Abstract
Background: Neostigmine has been found to improve survival in animal models of sepsis. However, its feasibility, efficacy, and safety in patients with sepsis or septic shock have not been investigated. Aim: This parallel randomized controlled double-blinded design aimed to investigate the efficacy and safety of neostigmine as an adjunctive therapy in patients with sepsis or septic shock. Patients and Methods: A total of 167 adult patients with sepsis or septic shock were assessed for eligibility; 50 patients were randomized to receive a continuous infusion of neostigmine (0.2 mg/h for 120 h; neostigmine arm) or 0.9% saline (control arm) in addition to standard therapy. The primary outcome was the change in Sequential Organ Failure Assessment (SOFA) scores 120 h after therapy initiation. Secondary outcomes included mortality rates and changes in procalcitonin level. Results: The median (interquartile range) change in SOFA scores improved significantly in the neostigmine arm [−2 (−5, 1)] as compared with the control arm [1.5 (0, 2.8); p = 0.007]. Progression from sepsis to septic shock was more frequent in the control arm (p = 0.01). The incidence of shock reversal in patients with septic shock was significantly lower in the control arm than in the neostigmine arm (p = 0.04). Differences in 28-days mortality rates did not reach statistical significance between the control and neostigmine arms (p = 0.36). Percentage change in procalcitonin levels was similar in both arms (p = 0.74). Conclusion: Neostigmine adjunctive therapy may be safe and effective when administered in patients with sepsis or septic shock.Clinical Trial Registration: NCT04130230.
Highlights
Neostigmine adjunctive therapy may be safe and effective when administered in patients with sepsis or septic shock
Sepsis is a life-threatening sequential organ failure resulting from an unregulated host response to infection, whereas septic shock is a subgroup of sepsis characterized by underlying circulatory, cellular, and metabolic abnormalities that augment short-term mortality (Rhodes et al, 2016)
One patient was diagnosed with COVID-19 and transferred to another intensive care unit (ICU), one patient withdrew from study, and two patients were transferred to another ICU
Summary
Sepsis is a life-threatening sequential organ failure resulting from an unregulated host response to infection, whereas septic shock is a subgroup of sepsis characterized by underlying circulatory, cellular, and metabolic abnormalities that augment short-term mortality (Rhodes et al, 2016). Given the high morbidity and mortality rates of septic shock, new therapeutic approaches that focus on modifying the unregulated host response to infection added to standard therapy are required to decrease mortality rates and improve patient outcomes (Hwang et al, 2020). The concept is based on the inflammatory reflex of the vagus nerve through the suppression of systemic inflammation and protection against cytokine-mediated diseases (Wang et al, 2021). This suppression was found to be mediated by nicotinic alpha acetylcholine receptors (α7nAChR) on immune cells and macrophages (Wang et al, 2009). Its feasibility, efficacy, and safety in patients with sepsis or septic shock have not been investigated
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