Effect of Esketamine on Cognitive Recovery After Propofol Sedation for Outpatient Colonoscopy: A Randomized Clinical Trial

Drug Des Devel Ther. 2025 Jan 21:19:425-437. doi: 10.2147/DDDT.S503129. eCollection 2025.

Abstract

Purpose: While esketamine shows promise as an adjunct in procedural sedation, its impact on postoperative cognitive recovery remains incompletely characterized. This study investigated the effects of esketamine on multiple dimensions of recovery, particularly cognition, in patients undergoing colonoscopy with propofol-based sedation.

Patients and methods: We conducted this randomized, double-blinded, placebo-controlled trial from January 6, 2023, to May 20, 2024, at two hospitals in China. Patients were randomized in a 1:1 ratio to receive either esketamine 0.2 mg/kg (n = 126) or placebo (n = 126), followed by propofol 1 mg/kg. We administered additional propofol boluses (0.5 mg/kg) to maintain sedation. The study assessed cognitive recovery on postoperative day 3 as the primary outcome, measured by the Postoperative Quality of Recovery Scale (PostopQRS). Secondary outcomes included overall recovery, recovery in other PostopQRS domains, time to discharge, and adverse events.

Results: Esketamine significantly enhanced cognitive recovery compared to placebo on postoperative day 3 (95.2% vs 83.3%, relative risk = 1.14; 95% confidence interval: 1.05-1.25, P = 0.002). Discharge times were comparable between groups (odds ratio = 0.70; 95% confidence interval: 0.43-1.16, P = 0.163). The esketamine group demonstrated higher satisfaction (P = 0.003) and significantly reduced incidences of hypotension (14.3% vs 36.5%, P < 0.001), bradycardia (5.6% vs 15.1%, P = 0.013), hypoxemia (2.4% vs 8.7%, P = 0.028), and injection site pain (21.4% vs 48.4%, P < 0.001).

Conclusion: Adding esketamine 0.2 mg/kg to propofol for colonoscopy sedation improved postoperative cognitive recovery, enhanced patient satisfaction, and reduced cardiopulmonary adverse events without prolonging discharge time. These findings establish low-dose esketamine as a beneficial adjunct to propofol in procedural sedation for colonoscopy.

Keywords: Propofol; cognitive recovery; colonoscopy; esketamine; procedural sedation; quality of recovery.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Case Reports
  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Cognition* / drug effects
  • Colonoscopy*
  • Double-Blind Method
  • Female
  • Humans
  • Hypnotics and Sedatives* / administration & dosage
  • Hypnotics and Sedatives* / pharmacology
  • Ketamine* / administration & dosage
  • Ketamine* / pharmacology
  • Male
  • Middle Aged
  • Outpatients
  • Propofol* / administration & dosage
  • Propofol* / pharmacology

Substances

  • Propofol
  • Ketamine
  • Esketamine
  • Hypnotics and Sedatives

Grants and funding

This study was supported by the Science and Technology Program of Haicang District of Xiamen, China (350205Z20232004), Natural Science Foundation of Xiamen, China (3502Z202374068), Natural Science Foundation of Ningde, China (2022J58), Fujian Strait Medical and Health Exchange Association Precision Anesthesia Research Project (2024HYHMZ04), Natural Science Foundation of Fujian Province (2023J011201, 2024J011039), Fujian Provincial Health Technology Project (2022CXA007), and the Joint Funds for the Innovation of Science and Technology, Fujian Province (2023Y9275).