Mini-dose esketamine–dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial

Abstract

Background

Patients often experience severe pain after scoliosis correction surgery. Esketamine and dexmedetomidine each improves analgesia but can produce side-effects. We therefore tested the hypothesis that a mini-dose esketamine-dexmedetomidine combination safely improves analgesia.

Methods

Two hundred male and female adults having scoliosis correction surgery were randomised to patient-controlled sufentanil analgesia (4 μg kg⁻¹ in normal saline) with either a combined supplement (esketamine 0.25 mg ml⁻¹ and dexmedetomidine 1 μg ml⁻¹) or placebo. The primary outcome was the incidence of moderate-to-severe pain within 72 h, defined as a numeric rating scale (NRS: 0=no pain and 10=worst pain) score ≥4 at any of seven time points. Amongst secondary outcomes, subjective sleep quality was assessed with an NRS score (0=best sleep and 10=worst sleep) for the first five postoperative nights.

Results

There were 199 subjects included in the intention-to-treat analysis. Mean infusion rates were 5.5 μg kg⁻¹ h⁻¹ for esketamine and 0.02 μg kg⁻¹ h⁻¹ for dexmedetomidine. The primary outcome incidence was lower with the combined supplement (65.7% [65/99]) than with placebo (86.0% [86/100]; relative risk 0.76; 95% confidence interval: 0.65–0.90; P=0.001). Subjects given the combined supplement had lower pain intensity at rest at five time points (median difference –1 point; P≤0.005), lower pain intensity with movement at six time points (median difference –1 point; P≤0.001), and better subjective sleep quality for the first 5 postoperative nights (median difference –2 to –1 points; P<0.001). Adverse events did not differ between groups.

Conclusions

The mini-dose esketamine–dexmedetomidine combination safely improved analgesia and subjective sleep quality after scoliosis correction surgery.

Clinical trial registration

NCT04791059.