Background: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy.

Methods: Seventy-five patients aged ≥65 years and American Society of Anesthesiologists (ASA) class I-III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F₁, group F₂, and group F₃, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F₁, 0.2 mg/kg in group F₂, 0.15 mg/kg in group F₃. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate.

Results: The ED50 of remimazolam tosilate in group F₃ was lower than that in group F₁ and F₂ (0.095 [0.088-0.108] mg/kg vs 0.162 [0.153-0.171] mg/kg; 0.258 [0.249-0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264-0.295 mg/kg) in group F₁, 0.175 mg/kg (95% CI: 0.167-0.200 mg/kg) in group F₂ and 0.109 mg/kg (95% CI: 0.101-0.135 mg/kg) in group F₃. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F₁ compared to groups F₂ and F₃ (p < 0.05). The patients in group F₃ had a lower incidence of hypotension than in groups F₁ and F₂ (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups.

Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.