Fospropofol Disodium

Fospropofol disodium (fospropofol), a water‐soluble prodrug of propofol, reduces injection pain and anesthetic requirements but frequently causes paresthesia. Intravenous lidocaine has been shown to alleviate dexamethasone‐induced paresthesia, yet its effect on fospropofol‐related symptoms remains uncertain. We combined preclinical and clinical studies, first evaluating the safety and pharmacological changes of fospropofol premixed with lidocaine through in vitro and in vivo experiments and then conducting a randomized controlled trial in adult surgical patients to evaluate whether the lidocaine premixing strategy affects the occurrence of fospropofol‐induced paresthesia. In the preclinical study, the findings indicated that mixture of fospropofol and lidocaine remained physicochemically stable, with faster onset and longer sedation duration compared with fospropofol alone, without additional adverse effects. In the clinical trial, 74 patients received fospropofol dissolved in either 20 mL of normal saline or 0.75% lidocaine and 72 were included in the primary outcome analysis of paresthesia. This adverse reaction occurred in 83.3% of patients in both groups, mainly within 40–60 s after administration. No group differences were observed in plasma inflammatory markers and phosphate; however, phosphate levels increased postadministration in both groups. This study provides important guidance for clinical practice, showing that premixing lidocaine does not effectively alleviate paresthesia induced by fospropofol.