Influence of Neostigmine on Early Postoperative Cognitive Dysfunction in Older Adult Patients Undergoing Noncardiac Surgery: A Double-Blind, Placebo-Controlled, Randomized Controlled Trial

Anesth Analg. 2024 Mar 1;138(3):589-597. doi: 10.1213/ANE.0000000000006687. Epub 2024 Feb 16.


Background: The goal of this study was to investigate the efficacy of neostigmine on postoperative cognitive dysfunction (POCD) and determine its effect on systematic markers of oxidative stress in older patients.

Methods: This double-blind placebo-controlled trial enrolled 118 elderly patients (≥65 years) undergoing noncardiac surgeries who were allocated to a neostigmine treatment group (0.04 mg/kg) or a placebo control group (normal saline) postoperatively. POCD was diagnosed if the Z -scores for the mini-mental state examination and the Montreal Cognitive Assessment were both ≤-1.96. Postoperative serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were also compared. Multivariable regression analysis with dose adjustment of atropine was used to demonstrate the influence of neostigmine on the incidence of POCD.

Results: Patients receiving neostigmine had a significantly reduced incidence of POCD compared to patients who were treated with placebo on the first day after surgery (-22%, 95% confidence interval [CI], -37 to -7), but not on the third (8%, 95% CI, -4 to 20) or seventh day after surgery (3%, 95% CI, -7 to 13). Postoperative plasma MDA levels were significantly lower ( P = .016), but SOD and BDNF levels were increased ( P = .036 and .013, respectively) in the neostigmine group compared to the control group on the first day after surgery.

Conclusions: Neostigmine reduced POCD on the first day after noncardiac surgery in older patients. Neostigmine treatment inhibited oxidative stress and increased serum BDNF levels. There was no significant influence of neostigmine on POCD on the third or seventh day after surgery. The clinical influence of neostigmine on POCD should be further investigated.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Brain-Derived Neurotrophic Factor
  • Cognitive Dysfunction* / complications
  • Double-Blind Method
  • Humans
  • Neostigmine / adverse effects
  • Postoperative Cognitive Complications* / chemically induced
  • Postoperative Cognitive Complications* / diagnosis
  • Postoperative Cognitive Complications* / epidemiology
  • Postoperative Complications / chemically induced
  • Postoperative Complications / diagnosis
  • Postoperative Complications / epidemiology
  • Superoxide Dismutase


  • Brain-Derived Neurotrophic Factor
  • Neostigmine
  • Superoxide Dismutase