This study is a multicenter, prospective, randomized, open-label, parallel-group clinical trial. It will be conducted at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, together with two additional tertiary hospitals in Zhejiang Province, with a planned enrollment of 170 patients. Recruitment and follow-up for ERCP procedures will take place from November 2025 to April 2026. The study flow diagram is presented in Figure 1.

The primary outcome is the incidence of a composite endpoint of SRAEs (Intraoperative and during the recovery room period): hypotension (15, 16) (blood pressure decrease exceeding 20% of baseline or mean arterial pressure ≤ 65mmHg, blood pressure was measured again, if the result is still lower than 20%, confirm as hypotension), hypertension (17) (blood pressure increase exceeding 20% of baseline or mean arterial pressure ≥105mmHg, blood pressure was measured again, if the result is still higher than 20%, confirm as hypertension), hypoxemia (SpO₂ ≤ 90% for >10 s) (18, 19), laryngospasm, bronchospasm (20) (Table 1).

Previous studies conducted under general anesthesia have reported postoperative hypoxemia rates of approximately 10%-22.5% in the post-anesthesia care unit (PACU) (21), while the incidence of intraoperative hypotension in patients undergoing prone procedures has ranged from 20.6% to 62.5% (22, 23). Based on these findings and our pilot data, we hypothesize that ciprofol-based deep analgosedation assisted with a nasopharyngeal airway could reduce the incidence of the composite outcome (hypoxemia or hypotension) from 39% to 19%, representing an absolute risk reduction of 20%. Using a two-sided test with a significance level of α = 0.05 and 80% power, 77 participants per group are required. Allowing for potential loss to follow-up, a total of 170 patients (85 per group) will be recruited.

Secondary outcomes include: Nasopharyngeal airway requires face mask ventilation or switching to tracheal intubation (Intraoperative), Reintubation after the tracheal intubation is removed (During the recovery room period); Tachycardia (>100 beats/minute) or bradycardia (< 50 beats/minute; Intraoperative and during the recovery room period); Rating of reflux degree (Intraoperative); Recovery room time (time from endoscope removal to achieving an Aldrete score of 10 and discharge from the endoscopy recovery unit; During the recovery room period); Early postoperative recovery quality (QoR-15 score) on postoperative day1 (POD 1); Postoperative nausea and vomiting (POD 1); Postoperative cognitive function assessment (Montreal Cognitive Assessment; POD 1); The incidence of perioperative respiratory failure (postoperative period); The incidence of acute respiratory distress syndrome (ARDS) during the postoperative period; Patient/endoscopist satisfaction (10-pointVAS; POD 1); Hospitalization duration (Table 1). Data will be analyzed using a modified intention-to-treat approach.

This is an open-label, two-arm randomized controlled trial enrolling 170 participants allocated 1:1 to the GA or DAS group. An independent biostatistician will generate the randomization sequence using an online system (https://www.sealedenvelope.com/simple-randomiser/v1/lists), with permuted blocks of 2 and 4 and stratification by center and baseline hypertension status (yes/no). Allocation will be concealed using sealed, sequentially numbered opaque envelopes, which will be opened only after patient arrival in the operating room. Due to the inherent nature of the interventions-endotracheal intubation vs. natural-airway management with a nasopharyngeal airway-blinding of the anesthesiology and endoscopy teams is not feasible. However, postoperative outcome assessors, data managers, and statisticians will remain blinded to group allocation to reduce detection and analytical bias.

All patients will fast for at least 8 h and abstain from water for 4 h before the procedure. Upon arrival in the operating room, a peripheral intravenous line will be established. Continuous intraoperative monitoring will include noninvasive blood pressure, pulse oximetry, heart rate, Bispectral Index (BIS) (24), and respiratory parameters such as respiratory rate and end-tidal carbon dioxide (PETCO₂) (25). All anesthesia and sedation procedures will be administered by experienced anesthesiologists, while ERCP will be performed by a consistent team of qualified endoscopists at each participating center. Following the procedure, all patients, regardless of group allocation, will be transferred to the endoscopy recovery area for postoperative monitoring. Continuous physiological monitoring will be conducted by anesthesiologists, who will assess recovery status and ensure that the Aldrete score reaches 10 before patients are transferred back to the ward.

NPA-assisted DAS Group, patients will be positioned in prone position. The nasal cavity will be pre-treated with lubricant and vasoconstrictive nasal spray. Preoxygenation will be performed via facemask (6 L/min), followed by intravenous administration of ciprofol (0.3–0.4 mg/kg) and sufentanil [5–10 μg (26), dosed at 0.1 μg/kg (27–29)]. After loss of consciousness, a nasopharyngeal airway will be gently inserted and connected to the anesthesia machine for low tidal volume/high-frequency oxygen delivery. Continuous infusions of ciprofol (0.8–1.2mg/kg/h) and remifentanil (0.05–0.2μg/kg/min) will be titrated based on age, weight, and clinical status to maintain stable sedation (BIS 40–60) (30). If nasopharyngeal airway placement failed in one nostril, the contralateral side was attempted. Patients will be excluded after four unsuccessful attempts or in cases of significant epistaxis.

General Anesthesia (GA) Group: Patient will be placed in supine position, anesthesia will be induced with propofol, sufentanil, and rocuronium (0.6 mg/kg) for neuromuscular blockade. After endotracheal intubation, mechanical ventilation will be initiated (tidal volume 6–8 ml/kg), FiO₂ 40%−60%, with respiratory rate adjusted to maintain PETCO₂ at 35–45 mmHg, then patient will be turned to the prone position. Anesthesia depth will be maintained using propofol and remifentanil as the deep sedation group with BIS-guided titration.

Data collection will encompass a range of patient characteristics, including Age, sex, ASA score, BMI, smoking status, pre-existing comorbidities, Mallampati score, interincisal distance, thyromental distance, ERCP complexity grading (14), and procedure duration (from endoscope insertion to withdrawal). Anesthesia medication dosages will be recorded. Assessors of subjective outcomes (outcomes that assessed postoperative) are blinded to group allocation. All data will be documented in case report forms (CRFs) and subsequently entered into the electronic database under the supervision of the principal investigator. An independent Data Monitoring Committee (DMC) will continuously monitor the data collection process. After all patients have completed this trial, the primary investigator and data administrator will check and confirm the integrity and accuracy of the data. Thereafter, all data will be locked. The administrator will import the data into a designated form and send it to a statistician for final statistical analyses. Any serious adverse events (SAEs), whether related or unrelated to the study (e.g., persistent hemodynamic instability or hypoxia), must be reported immediately to the principal investigator. In such cases, the perioperative care team should take the necessary measures to ensure the safety of the participants. These events must also be reported to the DMC within 24 h for further discussion and determination of whether modifications to the study interventions or termination of the study are necessary.

The normality of continuous variables will be assessed using the Shapiro-Wilk test. Normally distributed variables will be summarized as mean (standard deviation, SD) and compared between groups using independent-samples t-tests. Non-normally distributed variables will be presented as median (interquartile range, IQR) and compared using the Mann–Whitney U test. Categorical variables will be expressed as counts (percentages) and compared using chi-square (χ²) tests or Fisher's exact tests when appropriate.

The primary endpoint-the composite incidence of perioperative sedation-related adverse events (SRAEs), including hypotension, hypertension, hypoxemia, laryngospasm, or bronchospasm-will be compared between groups using χ² tests. Risk estimates including odds ratios (ORs) and corresponding 95% confidence intervals (CIs) will be reported. To account for potential confounding effects, multivariable logistic regression analyses will be conducted with prespecified covariates such as age, hypertension status, ASA classification, and procedure duration, providing adjusted ORs with 95% CIs.

Secondary outcomes, including postoperative recovery quality (QoR-15) on postoperative day1, cognitive function (MoCA) on POD1, and hospital length of stay, will be analyzed using t-tests or Mann–Whitney U tests depending on distribution characteristics. Secondary categorical outcomes (e.g., postoperative nausea and vomiting, escalation of airway interventions) will be analyzed using χ² tests or Fisher's exact tests as appropriate. As no multiple testing corrections are planned for secondary outcomes, these results should be interpreted as exploratory.

All primary analyses will follow a modified intention-to-treat (mITT) principle, including all randomized participants with available outcome data. A per-protocol (PP) analysis will also be conducted to evaluate robustness of results among participants without major protocol deviations. If missing data for the primary endpoint exceed 5%, sensitivity analyses using multiple imputation and inverse probability weighting methods will be performed to assess consistency of findings.

All statistical tests will be two-sided, with P < 0.05 considered statistically significant. Analyses will be performed using SPSS software (version 25.0; IBM, USA).

Patients and the public will not participate in the study's design, recruitment, conduct, or reporting. Study results will be shared with participants via email.

This study has several limitations. First, as an open-label trial, the lack of blinding may introduce bias, particularly in subjectively assessed secondary outcomes such as satisfaction and recovery quality. However, objective physiological parameters were selected as the primary outcomes, which helps minimize this concern. Second, follow-up is restricted to the hospitalization period, which may overlook delayed or long-term complications; future studies with extended follow-up are needed. Third, the exclusion of patients with severe chronic comorbidities may limit the generalizability of the findings to the broader ERCP population. Finally, although a composite primary endpoint was used to comprehensively assess sedation-related adverse events, the diagnostic thresholds, particularly for hypotension and hypertension, may be relatively stringent. However, strict hemodynamic control is clinically warranted in elderly patients with reduced cardiovascular reserve, supporting the relevance of these criteria in this population.