Drug Design, Development and Therapy (Aug 2024)
The Impact of Fentanyl on the Effective Dose of Remimazolam-Induced Sedation in Elderly Female Patients: An Up-and-Down Sequential Allocation Trial
Abstract
Xiao-Dong Huang,1,* Jia-Bao Chen,2,* Xiao-Yun Dong,1 Wei-Long Wang,1 Jin Zhou,1 Zhen-Feng Zhou1 1Department of Anesthesiology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People’s Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, People’s Republic of China; 2Department of Anesthesiology, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medicine College), Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen-Feng Zhou, Department of Anesthesiology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People’s Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, 310008, People’s Republic of China, Tel +86-571-56005077, Email [email protected]: This study aimed to investigate the influence of fentanyl on the effective dose of remimazolam-induced sedation in elderly female patients undergoing general anesthesia.Patients and Methods: Sixty female patients aged 65– 80 years undergoing selective general anesthesia were randomized into two groups: Group R+F received an initial dose of remimazolam (7.5 mg) with fentanyl (1 μg/kg), while Group R received remimazolam alone. Dosing adjustments (± 2.5 mg) were made based on the response of the preceding patient using the up-and-down allocation technique. The ED50 and ED95 were calculated using a sequential formula and probit regression. Probit regression was also used to assess the relative potency of remimazolam between groups. Sedation levels were evaluated using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale.Results: The ED50 for remimazolam was significantly lower in Group R+F compared to Group R (p= 0.007). Probit regression estimated the ED50 and ED95 values for Group R+F at 4.878 mg (95% CI, 3.845– 5.859) and 8.184 mg (95% CI, 6.636– 13.546), respectively. In contrast, Group R demonstrated ED50 and ED95 values of 6.733 mg (95% CI, 5.533– 8.068) and 11.298 mg (95% CI, 9.101– 19.617), respectively.Conclusion: This study provides compelling evidence that the administration of 1 μg/kg of fentanyl significantly reduces the required sedative dose of remimazolam by approximately 30% during induction in elderly patients. Importantly, the concomitant use of 1 μg/kg of fentanyl does not increase the risk of adverse effects such as hypotension, respiratory depression.Keywords: remimazolam, fentanyl, effective dose, elderly
