Study of remimazolam besylate for general anaesthesia and population pharmacokinetics-pharmacodynamics in elderly, hepatic or renal-insufficient patients: a protocol for a multicentre randomised controlled trial in China.

backgroundRemimazolam, an ultra-short-acting benzodiazepine, is characterised by rapid onset and recovery, metabolism independent of hepatic or renal function and haemostability. Despite the above pharmacokinetic (PK) advantages and potential benefits for renal- or hepatic-insufficient patients and the elderly patients, the effects and population pharmacokinetics-pharmacodynamics (popPK/PD) of remimazolam for general anaesthesia in elderly, hepatic or renal insufficient patients from large, randomised controlled trials remain unknown. METHODS AND ANALYSIS: This is a randomised controlled single-blind multicentre study. Patients undergoing selective surgeries (eg, abdominal, orthopaedic or urologic procedures) will be screened and randomised into the elderly (age ≥65 years), hepatic insufficiency (Child-Pugh class B or C) or renal insufficiency (estimated glomerular filtration rate <60 mL/min/1.73 m²) groups, with a target of 752 subjects per group. Patients in each group will randomly receive remimazolam or propofol for general anaesthesia induction and maintenance. The primary outcome is the quality of induction and maintenance of general anaesthesia (the time of maintaining bispectral index (BIS) 35-65 divided by the time for test-drug administration). Secondary outcomes are PK and PD characteristics of remimazolam in the target populations, which include: the incidence of hypotension; incidence and amount of vasoconstrictor agents; area under the curves of blood pressure over time; pain on injection; eye opening time; extubation time; time to reach modified Aldrete scores 9; nursing delirium screening scores and incidence of intraoperative awareness. Exploring outcomes are remimazolam besylate plasma concentrations; the ideal target remimazolam besylate plasma concentrations (plasma concentrations corresponding to a BIS value between 35 and 65) and the optimal dosage regimen based on the popPK/PD model. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of West China Hospital, Sichuan University, on 30 August 2024, and registered at the Chinese Clinical Trial Registry. The findings of this study will be disseminated through presentations at relevant conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2400089033.