Pudendal block at the time of transvaginal prolapse repair: A randomized controlled trial

Abstract

Importance:

The utility of pudendal nerve blocks (PNB) at the time of transvaginal surgery is mixed in the literature. No published study has evaluated the efficacy of PNB since the widespread adoption of Enhanced Recovery after Surgery (ERAS) pathways.

Objective:

To determine if PNB in addition to ERAS measures at the time of vaginal reconstructive surgery reduces opioid use in the immediate postoperative period.

Study Design:

In this randomized, blinded, controlled trial, women scheduled for transvaginal multicompartment prolapse repair were randomized to bilateral PNB prior to incision with 20 ml of 0.5% bupivacaine versus usual care. Primary outcome was opioid use in morphine milligram equivalents (MME) for the first 24 hours. The study was powered to detect a 5.57 MME difference in opioid use in the first 24 hours between groups.

Results:

Forty-four patients were randomized from January 2020 to April 2022. The PNB and control groups were well matched in demographic and surgical data. There was no difference in opioid use in first 24 hours between the control and PNB group (8[0-20] vs 6.7[0-15], p 0.8). Median pain scores at 24 and 48 hours did not differ between groups (4±2 vs 3±3, p 0.44) and 90% of participants were satisfied with pain control across both groups. Time to return to normal activities (median: 10 days) was also not different between the groups.

Conclusion:

As pain satisfaction following transvaginal surgery in the era of ERAS is high, with overall low opioid requirements, PNB provides no additional benefit.

Introduction

Enhanced Recovery After Surgery (ERAS), a multi-disciplinary care pathway composed of evidence-based interventions, is aimed at improving peri-operative outcomes, and decreasing recovery time in those undergoing major surgery. With the widespread adoption of ERAS protocols, there is an emphasis on multi-modal pain management, early ambulation and decrease need for prolonged inpatient stays. Studies in a Urogynecologic population have shown after implementation of ERAS same day discharge increased from 25% to 92%.¹ Similarly intraoperative and postoperative opioid use decreased after the adoption of ERAS (54 vs. 37 morphine milligram equivalents (MME)).²

A key component of ERAS pathways is utilizing regional anesthesia and local nerve blocks for intra- and postoperative pain control. Pudendal nerve block (PNB) is one such anesthetic technique considered for pelvic reconstructive surgery. The pudendal nerve controls motor input to the anal and urethral sphincter and sensory input from the vagina, labia, perineum, and pelvic floor in women. PNB can be efficiently performed transvaginally by locating the nerve as it runs just medial and caudal to the ischial spine.

Although methodologies vary, research assessing preemptive analgesia before vaginal prolapse procedures has yielded mixed results. PNB at the time of anterior and/or posterior vaginal wall repair demonstrated reductions in pain and opioid use compared to no block.³ It has also been shown to be an alternative to general anesthesia for prolapse repair.⁴ Other studies, however, revealed no differences in opioid consumption with use of PNB compared to sham. These studies, however, were conducted in a pre-ERAS era when high-dose opioid use for postoperative pain control was common.⁵

No published study has evaluated the efficacy of PNB since the widespread adoption of the Enhanced Recovery after Surgery (ERAS) pathway in Urogynecologic surgery. We hypothesized that a transvaginal PNB with bupivacaine at the time of transvaginal surgery would decrease the amount of opioid use in the first 24 hours after surgery and improve numeric rating scale (NRS) pain scores.

Materials and Methods

This was a randomized, prospective, blinded controlled trial (ClinicalTrials.gov: NCT04171050) conducted from January 2020 to May 2022 at a large academic teaching hospital. All surgeries were performed by one of six Urogynecology and Reconstructive Pelvic Surgery (URPS) surgeons with similar operative techniques. The study received institutional review board approval (IRB#19-001550) and followed the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

All woman 18 years and older undergoing transvaginal native tissue reconstructive surgery of at least 2 compartments (anterior, posterior and/or apical suspension including hysteropexy) were recruited to participate. Exclusion criteria included concomitant vaginal hysterectomy or abdominal surgery; inability to tolerate NSAIDs, acetaminophen, opioids and local anesthetic agents; allergy to study medications; coagulation disorder; and known chronic pain syndrome requiring ongoing pain medication usage. Vaginal hysterectomy was excluded due to the variable complexity and duration of surgery which may effect response to PNB.

At the time of surgery booking, candidate subjects were identified and verbally consented to participate, although they could withdraw participation at any time. Just prior to surgery, subjects signed consents and were randomized 1:1 using a random number generator prior to initiation of anesthesia. Patients were randomized to receive either a total of 20 mL of 0.5% plain bupivacaine bilateral PNB or usual care. Usual care involved infusion of local anesthesic agents per surgeon preference. PNB was performed by the surgical team after anesthesia induction, lithotomy positioning, and surgical site preparation, prior to any incisions. After palpating the ischial spine, a standard pudendal block tray (Cat 4540A, CareFusion, San Diego, CA) was used to inject 10 mL of 0.5% bupivacaine inferior to the spine with the Iowa trumpet as a needle guide. This procedure was performed bilaterally for a total of 20 mL. As nerve hydrodissection with saline alone has been shown to provide some analgesic effect, no sham injection was performed in the usual care arm.⁶

All patients received well-established pre- and postoperative enhanced recovery after surgery (ERAS) protocols,^7,8 which included preoperative warming, clear fluids up to 2 hours before surgery, and preoperative administration of oral acetaminophen 650mg, gabapentin 600mg, and celecoxib 400mg. All patients received the same intraoperative care and postoperative pain medications, including scheduled acetaminophen, ketorolac, and as needed tramadol or oxycodone for moderate and severe pain, with an option to add postoperative gabapentin. Intravenous opioids were available for breakthrough pain not controlled with oral medications. Patients were routinely asked by the nursing staff their pain level on a 0 to 10 NRS per hospital policy⁹. Anesthesia and postoperative care teams were blinded to study group. Patients were discharged when routine postoperative milestones had been met. All patients were instructed to continue scheduled acetaminophen and ibuprofen for the first 72 hours postoperatively.

If discharged prior to 48 hours postoperatively, subjects were provided with a diary to document pain medication usage for the first 48 hours postoperatively, pain scores at 24 and 48 hours postoperatively. All patients received a diary to record date they returned to normal daily activities. Patients were contacted via phone at 48 hours postoperatively by the study team and asked about pain medication usage, NRS pain scores, and satisfaction with postoperative pain control using a verbal scale ranging from very satisfied to very dissatisfied (1: very satisfied, 2: somewhat satisfied, 3: neither satisfied nor dissatisfied, 4: somewhat dissatisfied, 5: very dissatisfied). Patients were contacted at 2 weeks and 6 weeks postoperatively either by phone or during their scheduled office visit and were asked about their time to return to normal activity, any adverse events, as well as their satisfaction with postoperative pain control. For these assessments, the study team was blinded to subject intervention group.

The primary outcome was opioid use measured in MME over the first 24 hours after surgery. Secondary outcomes included opioid use measured in MME at 48 hours after surgery, average pain scores in the first 24 hours after surgery, time to return to normal daily activities, patient satisfaction with postoperative recovery at 48 hours, 2 weeks and 6 weeks after surgery, rate of urinary retention requiring catheterization at >48 hours after surgery and length of hospital stay in hours.

Sample sizes were calculated based on the most robust data available at time of study initiation comparing general anasthesia with and without PNB at the time of posterior repair.³ Assuming a two-sampled t-test with a standard deviation of supplemental pain medication use of 4.61 to 6.87 MME based on Ismail et al³ and an alpha of 0.05 with 80% power, 19 patients per arm were need to detect a clinically significant difference in supplemental pain medication use of 5.57 MME at 24 hours after surgery. With an anticipated 15% loss to follow-up, goal recruitment was 22 subjects per arm. This sample size also allowed for the detection of a 20% reduction in mean pain scores at 24 hours with a standard deviation of 0.74 – 1.32.

Statistical analysis was performed using R version 2023.03.0+386 (RStudio, Boston, MA). Demographic, clinical, surgical, and anesthetic outcomes of each group were compared using t tests, χ2, and Fisher exact tests, where appropriate. p values <0.05 were considered statistically significant for all comparisons.

Results

Of 104 patients assessed for eligibility, 44 were enrolled and randomized between January 2020 and May 2022. No subjects dropped out after randomization. Two subjects randomized to the PNB group did not receive the block due to provider error (Figure 1). One subject in each arm was lost to follow up. Intention to treat analysis was performed for all data analysis except when otherwise stated.

Figure 1:

The randomized trial flow diagram including enrollment, intervention allocation and analysis

The two groups did not differ in baseline demographic and clinical characteristics, although more subjects in the control group were taking medication for depression (50% vs 18%, p<0.05) (Table 1). Subjects were primarily white, postmenopausal women with a median age of 64 years old. No significant differences were noted between the two groups in surgical data apart from more anterior repairs being performed in the PNB group (59% vs 86%, p=0.04) (Table 2). There was 100% adherence to ERAS pathway in both groups. There were no differences in operative time or estimated blood loss with surgery. The PNB group received more total local bupivacaine intraoperatively (131±25mg vs 65±41mg, p<0.05) when combining locally infiltrated bupivacaine with bupivacaine administered with PNB. There was no difference in time spent in the hospital following surgery or opioid MME received during surgery. NRS pain scores collected immediately postoperatively until the time of hospital discharge were low, with no differences between the groups (Figure 2).

Table 1:

Baseline participant demographic data

	Control n=22	Pudendal Block n=22	p
Age (median [IQR])	63 [59, 69]	66 [53, 70]	0.71
Insurance Type
Commercial	13 (59)	9 (41)	0.24
Medicare	9 (41)	13 (59)	0.23
Race			0.4
White	18 (82)	16 (72)
Black	0 (0)	0 (0)
Asian	1 (4.5)	2 (9)
Other	1 (4.5)	2 (9)
Refuse to answer	2 (9)	2 (9)
Parity (median [IQR])	2 [2, 3]	2 [2, 2]	0.12
BMI (mean[SD])	27.6 [±6.4]	26.0 [±4.5]	0.36
Post-menopausal	20 (91)	16 (73)	0.3
History of Prolapse Repair	3 (15)	2 (9)	0.64
Prolapse Stage (median[IQR])	2 [2, 2]	2 [2, 2]	0.58
Prior Hysterectomy			0.2
No	15 (68)	16 (73)
Yes, prolapse	3 (15)	1 (4.5)
Yes, for reason other than prolapse	4 (18)	5 (22)
Medical Comorbidities
Diabetes Mellitus	2 (9)	4 (18)	0.4
Hypertension	6 (27)	6 (27)	1
Asthma	3 (14)	3 (14)	1
Cardiac Disease	1 (5)	2 (9)	0.5
Depression, on medication	11(50)	4 (18)	<0.05

Table 2:

Surgical Data

	Control n=22	Pudendal Block n=22	p
Prolapse surgery
Anterior Repair	13 (59)	19 (86)	0.04
Posterior Repair	19 (86)	17 (77)	0.45
Perineorrhaphy	12 (55)	10 (45)	0.56
USLS	12 (55)	10 (45)	0.56
SSLF	9 (41)	11 (50)	0.48
Other†	1 (5)	1 (5)	1
Mesh Sling	6 (27)	6 (27)	1
Vaginal pack placed postoperatively	5(23)	6(27)	0.73
MME Used Intraoperatively (mean[SD])	31 [±15]	39 [±21]	0.14
Total bupivacaine used intraoperatively (including PNB) (mg) (mean[SD])	65.3 [±41]	131.5 [±25]	<0.05
Total lidocaine used intraoperatively (mg) (mean[SD])	110 [±70]	142 [±37]	0.44
Postoperative Disposition			0.29
Same day surgery	7 (32)	10 (45)
23 hour observation	11 (50)	7 (32)
>23 hour observation	4 (18)	5 (23)
Postoperative Complications	6 (27)	8 (36)	0.73
Readmission	0 (0)	1 (5)
Pudendal nerve entrapment	0 (0)	1 (5)
Significant postoperative nausea	1 (5)	0 (0)
Anesthetic complications (chest pain)	1 (5)	0 (0)
Urinary retention at 48hr*	4 (18)	6 (27)

^†Other procedures include endometrial biopsy, labial biopsy.

^*This trend towards higher retention rates in the PNB group did not hold up in the per-protocol analysis

Figure 2:

NRS pain scores collected during hospital stay

Pain scores were overall low and did not differ between the two groups

The primary outcome, MME of opioid used in the first 24 hours, did not differ between the control and PNB groups [8 (IQR 0-20) vs. 6.75 (IQR 0-15), p=0.88] (Table 3). This is roughly equivalent to 5mg of oxycodone consumed in the first 24 hours. Per protocol analysis, excluding subjects in the PNB group who did not receive the block, did not change the outcome. Pain scores at 24 and 48 hours postoperatively also did not differ between the two groups. Subjects in both groups were highly satisfied with pain control following surgery; 90% were very satisfied or somewhat satisfied with pain control at the 48-hour, 2-week, and 6-week time points, which did not differ between groups.

Table 3:

Primary and Secondary Outcomes (n=44) - Intention to treat analysis

	Control n=22	Pudendal Block n=22	p
Primary Outcome
Opioid use at 24 hours postop (MME)	8 (0-20)	6.75 (0-15)	0.88
Secondary Outcomes
Operative time (min) (mean (SD))	153 (±54)	151 (±36)	0.87
EBL (ml)	100 (50-100)	75 (50-100)	0.31
Length of hospital stay (hr)	16.5 (4.5-24)	9 (5-23)	0.89
Opioid use at 48 hours postop (MME)	8 (0-26)	7 (0-35)	0.63
Postoperative NRS pain score (mean(SD))
0-2h	1.2 (±1.8)	1.6 (±2.4)	0.49
2-4h	1.4 (±1.7)	1.1 (±1.8)	0.55
4-8h	1.9 (±1.8)	1.4 (±2.0)	0.48
24hr	4 (±2)	3 (±3)	0.44
48hr	3 (±2)	4 (±3)	0.42
Time to return to normal activity (days)*	10 (6-18)	10 (7-11)	0.42
Time to return to activity, outliers excluded (days)	10 (6-18)	9 (6-10)	0.05
Satisfaction with pain control at 48 hours			0.49
Very satisfied	16 (76.2)	13 (61.9)
Somewhat satisfied	3 (14.3)	4 (19.0)
Neither satisfied nor dissatisfied	0 (0.0)	1 (4.8)
Somewhat dissatisfied	0 (0.0)	2 (9.5)
Very dissatisfied	1 (4.8)	0 (0.0)
Not obtained	1 (4.8)	1 (4.8)
Satisfaction with pain control at 2 weeks			0.37
Very satisfied	15 (75.0)	17 (77.3)
Somewhat satisfied	0 (0.0)	2 (9.1)
Neither satisfied nor dissatisfied	2 (10.0)	0 (0.0)
Somewhat dissatisfied	0 (0.0)	1 (4.5)
Very dissatisfied	2 (10.0)	1 (4.5)
Not obtained	1 (5.0)	1 (4.5)

Data are median (interquartile range) or n (%) unless otherwise specified

^*Time to return to normal activities defined as walking, sitting, and performing daily household tasks comfortably.

There was one readmission in the PNB group at two weeks postoperatively for vaginal bleeding requiring transfusion. There were no differences in intraoperative and postoperative complications between the two groups. There was a trend towards increased rates of urinary retention in the PNB group, however per protocol analysis was performed as two patients in the PNB arm did not receive the block, and then is trend did not persist. There was no difference in the time to return to normal activity, which was 10 days for both groups (Figure 3).

Figure 3:

Time to return to normal activity level

There were no stastitically significant difference in days to return to normal activity between the two groups. Three notable outliers in the PNB group represented unique postoperative complications not related to use of PNB.

Discussion

This is one of the first published studies evaluating PNB in conjunction with ERAS pathways for pelvic organ prolapse surgery. Pelvic reconstructive surgery accounts for an increasing operative volume each year because of the widespread prevalence of pelvic prolapse within the aging female population. Therefore, safe techniques that enhance patient recovery in a cost-effective manner have the potential for widespread application. ERAS pathways significantly decrease time to return to normal activity, pain medication requirements, and increase patient satisfaction.¹⁰ This study demonstrates the addition of PNB to strict ERAS pathways at the time of multicompartment transvaginal prolapse surgery does not improve pain scores, decrease opioid use, or improve patient satisfaction.

This study adds further level 1 evidence to contempary ERAS era work demonstrating no benefit of PNB vs saline sham injection at the time of pelvic floor prolapse repair.^11,12 In Giugale et al. transobturator levator muscle injections were performed alongside PNB, and both Guigale et al¹¹ and Slopnick et al¹² injected saline as the control arm. Nerve hydrodissection with saline alone has been shown to provide some analgesic effect⁶, thus the work presented here provides important additional confirmation that PNB does not add benefit over current standard of care, no injection.

Multiple studies have shown that blocking pain receptors before trauma, or first incision, down-regulates patient pain perception postoperatively.¹⁴ Blocking afferent pain signals to the central nervous system from the affected surgical site is thought to have a protective effect on the nociceptive system; thus, preadministered local anesthetic has the potential to be more effective than similar treatment initiated after surgery.¹⁵ It is possible, however, that the duration of PNB may have been too short to achieve effective preemptive analgesia. The half-life of bupivacaine is 2.7 hours, and the mean surgery duration was 2.5 hours, meaning the majority of the effect of the block may have been dissipated by the time patient reached the postoperative recovery area, limiting the ability to see therapeutic benefit. Since central sensitization is not only induced during surgery, but also postoperatively by inflammatory processes, a prolonged block of ongoing nociceptive input may be required for efficacy. Subsequent studies have shown that patients who received PNB with liposomal bupivacaine have lower pain scores than those given plain bupivacaine.¹⁶ Preoperative PNB may have proven more effective with the use of a more durable analgesic. Additionally, we could not assess the effectiveness of the block immediately after injection because it was performed while the patients were under general anesthesia. There is potential for variability in the efficacy of injection based on provider training and level.

Another possible explanation for the negative findings of our study is that preoperative administration of gabapentin, celecoxib and acetaminophen are likely enough to dampen afferent pain signals for this type of surgery. The noxious inputs generated by transvaginal native tissue repair in the context of ERAS pathways may be too weak to produce significant enough pain to detect differences between the study groups, again suggesting ERAS alone is enough to provide effective analgesia for this type of surgery. Or alternatively, the noxious inputs generated from transvaginal prolapse repair itself is already minimal.

There was no difference in time to return to normal activity between the two groups. There were, however, three notable outliers in the PNB group that increased the median recovery time in this group. These outliers included one patient who was readmitted for postoperative bleeding requiring transfusion, one patient with pudendal nerve entrapment requiring suture removal, and one symptomatic COVID-19 infection. Exclusion of these outliers, did result in a significant difference, with PNB providing a faster return to normal activity (10.3 vs 9, p=0.05). Given these limitations, a larger sample size may have been able to detect a functional status improvement with PNB.

The strengths of this study include that it is a prospective randomized, blinded, controlled trial of a technique that is commonly performed by URPS surgeons, making this technique easy to implement. The study achieved planned enrollment and was appropriately powered. A variety of transvaginal prolapse repairs were performed by this study and performed by 6 different URPS surgeons strengthening the generalizability of the study.

Several limitations of this study stem from our strict adherence to ERAS guidelines. Postoperative ERAS pathways are commonly adhered to, however the adoption of premedication is lower.¹⁷ These findings should be generalized with caution to a practice where ERAS is only partially adhered to. Additionally thirty subjects with allergies to NSAIDs, acetaminophen, celecoxib, or gabapentin were excluded from participation. As this is a group with limited non-opioid pain control options, they may experience more benefit from PNB, which may be worth further study. Patients with chronic pain conditions were excluded from participation, another group with potentially greater benefit from PNB. Baseline pain scores between the groups were not compared. Patients undergoing hysterectomy were excluded, limiting generalizability. Future trials studying the efficacy of PNB in groups with multiple drug allergies or chronic pain conditions may see more benefit from non-opioid pain control.

Conclusions:

In summary, pain satisfaction following transvaginal surgery with strict adherence ERAS is high with low overall opioid requirements and quick return to baseline activity level. The use of PNB with 0.5% plain bupivacaine with transvaginal prolapse repair does not provide a statistically significant decrease in opioid use or pain scores. Multimodal pain control, the cornerstone to ERAS, dampens any potential effect of PNB that has been seen in other studies.

Simply Stated:

Strategies to improve postoperative pain and decrease opioid use are important, particularly when performing quality of life surgery. Efforts have been made to enhance patient recovery after surgery with an emphasis on non-opioid pain control. A local anesthetic block targeting the pudendal nerve, which is responsible for sensation at the perineum, vagina, and vulva, is one potential strategy to improve postoperative pain. This study evaluates if a pudendal block makes a significant improvement in patient’s postoperative pain, analgesic medication use, and satisfaction. No benefit was found. In both groups postoperative pain was low, patient satisfaction was greater than 85%, and opioid use in the first 24 hours was minimal (equivalent to one oxycodone tab). This shows the efficacy of enhanced recovery after surgery pathways on their own and should encourage hospital systems to adopt these pathways in a widespread manner.

Why This Matters:

• Pudendal block has been studied in conjunction with transvaginal prolapse repair, however data are mixed and all studies were performed prior to the adoption of Enhanced Recovery After Surgery (ERAS).

• This is the first published RCT evaluating PNB impact on postoperative opioid use, pain scores and return to normal activity, in those undergoing multicompartment prolapse repair with strict adherence to ERAS guidelines.

• PNB did not significantly decrease MME of opioid used in first 24 hours, improve patient satisfaction, or time to return to normal activity.

• Overall patients had extremely low pain scores in first 24 hours, and consumed equivalent to one 5mg tab of oxycodone in the first 24 hours postoperatively, suggesting that pain with the strict adherence to ERAS is already low, and that there are no added benefits of a PNB.