Effect of Opioid-free Anaesthesia on Postoperative Delirium in Elderly Patients Undergoing Gastrointestinal Surgery

Effect of Opioid-free Anaesthesia on Postoperative Delirium in Elderly Patients Undergoing Gastrointestinal Surgery: a Single-centre, Prospective, Randomized Controlled Trial

Background 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.

Methods and analysis:

This single-centre, prospective, randomized controlled trial will be conducted at the First Affiliated Hospital of Shandong First Medical University, China. A total of 406 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.

Discussion:

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.

gastrointestinal surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Opioid-Free Anaesthesia; Delirium - Postoperative
• Intervention / Treatment: Drug: Sufentanil; Drug: Remifentanil; Drug: Dexmedetomidine; Drug: Esketamine; Drug: Esmolol

• Study Type: Interventional
• Enrollment (Estimated): 406
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yongtao Sun, Ph.D. in Anesthesiology; Phone Number: +86 18660795201; Email: ytsun@sdfmu.edu.cn

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250014
      • The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital
      • Contact: Yongtao Sun; Phone Number: +8618660795201

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age ≥ 65 years
2. American Society of Anesthesiologists (ASA) physical status classification I-III
3. Scheduled for elective gastrointestinal surgery under general anaesthesia
4. Body mass index (BMI) between 18.0 and 30.0 kg/m²

Exclusion Criteria:

1. Refusal to undergo surgery
2. Emergency surgery
3. Language impairment or severe hearing or visual deficits that hinder effective communication with research or surgical staff
4. History of neurological or psychiatric disorders, including Alzheimer's disease (AD), other forms of dementia, stroke, or psychosis
5. Long-term use of psychotropic medications (e.g., clozapine, risperidone, olanzapine, haloperidol, chlorpromazine)
6. Cardiac or craniocerebral surgery within the past year
7. Participation in other interventional clinical studies within the past 3 months
8. Preoperative cognitive impairment defined as a modified Telephone Interview for Cognitive Status (TICS-M) score ≤ 27
9. Patients will only be enrolled once, even if a subsequent surgery related to the primary procedure is performed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Opioid-Based Anaesthesia (OBA) Group; Patients receive conventional opioid-based general anaesthesia, including sufentanil and remifentanil during surgery and sufentanil-based patient-controlled intravenous analgesia (PCIA) postoperatively.	Drug: Sufentanil; 0.3-0.5 μg/kg induction; 0.15 μg/kg at closure; 2 μg/kg in 100 mL for PCIA; Drug: Remifentanil; 0.2-1.0 μg/kg/min maintenance
Experimental: Opioid-Free Anaesthesia (OFA) Group; Patients receive opioid-free anaesthesia using a standardized multimodal regimen (dexmedetomidine, esmolol, and esketamine) for intraoperative management and esketamine-based PCIA postoperatively.	Drug: Dexmedetomidine; Continuous infusion at 0.5-1.0 μg/kg/h during surgery; Drug: Esketamine; Induction dose 0.3-0.5 mg/kg; maintenance 0.2-0.5 mg/kg/h; 0.02 mg/kg at closure; PCIA: 1.5 mg/kg in 100 mL saline; Drug: Esmolol; Maintenance 20-100 μg/kg/min during surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of POD at discharge or within 7 days after surgery.	The proportion of participants who develop postoperative delirium, assessed either at discharge or within 7 days after surgery. Diagnosis of POD will be based on standardized clinical assessment tools (e.g., Confusion Assessment Method, CAM).Results will be reported as the percentage of participants (%).	Discharge or within 7 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day All-Cause Mortality	The proportion of participants who die from any cause during the initial hospitalization or within 30 calendar days following the index surgical procedure.The proportion of participants who die from any cause during the initial hospitalization or within 30 calendar days following the index surgical procedure. Results will be reported as the percentage of participants (%).	Up to 30 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative Haemodynamic Changes	Changes in mean arterial pressure and heart rate recorded during surgery. Results will be reported as the mean change from baseline (mmHg or beats per minute).	Intraoperative (from anesthesia induction to surgical closure)
Quality of Recovery-15 (QoR-15) Scores	QoR-15 scores assessed at 24 hours, 48 hours, and 72 hours after surgery. Results will be reported as the total score on the QoR-15 scale (range 0-150).	24, 48, and 72 hours after surgery
Postoperative Complications	Incidence of complications during postoperative hospitalization, including lung infection, urinary tract infection, cardiovascular and cerebrovascular accidents, abnormal liver function, postoperative bleeding, incision infection, deep venous thrombosis of the lower extremities, electrolyte imbalance, and hypoalbuminemia. Results will be reported as the percentage of participants (%).	From day of surgery through hospital discharge, up to 30 days
Pain Numerical Rating Scale (NRS) Score at 72 Hours	Pain intensity assessed using the NRS scale (0-10) at 72 hours after surgery. Results will be reported as the mean NRS score.	72 hours after surgery
Incidence of Nausea and Vomiting at 72 Hours	The proportion of participants experiencing nausea and/or vomiting at 72 hours after surgery. Results will be reported as the percentage of participants (%).	72 hours after surgery
Morphine Milligram Equivalent (MME) Consumption for Analgesics at 72 Hours	Total opioid consumption converted to morphine milligram equivalents (MME) at 72 hours after surgery. Results will be reported as total MME (mg).	72 hours after surgery
Duration of Anaesthesia	Time from induction of anaesthesia to discontinuation of anaesthetic agents. Results will be reported in minutes.	From administration of anaesthetic agents to discontinuation of anaesthetic agents， up to 2 hours
Duration of Surgery	Time from skin incision to the last suture. Results will be reported in minutes.	From skin incision to completion of wound closure, up to 2 hours
Length of Stay in the Post-Anesthesia Care Unit (PACU)	Time from arrival in the PACU to discharge from the PACU. Results will be reported in minutes.	From PACU admission to PACU discharge, measured in minutes, up to 60 minutes
Length of Hospital Stay	Total number of days from surgery to hospital discharge. Results will be reported in days.	From day of surgery to hospital discharge, up to 30 days
Long-Term Cognitive Function at 6 Months	Cognitive function assessed at 6 months after surgery using standardized cognitive testing methods. Results will be reported as cognitive assessment scores.	6 months after surgery

Collaborators and Investigators

• Sponsor: Qianfoshan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2025
• Primary Completion (Estimated): January 5, 2026
• Study Completion (Estimated): May 12, 2026

Study Registration Dates

• First Submitted: April 21, 2025
• First Submitted That Met QC Criteria: May 3, 2025
• First Posted (Actual): May 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2025
• Last Update Submitted That Met QC Criteria: May 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: postoperative delirium; elderly patients; gastrointestinal surgery; opioid-free anaesthesia
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Emergence Delirium; Delirium; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Analgesics, Opioid; Narcotics; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Antidepressive Agents; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adrenergic Antagonists; Remifentanil; Esketamine; Dexmedetomidine; Sufentanil; Esmolol
• Other Study ID Numbers: opioid-free anaesthesia

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No