Opioid-free Anesthesia and Postoperative Delirium

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

Interventions

DRUG

OFA group

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

DRUG

OBA group

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

Sponsors & Collaborators

• Qianfoshan Hospital

  lead OTHER

Principal Investigators

• Yongtao Sun · Shandong First Medical University

• Min Zhang · Shandong First Medical University

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-01

Primary Completion

2028-04-30

Completion

2028-06-30