RecruitingNot ApplicableNCT06817239

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

Effect of Perioperative Low-dose EsketaMine on dElirium in High-risk Elderly Patients uNdergoing elecTive Major Non-cardiac Surgery: a Multi-center Randomized Trial (ELEMENT Trial)

Sponsor

Nanfang Hospital, Southern Medical University

Enrollment

1,670 participants

Start Date

Feb 12, 2025

Study Type

INTERVENTIONAL

Conditions

Delirium in Old Age

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.

Eligibility

Min Age: 65 YearsMax Age: 90 Years

Inclusion Criteria4

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).

Exclusion Criteria11

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.

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Interventions

DRUGEsketamine

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.

DRUGNormal 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.