Cuiyuan Huang, Yue Song, Jia Li, Yanping Lu, Guangyi Lai, Zuofeng Wang, Shan Ou
Background Patients with elevated body mass index (BMI) are particularly susceptible to propofol-induced hypotension during anesthesia induction. Fospropofol, a water-soluble prodrug of propofol, may confer hemodynamic advantages through gradual release kinetics, yet its profile in high-BMI patients remains incompletely characterized. Methods This pre-specified secondary analysis of a randomised controlled trial (ChiCTR2500101725) enrolled 120 patients with BMI ≥28 kg/m² scheduled for elective surgery, randomised to fospropofol (FOS, n = 60) or propofol (PRO, n = 60). The primary endpoint of this analysis was hypotension incidence (any MAP <65 mmHg) during the pre-incision phase. Key secondary endpoints included hypotension area under the curve (AUC), MAP variability, emergence time, extubation time, and hospital length of stay. Results Hypotension incidence was 30.0% (FOS) vs. 71.7% (PRO) [RR 2.39, 95% CI 1.57–3.63; p < 0.001; NNT 2.4 (i.e., one additional patient needs to be treated with fospropofol rather than propofol to prevent one case of hypotension)]. FOS patients had reduced hypotension burden (median AUC 0.0 vs. 29.5 mmHg·min; p < 0.001), lower MAP variability (8.7 ± 2.2% vs. 19.0 ± 7.4%; Cohen's d = 1.87), and higher MAP nadir (median 69.5 vs. 55.0 mmHg; p < 0.001). Emergence time was shorter with FOS (7.9 ± 2.7 vs. 10.7 ± 3.4 min; d = 0.91), as was extubation time (10.0 ± 2.7 vs. 12.7 ± 3.5 min; d = 0.86). A significant treatment × surgery interaction for extubation time ( p = 0.042) indicated amplified benefit in abdominal procedures ( Δ = −3.58 min vs. −1.07 min). Conclusions Fospropofol demonstrated superior hemodynamic stability during the pre-incision phase and faster early recovery compared with propofol in high-BMI patients, particularly in abdominal surgical procedures. Clinical Trial Registration https://www.chictr.org.cn/showproj.html?proj=253889 , identifier ChiCTR2500101725 (registered 29 April 2025).