1. Background and Rationale:
Endoscopic retrograde cholangiopancreatography (ERCP) is a complex procedure essential for diagnosing and treating various pancreaticobiliary disorders. Adequate sedation is critical for patient comfort and procedural success. Traditional conscious sedation with meperidine and diazepam remains widely used, particularly in resource-limited settings, but is associated with risks of respiratory depression, hypoxemia, hypotension, and inadequate sedation.
Transcutaneous electrical acupoint stimulation (TEAS) is a non-invasive modality derived from traditional acupuncture principles that delivers controlled electrical currents to specific acupoints via surface electrodes. TEAS has been shown to exert analgesic effects through the release of endogenous opioid peptides, modulate autonomic nervous system function, reduce perioperative opioid requirements, and decrease the incidence of postoperative nausea and vomiting.
However, robust evidence on its efficacy and safety specifically during ERCP with traditional conscious sedation is lacking. This multicenter trial aims to rigorously evaluate whether adjunctive TEAS improves procedural safety, tolerance, and clinical outcomes in patients undergoing ERCP.
2. Study Design and Methodology:
This is a prospective, randomized, sham-controlled, single-blind, parallel-group, multicenter trial conducted at three centers: Fifth Medical Center (lead site), First Medical Center, and Third Medical Center of Chinese PLA General Hospital.
Patients scheduled for elective diagnostic or therapeutic ERCP will be assessed for eligibility. Eligible and consenting participants will be randomly assigned (1:1) using a computer-generated random allocation sequence with permuted blocks of variable sizes (4 and 6), with allocation concealment in sequentially numbered, opaque, sealed envelopes.
Participants will be allocated to one of two groups:
1. Active TEAS Group: Receives real TEAS stimulation applied bilaterally to four predefined acupoints: Yinlingquan (SP9), Yanglingquan (GB34), Xuehai (SP10), and Neiguan (PC6). Acupoint locations will be determined according to WHO Standard Acupuncture Point Locations. Disposable self-adhesive electrodes (diameter 3 cm) will be connected to a Hwato SDZ-III electronic acupoint stimulator (Suzhou Medical Supplies Factory Co., Ltd., China). Stimulation parameters are set to dense-disperse wave mode (alternating frequencies of 2 Hz and 20 Hz, each for 3 seconds). The intensity is adjusted to the patient's maximum tolerable level (typically 2-5 mA). Stimulation begins 30 minutes before the procedure and continues throughout the endoscopic procedure.
2. Sham TEAS Group: Receives identical electrode placement at the same four bilateral acupoints using the same device, but no electrical current is delivered. The device appears active (indicator lights on) to maintain blinding. All patients in both groups are informed that they may or may not feel any sensation during the stimulation, which is normal.
3. Standardized Sedation Protocol (Both Groups): All participants receive standardized conscious sedation with intravenous meperidine (0.5 mg/kg) and diazepam (0.1 mg/kg) administered by an anesthesiologist or trained physician blinded to group assignment. Additional doses of diazepam (1/3 to 1/2 of initial dose) may be administered if needed based on patient response and Ramsay Sedation Scale (target score 2-4). ERCP procedures are performed by experienced gastroenterologists (each with \>300 prior ERCPs) who are also blinded to group assignment. A designated research assistant who is not involved in patient care, outcome assessment, or data analysis performs the TEAS or sham-TEAS intervention and ensures that the device display is shielded from the patient's view.
4. Blinding: A designated research assistant not involved in patient care, outcome assessment, or data analysis performs the TEAS or sham-TEAS intervention. The device display is shielded from the patient's view. Patients, endoscopists, outcome assessors, and data analysts are blinded to group assignment.
3.Sample Size Calculation: Based on the primary outcome measure (Visual Analogue Scale, VAS score), assuming a mean difference of 2.0 points between groups, a standard deviation of 3.0, α=0.05 (two-sided), and β=0.20 (80% power), the calculated sample size is approximately 36 patients per group. Considering potential dropouts (10-15%) and the need for subgroup analyses, the final sample size is set at 65 patients per group, for a total of 130 patients across all three centers. Sample size allocation will be balanced across centers (approximately 22 patients per group per center).
4.Statistical Analysis Plan:
1. Descriptive Statistics: Continuous variables: mean ± standard deviation (SD) if normally distributed, or median with interquartile range (IQR) if non-normally distributed. Categorical variables: frequencies and percentages (n, %).
Baseline Comparability.
2. Continuous variables: one-way analysis of variance (ANOVA) or Kruskal-Wallis test. Categorical variables: χ² test or Fisher's exact test.
3. Primary Outcome Analysis:The composite incidence of sedation-related adverse events will be compared between groups using χ² test. Center stratification will be performed using Cochran-Mantel-Haenszel test to account for potential center effects.
4. Secondary Outcome Analysis: Continuous variables (sedative doses, VAS scores, recovery time, discharge time): independent samples t-test for normally distributed data, Mann-Whitney U test for non-normally distributed data. Repeated measures (MAP, HR at multiple time points): repeated measures ANOVA or generalized estimating equations (GEE). Categorical variables (satisfaction scores, adverse events): χ² test or Fisher's exact test.
5. Multivariable Analysis: Binary logistic regression: factors influencing sedation success rate and adverse events, including covariates such as age, sex, BMI, ASA class, center, procedure type, and medication dosage. Multiple linear regression: factors influencing VAS score, recovery time, and discharge time, including the same covariates.
6. Center Effect: Heterogeneity across centers will be assessed using Cochran-Mantel-Haenszel test. If significant heterogeneity is detected, generalized linear mixed models (GLMM) with center as random effect will be used.
7. Statistical Software and Significance Level: SPSS version 27.0 or R software (version 4.0 or higher). Two-sided tests with significance level α=0.05; P \< 0.05 considered statistically significant.
5.Scientific Justification: The selection of specific acupoints (SP9, GB34, SP10, PC6) is based on traditional Chinese medicine principles and modern physiological understanding: targeting points associated with visceral analgesia (GB34, SP9), gastrointestinal motility regulation and anti-emesis (PC6, ST36-like effects), and calming effects (PC6). The sham-controlled design is crucial for isolating the specific effects of electrical neuromodulation from non-specific placebo effects. This trial addresses a significant gap in optimizing sedation for ERCP by evaluating a readily deployable, non-pharmacological adjunctive strategy that could enhance patient safety and procedural quality, particularly in settings where newer sedative agents or dedicated anesthesia services are not readily available.
