In a randomized controlled trial, researchers investigated the adjuvant use of continuous neostigmine infusion (0.2 mg/hr for 5 days) in patients with septic shock, leveraging its ability to enhance vagal cholinergic anti-inflammatory pathway (ChAP) activity and thereby attenuate systemic inflammation.

The primary endpoint—reduction in tumor necrosis factor-alpha (TNF-α) levels—was significantly achieved in the neostigmine group, with mean TNF-α concentrations dropping to 40 ± 36 pg/mL by day 5 compared to 67 ± 43 pg/mL in the standard-care control group (p = 0.002). This cytokine-lowering effect aligns with preclinical evidence that acetylcholine release, potentiated by neostigmine, dampens proinflammatory responses in sepsis.

Secondary outcomes further supported clinical benefit: the neostigmine group exhibited a marked decline in Sequential Organ Failure Assessment (SOFA) scores from day 1 to day 5 (p < 0.001), indicating improved multi-organ function. Hemodynamic stability, septic shock reversal rates, and procalcitonin trends favored the intervention arm, though specific values for these were not detailed. Most strikingly, 28-day mortality was halved in the neostigmine-treated patients (26%) compared to the control group (54%, p = 0.02), suggesting that targeted modulation of the cholinergic pathway could offer a novel, low-cost adjunctive strategy to improve survival in septic shock. These promising results warrant larger multicenter trials to confirm efficacy, safety (particularly regarding bradycardia or gastrointestinal effects), and optimal dosing.

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