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