Improving the design of muscle relaxant studies.

Abstract

Department of Anesthesiology, Allegheny University of the Health Sciences, Broad and Vine, Mail Stop 310, Philadelphia, Pennsylvania 19102–1192.To the Editor:-The paper by Lee et al. (Anesthesiology, 1997;86:48–54) raises important issues for research on the pharmacokinetics of muscle relaxants using adductor pollicis monitoring. It clearly indicates that the duration of ulnar nerve stimulation before muscle relaxant administration needs to be controlled within an individual experimental study, and considered when comparing results from different studies. As with any good study, we should ask questions concerning to what extent its findings can be generalized.1. Does the duration of predrug stimulation affect clinical judgments that are typically made on the basis of train-of-four (TOF) fade? One would not think so. But because the authors used TOF monitoring, they could provide us with some insight concerning whether the time course of T4/T1 was altered by the predrug stimulation, as was the T1.2. Might the importance of the predrug stimulation period depend on the preload conditions? In animal experiments in which the preload is adjusted to maximal twitch tension, we do not see as large a progressive increase in twitch tension as Lee et al. report during the first 10 min of stimulation in their patients.3. Do the authors have any data or expectations concerning the effect of predrug stimulation on adductor pollicis monitoring using electromyography (EMG) rather than isometric tension? If the increase in twitch tension which they observe during the predrug stimulation period is similar to the classic staircase (or treppe) phenomenon of muscle, then it may not be as important to control the duration of the predrug stimulation period in studies using EMG.The authors suggest that tetanic stimulation for 5 s obviates the need for a prolonged stabilization period for predrug stimulation. This conclusion is based on their finding that recovery times for short predrug stimulation periods, which included a tetanus, did not differ from those with prolonged pre-drug stimulation periods. However, more fundamental lessons can be learned from their study. First, a “control” period should not be considered a control until it can be expected to be stable over time. Second, researchers must exercise caution in comparing (and combining) findings from different studies. Consistent differences in seemingly unimportant experimental conditions can confound interpretation.Robert J. Storella, Jr., Ph.D.Department of Anesthesiology; Allegheny University of the Health Sciences; Broad and Vine; Mail Stop 310; Philadelphia, Pennsylvania 19102–1192(Accepted for publication April 25, 1997.)