Potency and Onset of Action of Neuromuscular Blocking Drugs

To the Editor: 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.Figure 1: Results of Dr. Kopman [3] (upper line) and our best fitting line (lower).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. Wierda, MD, PhD Lambertus van den Broek, MD Sjouke Schiere, MD Egidio Maestrone, MD Research Group for Experimental Anesthesiology and Clinical Pharmacology, University Hospital Groningen, 9700 EZ Groningen, The Netherlands