Transcutaneous tibial nerve stimulation versus sham stimulation for the treatment of catheter-related bladder discomfort in patients undergoing transurethral resection of the prostate: a prospective, randomized, placebo-controlled, double-blind trial

Abstract

Background

Catheter-related bladder discomfort (CRBD), characterized by urinary urgency, frequency, and suprapubic pain, is a clinically significant complication following transurethral resection of the prostate (TURP). Current CRBD pharmacotherapy faces inherent limitations due to adverse effect profiles. Transcutaneous tibial nerve stimulation (TTNS), a noninvasive neuromodulation therapy with demonstrated efficacy in bladder dysfunction management, shows particular promise as a safe and effective alternative for CRBD treatment.

Methods

This prospective, randomized, double-blind, placebo-controlled clinical trial enrolled patients undergoing TURP under general anesthesia. Participants were randomly allocated in a 1:1 ratio to either active TTNS intervention or sham stimulation. The primary outcome focused on CRBD-related discomfort severity assessed via the Numeric Rating Scale (NRS) immediately post-intervention. Secondary outcomes comprised CRBD severity and pain scores at 1-, 2-, and 6-h post-intervention intervals, analgesic consumption, patient satisfaction ratings, and occurrence of postoperative delirium.

Discussion

This protocol evaluates the therapeutic potential of TTNS for CRBD following TURP, exploring its viability as a non-invasive alternative to current CRBD management.

Trial registration

Chinese Clinical Trial Registry ChiCTR2400088488. Registered on 20th August 2024.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13063-026-09743-y.

Administrative information

Title {1}	Transcutaneous tibial nerve stimulation versus sham stimulation for the treatment of catheter-related bladder discomfort in patients undergoing transurethral resection of the prostate: a prospective, randomized, placebo-controlled, double-blind trial.
Trial registration {2a and 2b}.	www.chictr.org.cn identifier ChiCTR2400088488. Registered on 20th August 2024, http://www.chictr.org.cn/
Protocol version {3}	March 18, 2024, version 02
Funding {4}	This study is funded by Shanghai Traditional Chinese Medicine "Three-year Action Plan" [NO.ZY(2021-2023)-0211] and Shanghai Science and Technology Committee, Science and Technology Innovation Action Plan (No. 23Y11901700).
Author details {5a}	Yanwen Song, Acupuncture Anesthesia Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China Xiangyu Sun, Acupuncture Anesthesia Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China Ling Mei, Department of Anesthesiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China Yongqiang Wang, Department of Anesthesiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China,173430064@qq.com Jiangang Song, Department of Anesthesiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China,songjg1993@shutcm.edu.cn
Name and contact information for the trial sponsor {5b}	The trial sponsor is Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China Postal address: 528 Zhangheng Road, Shanghai, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.
Role of sponsor {5c}	The trial sponsor will participate in study design, data collection, management, analysis, interpretation, report writing, and the decision to submit the report for publication.

Introduction

Background and rationale {6a}

Catheter-related bladder discomfort

Patients with an indwelling urinary catheter often experience catheter-related bladder discomfort (CRBD) in the Post-Anesthesia Care Unit (PACU), manifesting as symptoms such as increased urinary frequency, urgency, pain during urination, and discomfort in the supra-pubic region [1]. The incidence of CRBD varies across different surgical procedures, ranging from 44.3% to 93.2% [2–5]. High-risk factors for CRBD include male gender, a history of indwelling urinary catheterization, postoperative urological surgeries, inadequate postoperative pain management, catheter size exceeding 18Fr, and insufficient lubrication during catheter insertion[3, 6]. CRBD clinically manifests as psychomotor agitation in catheterized patients, presenting verbalized urgency complaints, involuntary limb movements, and safety–critical behaviors such as attempted catheter removal. These manifestations elevate risks of surgical complications including incision dehiscence, hemorrhage, and urethral injury, prolong hospitalization duration, reduce care satisfaction, increase clinical workloads, and ultimately impede postoperative recovery [7–9].

Transurethral resection of the prostate (TURP) represents the surgical treatment of choice for benign prostatic hypertrophy (BPH) with lower urinary tract symptoms (LUTS) [10]. However, the inherent anatomical predisposition of the transurethral approach combined with mandatory postoperative large-caliber urinary catheterization significantly predisposes TURP patients to elevated CRBD incidence and more severe clinical manifestations than observed in other urological surgeries [11]. This presents significant challenges for both physicians and patients alike.

Pharmacologic agents, including antimuscarinics (oxybutynin, tolterodine, butylscopolamine) [12, 13], anesthetic adjuvants (ketamine, sevoflurane, desflurane, propofol, dexmedetomidine) [14–17], tramadol [18], and magnesium [1] have demonstrated preventive and therapeutic potential for CRBD in clinical investigations. However, these pharmaceutical interventions are not exempt from manifesting a spectrum of adverse effects, encompassing postoperative nausea and vomiting, xerostomia, cephalalgia, facial flushing, hypotension, and visual disturbances [12, 13, 18]. Furthermore, the current clinical landscape is devoid of standardized or consensus guidelines governing the prevention and management of CRBD. Hence, the imperative is the exploration of therapeutic modalities for CRBD characterized by enhanced safety profiles, minimal toxicity, and heightened efficacy.

Transcutaneous tibial nerve stimulation

Tibial nerve stimulation (TNS) is a recognized neuromodulation therapy for the treatment of non-neurogenic lower urinary tract dysfunction (LUTD) [19].

TNS utilizes targeted electrical pulses to stimulate the tibial nerve, dampening detrusor muscle contraction activity. This approach constitutes a neuromodulatory technique employed in the management of bladder dysfunction [20]. At the spinal level, stimulation of tibial nerve afferents inhibits aberrant bladder signaling via the sacral reflex arc. Regarding supraspinal involvement, recent research has provided evidence that tibial neuromodulation can directly alter voiding urge and efficiency in humans [21], suggesting the engagement of central processing pathways. The tibial nerve, a compound nerve incorporating sensory and motor fibers spanning from L4 to S3, shares a common spinal cord segment origin with the nerves governing the bladder and pelvic floor [22]. Given this shared anatomical origin, it is postulated that TTNS functions similarly to Sacral Neuromodulation (SNM). SNM operates by modulating brainstem centers such as the periaqueductal gray (PAG) and pontine micturition center (PMC) [23]. Therefore, TTNS may also utilize these ascending pathways to restore the balance of descending inhibitory control over the detrusor muscle.

Due to the therapeutic mechanism of TNS, percutaneous tibial nerve stimulation (PTNS) received FDA approval in 2010 for the management of refractory overactive bladder (OAB) [24]. Guidelines also endorse TNS as a therapeutic modality for improving OAB [25]. CRBD and OAB share symptomatic similarities, both attributed to detrusor smooth muscle-mediated involuntary contractions in the bladder [12, 26]. Published studies have reported therapeutic effects of physical therapies, including wrist-ankle acupuncture [27] and transcutaneous electrical acupoint stimulation (TEAS) [28], in CRBD management. Recently, a prospective study [29] reported that TTNS could significantly reduce the postoperative incidence of moderate-to-severe CRBD. However, evidence regarding the efficacy of TTNS as a therapeutic intervention for CRBD remains limited. Hence, we designed this study to systematically evaluate the therapeutic efficacy of TTNS in managing CRBD subsequent to TURP.

Objectives {7}

The main objective of this trial was to evaluate the therapeutic efficacy of TTNS in alleviating CRBD among patients undergoing TURP and assess the potential of TTNS as a novel clinical intervention for postoperative CRBD management.

Trial design {8}

This prospective, single-center, randomized, placebo-controlled, double-blind, parallel-group superiority trial was approved by the Ethics Committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval No: 2024-1427-010-01). It was registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2400088488) before the first patient enrollment.

Methods: participants, interventions and outcomes

Study setting {9}

This trial will be conducted at Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Eligibility criteria {10}

Inclusion criteria

1. Patients undergoing TURP under general anesthesia with postoperative catheterization, presenting with moderate-to-severe CRBD according to the predefined grading scale (see CRBD Assessment and Grading section).

2. Age within the range of 18 to 74 years, classified as American Society of Anesthesiologists (ASA) Class I-II.

3. Cognitively intact individuals capable of coherent communication, providing detailed descriptions of their symptoms, and successfully completing the requisite assessments.

4. Voluntary consent to participate in the study, demonstrated through the informed and documented agreement by signing the informed consent form.

Exclusion criteria

1. Subjects equipped with cardiac pacemakers or implanted defibrillators.

2. Individuals exhibiting contraindications to electrical stimulation, cutaneous hypersensitivity, dermal lesions, or localized infections at the stimulation site.

3. Participants with a documented history of prior transcutaneous tibial nerve stimulation device usage.

4. Patients presenting with additional urological pathologies potentially confounding study outcomes, including conditions such as OAB.

5. Patients diagnosed with psychiatric disorders, like schizophrenia depression, or cognitive impairments, rendering them unable to actively participate in the study.

6. Individuals under prolonged administration of opioid analgesics.

Who will take informed consent? {26a}

The informed consent form must be signed by the patient (or legal representative) and research team members, confirming mutual agreement on the study’s terms.

Additional consent provisions for collection and use of participant data and biological specimens {26b}

N/a. No biological specimens will be collected.

Interventions

Explanation for the choice of comparators {6b}

A sham-controlled design was employed primarily to enable a double-blind protocol. While pharmacological agents have been investigated, there is currently no standardized guideline or consensus for the routine prophylaxis of CRBD [10]. Furthermore, compared to pharmacological controls, a sham device avoids systemic side effects. To maintain blinding while limiting physiological confounding, the sham unit utilized a micro-vibration motor attached to the outer surface of the electrode pad. This configuration buffers the mechanical transmission to the skin. Importantly, effective tibial neuromodulation typically requires electrical stimulation intensity approaching the motor threshold (MT) to recruit deep nerve fibers [30]. The superficial vibration in the sham group, lacking electrical current and depth penetration, is incapable of reaching the MT, thereby functioning solely to maintain blinding integrity rather than acting as a therapeutic neuromodulatory stimulus.

Intervention description {11a}

Clinical procedures

Upon the patient’s entry into the operating room, standard anesthesia monitoring is initiated, encompassing pulse oximetry, noninvasive blood pressure monitoring, electrocardiography, and assessment using the bispectral index (BIS). Train-of-four (TOF) monitoring with four consecutive stimuli is employed to monitor neuromuscular blockade. Post-surgery, urinary catheterization involves initial urethral surface anesthesia using lidocaine gel (approval number: National Drug Approval H61022993; manufacturer: Xi’an Lijun Jinghua Pharmaceutical Co., Ltd.) administered to the urethra (approximately 5 g). After 2 min, adequate surface anesthesia is achieved, and a lubricated latex catheter is inserted into the patient’s urethra and bladder, with a 10 ml saline solution inflation of the catheter balloon to prevent displacement. Subsequently, according to urologist guidelines for post-TURP care, continuous saline irrigation into the bladder through the catheter is performed. During the postoperative awakening phase under general anesthesia, the anesthesiologist assesses the patient’s level of consciousness and neuromuscular function (bispectral index BIS greater than 90, and TOF ratio greater than 90%). Once these parameters meet the criteria, the endotracheal tube is removed, and the patient is transferred to the PACU.

CRBD assessment and grading

Upon the patient’s arrival at the PACU, an independent investigator evaluates the severity of CRBD based on spontaneous clinical manifestations. The condition is categorized into four grades [12, 31]:

1. None: No symptoms.

2. Mild: Discomfort reported only upon inquiry.

3. Moderate: Spontaneous complaints of urgency or pain without behavioral responses.

4. Severe: Spontaneous complaints accompanied by behavioral responses, such as agitation, flailing limbs, or attempts to remove the catheter.

Patients identified with moderate or severe CRBD will proceed to randomized allocation for either active TTNS or sham stimulation. Patients with mild symptoms are excluded from the intervention.

TTNS intervention

In response to self-reported CRBD, patients are subjected to therapeutic intervention utilizing the butterfly-shaped TTNS device (General Stim Inc., Hangzhou, Zhejiang, China) (Fig. 1). Preceding the initiation of treatment, a unilateral lower limb is meticulously chosen, and the TTNS device is positioned around the subject’s ankle, targeting the tibial nerve area. Parameters of the TTNS device are configured to a frequency of 20 Hz (constant biphasic frequency), a pulse width of 200 μs, and a customizable current intensity within the range of 0 to 30 mA [32]. The stimulation commences at 0 mA, with gradual increments of 0.5 mA until the subject exhibits the inaugural contraction of the toe flexor muscle, splaying of adjacent toes, or reports a tingling sensation on the plantar surface. The resulting current intensity represents the motor threshold (MT) for TTNS. Subsequent to this determination, the intensity is reduced by 0.5–1 mA to forestall any inadvertent motor responses. The subject is then subjected to a 30-min session of transcutaneous tibial nerve electrical stimulation at this adjusted and secure current intensity.

Fig. 1.

The butterfly-shaped TTNS device

The sham stimulation

The sham stimulation device (Fig. 2) matches the active TTNS device in both physical appearance and operational indicators. Identical in external design, it mimics the authentic device’s illuminated status lights during treatment while delivering no therapeutic current. Both devices are positioned at the same lower leg landmark along the tibial nerve pathway.

Fig. 2.

The sham stimulation device

Criteria for discontinuing or modifying allocated interventions {11b}

If participants withdraw their consent to continue in the study at any time, they will be withdrawn from the study.

Strategies to improve adherence to interventions {11c}

Our team conducts meticulous follow-up assessments for participants upon self-reporting of CRBD and at 0, 1, 2, and 6 h post-completion of either TTNS or sham stimulation interventions.

Relevant concomitant care permitted or prohibited during the trial {11d}

There are no specific restrictions on concomitant care during this study.

Provisions for post-trial care {30}

N/a. Our intervention utilizes an externally applied non-invasive device that carries no additional risk of harm to participants.

Outcomes {12}

The primary trial outcome is the NRS score quantifying the severity of CRBD at intervention completion. The assessment utilizes the NRS, a quantification tool ranging from 0 (absence of discomfort) to 10 (maximum discomfort severity), to evaluate the extent of CRBD-related discomfort [13]. Secondary outcomes encompass NRS scores for CRBD at 1, 2, and 6 h post-intervention, NRS scores for postoperative pain at 0, 1, 2, and 6 h post-intervention (0 absence of pain to 10 maximum pain severity), postoperative analgesic utilization (quantified within 6 h post-treatment for tramadol and sufentanil), patient satisfaction scores (assessed on a 7-point Likert scale at 6 h post-intervention, (1 = strongly dissatisfied, 2 = moderately dissatisfied, 3 = slightly dissatisfied, 4 = neutral, 5 = slightly satisfied, 6 = moderately satisfied, 7 = extremely satisfied), and the incidence of postoperative delirium evaluated within 6 h using the Chinese version of the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM).

Participant timeline {13}

The drafting of this research protocol manuscript adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) [33] (Table 1) (Fig. 3).

Table 1.

The schedule of enrolment, interventions, and assessments based on the Standard Protocol Items Recommendations for Interventional Trials (SPIRIT) guideline

t₀: Patient actively reported symptoms of CRBD

t₁: Before the start of the intervention

t₂: At the end of the intervention

t₃: 1 h after the end of the intervention

t₄: 2 h after the end of the intervention

t₅: 6 h after the end of the intervention

Fig. 3.

Study design flow chart

Sample size {14}

This study employs a randomized controlled trial design with the TTNS group as the test arm and the sham stimulation group as the control arm. The primary outcome measure is the post-treatment discomfort level of CRBD assessed through the NRS, where a mean NRS for CRBD is established at 7.5 for the control group based on the literature. Anticipating a reduction to 5.5 (a decrease of 2 with a standard deviation of 2.5) post-intervention for the test group, with a two-sided α of 0.05, power (1-β) of 0.8, and a 1:1 sample size ratio between groups, R software calculations determine a sample size of 25 in each group [34]. Factoring in a 10% attrition rate, a final minimum of 28 subjects per group is deemed necessary, yielding a total sample size of 56.

Recruitment {15}

Participants will be recruited through Shuguang Hospital, Shanghai University of Traditional Chinese Medicine.

Assignment of interventions: allocation

Sequence generation {16a}

Employing a stratified block randomization methodology, the study cohort is categorized into two strata based on age: 50 years and below, and above 50 years. The block size is defined as 4, and the allocation of subjects transpires in a 1:1 ratio between the TTNS group and the sham stimulation group. Randomization tables will be generated utilizing statistical software on a computer, ensuring the preservation of the random sequence order.

Concealment mechanism {16b}

Randomization will be conducted using sequentially numbered, opaque, sealed envelopes to maintain allocation concealment.

Implementation {16c}

The allocation sequence will be generated by an independent statistician who has no contact with the study participants. A dedicated research coordinator, distinct from the intervention and assessment teams, is responsible for screening and enrolling participants. Upon enrollment, the coordinator will open the sequentially numbered, opaque, sealed envelope and communicate the group assignment only to the intervention nurse.

Assignment of interventions: blinding

Who will be blinded {17a}

While blinding is not attainable for the interventionists, it is strictly maintained for the participants and outcome assessors. To ensure blinding fidelity, the sham unit replicates the tactile feedback of active TTNS through a vibration system, preventing participants from distinguishing the group assignment. Procedural safeguards further ensure that outcome assessors remain blinded: strict role separation prohibits interventionists from communicating allocation details, and the device display is obscured with an opaque cloth immediately after setup. Assessors are permitted to enter the PACU and evaluate NRS scores only after the intervention has commenced and all operational indicators are fully concealed.

Procedure for unblinding if needed {17b}

Emergency unblinding will be permitted only in the event of a serious adverse event (SAE) where the clinical management of the participant depends on the knowledge of their group assignment. The investigator must obtain authorization from the Principal Investigator (PI) before unblinding. The date, reason, and names of individuals involved in the unblinding will be meticulously documented in the Case Report Form (CRF).

Data collection and management

Plans for assessment and collection of outcomes {18a}

In this trial, the database will be developed using clinical data collected through a questionnaire, utilizing Excel and SPSS software. Researchers will gather data at baseline and during follow-up, recording the information both on paper checklists and in a pre-designed Excel datasheet. Subsequently, the collected data will be analyzed using SPSS.

Plans to promote participant retention and complete follow-up {18b}

All participants will complete a standardized 6-h postoperative observation period, during which the majority remain hospitalized. We are committed to ensuring maximal adherence to assessment protocols while accommodating individual clinical conditions.

Data management {19}

Qualified clinicians will perform all interventions and assessments. Trained study staff will document data on Case Report Forms (CRFs). Data integrity will be ensured through two-phase verification: initial cross-checking against source records prior to Excel entry, followed by independent duplicate entry with reconciliation of discrepancies. Statistical analyses will commence post-trial according to the predetermined plan.

Confidentiality {27}

All records of trial participants will be stored using identification numbers and initials in CRFs and remain confidential.

Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}

N/a. No biological specimens will be collected.

Statistical methods

Statistical methods for primary and secondary outcomes {20a}

The primary outcome, NRS score assessed immediately post-treatment, will be analyzed using an analysis of covariance (ANCOVA) model, with the treatment group and age (stratification factor) as independent variables and baseline NRS score as a covariate.

For longitudinally measured secondary outcomes, a linear mixed-effects model will be fitted, incorporating fixed effects for baseline score, treatment group, age (stratification factor), and the time-by-treatment interaction. The model will include random intercepts for individual participants to account for within-subject correlation, and random slopes for time to accommodate heterogeneous treatment trajectories across participants. Sensitivity analyses using complete case analysis for the primary outcome will be reported.

Interim analyses {21b}

N/a. No interim analyses are planned for this study. Given the relatively short duration of data collection and the total sample size of 56 patients, we have not included an interim analysis in the study design.

Methods for additional analyses (e.g., subgroup analyses) {20b}

Between-group comparisons for secondary outcomes will employ appropriate statistical tests based on data characteristics. For categorical variables, Pearson’s chi-square test will be used when expected cell frequencies are adequate (≥5), while Fisher’s exact test will be applied for sparse contingency tables. Continuous variables will be analyzed using independent samples t-test when normality assumptions are met (assessed via Shapiro–Wilk test and Q-Q plots), with Mann–Whitney U test serving as the nonparametric alternative when these assumptions are violated.

Pre-specified subgroup analyses will be conducted by age strata (<50 years versus ≥50 years) using the same analytical approach as the primary analysis. Treatment effects within each subgroup will be estimated, and an interaction test between treatment and subgroup variable will be performed to assess effect modification.

Secondary outcomes and pre-specified subgroup analyses will be analyzed without adjustments for multiple comparisons. While p-values and 95% confidence intervals will be reported for transparency, these results should be interpreted as exploratory rather than confirmatory.

Statistical significance will be defined at a two-sided alpha level of 0.05. All statistical analyses will be performed using IBM SPSS Statistics (Version 27.0, IBM Corporation, Armonk, NY, USA).

Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

Statistical analyses will primarily follow the intention-to-treat (ITT) principle, which includes all randomized participants according to their assigned groups, regardless of whether they received the intervention or withdrew from the study at any stage, including before or during the intervention session. To ensure the integrity of the findings, missing data arising from withdrawals, loss to follow-up, or missed assessments—such as a missing 6-h post-intervention score—will be addressed under the missing-at-random (MAR) assumption using multiple imputation with chained equations (MICE).

To evaluate the robustness of the primary findings, a per-protocol (PP) analysis will be conducted as a sensitivity analysis. The PP population is restricted to participants who completed the full 30-min intervention and provided a complete set of assessments across all time points (0, 1, 2, and 6 h) without significant protocol deviations. Specifically, participants will be excluded from the PP analysis in the event of: (1) post-randomization identification of eligibility criteria violations; (2) failure to complete the entire stimulation session for any reason, including early withdrawal; (3) presence of any missing data points during the 6-h follow-up period; or (4) administration of rescue analgesics, such as tramadol or sufentanil, before the primary outcome assessment. For transparency, the reasons for all withdrawals, missing data, and exclusions will be meticulously documented.

Plans to give access to the full protocol, participant level-data and statistical code {31c}

The datasets analyzed during the current study, along with the statistical code, are available from the corresponding author upon reasonable request, as is the full protocol.

Oversight and monitoring

Composition of the coordinating center and trial steering committee {5d}

The trial coordination center, based within the Department of Anesthesiology at Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, manages all operational aspects of the study. This includes protocol development, regulatory compliance oversight, data management, and timeline adherence. Additionally, the center monitors recruitment progress and implements quality control procedures to ensure robust data collection.

An independent Steering Committee, composed of hospital administration professionals and ethics board representatives, remains operationally separate. This committee maintains authority to review and approve protocol modifications while providing strategic oversight of participant safety and overall trial conduct.

Composition of the data monitoring committee, its role and reporting structure {21a}

N/a. The NCH IRB did not require a data monitoring committee (DMC) as this is a minimal-risk study.

Adverse event reporting and harms {22}

In the event of persistent CRBD with an NRS score exceeding 7 post-TTNS intervention, the administration of tramadol at a dose of 1 mg/kg is instituted. Should patients experience postoperative pain beyond an NRS score of 7, a pain management strategy involves administering sufentanil at a dose of 0.1 μg/kg. Detailed records of tramadol and sufentanil consumption by patients throughout the study period are meticulously maintained.

Frequency and plans for auditing trial conduct {23}

An independent Clinical Research Associate will conduct routine on-site monitoring throughout the trial duration. If significant protocol deviations or critical findings are identified during monitoring activities, an independent audit may be initiated to ensure compliance and data integrity.

Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}

Any important protocol modifications are reported as soon as possible to all relevant parties, typically the Institutional Review Board and study staff.

Dissemination plans {31a}

Study personnel and researchers will have access to the trial database and related materials. The research findings will be published in peer-reviewed open-access journals within 12 months after trial completion.

Discussion

This prospective, randomized, placebo-controlled, double-blind trial evaluates TTNS efficacy in managing moderate-to-severe CRBD after TURP. By targeting the tibial nerve’s natural pathway for bladder control through sacral nerve connections [19], our protocol delivers TTNS along key nerve areas using stimulation intensities calibrated to individualized motor thresholds and strategically reduced to prevent muscle reactivity [30]. Dynamic multi-timepoint assessments (0,1,2,6 h) track CRBD severity, pain levels, delirium incidence, and satisfaction ratings. Outcomes will clarify TTNS’s therapeutic timeline and inform neuromodulation integration in postoperative care.

Currently, three modalities of TNS are in practice: implantable tibial nerve stimulation (ITNS) [21], PTNS [20], and TTNS [22]. During PTNS, insertion of the needle electrode tip proximal to the internal malleolus introduces a spectrum of complications, including postprocedural hematoma formation, infection-related morbidities, and neurogenic pain responses. ITNS requires surgical implantation of the neurostimulator along the tibial nerve pathway, demonstrating complication profiles substantially similar to those of PTNS [23]. Additionally, both PTNS and ITNS require deployment by certified physicians, whereas TTNS presents distinct clinical advantages through non-invasive methodology and technically simple bedside application requiring minimal training. This non-invasive modality anticipates favorable tolerability profiles that could enhance treatment adherence, offering a practical clinical alternative for managing CRBD.

Current evidence establishes TTNS efficacy in managing OAB, supported by its neuromodulatory effects on sacral reflex pathways [35]. Notably, OAB and CRBD share pathophysiological features characterized by detrusor overactivity, likely mediated through overlapping neural circuits [36]. The therapeutic potential of non-invasive neuromodulation is further corroborated by studies demonstrating TENS effectiveness in reducing CRBD incidence following transurethral resection of bladder tumors (TURBT) [31]. More directly, recent findings [29] confirmed that TTNS significantly reduces the postoperative incidence of CRBD. Extending this preventive efficacy to a therapeutic context, we hypothesized that TTNS might similarly alleviate established CRBD symptoms.

Beyond efficacy, participant safety and comfort are central to the protocol. Stimulation intensity is individualized based on the motor threshold (MT) and maintained at a sub-motor level to ensure tolerability without inducing muscle contraction or pain. Ethical provisions also include the administration of rescue analgesics for patients with persistent moderate-to-severe CRBD to minimize distress. Moreover, specific criteria for early termination, such as skin irritation or intolerance, are established to safeguard patient well-being.

This trial has limitations requiring acknowledgment. Firstly, as a single-center study, differences in patient demographics and healthcare settings may limit generalizability. Furthermore, given the limited data on TTNS as a therapeutic intervention, the sample size was derived from analogous literature; consequently, the study may be underpowered for secondary analyses, and such findings should be interpreted as exploratory. Secondly, to safeguard the reliability of patient-reported outcomes by minimizing delirium-related confounding [37], we excluded the “old-old” population (≥75 years), which limits generalizability to advanced elderly patients. Thirdly, existing CRBD assessment methods remain dependent on patient-reported measures given the current lack of validated objective biomarkers and the low specificity of hemodynamic parameters in the PACU. Fourthly, regarding the sham design, although the vibration was devoid of electrical current and physically buffered to remain sub-threshold, potential activation of cutaneous mechanoreceptors represents an inherent limitation. Finally, our exclusive focus on TURP leaves TTNS efficacy for CRBD following other surgical interventions unconfirmed. These findings warrant validation in future large-scale, multicenter trials involving broader patient demographics and surgical contexts.

This protocol evaluates the therapeutic potential of TTNS for CRBD following TURP, exploring its viability as a non-invasive alternative to current CRBD management. Confirmation of feasibility may offer new perspectives for developing non-pharmacological strategies in clinical CRBD management.

Trial status

The current protocol is version 02 and was issued on 18 March 2024. Recruitment commenced in October 2024 and has been completed. At present, the study has transitioned to the data analysis phase.

Abbreviations

CRBD

Catheter-related bladder discomfort

TURP

Transurethral resection of the prostate

TTNS

Transcutaneous tibial nerve stimulation

NRS

Numeric Rating Scale

PACU

Post-Anesthesia Care Unit

BPH

Benign prostatic hypertrophy

LUTS

Lower urinary tract symptoms

TNS

Tibial nerve stimulation

LUTD

Lower urinary tract dysfunction

PTNS

Percutaneous tibial nerve stimulation

OAB

Overactive bladder

TEAS

Transcutaneous electrical acupoint stimulation

ASA

American Society of Anesthesiologists

BIS

Bispectral index

TOF

Train-of-four

MT

Motor threshold

3D-CAM

3-Minute Diagnostic Confusion Assessment Method

CRFs

Case report forms

ITT

Intention-to-treat

ANCOVA

Analysis of covariance

MAR

Missing-at-random

MICE

Multiple imputation with chained equations

ITNS

Implantable tibial nerve stimulation

TURBT

Transurethral resection of bladder tumors

Authors’ contributions {31b}

Jiangang Song and Yongqiang Wang planned the study. Ling Mei managed the recruitment process for the trial. All authors contributed to the design and development of the trial. Yanwen Song and Xiangyu Sun drafted the manuscript. Jiangang Song and Yongqiang Wang revised the manuscript. The authors read and approved the final manuscript.

Funding {4}

This study is funded by Shanghai Traditional Chinese Medicine “Three-year Action Plan” [NO.ZY(2021-2023)−0211] and Shanghai Science and Technology Committee, Science and Technology Innovation Action Plan (No. 23Y11901700).

Data availability {29}

Any data required to support the protocol can be supplied on request.

Declarations

Ethics approval and consent to participate {24}

This trial was approved by the Ethics Committee of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine (Approval No: 2024-1427-010-01). Informed consent to participate will be obtained from all participants.

Consent for publication {32}

N/a. We have included an example consent form with this submission.

Competing interests {28}

N/a. We have no competing interests.