Effect of physostigmine on recovery from septic shock following intra-abdominal infection – Results from a randomized, double-blind, placebo-controlled, monocentric pilot trial (Anticholium® per Se)
Journal of Critical Care(2019)
Abstract
Purpose
The cholinergic anti-inflammatory pathway has been shown to be accessible by physostigmine salicylate in animal models. However, the cholinesterase inhibitor is not approved for adjunctive therapy in sepsis, and tolerability and safety of high initial doses followed by continuous infusion have not been investigated.
Materials and methods
In this trial, 20 patients with perioperative septic shock due to intra-abdominal infection were eligible. The physostigmine group received an initial dose of 0.04 mg/kg physostigmine salicylate, followed by continuous infusion of 1 mg/h for 120 h; the placebo group was treated with 0.9% sodium chloride. Primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score during treatment and up to 14 days.
Results
Administration of physostigmine salicylate was well tolerated. Mean SOFA scores were 8.9 ± 2.5 and 11.3 ± 3.6 (mean ± SD) for physostigmine and placebo group, respectively. Adjusted for age, difference between means was not statistically significant (−2.37, 95% CI: −5.43 to 0.70, p = 0.121). Norepinephrine doses required only appeared lower in the physostigmine group (p = 0.064), along with a more rapid reduction from an elevated heart rate possibly indicating less hemodynamic instability.
Conclusions
Treatment with physostigmine salicylate was feasible and safe. Further studies are justified to assess the effect on recovery from septic shock.
Trial registration
EudraCT Number 2012-001650-26, ClinicalTrials.gov identifier NCT03013322.
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Key words
Antilirium,Cholinesterase inhibitor,Adjunctive therapy,Cholinergic anti-inflammatory pathway,Sequential Organ Failure Assessment (SOFA) score,Perioperative sepsis
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