Clinical TrialNeurocognitive DisordersEsketaminePlaceboRecruiting

Effect of Low-dose Esketamine on Delirium in High-risk Elderly Patients Undergoing Elective Surgery (ELEMENT)

Double-blind, placebo-controlled randomised trial (n=1670) testing low-dose intraoperative and postoperative esketamine versus placebo to prevent postoperative delirium in high-risk elderly patients undergoing major non-cardiac surgery.

Target Enrollment
1670 participants
Study Type
Phase NA interventional
Design
Randomized, double Blind

Detailed Description

Postoperative delirium is a common, acute neurocognitive disorder among older surgical patients and is associated with worse short- and long-term outcomes; this multicentre trial tests whether intraoperative and postoperative low-dose esketamine reduces delirium incidence in high‑risk elderly patients undergoing major non‑cardiac surgery.

Esketamine has anti‑inflammatory and neuroprotective effects; the trial administers a 0.2 mg/kg loading dose after induction with 0.1 mg/kg/h maintenance until 40 minutes before surgery end, plus postoperative PCIA containing esketamine and sufentanil, compared with matched saline infusion and sufentanil‑only PCIA; outcomes include delirium incidence and cognitive and safety measures.

Study Arms & Interventions

Esketamine

experimental

IV intraoperative loading and maintenance esketamine infusion plus postoperative esketamine-containing PCIA for analgesia.

Interventions

  • Esketamine0.2 mg/kg
    via IV• loading + infusion

    Loading 0.2 mg/kg after induction (1.2 ml/kg/h over 10 min at 1 mg/ml), then maintenance 0.1 mg/kg/h until 40 min before end of surgery; postoperative PCIA: esketamine 50 mg + sufentanil 200 μg in 200 ml, background 2 ml/h, bolus 2 ml, lockout 15 min.

Placebo (normal saline)

inactive

Normal saline infusion intraoperatively and standard sufentanil-only PCIA postoperatively (placebo comparator).

Interventions

  • Placebo
    via IV• infusion + PCIA

    Normal saline infusion matching esketamine rates intraoperatively; postoperative PCIA contains sufentanil 200 μg in 200 ml, background 2 ml/h, bolus 2 ml, lockout 15 min.

Participants

Ages
65 – 90
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Age ≥65 years and <90 years;
  • Scheduled to undergo major non-cardiac surgery;
  • Fulfil at least one of the following risk factors: history of stroke; history of delirium; hypertension; congestive heart failure; coronary artery disease; atrial fibrillation; peripheral artery disease; chronic obstructive pulmonary disease; obstructive sleep apnoea; diabetes; chronic kidney disease; anaemia; malnutrition; hypoalbuminaemia; chronic pain; anxiety and depression; poor sleep quality; smoker; alcoholism;
  • Scheduled to receive patient-controlled intravenous analgesia (PCIA).

Exclusion Criteria

  • Exclusion Criteria:
  • 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;
  • Contraindication to ketamine or esketamine;
  • Other situations where the investigator or physician considers the patient ineligible for the study.

Study Details

Locations

Fujian Provincial Hospital — Fuzhou, Fujian, China
Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China
Nanfang Hospital, Southern Medical University — Guangzhou, Guangdong, China
The First Affiliated Hospital of JiNan University — Guangzhou, Guangdong, China
The Eighth Affliated Hospital of Southern Medical Universily — Guangzhou, Guangdong, China
Ganzhou People's Hospital — Ganzhou, Jiangxi, China

Your Library