title: Twitch potentiation influences the time course of twitch depression in muscle relaxant studies: a pharmacokinetic-pharmacodynamic explanation.
abstract: The time course of twitch depression following neuromuscular blocking agent (NMBA) administration is influenced by the duration of control neuromuscular monitoring (twitch stabilization). The physiological mechanism for this interaction is not known. During twitch stabilization twitch response often increases to a plateau, this is known as twitch potentiation or the staircase phenomenon. Since twitch potentiation contributes to the observed twitch response it may also influence the time course of twitch depression following NMBA administration. Our objective was to estimate the degree that twitch potentiation influences the time course of twitch depression following NMBA administration under conditions typical for muscle relaxation studies. We used previousy described pharmacokinetic-pharmacodynamic (PK-PD) and twitch potentiation models to simulate twitch data. Simulations consisted of twitch stabilization followed by a NMBA bolus dose and subsequent onset and recovery from muscle relaxation. Twitch data were analyzed for onset and recovery characteristics and the results compared to clinical muscle relaxation studies in existing literature. We found that twitch potentiation likely plays a minor role in shortened onset time and increased duration of twitch depression observed with long periods of twitch stabilization.
authors.affiliation: Research Group for Experimental Anesthesiology and Clinical Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 30001, Groningen, 9700 RB, The Netherlands. d.j.eleveld@anest.umcg.nl
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Eleveld
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Proost
authors.forename: J Mark K H
authors.initials: JM
authors.lastname: Wierda
mesh_terms: D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology* / Q000506:poisoning*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology
chemical_list: D009466:Neuromuscular Blocking Agents