A comparison of ciprofol-nalbuphine versus propofol-nalbuphine on safety and efficacy during gastrointestinal endoscopy: a randomized controlled trial

Procedural sedation/anesthesia for gastrointestinal endoscopy (GE) is frequently associated with hypotension. Ciprofol, a novel anesthetic agent with a pharmacological profile similar to propofol, may offer improved cardio-respiratory stability. This study aimed to compare the safety and efficacy of ciprofol-nalbuphine versus the traditional propofol-nalbuphine in GE patients. A total of 270 adults scheduled for consecutive gastroscopy and colonoscopy were randomly assigned to the propofol-nalbuphine group (PNG) or the ciprofol-nalbuphine group (CNG). The primary outcome was the incidence of hypotension, analyzed at two thresholds: (1) hypotension, defined as a > 20% decrease in mean arterial pressure (MAP) from baseline; and (2) severe hypotension, defined as a > 30% decrease in MAP from baseline. Secondary outcomes comprised hemodynamic parameters, Narcotrend stage and index, anesthesia duration and drug dosage, and the incidence of injection pain, respiratory depression, and other predefined safety endpoints. Compared with the PNG, the CNG had a lower incidence of hypotension (33.6% vs. 46.2%, P = 0.033), severe hypotension (6.7% vs. 16.2%, P = 0.015), respiratory depression (5.2% vs. 13.3%, P = 0.022), and injection pain (1.5% vs. 31.1%, P < 0.001). After adjusting for baseline values, systolic blood pressure was significantly higher in the CNG at 1 and 5 min post-induction, as well as significantly higher MAP and diastolic blood pressure at 5 min post-induction. The CNG demonstrated more stable anesthesia depth control, with a higher Narcotrend index at 1 min post-induction (36.9 ± 0.6 vs. 30.4 ± 0.6, P < 0.001) but lower at 10 min post-induction (58.2 ± 0.9 vs. 62.5 ± 1.1, P = 0.003) and at the end of GE (68.9 ± 1.0 vs. 77 ± 0.8, P < 0.001), with a more favorable anesthesia depth stage distribution. Additionally, the CNG required significantly lower total equivalent anesthetic dosage (192.1 ± 39.0 vs. 239.7 ± 54.1 mg, P < 0.001). Compared with the PNG, the CNG demonstrated fewer hypotensive episodes, more stable intraprocedural hemodynamics, and along with a lower incidence of adverse events, suggesting that ciprofol might be a suitable alternative for sedation/anesthesia in GE. The trial was retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2500113434) on November 28, 2025.