The effect of combined pudendal nerve and spermatic cord block or caudal epidural block on postoperative analgesia after posterior urethroplasty: a randomized trial

Abstract

Background

Postoperative pain management remains a significant challenge for patients undergoing posterior urethroplasty (PU). In a previous study, we proposed a novel technique of combined pudendal nerve (PN) and spermatic cord (SC) block to manage pain after PU. The present trial was conducted to test the hypothesis that this technique is effective for pain control after PU and provides longer-lasting analgesia than caudal epidural block (CB).

Methods

Sixty patients undergoing PU were randomized into two groups: Group NB received combined PN and SC block, and Group CB received CB. General anesthesia with a laryngeal mask was performed. The primary outcome was the postoperative analgesic duration, and the secondary outcomes included the Numeric Rating Scale (NRS) scores for pain and the number of patients with different motor scores of the lower limb at 3, 6, 12, and 24 h postoperatively.

Results

Two patients in Group CB were withdrawn due to block failure. The postoperative analgesic duration was statistically longer in Group NB compared with Group CB (mean difference [95% confidence interval], 115.78 min [17.80, 213.75]; P = 0.021). The NRS scores for pain at 12 and 24 h after surgery were statistically lower in Group NB compared with Group CB. Group NB had statistically more patients with motor score 0 at 3 h postoperatively than Group CB.

Conclusions

PN combined with SC block is an effective technique for postoperative analgesia in PU. This technique can achieve a longer duration of analgesia and lower pain scores, especially 12 h after surgery, than a CB.

Trial registration

This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2100042971, registration date on 2/2/2021).

Background

Urethral stricture is a prevalent and recurrent issue in contemporary urology [1]. Urethroplasty, specifically posterior urethroplasty (PU), is the standard treatment for lower urethral strictures [2].

Due to the posterior urethra’s deep pelvic location, larger surgical wounds are often required for adequate exposure [3], posing challenges for postoperative pain management in PU. Despite recent advancements in analgesic techniques, postoperative pain remains a significant concern associated with urethroplasty [4]. Remarkably, few randomized controlled trials address postoperative pain management for PU.

Caudal epidural block (CB) is a common adjunctive analgesic technique for lower abdominal and anoperineal surgeries, used alongside general anesthesia [5]. However, it has notable limitations. First, single-shot CB may be inadequate for effective postoperative pain management due to its brief analgesic duration [6, 7]. Second, the highly variable anatomy of the sacral hiatus and caudal canal can affect the effectiveness and safety of CB [8]. Third, the incidence of inadvertent intravascular injections and local anesthetic toxicity during CB is higher compared to other regional anesthesia [9, 10]. Fourth, serious complications may occur during CB, including total spinal anesthesia [11].

The utilization of an inverted “Y” lambda incision for the PU is prevalently employed in addressing urethral strictures. (Fig. 1) [3]. Anatomical findings indicate that sensory innervation in the surgical region is supplied by the ilioinguinal nerve, genital branch of the genitofemoral nerve in the spermatic cord (SC), and the pudendal nerve (PN) [12,13,14]. Hence, a combined PN and SC block may theoretically be effective for post-PU analgesia. In 2021, we demonstrated the long-lasting analgesic efficacy of this technique in patients with urethral strictures after PU [15]. Based on this theory and our previous clinical study, we hypothesize that this technique may offer more effective post-PU analgesia with a longer duration than CB.

Fig. 1

Surgical field and incision for posterior urethroplasty. A Intraoperative surgical field; B Postoperative surgical incision

This study aimed to compare the postoperative analgesic efficacy of a combined PN and SC block versus CB in PU patients through a randomized trial. The primary outcome was the duration of postoperative analgesia, while secondary outcomes included rescue analgesic dose, pain intensity measured by the Numerical Rating Scale (NRS) score, and complication incidence.

Methods

Ethics and registration

This prospective, single-center, randomized clinical study received ethical approval from the Ethics Committee of Shanghai Sixth People’s Hospital East Campus (Ethical Committee Number 2020-084), Shanghai, China (Chairperson Ying-Sheng Cheng) on 27 September 2020. The trial was registered at http://www.chictr.org.cn (Registration Number ChiCTR2100042971) on 2 February 2021. The study adhered to the Consolidated Standards of Reporting Trials (CONSORT) Guidelines.

Participants

This study, conducted at Shanghai Sixth People’s Hospital from January 2020 to December 2022, enrolled men aged 18 years or older with American Society of Anesthesiologists physical status I-II who were scheduled for primary anastomotic PU using an inverted “Y” shaped lambda incision after obtaining written informed consent. Recruitment leaflets were distributed in the urology ward. Exclusion criteria included psychiatric disorders, inability to communicate in Chinese, chronic pain, pain medication intake, loss of pain perception in the surgical area, contraindications to nonsteroidal anti-inflammatory drugs, or contraindications to regional anesthesia.

Randomization and blinding

Patients were randomized into Group CB and Group NB at a 1:1 ratio using a sequence generator from http://www.random.org. Allocation concealment was achieved with sealed, opaque, sequentially numbered envelopes provided to the research coordinator, who gave an envelope to the block-performing anesthesiologist on the surgery day. To reduce performance bias, two anesthesiologists were assigned to CB, while two others managed PN and SC blocks. Block-administering anesthesiologists were not involved in other study aspects. Patients, research coordinator, statistician, surgeons, and intraoperative anesthesiologists were blinded to group allocation.

Preparation for block

After entering the operating room, the patient’s ECG, SpO2, noninvasive blood pressure, and BIS were monitored. Midazolam (2 mg/kg) was administered to alleviate anxiety, and the surgeon marked the inverted “Y”-shaped lambda incision.

Block techniques

Group CB

The ultrasound-guided CB was performed as described in the previous publication [16]. The patient was placed in the lateral decubitus position. A screening scan was done by initially placing a linear high-frequency probe (SonoSite SII; Fujifilm Sonosite, Inc., Bothell, WA, USA) in the transverse view across the sacrum to view the sacral median crest, and the probe was slid caudad to view the sacral hiatus, sacrococcygeal ligament, sacral cornua and dorsal surface of the sacrum. At this level, the ultrasound transducer is rotated 90 degrees to obtain the longitudinal view of sacral hiatus. A 23 G needle using an in-plane approach pierced the sacrococcygeal ligament into the sacral hiatus. After negative aspiration of blood and/or spinal fluid, few milliliters of anesthetic were injected in a pulsatile manner. If the expansion of the epidural space was observed, 20 mL 0.5% ropivacaine was injected (Fig. 2A-C).

Fig. 2

Ultrasound-guided caudal epidural block. A Schematic anatomical illustration of caudal epidural block. B Probe position of caudal epidural block. C Sonography of caudal epidural block. MSC, median sacral crest; SL, sacrococcygeal ligament; SH, sacral hiatus. Green boxes represented the probe position for the block. Dashed arrows represented the needle trajectory

Group NB

Following the method described in a previous publication [15], the ultrasound-guided bilateral PN block was performed with the patient in a lateral decubitus position and a convex array probe (Aeroscan CD25 Pro, KonicaMinolta) was placed on the ischial tuberosity in a vertical orientation. The probe was shifted cranially along the line connecting the ischial tuberosity and the posterior superior iliac spine until the image of ischial spine appeared. The pulsating pudendal artery was then identified near the ischial spine. The pudendal nerve was located close to the pudendal artery and the ischial spine, which was not easily to be identified under ultrasound. The upper side was blocked first using a 23-G needle targeting the site near the pudendal artery and medial to the ischial spine (Fig. 3A-C). The lower side was subsequently blocked by inserting the needle from the probe’s medial side. Five milliliters of 0.5% ropivacaine was injected to each side after negative aspiration of blood.

Fig. 3

Ultrasound-guided pudendal nerve block. A Schematic anatomical illustration of pudendal nerve block. B Probe position of pudendal nerve block. C Sonography of pudendal nerve block. PSIS, posterior superior iliac spine; IS, ischial spine; IT, ischial tuberosity; SN, sciatic nerve; PN, pudendal nerve; PA, pudendal artery; GM, gluteus maximus. Green boxes represented the probe position for the block. Dashed arrows represented the needle trajectory

Similarly, based on the technique in the previous publication [15], the ultrasound-guided bilateral SC block was performed. The patient was placed in supine position. A linear array probe was placed under the umbilicus in a transverse orientation and the image of rectus abdominis was displayed. Shift the probe caudally until the image of rectus abdominis vanished and the image of pubis appeared. Then shift the probe laterally of either side and the image of honeycombed spermatic cord was identified outside the pubic tubercle. The pulsating testicular artery was identified inside the spermatic cord. The 23-G needle was inserted from the lateral side of the probe to the target site near the SC (Fig. 4A-C). After shifting the probe to the contralateral side, the other SC was located, and the needle was inserted from the medial side of the probe to the target site. Five milliliters of 0.5% ropivacaine was injected to each side.

Fig. 4

Ultrasound-guided spermatic cord block. A Schematic anatomical illustration of spermatic cord block. B Probe position of spermatic cord block. C Sonography of spermatic cord block. FGFN, femoral branch of the genitofemoral nerve; GGFN, genital branch of the genitofemoral nerve; IIN, ilioinguinal nerve; DD, deferent duct; SC, spermatic cord; TA, testicular artery; PT, pubic tubercle; PS, pubic symphysis. Green boxes represented the probe position for the block. Dashed arrows represented the needle trajectory

Intraoperative management

The surgery commenced 30 min after the nerve block. General anesthesia was induced with propofol (1.5 mg/kg) and sufentanil (0.2 µg/kg) followed by insertion of a laryngeal mask. Intraoperative anesthesia was maintained with sevoflurane while monitoring bispectral index values between 40 and 60. An intravenous bolus of 10 µg of sufentanil was administered as needed to manage hemodynamic increases (heart rate or blood pressure) of more than 20% above preinduction baseline values. Intravenous ondansetron 4 mg was given before the end of surgery to prevent postoperative nausea and vomiting (PONV).

Patients who experienced block failure, defined as puncture failure or incomplete/no pinprick sensation loss at the surgical incision site 30 min after the block, were managed with general anesthesia and endotracheal intubation.

Postoperative management

Patients received continuous intravenous sufentanil 3 µg/h as postoperative pain management for 24 h. If NRS score, ranging from 0 (indicating no pain) to 10 (indicating excruciating pain), was found to be equal to or higher than 4, intramuscular parecoxib 40 mg served as rescue analgesia. Intravenous ketorolac 30 mg was supplemented for failed rescue parecoxib 15 min later and could be repeated every 6 h up to 120 mg per day. Patients with PONV were treated with 10 mg of intravenous metoclopramide.

Two-week postoperative telephone follow-ups assessed potential nerve injuries, such as pain, paresthesia, dysesthesia, and motor power weakness.

Outcome measures

The primary outcome of this study was postoperative analgesia duration, defined as the period between surgery completion and pain onset.

Secondary outcomes included preoperative, intraoperative, and postoperative assessments. Preoperative assessment evaluated the onset time of complete pinprick sensation loss, block-related complications (paresthesia, vascular injury, hematoma, local anesthetic systemic toxicity), and block failure rates. Intraoperative assessment measured the supplemental dose of intraoperative sufentanil, the number of patients requiring intraoperative sufentanil supplementation, and the duration of surgery. Postoperative assessment examined the number of patients requiring rescue analgesia within 24 h, parecoxib and ketorolac consumption, NRS pain scores at 3, 6, 12, and 24 h postoperatively, motor scores of the lower limb at 3, 6, 12, and 24 h postoperatively (motor score of lower limb: 0 = no observable weakness; 1 = slight incoordination or weakness, but walks unaided; 2 = stands unaided, but walks with assistance; 3 = cannot stand unaided; 4 = no movement of lower limbs [17]), PONV incidence, metoclopramide dose, and nerve injury reported by patients.

In patients experiencing block failure, only demographic characteristics were recorded, excluding post-failure data. The research coordinator conducted all evaluations and data acquisition.

Sample size considerations

Power calculations were performed using PASS 15 software (Stata Corp. LP, College Station, Texas, USA) based on primary outcomes. From the pilot study, assumed mean postoperative analgesic duration was 648.19 min (Group NB) and 514.86 min (Group CB), with respective standard deviations (SDs) of 139.47 min and 189.35 min. To detect this intergroup difference with two-sided α = 0.05 and a power of 80%, a sample size of 24 patients in each group would be required. To allow for 20% dropouts, 30 patients were assigned to each group.

Statistical analysis

Statistical analyses were conducted using IBM SPSS Statistics 22 (IBM Corp., Armonk, NY, USA). Normality of continuous data was assessed using the Kolmogorov-Smirnov test, while variance homogeneity was evaluated with the Levene test. Normally distributed continuous data with homogeneity of variance were presented as mean ± SD and compared using the Student’s t-test, calculating mean difference (MD) and corresponding two-sided 95% confidence interval (CI). Non-normally distributed continuous data were presented as median (range) and analyzed using the Mann-Whitney U test. Categorical variables were expressed as numbers (%) and evaluated using the Mann-Whitney U test for ordered data or Pearson’s χ² test/Fisher’s exact test for unordered data, calculating relative risk (RR) and corresponding two-sided 95% CI.

Intention-to-treat (ITT) and per-protocol (PP) analyses were performed for outcome analysis. PP analyses included patients meeting inclusion criteria with successful blocks and no major protocol violations. ITT analyses included all randomized patients, imputing missing data using the windowed worst observation carried forward (wWOCF) plus last observation carried forward (LOCF) method [18].

Results

Whilst n = 74 patients were screened as potentially suitable, n = 60 met inclusion criteria and were randomized equally into Group CB or Group NB (Fig. 5). Baseline demographic characteristics were shown in Table 1. Although two cases in group CB experienced puncture failure due to the anatomical deformities in sacral canal, the difference of block failure rate between the two groups was not statistically significant(P = 0.492) (Table 1). Due to the missing data after block failure, ITT analysis was conducted on 60 patients, while PP analysis was performed on 58 patients (Fig. 5). ITT analysis generated similar results to the PP analysis, presenting in the text. The results of the PP analysis can be found in the online supplemental materials (Supplementary Material 1 and Supplementary Material 2 online content only).

Fig. 5

Consolidated Standards of Reporting Clinical Trials flow diagram. n, number of patients; ITT, intention-to-treat; PP, per-protocol; CB, caudal epidural block; PB, pudendal nerve block; SB, spermatic cord block

Table 1 Demographic characteristics

Primary outcome

In Group CB, the mean ± SD postoperative analgesic duration was 540.4 ± 211.2 min, while in Group NB, it was 653.6 ± 152.3 min. Group NB had a statistically longer postoperative analgesic duration than Group CB (MD (95% CI), 113.2 (18.0, 208.4); P = 0.021) (Table 2).

Table 2 Postoperative assessment (intention-to-treat analysis)

Secondary outcomes

Postoperative outcomes

The NRS scores for pain at 12 and 24 h after surgery were significantly lower in Group NB compared to Group CB (12 h, median (range), 0.5 (0.0, 5.0) vs. 2.0 (0.0, 6.0), P = 0.001; 24 h, 1.0 (0.0, 3.0) vs. 2.0 (1.0, 6.0), P = 0.002) (Table 3). At 3 h postoperatively, Group NB had significantly more patients with a motor score of 0 than Group CB (n (%), 28 (93.3%) vs. 22 (73.3%); RR (95% CI), 5.1 (1.0, 26.4); P = 0.038). However, there were no statistically significant differences between the two groups in the number of patients requiring rescue analgesia, parecoxib, and ketorolac consumption, number of patients with PONV, and the dose of metoclopramide (Table 2). None of the patients reported nerve injury two weeks after surgery in either group (Table 2).

Table 3 Preoperative and intraoperative assessment (intention-to-treat analysis)

Preoperative and intraoperative outcomes

No significant differences were found between the two groups in supplemental dose of intraoperative sufentanil, number of patients requiring sufentanil supplementation during surgery, onset time of complete pinprick sensation loss, and duration of surgery (Table 3). One patient in Group CB and two patients in Group NB suffered vascular injury. In all of them, when the needle was inserted to the target location, some blood was drawn back upon negative aspiration. Then the needle was adjusted until no blood was aspired, following by the injection of 3-5 ml local anesthetic. The procedure of aspiration and injection was repeated until total volume of local anesthetic was injected. No other complications occurred to them in the remaining study. Only one patient in Group CB experienced local anesthetic systemic toxicity, which manifested as numbness of the lips and twitching of facial muscles but resolved within 10 min without any intervention. No significant differences in block-related complications were observed between the two groups (Table 3).

Discussion

This study revealed three main findings. First, the novel combined nerve block technique exhibited a high success rate and provided effective pain management for 654 min postoperatively in our study, showing promise for pain management after PU. Second, no nerve injuries and minor block-related complications occurred in our study with small sample quantity, suggesting a potentially safe profile. Third, this novel combined nerve block technique provided lower pain scores at 12 and 24 h post-PU and statistically longer postoperative analgesic duration compared to CB in our study.

Although CB is a well-established regional anesthesia technique, its limited analgesic duration following a single injection may hinder postoperative pain management efficacy [6, 7]. Prolonging the analgesic duration of CB can be achieved by increasing the concentration, dose and volume of local anesthetics, adding adjuvants, and placing catheters, but potentially raising risks of systemic toxicity, nerve injury, and infection [7, 19]. Studies have shown that the addition of adjuvants such as α2 agonists, opioids, and ketamine to local anesthetics can prolong the postoperative analgesic duration of CB [20, 21]. However, α2 agonists carry the risk of hypotension and bradycardia [22]; ketamine is associated with the risk of neurotoxicity [23, 24]; the risk of postoperative urinary retention, nausea and vomiting, pruritus, and respiratory depression will increase when opioid is used as a local anesthetic adjuvant [24, 25]. Hence, the utilization of adjuvants should be limited to carefully selected patients. Our present study showed that this novel combined nerve block technique not only had a long duration of analgesia, but also could avoid the potential risks caused by the above-mentioned methods for prolonging the duration of CB. In addition, previous studies have shown that the addition of adjuvants during peripheral nerve block can also extend the duration of sensory blockade [26, 27]. Further study is required to confirm whether the addition of adjuvants during combined PN and SC block prolongs analgesic duration after PU and how it differs in analgesic efficacy compared to adding adjuvants to CB.

In our study, we observed an interesting finding that this combined nerve block technique had a greater advantage in reducing pain scores 12–24 h after surgery compared to CB, meriting further exploration. Previous literature has shown that the superiority of dorsal penile nerve block or PN block regarding postoperative analgesic efficacy was only within the first 12 h after hypospadias surgery [28, 29]. Hence, considering our primary outcome, this novel combined nerve block technique could provide a longer analgesic duration in perineal area surgeries.

The quantity of capillaries at the site of local anesthetic injection is one of the important factors influencing the duration of analgesia in regional anesthesia [30, 31]. Administering local anesthetic in a highly vascularized site reduces analgesic duration due to increased plasma uptake and faster systemic absorption. Early studies have already demonstrated that the absorption rate of local anesthetics during CB exceeds that of most peripheral nerve blocks [32, 33]. Recent controlled studies have also indicated that peripheral nerve block provides a longer duration of analgesia compared to CB [34, 35]. In comparison to the region around ischial spine and spermatic cord, the caudal epidural space contains an abundant capillary network, leading to a faster local anesthetic absorption rate. This is likely the primary reason for the prolonged postoperative analgesic duration after combined PNB and SCB compared to CB in our study.

Studies have reported that blocking the PN or its branches alone benefits postoperative pain management in urethral, perineal, or anal surgeries [28, 36,37,38]. However, the surgical wounds and areas reported in these studies were relatively limited. In complex urethral stricture scenarios, an inverted “Y” shaped lambda incision is applied, including the urethra, scrotum, perineum, and perianal area (Fig. 1) [39]. Hence, the analgesic efficacy of PN block alone for PU is suboptimal due to the involvement of other sensory nerves in the innervation of the surgical field. Several studies reported significant analgesic efficacy of SC block in scrotal surgery and chronic scrotal content pain [14, 40, 41], highlighting the ilioinguinal nerve and genital branch of the genitofemoral nerve’s involvement in scrotal pain. Classical anatomy texts corroborate the sensory innervation of these nerves to the scrotum and perineum [12]. Therefore, combining PN block with SC block optimizes postoperative analgesia for PU.

Motor weakness, a common regional anesthesia side effect, can cause patient discomfort, accidental falls, and prolonged hospitalization [42]. The prevalence of lower limb weakness after CB remains contentious, with pediatric incidences reaching 48.15% [17, 43] while adult data remaining scarce. Our study revealed 28.6% of adults experienced lower limb weakness 3 h post-CB, and most of them could ambulate independently. This may be attributed to the challenge of achieving adequate diffusion of 20 ml local anesthetic to reach the lumbosacral nerve roots in adults. In comparison, combined SC and PN block exhibited a lower incidence of motor weakness. However, some patients in NB group still experienced this side effect. Local anesthetic diffusion to the sciatic nerve during the block procedure may contribute to motor weakness. To minimize the incidence of sciatic nerve block, it is essential to avoid anesthetic injection on the ischium surface or lateral to the ischial spine. Despite short duration and low degree of motor weakness to lower limbs, falls prevention remains essential, particularly within 3 h postoperatively. In summary, while the number of patients with motor score 0 was more at 3 h postoperatively in NB group compared to CB group, this statistical difference might not be clinically important. Studies with larger sample size are required to further evaluate the clinical significance of impact on lower limb mobilization with the two block techniques.

This study holds significance for clinical application and trial. First, prospective randomized trials investigating optimal post-PU analgesia are scarce, and our findings may provide a foundation for future research on perioperative analgesia in PU. Second, urethral stricture is commonly trauma-induced, causing severe pelvic deformity and lumbosacral canal stenosis, complicating CB manipulation, even with ultrasound guidance. Additionally, some PU patients have CB contraindications, such as increased intracranial pressure. Thus, this combined nerve block technique may become the preferred post-PU analgesia for these patients.

Some limitations in the present study need to be noted. First, the inability to blind the anesthesiologists performing the blocks should be acknowledged. However, the assignment of four anesthesiologists into two groups, performing CB and combined nerve block separately, may have reduced potential bias from unblinded operators. Second, the combined nerve block necessitates more puncture attempts than CB, potentially limiting its clinical applicability. Hence, general anesthesia with a laryngeal mask followed by a nerve block might be a more pragmatic approach without compromising patient comfort. Finally, the sample size was relatively small which limited generalizability of results, and might lead to false negative results [44, 45]. Future prospective clinical trials including a higher number of participants will be done to confirm the efficacy and safety of this combined nerve block technique.

Conclusions

PN combined with SC block is a safe and effective regional block technique for postoperative pain management in PU. This technique can achieve a longer duration of analgesia, and lower pain scores especially 12 h after surgery compared to CB, without increasing the incidence of block-related complications and adverse events.