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Excerpt
Dr. Kopman [1], in his reply to Bartkowski et al.'s study [2], pointed out that the relatively fast onset of rocuronium cannot be satisfactorily explained by the difference in molar potency, expressed as ED95, compared with the other neuromuscular blockers d-tubocurarine (d-TC), gallamine, pancuronium, vecuronium, and atracurium. We agree with Bartkowski and Witkowski in their response to Kopman [1], that a different stimulation mode and anesthetic technique may be of influence. In the past we repeated the study of Kopman [3] in 18 patients under thiopental/fentanyl anesthesia with a mixture of N2 O and O2. Three groups of six patients each received d-TC, gallamine, and pancuronium, respectively. In contrast to Kopman, who monitored the neuromuscular block with train-of-four (TOF) stimulation, 2 Hz every 20 s, we determined the TOF, 2 Hz every 12 s. We found only a weak relationship between onset and potency (y = -2.6432x + 4.7656; see Figure 1). Since the calculated ED95 value for d-TC deviates significantly from the previous findings of Kopman [3], the higher potency of d-TC in our study may be related to its more pronounced intrinsic activity to prejunctional receptors, which is extensively described by Bowman et al. [4,5]. Blockade of prejunctional receptors coincides with a more pronounced fade at higher stimulation frequencies, e.g., TOF and tetanic stimulation. This view is supported by several papers. Gibson and Mirakhur [6] demonstrated that d-TC and atracurium produce more fade than vecuronium and pancuronium, especially during onset (TOF 2 Hz every 10 s). Pearce et al [7] showed previously in their experiment that during onset atracurium produced significantly more fade than vecuronium, using TOF stimulation of 2 Hz with a stimulation-free interval of 12 s.
With a little more intense TOF stimulation pattern of 4 Hz, Williams et al. [8] showed significant differences between pancuronium and d-TC and also between pancuronium and gallamine.
This suggests that compounds with a more pronounced prejunctional affinity will display a higher potency with an increasing stimulation frequency and/or a decreasing stimulation-free interval.
Consequently, the high correlation found by Kopman [3] is valid only for these three muscle relaxants, under the specified experimental conditions.
J. Mark K. H.
