Train-of-four fade and neuromuscular block in rats: a comparison between pancuronium, vecuronium, and rocuronium

Abstract

Purpose: To clarify the relationship between neuromuscular block and train-of-four fade and to investigate the causes of these drug-dependent differences, we compared the neuromuscular block and TOF fade after pancuronium, vecuronium and rocuronium.Methods: In 24 anesthetized rats, the sciatic nerve was stimulated, and the twitch of left tibialis anterior muscle was recorded. After T 1 (first twitch response) was kept constant at 95% block by administration of pancuronium, vecuronium, or rocuronium (n=8, in each), the TOF fade was measured when T 1 block was decreased to 40% and 20%. In addition, using 24 phrenic nerve-diaphragm preparations, the fade was measured when the T 1 block increased to 20% and 40% by titrating of either one of the three drugs (n=8, in each). Results: In in vivo experiments, the fade produced by pancuronium was greater than that by vecuronium or rocuronium when T 1 block was at 40% (81 ± 9 vs 63 ± 15 and 63 ± 6%, respectively) and at 20% (66 ± 13 vs 34 ± 17 and 40 ± 6%, respectively). In contrast, in in vitro experiments, the differences did not reach significant levels among the three drugs either at 20% (32 ± 19 vs 33 ± 10 and 32 ± 17%) or 40% of block (62 ± 29 vs 65 ± 14 and 55 ± 14%). Conclusions: For vecuronium and rocuronium, the results were similar in vivo and in vitro. For pancuronium, fade was greater in vivo. These results suggest that different neuromuscular blocking agent have different relationships between the fade and the block. In vitro results might not be the same as in vivo, possibly due to pharmacokinetic differences.

Time course and train-of-four fade of mivacurium block during sevoflurane and intravenous anaesthesia

“…The clinical significance of this prejunctional action is not clear and it has not been correlated with the potency of the drug or the speed of onset of the neuromuscular block [12,13]. Recent studies have found no differences in TOF fade between the more frequently used agents (mivacurium, atracurium, rocuronium, vecuronium and cisatracurium), although there have been previously reported differences between pancuronium and d-tubocurarine [13,14].…”

“…The degree of fade in response to TOF stimulation is correlated to the action of the neuromuscular blocking agent on the presynaptic receptor [12,13]. This action induces an inhibition of the positive feedback decreasing transmitter output [14]. The clinical significance of this prejunctional action is not clear and it has not been correlated with the potency of the drug or the speed of onset of the neuromuscular block [12,13].…”

Utility of Electromyography for Nerve Root Monitoring During Spinal Surgery

“…Some texts suggest that a fourth twitch of any amplitude is sufficient for valid pedicle screw threshold determination (Holland, 2008), while others caution from experience that a fourth twitch of small amplitude may result in inaccurate threshold determinationpresumably via diminution of the stimulus-evoked CMAP-and recommend a minimum fourth twitch ratio such as 0.1 (Toleikis, 2002) or 0.3 (Minahan and Mandir, 2008). However, it should be appreciated that non-depolarizing blocking agents exhibit varying fade characteristics (Itoh et al, 2000).…”

Neurotransmission in the carotid body and anesthesia

“…Inhibition of chemoreceptor nerve activity by vecuronium occurred at a dose lower than the ED 50 for the phrenic nerve-hemidiaphragm preparation in rats [120,121]. In humans, the ventilatory response to hypoxia was depressed during continual administration of vecuronium with which a train-of-four-ratio was maintained at 0.7 [116][117][118].…”