The effect of oxycodone vs. sufentanil on postoperative delirium in elderly patients undergoing major abdominal surgery: a randomized trial

Background: Postoperative delirium (POD) is a neurological disorder that frequently affects elderly patients undergoing major abdominal surgery. Existing research indicates that perioperative administration of oxycodone may enhance postoperative cognitive function. This study was conducted to examine the impact of preemptive analgesia with oxycodone on the occurrence of POD in elderly patients undergoing major abdominal surgery. Methods: We randomly assigned 120 patients to receive oxycodone versus sufentanil. Both oxycodone and sufentanil were administered ten minutes before the induction of anesthesia. The primary outcome was the incidence of POD within 7 days post-surgery (or before discharge). Delirium was assessed twice daily using either a Diagnostic Interview for the Confusion Assessment Method or the Confusion Assessment Method for the Intensive Care Unit. Secondary outcomes included postoperative opioid consumption, pain score, patient satisfaction score, and adverse events. Results: The final analysis included 112 patients and the incidence of POD was similar between oxycodone and sufentanil(risk ratio, 0.64; 95% confidence interval, 0.28 to 1.45; p = 0.282). However, patients treated with oxycodone had lower postoperative opioid consumption, reduced pain scores and postoperative nausea and vomiting. Conclusions: Although oxycodone preemptive analgesiadid not reduce the incidence of POD, it demonstrated effective analgesic properties and reduced postoperative adverse events. Clinical Trial Registration: The study was registered with the Chinese Clinical Trial Registration Center (ChiCTR2200064308, 02 October 2022).

Delirium; Preemptive analgesia; Oxycodone

[1] Wildes TS, Mickle AM, Ben Abdallah A, Maybrier HR, Oberhaus J, Budelier TP, et al.; ENGAGES Research Group. Effect of electroencephalography-guided anesthetic administration on postoperative delirium among older adults undergoing major surgery: the ENGAGES randomized clinical trial. JAMA. 2019; 321: 473–483.

[2] Evered LA, Chan MTV, Han R, Chu MHM, Cheng BP, Scott DA, et al. Anaesthetic depth and delirium after major surgery: a randomised clinical trial. British Journal of Anaesthesia. 2021; 127: 704–712.

[3] Ding X, Gao X, Chen Q, Jiang X, Li Y, Xu J, et al. Preoperative acute pain is associated with postoperative delirium. Pain Medicine. 2021; 22: 15–21.

[4] Pirie K, Traer E, Finniss D, Myles PS, Riedel B. Current approaches to acute postoperative pain management after major abdominal surgery: a narrative review and future directions. British Journal of Anaesthesia. 2022; 129: 378–393.

[5] Lauretta MP, Marino L, Bilotta F. Safety and efficacy of opioid-sparing anesthesia compared with traditional opioid anesthesia: a scoping review. The Clinical Journal of Pain. 2025; 41: e1261.

[6] Dong P, Qu X, Yang Y, Li X, Wang C. Effect of oxycodone versus fentanyl for patient-controlled intravenous analgesia after laparoscopic hysteromyomectomy: a single-blind, randomized controlled trial. Scientific Reports. 2024; 14: 20478.

[7] Yang GW, Cheng H, Song XY, Yang YF, Liu H, Ji FH, et al. Effect of oxycodone-based multimodal analgesia on visceral pain after major laparoscopic gastrointestinal surgery: a randomised, double-blind, controlled trial. Drug Design, Development and Therapy. 2024; 18: 1799–1810.

[8] Wang Q, Guo J, Hou M. Effect of intercostal nerve block combined with oxycodone on the postoperative cognitive ability in elderly patients undergoing radical resection of lung cancer. American Journal of Translational Research. 2022; 14: 6277–6285.

[9] Gan J, Tu Q, Miao S, Lei T, Cui X, Yan J, et al. Effects of oxycodone applied for patient-controlled analgesia on postoperative cognitive function in elderly patients undergoing total hip arthroplasty: a randomized controlled clinical trial. Aging Clinical and Experimental Research. 2020; 32: 329–337.

[10] Xuan C, Yan W, Wang D, Li C, Ma H, Mueller A, et al. Efficacy of preemptive analgesia treatments for the management of postoperative pain: a network meta-analysis. British Journal of Anaesthesia. 2022; 129: 946–958.

[11] An Y, Zhao L, Wang T, Huang J, Xiao W, Wang P, et al. Preemptive oxycodone is superior to equal dose of sufentanil to reduce visceral pain and inflammatory markers after surgery: a randomized controlled trail. BMC Anesthesiology. 2019; 19: 96.

[12] Li Y, Dou Z, Yang L, Wang Q, Ni J, Ma J. Oxycodone versus other opioid analgesics after laparoscopic surgery: a meta-analysis. European Journal of Medical Research. 2021; 26: 4.

[13] Shah VS, Dornbos D, Hoang NA, Cua S, Rodgers B, Pezzutti D, et al. Preoperative prescription opioid use as an independent predictor of 90-day mortality and adverse events in craniotomy and craniectomy patients. Journal of Neurosurgery. 2024; 141: 455–460.

[14] Du Y, Cao J, Gao C, He K, Wang S. Correction: influence of intraoperative pain management on postoperative delirium in elderly patients: a prospective single-center randomized controlled trial. Pain and Therapy. 2025; 14: 769–773.

[15] Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. The BMJ. 2010; 340: c332.

[16] Tan H, Wang C, Jiang Y, Shi Q, Liang W, Li D. Postoperative effect of sufentanil preemptive analgesia combined with psychological intervention on breast cancer patients. BMC Anesthesiology. 2023; 23: 170.

[17] Shen QH, Li HF, Zhou XY, Lu YP, Yuan XZ. Relation of serum melatonin levels to postoperative delirium in older patients undergoing major abdominal surgery. The Journal of International Medical Research. 2020; 48: 300060520910642.

[18] Miyagawa Y, Yokoyama Y, Fukuzawa S, Fukata S, Ando M, Kawamura T, et al. Risk factors for postoperative delirium in abdominal surgery: a proposal of a postoperative delirium risk score in abdominal surgery. Digestive Surgery. 2017; 34: 95–102.

[19] Evered L, Silbert B, Knopman DS, Scott DA, DeKosky ST, Rasmussen LS, et al.; Nomenclature Consensus Working Group. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery—2018. British Journal of Anaesthesia. 2018; 121: 1005–1012.

[20] Yang GW, Zhuang MY, Shi HJ, Song XY, Liu H, Ji FH, et al. Oxycodone vs. sufentanil combined with quadratus lumborum block vs. transverse abdominis plane block in laparoscopic major gastrointestinal surgery: a randomized factorial trial protocol. Heliyon. 2024; 10: e36186.

[21] Staahl C, Upton R, Foster DJ, Christrup LL, Kristensen K, Hansen SH, et al. Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model. Journal of Clinical Pharmacology. 2008; 48: 619–631.

[22] Taumberger N, Schütz AM, Jeitler K, Siebenhofer A, Simonis H, Bornemann-Cimenti H, et al. Preemptive local analgesia at vaginal hysterectomy: a systematic review. International Urogynecology Journal. 2022; 33: 2357–2366.

[23] Gan TJ, Jin Z, Meyer TA. Rescue treatment of postoperative nausea and vomiting: a systematic review of current clinical evidence. Anesthesia and Analgesia. 2022; 135: 986–1000.

[24] Yu DH, Shen X, Lai L, Chen YJ, Liu K, Shen QH. Application of dexmedetomidine as an opioid substitute in opioid-free anesthesia: a systematic review and meta-analysis. Pain Physician. 2023; 26: E635–E649.

[25] Fiore JF III, El-Kefraoui C, Chay MA, Nguyen-Powanda P, Do U, Olleik G, et al. Opioid versus opioid-free analgesia after surgical discharge: a systematic review and meta-analysis of randomised trials. The Lancet. 2022; 399: 2280–2293.