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Background  Train-of-four stimulation pattern following the administration of non-depolarizing neuromuscular blocking drugs reveals fade on successive contractions. Fade is caused by the release of fewer acetylcholine molecules by the fourth (A 4 ) than by the first stimulus (A 1 ). The current study was conducted to define the relationship between the clinically observed fade and the simulated decline in acetylcholine release (A 4 /A 1 ) that would be necessary to produce it.    Methods  The T 4 /T 1  ratios produced by different doses of vecuronium (15–80 μg·kg -1 ) were plotted as a function of the concomitant T 1 . Separately in a model of neuromuscular transmission, T 1 , T 4 , and T 4 /T 1  were estimated using simulations in the presence and in the absence of a neuromuscular blocking drug and a stepwise decrease in A 4 , but constant A 1 .    Results  Vecuronium induced neuromuscular block was associated with larger T 4 /T 1  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 T 4 /T 1  was associated with the nadir of A 4 /A 1  and occurred at the beginning of T 1  recovery. The nadir of A 4 /A 1  was only marginally affected by the dose of vecuronium: 15 μg·kg -1  producing the minimum A 4 /A 1  of 0.8 and 80 μg·kg -1  the minimum A 4 /A 1  of 0.7.    Conclusion  The hysteresis in the fade between onset and offset appears to be caused by a delayed decrease of A 4 /A 1  as compared with the decrease in T 1 . Tentative estimates of the decrease in A 4 /A 1  during fade produced by vecuronium are offered. However, the validity of these estimates is dependent on the validity of the assumptions made in simulations.

theoretical biology and medical modelling

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