Improving the Design of Muscle Relaxant Studies. Stabilization Period and Tetanic Recruitment

Background: The results from studies of muscle relaxants show wide variations among institutions. The authors hypothesized that some of this variability could be explained by differences in duration of nerve stimulation before drug administration (stabilization period).

Methods: Train-of-four stimulation was applied every 12 s to both ulnar nerves and adductor pollicis twitch tension was measured in anesthetized participants given 30 micrograms/kg vecuronium. In phase 1, the stabilization period was > 30 min for both extremities. In phase 2-4, stabilization period was 20 min for one extremity and 2 min for the other. In addition, in phase 3, a 2-s 50-Hz tetanus initiated the 2-min stimulation period; in phase 4, duration of tetanus was 5 s. Twitch recovery was recorded until stable for more than 15 min. Time to 25% recovery (clinical duration) was calculated based on two indices: predrug and final (recovery) twitch tension. Values for onset and clinical duration were compared by paired parametric and nonparametric tests.

Results: In phase 1, predrug and recovery twitch tension were similar in each extremity, and onset and clinical duration did not differ between extremities, permitting paired comparisons in remaining studies. In phase 2, onset was more rapid with 20-min of prestimulation. With 20-min prestimulation, predrug and recovery twitch tension were similar; with 2-min prestimulation, recovery twitch tension exceeded predrug values. When referenced to predrug twitch tension, clinical duration was shorter with 2-min, that with 20-min prestimulation. Initiating stimulation with 2-s or 5-s 50-Hz tetani (phases 3, 4) abolished differences between extremities in onset and recovery.

Conclusions: With only train-of-four stimulation (no tetani), onset and clinical duration vary with duration of prestimulation, suggesting that a brief period of predrug stimulation is inadequate. However, lengthy prestimulation may be impractical in clinical studies. Tetanic stimulation for 2 or 5 s obviates the need for prolonged stabilization during studies of muscle relaxants.