  Whether or not 
you provide your consent for participation in this research study will have no effect on your 
current or future medical care at a UPMC hospital or affiliated health care provider or your 
current or future relationship with a health care insurance provider. 


                                                                          Page 7 of 8                                           
           
   University Of Pittsburgh          
     Institutional Review Board    
 
Approval Date: 11/6/2018 
Renewal Date:  11/5/2019 
 
IRB #:   PRO16110378 
 
 
 
Your doctor may be involved as an investigator in this research study.  As both your doctor and a 
research investigator, s/he is interested both in your medical care and the conduct of this research 
study.  Before agreeing to participate in this research study, or at any time during your study 
participation, you may discuss your care with another doctor who is not associated with this 
research study.  You are not under any obligation to participate in any research study offered by 
your doctor. 
 
May I withdraw, at a future date, my consent for participation in this research study? 
You may withdraw, at any time, your consent for participation in this research study, to include 
the use and disclosure of your identifiable information for the purposes described above.  (Note, 
however, that if you withdraw your consent for the use and disclosure of your identifiable 
medical record information for the purposes described above, you will also be withdrawn, in 
general, from further participation in this research study.)  Any identifiable research or medical 
information recorded for, or resulting from, your participation in this research study prior to the 
date that you formally withdrew your consent may continue to be used and disclosed by the 
investigators for the purposes described above. 
 
 
 
 
 
 
 
 
To formally withdraw your consent for participation in this research study you should provide a 
written and dated notice of this decision to the principal investigator of this research study at the 
address listed on the first page of this form. 
 
Your decision to withdraw your consent for participation in this research study will have no 
effect on your current or future relationship with the University of Pittsburgh.  Your decision to 
withdraw your consent for participation in this research study will have no effect on your current 
or future medical care at a UPMC hospital or affiliated health care provider or your current or 
future relationship with a health care insurance provider. 
 
If I agree to take part in this research study, can I be removed from the study without my 
consent? 
If the investigators feel that you cannot complete the study requirements safely (for example, you 
have an allergic reaction to a study medication), they may withdraw you from the study. 
 
FDA Clinical Trial Registry  
A description of this clinical trial will be available on http://www.clinicaltrials.gov as required by 
US Law. This website will not include information that can identify you. At most, the website 
will include a summary of the results. You can search this website at any time. 
 
 
 
 
 


                                                                          Page 8 of 8                                           
           
   University Of Pittsburgh          
     Institutional Review Board    
 
Approval Date: 11/6/2018 
Renewal Date:  11/5/2019 
 
IRB #:   PRO16110378 
 
 
****************************************************************************** 
VOLUNTARY CONSENT: 
All of the above has been explained to me and all of my current questions have been answered.  I 
understand that, throughout my participation in this research study, I am encouraged to ask 
questions about any aspect of this research study including the use and disclosure of my 
identifiable medical record information.  Such future questions will be answered by the 
investigators listed on the first page of this form.   
 
Any questions I have about my rights as a research participant or the research use of my medical 
information will be answered by the Human Subject Protection Advocate of the IRB Office, 
University of Pittsburgh (1-866-212-2668).  
 
By signing this form, I agree to participate in this research study and provide my authorization to 
share my medical records with the research team.  A copy of this consent form will be given to 
me. 
 
 
___________________________________  
________________________  
Subject’s Signature 
Date 
 
 
CERTIFICATION OF INFORMED CONSENT 
 
I certify that I have explained the nature and purpose of this research study to the above-named 
individual, and I have discussed the potential benefits and possible risks of study participation.  
Any questions the individual has about this study have been answered, and we will always be 
available to address future questions as they arise.  I further certify that no research component 
of this protocol was begun until after this consent form was signed. 
 
 
___________________________________  
________________________  
Printed Name of Person Obtaining Consent  
Role in Research Study  
 
 
_________________________________  
____________  
Signature of Person Obtaining Consent  
 
Date