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

NCT06817239 | Recruiting DMC

• 1 other identifier: NFEC-2025-016
• Study Type: interventional
• Target: 1,670
• Locations: 1 country
• Sites: 6

Brief 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

Keywords

Delirium; Elderly patients; Esketamine; Non-cardiac surgery

Outcome Measures

Primary Outcomes (2)

• The incidence of delirium within 5 days after surgery

  Delirium is assessed twice daily (8-10 am and 6-8 pm) with The Confusion Assessment Method (CAM) for non-intubated patients or The confusion assessment method for the Intensive Care Unit (CAM-ICU) for intubated patients.

  Up to 5 days after surgery

• Quality of recovery on postoperative day 1 (Sub-study)

  Quality of recovery is assessed once daily (6-8 pm) with 15-item Quality of Recovery Scale (QoR-15).

  On postoperative day 1

Secondary Outcomes (11)

• Intensity of pain during the first 3 postoperative days

  Up to 3 days after surgery

• Use of opioids during the first 3 postoperative days

  Up to 3 days after surgery

• Cognitive function at 30 days after surgery

  At the end of 30 days after surgery

• The incidence of delayed neurocognitive recovery

  At the end of 30 days after surgery

• Death rate at 30 days after surgery

  At the end of 30 days after surgery

Study Arms (2)

Esketamine

EXPERIMENTAL

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: Esketamine

Normal saline

PLACEBO COMPARATOR

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.

Drug: Normal saline

Interventions

Esketamine DRUG

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.

Esketamine

Normal saline DRUG

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.

Normal saline

Eligibility Criteria

• Age: 65 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥65 years and \<90 years;
• Scheduled to undergo major non-cardiac surgery.
• Fulfill at least one of risk factors as follows: history of stroke; history of delirium; hypertension; congestive heart failure; coronary artery disease; atrial fibrillation; peripheral artery disease; chronic obstructive pulmonary disease; obstructive sleep apnea; diabetes; chronic kidney disease; anemia; malnutrition; hypoalbuminemia; chronic pain; anxiety and depression; poor sleep quality; smoke; alcoholism.
• Scheduled to receive patient-controlled intravenous analgesia (PCIA).

You may not qualify if:

• Refuse to participate;
• Preoperative history of epilepsy, myasthenia gravis, Parkinson's disease, intracranial hypertension, delirium, schizophrenia, or other psychiatric diseases;
• Inability to communicate in the preoperative period because of coma, profound dementia, or language barrier;
• Preoperative uncontrolled severe hypertension (baseline SBP\>180 mmHg or DBP\>110 mmHg);
• Preoperative history of hyperthyroidism and pheochromocytoma;
• Acute cardiovascular event occurring within 30 days before surgery;
• Severe hepatic dysfunction (Child-Pugh class C), renal dysfunction (required preoperative dialysis), or expected survival ≤24 hours;
• Scheduled to undergo organ transplantation, vascular surgery, neurosurgery;
• Receiving treatment with ketamine or esketamine;
• Contradiction to ketamine or esketamine;
• Other situations where the investigator or physician considers the patient ineligible for the study.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (6)

Fujian Provincial Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

NOT YET RECRUITING

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

The First Affiliated Hospital of JiNan University

Guangzhou, Guangdong, 510632, China

ACTIVE NOT RECRUITING

The Eighth Affliated Hospital of Southern Medical Universily

Guangzhou, Guangdong, 528399, China

RECRUITING

Ganzhou People's Hospital

Ganzhou, Jiangxi, 341001, China

ACTIVE NOT RECRUITING

Related Publications (31)

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MeSH Terms

Conditions

Emergence Delirium; Cognitive Dysfunction; Pain, Postoperative; Delirium

Interventions

Esketamine; Saline Solution

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Pain

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ke-Xuan Liu, MD

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ke-Xuan Liu, MD

CONTACT

+86 13710684096; liukexuan705@163.com

Shuang-Jie Cao, MD

CONTACT

+86 13651119431; caosjie1994@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2025
• First Posted: February 10, 2025
• Study Start: February 12, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)