Effects of different doses of esketamine as an adjunct to sufentanil-based patient-controlled intravenous analgesia on postoperative analgesia and opioid consumption following lumbar decompression surgery: a dose-finding randomized controlled trial

Objective This study aimed to evaluate the effects of different doses of esketamine as an adjunct to sufentanil-based patient-controlled intravenous analgesia (PCIA) on postoperative analgesia and opioid consumption after lumbar decompression surgery and to explore its optimal risk–benefit dose. Methods A total of 120 patients scheduled for lumbar decompression surgery were randomly allocated to four groups. The control group (Group N, n = 30) received PCIA with sufentanil 2.5 μg/kg. To test the opioid-sparing hypothesis, the three experimental groups (Groups S1, S2, and S3, n = 30 each) received PCIA with a lower sufentanil dose (1.5 μg/kg) combined with esketamine at 0.25, 0.5, and 1.0 mg/kg, respectively. All PCIA solutions were diluted with normal saline to a total volume of 100 mL. The primary outcome was the Visual Analogue Scale (VAS) pain score at rest. Secondary outcomes included sufentanil consumption, PCIA press counts, requirement for rescue analgesia, Ramsay Sedation Scale (RSS) scores, and oxidative-stress markers; safety endpoints were analyzed as exploratory outcomes. Postoperative adverse effects, including nausea, vomiting, dizziness, respiratory depression, hypotension, and psychiatric symptoms (dissociation or nightmares), were recorded and compared across the four groups. Results All esketamine-containing regimens (S1–S3) showed significantly lower VAS scores at all postoperative time points compared with Group N (P < 0.05), with no statistically significant difference among S1, S2, and S3. The 24-h sufentanil consumption, effective PCIA presses, and rescue analgesia demand were also significantly reduced (P < 0.05). However, Ramsay sedation scores increased dose-dependently (S3 > S2 > S1). At 4 h postoperatively, SOD activity was higher, and concentrations of MDA, GLU, and COR were lower in all esketamine-containing regimens compared with Group N. Although the overall incidence of adverse events was comparable, the high-dose group (S3) had a significantly increased incidence of hypotension and dissociative symptoms. Conclusion Adding esketamine to a reduced-sufentanil PCIA regimen improved postoperative analgesia and reduced opioid consumption after lumbar decompression surgery. Analgesic benefit was similar across the tested doses (0.25–1.0 mg/kg), whereas dose-related adverse effects (sedation, hypotension, psychomimetic symptoms) increased with dose. These findings suggest that 0.25 mg/kg may provide a favorable efficacy-safety balance within the investigated dose range. Clinical Trial registration http://www.chictr.org.cn/showproj.aspx?proj=249890 , Identifier: ChiCTR2500095890.