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

Summary

In a double-blind RCT of septic shock patients, a 5-day neostigmine infusion (0.2 mg/h) significantly reduced TNF-α by day 5, lowered SOFA trajectories, and halved 28-day mortality compared with placebo. Findings support cholinergic anti-inflammatory pathway augmentation as an adjunctive sepsis therapy.

Key Findings

• Day-5 TNF-α levels were significantly lower with neostigmine vs 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).

Clinical Implications

Neostigmine infusion (0.2 mg/h for 5 days) could be considered as adjunct therapy in septic shock to attenuate systemic inflammation and potentially reduce mortality, pending multicenter replication and safety profiling.

Limitations

• Single-center study limits generalizability
• Primary endpoint focused on cytokine reduction; mechanistic and safety profiles need broader validation

Future Directions

Multicenter RCTs to confirm mortality benefit, dose–response studies, and exploration of patient phenotypes most likely to benefit from cholinergic anti-inflammatory augmentation.