Effects of nine sedative-analgesic combinations on fatigue after gastrointestinal endoscopy: a randomized controlled 3 × 3 factorial trial protocol

Post-procedural fatigue is common after sedated gastrointestinal endoscopy and prolongs recovery. We describe a protocol for a prospective, single-center, randomized, controlled, 3 × 3 factorial trial to evaluate the effects of different sedative–analgesic combinations on patient-reported fatigue after gastrointestinal endoscopy. Three hundred and fifteen patients (aged ≥ 45 years, ASA physical status I or II) presenting for gastrointestinal endoscopy with planned intravenous sedation will be randomly allocated (1:1:1:1:1:1:1:1:1; block sizes 9 and 18) to one of nine equip-sized groups generated by the factorial combination of three sedatives (propofol, ciprofol, remimazolam) with three adjuvant analgesics (sufentanil, esketamine, lidocaine). Sedation will be titrated to Modified Observer’s Assessment of Alertness/Sedation scores of 1–2. The primary outcome is the Christensen Fatigue Scale score (range 1–10; higher = worse) 30 min after the procedure. The secondary outcome is the composite incidence of intra-procedural hypotension (mean arterial pressure < 65 mmHg) and hypoxemia (SpO2 < 90% for ≥ 10 s). Primary analysis will employ two-way factorial ANOVA to test the main effects of sedatives and analgesics on the 30-min fatigue score, with an exploratory interaction analysis. The results of this trial will provide high-resolution evidence on which sedative or analgesic agent most effectively mitigates early post-endoscopy fatigue, thereby informing patient-centered sedation choices and enhancing recovery. Chinese Clinical Trial Registry (ChiCTR2500112657; registered on November 18, 2025)