• Nadine Pinder, Thomas Bruckner, Monika Lehmann, Johann Motsch, Thorsten Brenner, Jan Larmann, Phillip Knebel, Torsten Hoppe-Tichy, Stefanie Swoboda, Markus A Weigand, Stefan Hofer, and Johannes B Zimmermann.
• Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany; Pharmacy Department, Heidelberg University Hospital, Im Neuenheimer Feld 670, 69120 Heidelberg, Germany.
• J Crit Care. 2019 Aug 1; 52: 126-135.

PurposeThe 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 MethodsIn 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.ResultsAdministration 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.ConclusionsTreatment with physostigmine salicylate was feasible and safe. Further studies are justified to assess the effect on recovery from septic shock.Trial RegistrationEudraCT Number 2012-001650-26, ClinicalTrials.gov identifier NCT03013322.Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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