A randomized trial on the ED₅₀ and hemodynamic stability of a remimazolam-propofol combination for induction in elderly patients undergoing lumbar fusion surgery

Abstract

The appropriate remimazolam dosage for induction in elderly patients undergoing lumbar fusion surgery, when used alongside a fixed propofol dose of 1 mg/kg, is yet to be determined. We aimed to estimate the effective doses (ED₅₀ and ED₉₅) of remimazolam with propofol and to characterise peri-induction hemodynamic effects. This prospective, two-phase study enrolled patients aged 65–80 years with ASA physical status I–II. In the dose-finding phase ( n = 27), Dixon’s up-and-down method was used to determine the ED₅₀ and ED₉₅ of remimazolam combined with propofol 1 mg/kg, with success defined as sustained BIS < 60 within 2 min without rescue medication. In the randomized phase, 90 patients were allocated to propofol–midazolam (Group A: propofol 1 mg/kg + midazolam 0.03 mg/kg), remimazolam monotherapy (Group B: 0.2 mg/kg), or propofol–remimazolam (Group C: propofol 1 mg/kg + remimazolam at the ED₅₀). All patients received standardized sufentanil (0.3 µg/kg) and rocuronium (0.6 mg/kg). MAP, HR, BIS, and adverse events were recorded at pre-induction (T₀), pre-intubation (T₁), 1, 3, and 5 min post-intubation (T₂–T₄), and 1 min before and after prone positioning (T₅–T₆). The ED₅₀ and ED₉₅ of remimazolam were 0.14 mg/kg and 0.19 mg/kg, respectively, when combined with 1 mg/kg propofol. The incidence of hypotension (primary outcome) was 63.3% in Group A, 20.0% in Group B, and 6.7% in Group C. Group C had a significantly lower incidence than Group A (risk difference [RD] − 56.7%, 95% CI − 76.1 to − 37.2, P < 0.001) and Group B had a significantly lower incidence than Group A (RD − 43.3%, 95% CI − 65.7 to − 20.9, P < 0.001). Hypertension was more frequent in Group B (30.0%) than in Group A (0%; RD 30.0%, 95% CI 13.6–46.4, P < 0.001) and Group C (3.3%; RD − 26.7%, 95% CI − 44.3 to − 9.1, P = 0.003). Linear mixed-effects modelling revealed significant Group×Time interactions for HR, MAP, and BIS (all P < 0.01). MAP was consistently lower in Group A than in Groups B and C from T₁ to T₆; HR was lower in Group A than in Groups B and C at most time points from T₂ to T₆; BIS was lower in Groups A and C than in Group B during the maintenance phase. Injection pain was less frequent in Group B (0%) than in Group A (23.3%; RD − 23.3%, 95% CI − 38.5 to − 8.2, P = 0.003). In elderly patients having lumbar fusion surgery, the ED₅₀ of remimazolam with 1 mg/kg propofol is 0.14 mg/kg. The model-based ED₉₅ estimate of 0.19 mg/kg (95% CI: 0.17–0.37) should be interpreted with caution as an extrapolation beyond the observed dose range. Using the ED₅₀ dose with propofol 1 mg/kg during induction improved hemodynamic stability, reducing hypotension compared to propofol–midazolam and lowering hypertension compared to remimazolam alone. Chinese Clinical Trial Registry, ChiCTR2400079846, registered 15 January 2024.

The authors' abstract, as published at the source. BMC Anesthesiology, 2026 · DOI ↗