What is the clinical evidence from this study?

Study design: RCT. Population: Postoperative delirium (n=320). Intervention: Neostigmine/glycopyrrolate vs. Sugammadex 2 mg/kg. Primary outcome: Incidence of postoperative delirium within postoperative 7 days or until discharge.

What question did this study set out to answer?

Evaluate the effect of neostigmine/glycopyrrolate on postoperative delirium compared to sugammadex in older adults.

April 3, 2026Open Access

Effect of neostigmine/glycopyrrolate versus sugammadex on postoperative delirium in older adults: A triple-masked, randomized, controlled trial protocol

Key Result

This randomized controlled trial protocol will evaluate whether neuromuscular blockade reversal with neostigmine/glycopyrrolate reduces postoperative delirium compared with sugammadex in older adults.

Key Points

Evaluate the effect of neostigmine/glycopyrrolate on postoperative delirium compared to sugammadex in older adults.
Single-center, triple-masked, randomized controlled trial design.
320 older adults undergoing major non-cardiac surgery.
Participants randomized to receive either neostigmine/glycopyrrolate or sugammadex for neuromuscular blockade reversal.
Primary outcome measured is the incidence of POD within 7 days post-surgery.
Primary outcome will assess the incidence of postoperative delirium within 7 days of surgery.
Secondary outcomes will analyze the severity of POD, hospital days affected, and cognitive function at 30 days post-surgery.

Study Design

Type

RCT (n=320)

Blinding

Triple-masked

Randomization

1:1

Multicenter

Structured PICO

Does neostigmine/glycopyrrolate reduce postoperative delirium compared with sugammadex in older adults undergoing major non-cardiac and non-neurosurgical surgery?

Population

320 older adults scheduled for major non-cardiac and non-neurosurgical surgery

Intervention

Neostigmine 40 μg/kg plus glycopyrrolate 8 μg/kg for neuromuscular blockade reversal at the end of surgery

Comparator

Sugammadex 2 mg/kg for neuromuscular blockade reversal at the end of surgery

Outcome

Incidence of postoperative delirium (POD) within postoperative 7 days or until discharge, assessed twice daily with the validated Chinese version of 3-min Diagnostic Interview for Confusion Assessment Method

This trial protocol outlines a study to determine if neostigmine/glycopyrrolate reduces postoperative delirium compared to sugammadex in older adults undergoing major non-cardiac surgery.

Abstract

Background Postoperative delirium (POD) is an acute disturbance of attention and awareness in older adults undergoing surgery. It is associated with prolonged hospital stay and increased morbidity and mortality. Recent studies suggested that neostigmine, an acetylcholinesterase inhibitor used to reverse neuromuscular blockade, may reduce POD risk. We aim to evaluate whether neuromuscular blockade reversal with neostigmine/glycopyrrolate reduces POD compared with sugammadex. Methods This single-center, triple-masked, randomized, controlled superiority trial will enroll 320 older adults scheduled for major non-cardiac and non-neurosurgical surgery. Patients will be randomized (1:1) to receive either neostigmine 40 μg/kg plus glycopyrrolate 8 μg/kg or sugammadex 2 mg/kg for neuromuscular blockade reversal at the end of surgery. The primary outcome is the incidence of POD within postoperative 7 days or until discharge, assessed twice daily with the validated Chinese version of 3-min Diagnostic Interview for Confusion Assessment Method. Secondary outcomes include days with POD and proportion of hospital days affected; POD severity assessed using the highest score and the sum scores of Confusion Assessment Method Severity; and 30-day cognitive function assessed using the 10-item Telephone Interview of Cognitive Status. Discussion Results of this study will determine whether neostigmine/glycopyrrolate offers a simple, low-cost strategy to prevent POD and will inform evidence-based selection of neuromuscular reversal agents in older surgical patients. Trial registration Chinese Clinical Trial Registry (ChiCTR2400093158).