Effect of Neostigmine on Attenuation of Proinflammatory Cytokines When Given as an Adjuvant Therapy in Septic Shock: A Randomized Control Trial.
Summary
In a single-center double-blind RCT, continuous neostigmine infusion (0.2 mg/h for 5 days) significantly reduced TNF-α levels versus placebo (day-5 40±36 vs 67±43 pg/mL; p=0.002), improved SOFA scores (p<0.001), and was associated with lower 28-day mortality (26% vs 54%; p=0.02). Findings support cholinergic anti-inflammatory pathway activation in septic shock.
Key Findings
- Day-5 TNF-α levels were lower with neostigmine vs placebo (40±36 vs 67±43 pg/mL; p=0.002).
- SOFA scores decreased significantly from day 1 to day 5 with neostigmine (p<0.001).
- 28-day mortality was lower in the neostigmine group (26%) vs control (54%; p=0.02).
Clinical Implications
Neostigmine may serve as an adjuvant therapy in septic shock to dampen hyperinflammation and potentially improve survival; multicenter trials are warranted to confirm efficacy and safety.
Why It Matters
This is a randomized, double-blind, placebo-controlled trial reporting biomarker and mortality signals with an accessible, repurposed drug targeting a defined immunomodulatory pathway.
Limitations
- Single-center study with unspecified sample size
- Primary endpoint was biomarker reduction; mortality analysis may be underpowered
Future Directions
Conduct adequately powered multicenter RCTs assessing patient-centered outcomes, optimal dosing/duration, and safety across diverse septic shock phenotypes.
Study Information
- Study Type
- RCT
- Research Domain
- Treatment
- Evidence Level
- I - Randomized, double-blind, placebo-controlled clinical trial
- Study Design
- OTHER