Effect of Neostigmine on Attenuation of Proinflammatory Cytokines When Given as an Adjuvant Therapy in Septic Shock: A Randomized Control Trial.

Summary

In a randomized double-blind placebo-controlled ICU trial, continuous neostigmine (0.2 mg/h for 5 days) reduced TNF-α by day 5, improved SOFA scores, and was associated with lower 28-day mortality (26% vs 54%). Findings support augmenting the cholinergic anti-inflammatory pathway in septic shock.

Key Findings

• Neostigmine infusion (0.2 mg/h for 5 days) significantly reduced TNF-α on day 5 versus placebo (40±36 vs 67±43 pg/mL; p=0.002).
• Sequential Organ Failure Assessment (SOFA) scores decreased significantly from day 1 to day 5 in the neostigmine group (p<0.001).
• 28-day mortality was lower with neostigmine (26%) compared to control (54%; p=0.02).
• Trial was randomized, double-blind, placebo-controlled and registered (CTRI/2023/07/055054).

Clinical Implications

Neostigmine could be considered as an adjunct to standard care in septic shock pending confirmation in multicenter trials; clinicians should monitor for cholinergic adverse effects (e.g., bradycardia, secretions).

Limitations

• Single-center study with unspecified sample size, potentially underpowered for mortality
• Safety profile (e.g., bradyarrhythmias, secretions) not detailed in abstract

Future Directions

Conduct multicenter, adequately powered RCTs to confirm mortality benefit, define optimal dosing and duration, and evaluate safety and patient-centered outcomes.