Effect of Low-dose EsketaMine on dElirium in High-risk Elderly Patients uNdergoing elecTive Surgery (ELEMENT)

Summary

Delirium is an acutely occurred neurocognitive disorder characterized by fluctuating symptoms of inattention, altered consciousness and cognitive dysfunction. Delirium is reported to occur in 4% to 65% of postoperative patients depending on the population, and is especially common in older patients. Postoperative delirium is disturbing to patients and their families, and it is a strong predictor of both early and long-term worse outcomes including increased non-delirium complications, increased perioperative mortality, shortened overall survival, declined cognitive function, and lowered quality of life.

Although ketamine/esketamine has anti-inflammatory and neuroprotective effects, evidence on its efficacy in reducing postoperative delirium remains inconsistent and inconclusive. Existing studies are limited by heterogeneity, small sample sizes, single-center designs, and a focus on specific type of surgery. Research on elderly high-risk patients is lacking, and most studies administer the drug intraoperatively, with limited exploration of postoperative use. The optimal dosing and timing for POD prevention are unclear. This study aims to carry out a multicenter, single-blind, placebo-controlled, large-sample randomized controlled trial assessing the effect of low-dose esketamine, given intraoperatively and postoperatively, on delirium in elderly high-risk patients undergoing major non-cardiac surgery.

Conditions

• Delirium in Old Age
• Delirium, Postoperative
• Anesthesia
• Cognitive Dysfunction
• Pain, Postoperative
• Esketamine
• Non-cardiac Surgery

Interventions

DRUG

Esketamine

Esketamine (1mg/ml) will be administered at a loading dose of 0.2 mg/kg, namely at a infusion rate of 1.2ml/kg/h over 10 minutes after induction, then a maintenance infusion rate of 0.1 mg/kg/h until 40 minutes before the end of the surgery. For postoperative analgesia, patient-controlled intravenous analgesia (PCIA) is prepared with a formulation consisting of esketamine 50mg and sufentanil 200 μg, diluted to a total volume of 200 ml. The background dose is set at 2 ml/h, with a bolus dose of 2 ml and a lockout interval of 15 minutes.

DRUG

Normal saline

Normal saline will be administered at a infusion rate of 1.2ml/kg/h over 10 minutes after induction, then a maintenance infusion rate of 0.1 mg/kg/h until 40 minutes before the end of the surgery. For postoperative analgesia, patient-controlled intravenous analgesia (PCIA) is prepared with sufentanil 200μg, diluted to a total volume of 200 ml. The background dose is set at 2 ml/h, with a bolus dose of 2 ml and a lockout interval of 15 minutes.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University

  lead OTHER

Principal Investigators

• Ke-Xuan Liu, MD · Nanfang Hospital, Southern Medical University

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-02-12

Primary Completion

2027-06-30

Completion

2027-07-31

Countries

• China

Study Locations