The relationship between twitch depression and twitch fade during neuromuscular block produced by vecuronium: correlation with the release of acetylcholine

The T4/T1 ratios produced by different doses of vecuronium (15–80 μg·kg-1) were plotted as a function of the concomitant T1. Separately in a model of neuromuscular transmission, T1, T4, and T4/T1 were estimated using simulations in the presence and in the absence of a neuromuscular blocking drug and a stepwise decrease in A4, but constant A1.Vecuronium induced neuromuscular block was associated with larger T4/T1 ratios (less fade) during the onset than during the offset of the block. All doses caused similar fade during offset. Simulations revealed that the smallest T4/T1 was associated with the nadir of A4/A1 and occurred at the beginning of T1 recovery. The nadir of A4/A1 was only marginally affected by the dose of vecuronium: 15 μg·kg-1 producing the minimum A4/A1 of 0.8 and 80 μg·kg-1 the minimum A4/A1 of 0.7.The hysteresis in the fade between onset and offset appears to be caused by a delayed decrease of A4/A1 as compared with the decrease in T1. Tentative estimates of the decrease in A4/A1 during fade produced by vecuronium are offered. However, the validity of these estimates is dependent on the validity of the assumptions made in simulations.Non-depolarizing neuromuscular blocking drugs cause a dose-dependent decrease in the indirectly evoked muscle contractions (twitches). Upon repetitive stimulation, the successive twitches during partial nondepolarizing block are reduced more than the first twitch. This phenomenon is known as fade. The ratio of the twitch strength produced by the fourth stimulus (T4) compared to that produced by the first stimulus (T1), i.e. T4/T1, elicited by a train-of-four (TOF) stimuli is of interest to both anesthesiologists and physiologists. Anesthesiologists use the T4/T1 ratio as an indirect measure of the still present muscle paralysis [1-3], while physiologists study the fade to gain insight into the processes of neuromuscular transmission [4-6].Bowman [7] and others [4,8-10] have suggested that neuromuscular blocking drugs pro