A pharmacodynamic explanation for the rapid onset/offset of rapacuronium bromide

Abstract

Background: Nondepolarizing muscle relaxants differ in their time course at the laryngeal adductors and the adductor pollicis, a result of differences in equilibration delays between plasma and effect sites, the sensitivity of each muscle to the relaxant, and the steepness of the concentration-effect relation at each muscle (the Hill factor). To determine whether similar differences exist for rapacuronium, a muscle relaxant with rapid onset and offset, the authors determined its pharmacodynamic characteristics. Methods: The twitch tensions of the adductor pollicis and the laryngeal adductors (via a tracheal tube cuff positioned at the vocal cords) were measured in 10 volunteers who were anesthetized with propofol. Rapacuronium, 1.5 mg/kg, was given and blood samples were collected. A semiparametric effect compartment pharmacodynamic model was fit to values for rapacuronium plasma concentrations and twitch tension of the adductor pollicis and laryngeal adductors. Results: Equilibration between the rapacuronium plasma concentration and both effect sites was rapid (typical values for the rate constant for equilibration between plasma and the effect site are 0.405 per min for the adductor pollicis and 0.630 per min for the laryngeal adductors) and was more rapid at the laryngeal adductors than at the adductor pollicis (ratio, 1.59 ± 0.16; mean ±SD). The steady state rapacuronium plasma concentration that depressed twitch tension by 50% and the Hill factor were similar for the two muscles. Conclusions: The rapid onset and offset of rapacuronium can be explained by the rapid equilibration between concentrations in plasma and at the effect site. Unlike the finding for other nondepolarizing muscle relaxants, the laryngeal muscles are not resistant to rapacuronium.