AUTHOR=El-Tamalawy Mona M. , Soliman Moetaza M. , Omara Amany F. , Rashad Amal , Ibrahim Osama M. , El-Shishtawy Mamdouh M. 

TITLE=Efficacy and Safety of Neostigmine Adjunctive Therapy in Patients With Sepsis or Septic Shock: A Randomized Controlled Trial

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.855764

DOI=10.3389/fphar.2022.855764

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Aim:</bold> 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.</p><p><bold>Patients and Methods:</bold> 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.</p><p><bold>Results:</bold> 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); <italic>p</italic> = 0.007]. Progression from sepsis to septic shock was more frequent in the control arm (<italic>p</italic> = 0.01). The incidence of shock reversal in patients with septic shock was significantly lower in the control arm than in the neostigmine arm (<italic>p</italic> = 0.04). Differences in 28-days mortality rates did not reach statistical significance between the control and neostigmine arms (<italic>p</italic> = 0.36). Percentage change in procalcitonin levels was similar in both arms (<italic>p</italic> = 0.74).</p><p><bold>Conclusion:</bold> Neostigmine adjunctive therapy may be safe and effective when administered in patients with sepsis or septic shock.</p><p>Clinical Trial Registration: NCT04130230.</p>