Dose-dependent effects of esketamine on the prevention of propofol-induced injection pain: a randomized controlled trial.

Abstract

BACKGROUND: In our previous study, we showed that a low dose of esketamine could alleviate propofol-induced injection pain during general anesthesia induction. However, the dose-response relationship of esketamine remains unclear. This study aims to evaluate the dose-dependent efficacy of esketamine in preventing propofol-induced injection pain. METHODS: In this double-blind, randomized controlled trial, patients scheduled for elective ear surgery were randomized into five groups: Group NS (normal saline), Group L (40 mg lidocaine), Group S0.075 (0.075 mg/kg esketamine), Group S0.15 (0.15 mg/kg esketamine), and Group S0.3 (0.3 mg/kg esketamine). Study medications were administered intravenously 30 seconds before manual injection of propofol (2 mg/kg). The primary outcome was the incidence of propofol-induced injection pain. Secondary outcomes included the severity of injection pain, hemodynamic changes, and drug-related adverse events. RESULTS: A total of 171 patients were analyzed. The incidence of propofol-induced injection pain was 71% in the NS group, and significantly decreased to 47%, 29%, and 9% in the S0.075, S0.15, and S0.3 groups, respectively (all P < 0.05). Notably, the S0.3 group demonstrated superior efficacy compared to the lidocaine group (9% versus 32%, P < 0.05). The incidence and pain scores of injection pain were significantly lower in the L, S0.15, and S0.3 groups compared to the NS group (P < 0.05). Moreover, pretreatment with 0.15 and 0.3 mg/kg esketamine was associated with better hemodynamic stability compared to both the NS and lidocaine groups (P < 0.05). Importantly, no statistically significant differences were observed in the incidence of adverse events among all groups. CONCLUSIONS: Esketamine pretreatment exhibits dose-dependent efficacy in preventing propofol-induced injection pain, with the 0.3 mg/kg dose providing the most pronounced protective effect. Additionally, both the 0.15 and 0.3 mg/kg doses of esketamine help maintain hemodynamic stability during anesthesia induction. Therefore, 0.3 mg/kg esketamine is recommended as the preferred pretreatment dose, offering effective prevention of propofol-induced pain and stable hemodynamics during induction. TRIAL REGISTRATION: ChiCTR2100043324. Trial Registration Date: February 10, 2021. Date of enrolment of the first research participant: February 23, 2021.

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