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

• Main Authors: Mona M. El-Tamalawy (Author), Moetaza M. Soliman (Author), Amany F. Omara (Author), Amal Rashad (Author), Osama M. Ibrahim (Author), Mamdouh M. El-Shishtawy (Author)
• Format: Book
• Published: Frontiers Media S.A., 2022-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2022.855764
• Keywords: cholinergic anti-inflammatory pathway; choline esterase inhibitor; procalcitonin; sepsis; septic shock; SOFA score; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 13 (2022)

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.