• B I Valk, A R Absalom, P Meyer, S Meier, I den Daas, K van Amsterdam, J A Campagna, S P Sweeney, and Struys M M R F MMRF University of Groningen, University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands; Department of Anaesthesia and .
• University of Groningen, University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands. Electronic address: b.i.valk@umcg.nl.
• Br J Anaesth. 2018 Jun 1; 120 (6): 1401-1411.

BackgroundCyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers.MethodsFive cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg-1 min-1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring.ResultsNo serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift.ConclusionsInfusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern.Clinical Trial RegistrationNTR4735.Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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