What question did this study set out to answer?

Evaluate the comparative effect of neostigmine versus sugammadex on postoperative cognitive disorders in elderly surgical patients.

February 12, 2026Open Access

Effect of Reversal Agents on Postoperative Cognitive Disorders Following General Anesthesia in the Elderly Population: A Systematic Review and Meta-Analysis

Key Points

Evaluate the comparative effect of neostigmine versus sugammadex on postoperative cognitive disorders in elderly surgical patients.
Conducted a systematic search of multiple databases following PRISMA 2020 guidelines.
Included randomized controlled trials involving elderly patients undergoing general anesthesia.
Compared the incidence of POCD between neostigmine and sugammadex with validated cognitive assessment tools.
Performed meta-analysis using Review Manager 5.4.1 with results expressed as odds ratios.
Pooled data from six trials involving 795 elderly patients showed neostigmine linked to higher POCD risk than sugammadex (OR 1.74).
Higher doses of neostigmine were associated with lower POCD incidence (OR 0.31).
Secondary outcomes related to POCD management were inconsistently reported.

Abstract

Background/Objectives: Perioperative neurocognitive disorders (PND), including postoperative delirium and cognitive dysfunction (POCD), represent significant complications in elderly surgical patients undergoing general anesthesia. The choice of neuromuscular blockade reversal agent may influence POCD risk through different mechanisms and side effects. This systematic review and meta-analysis evaluated the comparative effect of neostigmine versus sugammadex on POCD incidence in elderly patients. Methods: A systematic search of PubMed, Web of Science, Scopus, and Google Scholar was conducted from database inception to September 2025, following PRISMA 2020 guidelines with PROSPERO registration (CRD420251058187). Randomized controlled trials involving elderly patients (≥60 years) undergoing general anesthesia with neuromuscular blockade were included, comparing neostigmine and sugammadex for reversal. Primary outcomes included POCD incidence, assessed using validated cognitive tools, including the Mini-Mental State Examination and Montreal Cognitive Assessment. Meta-analysis was performed using Review Manager 5.4.1, with results expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Results: Six randomized controlled trials involving 795 elderly patients published between 2017 and 2024 met the inclusion criteria. Studies encompassed non-cardiac surgery, robotic-assisted radical cystectomy, and pars plana vitrectomy. Pooled meta-analysis showed neostigmine was associated with a higher risk of POCD than sugammadex (OR 1.74, 95% CI 1.00–3.02, p = 0.05), with low heterogeneity (I2 = 39%). Secondary outcomes, including prevention of POCD, management strategies, and related complications, were inconsistently reported and unavailable across all six RCTs. Subgroup analysis stratified by neostigmine dosage demonstrated that administration of a higher dose (≥0.04 mg/kg) was associated with reduced POCD incidence compared to a lower dose (<0.04 mg/kg) (OR 0.31, 95% CI 0.15–0.63, p = 0.001), with negligible heterogeneity (I2 = 0%). Conclusions: This meta-analysis suggests that sugammadex may be associated with reduced early postoperative neurocognitive disorders compared to neostigmine in elderly patients, likely through rapid neuromuscular blockade reversal that minimizes residual paralysis and respiratory complications.

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