The train-of-four count and kinetic-dynamic modelling

The intraoperative monitoring of neuromuscular blockade usually involves measurement of the muscular responses to motor nerve stimulation. Although researchers have the time and technology to obtain predrug control measurements of the twitch responses, these are seldom available to the clinician. During surgically useful relaxation, there is progressive inhibition of responses to train-of-four (TOF) stimulation in the presence of a nondepolarizing relaxant, and the clinician can count the number of responses to predict the likely time-course of paralysis. At the extremes, a count of four (of four) responses may indicate a need for further relaxant, whereas with profound paralysis, the absence of responses may suggest that reversal with an anticholinesterase may be ineffective. Concentrations in the effect compartment associated with these two extremes of the TOF count are combined with concentration-time profiles of vecuronium with various dose regimens. This study models the effect compartment concentrations associated with vecuronium-induced paralysis, combining them explicitly with the range of concentrations associated with the TOF count to demonstrate the kinetic mechanisms underlying the time-course of paralysis.