# Premixed Lidocaine With Fospropofol Disodium for Safety and Clinical Evaluation Regarding Paresthesia Upon Fospropofol Disodium Injection: A Preclinical Experimental Study and a Randomized Controlled Trial

## TL;DR

This study tested if mixing lidocaine with fospropofol reduces injection-related paresthesia but found no difference in symptoms between groups.

## Contribution

The novel contribution is evaluating lidocaine's effectiveness in reducing fospropofol-induced paresthesia through preclinical and clinical trials.

## Key findings

- Premixing lidocaine with fospropofol did not reduce paresthesia occurrence in clinical trials.
- Paresthesia occurred in 83.3% of patients in both groups, typically 40–60 seconds after administration.
- Plasma phosphate levels increased post-administration in both groups, but no group differences were observed.

## Abstract

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.

This study explored the effect of lidocaine premixing on fospropofol‐induced paresthesia. While the mixture of fospropofol (FP) and lidocaine (LD) proved chemically stable and safe in preclinical tests, clinical results from randomized controlled trial showed no reduction in paresthesia in FP+LD group compared with FP+NS group. And paresthesia typically occurred 40–60 s after administration, accompanied by postadministration increases in plasma phosphate levels in both groups.