Effects of different administration routes of esketamine on postoperative hyperalgesia in elderly patients undergoing laparoscopic gastrointestinal tumour surgery: a single-centre, prospective, randomised, double-blind, controlled trial

<title>Abstract</title> <p> <bold>Background</bold> Opioid-induced hyperalgesia is a significant concern in elderly patients undergoing laparoscopic gastrointestinal tumour surgery. Esketamine, an N-methyl-D-aspartate receptor antagonist, may mitigate this risk; however, the optimal administration regimen in this population remains undefined. <bold>Methods</bold> To compare the effects of continuous infusion versus intermittent bolus administration of esketamine on postoperative hyperalgesia in elderly patients undergoing laparoscopic gastrointestinal tumour surgery.A single-centre, prospective, randomised, double-blind, placebo-controlled, parallel-group superiority trial with a 1:1:1 allocation ratio. Xing'an League People's Hospital, Inner Mongolia, China, from December 2023 to April 2025.Ninety-nine elderly patients (aged 60–76 years, ASA physical status II–III) scheduled for elective laparoscopic gastrointestinal tumour surgery. Patients were randomly allocated to three groups (n = 33 each): Group K1 received esketamine 0.25 mg·kg⁻¹ loading dose followed by continuous infusion at 0.2 mg·kg⁻¹·h⁻¹ until 30 min before the end of surgery; Group K2 received the same loading dose plus an additional 0.2 mg·kg⁻¹ bolus 30 min before wound closure; Group S (control) received sufentanil 0.2 µg·kg⁻¹ for induction plus normal saline infusion.The primary outcome was mechanical pain threshold (kgf) measured at 5 cm from the incision and at the medial forearm using an electronic Von Frey algometer preoperatively and at 2, 24, and 48 h postoperatively. Secondary outcomes included Visual Analogue Scale scores, perioperative opioid consumption, patient-controlled analgesia demands, and adverse events. <bold>Results</bold> Postoperative mechanical thresholds differed significantly among groups (p &lt; 0.05). Group K1 showed lower Visual Analogue Scale scores, reduced intraoperative and 48-h postoperative opioid consumption, and fewer patient-controlled analgesia demands than Groups S and K2 (p &lt; 0.05). Compared with Group S, Group K1 also had lower incidences of postoperative nausea and vomiting, breakthrough pain, and rescue analgesia (p &lt; 0.05). No patient developed postoperative delirium. <bold>Conclusions</bold> Both continuous infusion and intermittent bolus administration of esketamine reduce postoperative hyperalgesia in elderly patients undergoing laparoscopic gastrointestinal tumour surgery; however, continuous infusion is superior in reducing opioid consumption and opioid-related adverse events. <bold>Trial registration</bold> The trial is registered with the China Clinical Trials Registry Registration Number: ChiCTR2400083196. </p>