Opioid-free Anesthesia and Postoperative Delirium

NCT07603596 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: YXLL-KY-2025（079）
• Study Type: interventional
• Target: 174
• Locations: 0 countries
• Sites: N/A

Brief Summary

Postoperative delirium (POD) is a common acute and transient form of brain dysfunction in elderly patients following surgery that can lead to serious adverse clinical outcomes and even death. Although existing studies have preliminarily investigated the effects of opioid-free anaesthesia (OFA) on POD, high-quality evidence on these effects for elderly patients undergoing gastrointestinal surgery remains limited. This study aims to investigate the effects of OFA on the development of POD in elderly patients following gastrointestinal surgery. This single-centre, prospective, randomized controlled trial will be conducted at the First Affiliated Hospital of Shandong First Medical University, China. A total of 654 patients aged 65 years or older who are scheduled for elective gastrointestinal surgery will be randomly allocated to receive either opioid-free anaesthesia (OFA; dexmedetomidine, esmolol, and esketamine) or conventional opioid-based anaesthesia (OBA). The primary outcome is the incidence of POD 7 days after surgery. The secondary outcomes are all-cause mortality within 30 days after surgery, intraoperative haemodynamic changes, the 15-item quality of recovery (QoR-15) scores at 24 h, 48 h, and 72 h after surgery, complications during postoperative hospitalization, pain numerical rating scale (NRS) score at 72 h after surgery, incidence of nausea and vomiting at 72 h after surgery, morphine milligram equivalent for analgesics at 72 h after surgery, duration of anaesthesia (from induction to discontinuation), duration of surgery (from skin incision to the last suture), duration of post-anaesthesia care unit (PACU) stay, and length of hospital stay. The results of this study may shed light on the effects of OFA on POD in elderly patients undergoing gastrointestinal surgery. The study is designed on the basis of the following key hypothesis: the use of opioid drugs for anaesthesia may increase the risk of POD through mechanisms such as blood-brain barrier destruction, neuroinflammatory responses, and central nervous system depression. Through the single-centre and prospective design of this randomized controlled trial, this study will directly analyse differences in the effects of OFA and conventional OBA on the incidence of POD, haemodynamic stability and long-term cognitive function in elderly patients.

Conditions

Postoperative Delirium; Gastrointestinal Tumors

Keywords

elderly patients; opioid-free anaesthesia; postoperative delirium; gastrointestinal surgery

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium (POD) within 7 days after surgery or at discharge

  7 days after surgery or at discharge

Secondary Outcomes (19)

• All-cause mortality within 30 days after surgery

  30 days after surgery

• Serum tumour necrosis factor-α (TNF-α, pg/mL) concentration

  10 minutes after anaesthesia induction; 10 minutes and 1 hour after pneumoperitoneum; and 24 hours and 48 hours after surgery

• Serum cortisol concentration (nmol/L)

  10 minutes after anaesthesia induction; 10 minutes and 1 hour after pneumoperitoneum; and 24 hours and 48 hours after surgery

• Quality of Recovery-15 (QoR-15) score

  24 hours, 48 hours, and 72 hours after surgery

• Postoperative complications during hospitalization

  During the index hospitalization, from the end of surgery until hospital discharge (assessed daily; reported for the entire hospitalization period) Alternative specific phrasing: "Up to 30 days" if discharge may occur earlier.

Study Arms (2)

Opioid-free anaesthesia group

ACTIVE COMPARATOR

In the OFA group, anaesthesia will be induced with 1.5-2.5 mg/kg propofol, 0.3-0.5 mg/kg esketamine, and 0.6-1.0 mg/kg rocuronium. Endotracheal intubation or laryngeal mask placement will be performed when the BIS value is observed at 40-60.

Drug: OFA group

opioid-based anaesthesia group

ACTIVE COMPARATOR

In the OBA group, anaesthesia will be induced with 1.5-2.5 mg/kg propofol, 0.6-1.0 mg/kg rocuronium, and 0.3-0.5 μg/kg sufentanil. Endotracheal intubation or laryngeal mask airway insertion will be performed when the BIS value decreases to 40-60.

Drug: OBA group

Interventions

OFA group DRUG

In the OFA group, anaesthesia will be induced with 1.5-2.5 mg/kg propofol, 0.3-0.5 mg/kg esketamine, and 0.6-1.0 mg/kg rocuronium. Endotracheal intubation or laryngeal mask placement will be performed when the BIS value is observed at 40-60. Intraoperative continuous intravenous infusion of 2-6 mg/kg/h propofol, 0.5-1.0 μg/kg/h dexmedetomidine, 0.2-0.5 mg/kg/h esketamine, 5-6 μg/kg/min rocuronium bromide, 20-100 μg/kg/min esmolol, and inhaled 1% sevoflurane will be utilized to maintain anaesthesia. At the end of the procedure (after the last suture), all maintenance drugs will be discontinued. Afterwards, 8 mg of ondansetron and 0.2 mg/kg esketamine-assisted sufentanil will be intravenously administered. Postoperative analgesia will be performed by using an intravenous patient-controlled analgesia pump consisting of 1.5 mg/kg esketamine and 16 mg of ondansetron. The volume will be adjusted to 100 mL in 0.9% normal saline; moreover, the continuous infusion rate will be set at 2 mL/h, an

Also known as: Opioid-free anaesthesia

Opioid-free anaesthesia group

OBA group DRUG

In the OBA group, anaesthesia will be induced with 1.5-2.5 mg/kg propofol, 0.6-1.0 mg/kg rocuronium, and 0.3-0.5 μg/kg sufentanil. Endotracheal intubation or laryngeal mask airway insertion will be performed when the BIS value decreases to 40-60. During surgery, 2-6 mg/kg/h propofol, 0.2-1.0 μg/kg/min remifentanil, and 5-6 μg/kg/min rocuronium will be continuously pumped to maintain anaesthesia. Both groups will receive inhalation of 1% sevoflurane during anaesthesia maintenance. At the end of the procedure (after the last suture), all maintenance drugs will be discontinued. Afterwards, 8 mg of ondansetron and 0.15 μg/kg sufentanil will be intravenously injected. Postoperative analgesia will be performed by using an intravenous patient-controlled analgesia pump; the formulation will involve 2 μg/kg sufentanil and 16 mg of ondansetron, which will be diluted to 100 mL with 0.9% normal saline. Moreover, the background infusion rate will be set at 2 mL/h, and the lockout interval will be 1

Also known as: opioid-based anaesthesia

opioid-based anaesthesia group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients who plan to undergo elective gastrointestinal surgery under general anaesthesia
• Age ≥65 years
• American Society of Anaesthesiologists (ASA) grade I-III
• Body mass index (BMI) of 18.0-30.0 kg/m²
• Frailty: mFI ≥ 0.27
• Signed informed consent

You may not qualify if:

• Patients undergoing emergency surgery
• Patients with language disorders or severe hearing or vision impairment that prevent communication
• Patients with a history of neurological and psychiatric disorders, including Alzheimer's disease (AD), other types of dementia, stroke, and psychosis
• Patients with long-term use of psychotropic medications (such as clozapine, risperidone, olanzapine, haloperidol, and chlorpromazine)
• Patients who have undergone cardiac surgery or craniocerebral surgery within the past year
• Patients who have participated in other relevant clinical trials within the past 3 months
• Patients with preoperative cognitive impairment (Telephone Interview for Cognitive Status-modified (TICS-m) score ≤ 27), as determined via the TICS-M test
• Each patient can be included only once, regardless of whether the reason for the second surgery is related to the primary cause
• Let me know if you need this in a different bullet style (e.g., asterisks) or with indentation adjustments.

Sponsors & Collaborators

• Qianfoshan Hospital: lead

Related Publications (10)

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  PMID: 41354156 BACKGROUND

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  PMID: 40562634 BACKGROUND

• Hoogendijk EO, Afilalo J, Ensrud KE, Kowal P, Onder G, Fried LP. Frailty: implications for clinical practice and public health. Lancet. 2019 Oct 12;394(10206):1365-1375. doi: 10.1016/S0140-6736(19)31786-6.

  PMID: 31609228 BACKGROUND

• Desrochers RM, Lynch LJ, Gates JD, Ricaurte D, Wade JT, Dicks RS, Keating JJ. Outcomes in Post-operative Delirium Following Bowel Resection: A Single Center Retrospective Review. J Surg Res. 2022 Dec;280:163-168. doi: 10.1016/j.jss.2022.07.009. Epub 2022 Aug 13.

  PMID: 35973340 BACKGROUND

• Li H, Liu C, Yang Y, Wu QP, Xu JM, Wang DF, Sun JJ, Mao MM, Lou JS, Liu YH, Cao JB, Duan CY, Mi WD. Effect of Intraoperative Midazolam on Postoperative Delirium in Older Surgical Patients: A Prospective, Multicenter Cohort Study. Anesthesiology. 2025 Feb 1;142(2):268-277. doi: 10.1097/ALN.0000000000005276. Epub 2024 Oct 29.

  PMID: 39470760 BACKGROUND

• Dilmen OK, Meco BC, Evered LA, Radtke FM. Postoperative neurocognitive disorders: A clinical guide. J Clin Anesth. 2024 Feb;92:111320. doi: 10.1016/j.jclinane.2023.111320. Epub 2023 Nov 8.

  PMID: 37944401 BACKGROUND

• Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Aceto P, Audisio R, Cherubini A, Cunningham C, Dabrowski W, Forookhi A, Gitti N, Immonen K, Kehlet H, Koch S, Kotfis K, Latronico N, MacLullich AMJ, Mevorach L, Mueller A, Neuner B, Piva S, Radtke F, Blaser AR, Renzi S, Romagnoli S, Schubert M, Slooter AJC, Tommasino C, Vasiljewa L, Weiss B, Yuerek F, Spies CD. Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients. Eur J Anaesthesiol. 2024 Feb 1;41(2):81-108. doi: 10.1097/EJA.0000000000001876. Epub 2023 Aug 30.

  PMID: 37599617 BACKGROUND

• Sim JH, Kim KM, Lee U, Lee EK, Noh GJ, Choi BM. Incidence of postoperative delirium and quality of recovery in older patients undergoing gastrectomy under general anaesthesia with remimazolam vs. propofol: a randomised non-inferiority study. Anaesthesia. 2025 Nov;80(11):1370-1380. doi: 10.1111/anae.16684. Epub 2025 Jul 14.

  PMID: 40653956 BACKGROUND

• Scholz AF, Oldroyd C, McCarthy K, Quinn TJ, Hewitt J. Systematic review and meta-analysis of risk factors for postoperative delirium among older patients undergoing gastrointestinal surgery. Br J Surg. 2016 Jan;103(2):e21-8. doi: 10.1002/bjs.10062. Epub 2015 Dec 16.

  PMID: 26676760 BACKGROUND

• Liu J, Wang T, Song J, Cao L. Effect of esketamine on postoperative analgesia and postoperative delirium in elderly patients undergoing gastrointestinal surgery. BMC Anesthesiol. 2024 Feb 1;24(1):46. doi: 10.1186/s12871-024-02424-w.

  PMID: 38302882 BACKGROUND

MeSH Terms

Conditions

Emergence Delirium; Digestive System Neoplasms

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Neoplasms by Site; Neoplasms; Digestive System Diseases

Study Officials

• Yongtao Sun

  Shandong First Medical University

  PRINCIPAL INVESTIGATOR

• Min Zhang

  Shandong First Medical University

  STUDY CHAIR

Central Study Contacts

Yongtao Sun, PHD. MD.

CONTACT

+8618660795201; science2020@hotmail.com

Min Zhang

CONTACT

Zhangmin201609@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director

Study Record Dates

• First Submitted: April 6, 2026
• First Posted: May 22, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 3 years after the publication of results.
• Access Criteria: Who Qualified researchers from academic, non-profit, or commercial institutions with an approved research proposal; regulatory authorities; and direct collaborators. What Anonymized IPD, data dictionary, protocol, SAP, and ICF summary. No direct or indirect participant identifiers. How Submit proposal via online portal. Independent review committee approval. Sign data use agreement (non-identification, non-commercial, no third-party sharing). Access via secure virtual research environment or encrypted download; time-limited (e.g., 12 months); audit logs kept.