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
Phase: PHASE1
Conditions: Pelvic Organ Prolapse, Surgery, Postoperative Pain
Sponsor: Lauren Giugale, MD

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. 

Page 6 of 6 
 
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.