Local infiltration versus intramuscular esketamine for procedural pain and postoperative PHQ-9 scores in older adults undergoing percutaneous kyphoplasty: a randomised controlled trial

Older adults undergoing percutaneous kyphoplasty (PKP) under local anaesthesia may experience substantial procedural pain. It remains uncertain whether local infiltration and intramuscular administration of esketamine differ in their effects on procedural pain, postoperative PHQ-9 depressive symptom scores, and short-term tolerability. In this single-centre, double-blind, three-arm randomised trial, 99 older adults were allocated 1:1:1 to intramuscular esketamine 25 mg, local infiltration of esketamine 25 mg combined with lidocaine, or control treatment. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) score on postoperative day 1, analysed using analysis of covariance adjusted for baseline score. Pre-specified comparisons were local infiltration versus control and local infiltration versus intramuscular administration, each tested at α = 0.025. Key secondary outcomes included pain scores during pedicle puncture, balloon inflation, and bone cement injection. All 99 randomised participants, with a mean (SD) age of 69.6 (3.1) years, completed follow-up and were included in the analysis. Using the standard 2-week recall period, mean (SD) PHQ-9 scores on postoperative day 1 were 2.15 (0.71), 3.88 (1.17), and 4.82 (1.38) in the local infiltration, intramuscular, and control groups, respectively. After adjustment for baseline PHQ-9 score, scores were lower in the local infiltration group than in the control group (adjusted mean difference, − 2.37; 95% CI, − 2.71 to − 2.02; P < 0.001) and the intramuscular group (− 1.62; 95% CI, − 1.96 to − 1.28; P < 0.001). Procedural pain scores during all three key surgical stages were also lower in the local infiltration group than in both comparator groups (all adjusted P < 0.001). At least one adverse event occurred in 1 of 33 (3.0%), 8 of 33 (24.2%), and 1 of 33 (3.0%) participants in the local infiltration, intramuscular, and control groups, respectively. In older adults undergoing percutaneous kyphoplasty under local anaesthesia, local infiltration with esketamine 25 mg was associated with lower procedural pain scores and lower PHQ-9 scores on postoperative day 1 than either intramuscular esketamine 25 mg or control. PHQ-9 scores remained lower on postoperative days 3 and 7, but not on day 30. Fewer adverse events were observed in the local infiltration group than in the intramuscular group. The clinical importance of the PHQ-9 differences remains uncertain because of the instrument’s 2-week recall period and the lack of an established minimum clinically important difference in this perioperative setting. The study was retrospectively registered at ChiCTR.org.cn with the registration number ChiCTR2500095649 on 9 January 2025.