Onset of the nondepolarizing neuromuscular block in humans: quantitative aspects

The purpose of our study was a unified description of the time course for the onset of the neuromuscular block produced by different muscle relaxants after bolus intravenous injections. The environment of the receptors on the motor end plate was assumed to be a part of the interstitial space of the muscle. A unified consideration of four muscle relaxants was accomplished by expressing the concentrations of each relaxant in the interstitial space as multiples of the relaxant's dissociation constant. A flow-limited model was developed to describe the time course of the relaxant's concentration in the interstitial space as a function of its plasma concentration, the plasma flow to the muscle, and the volume of the interstitial space. The results show that those relaxants whose plasma concentrations decrease rapidly achieve an earlier (4-8 min), but relatively lower, peak concentration in the interstitial space. The relaxants with more sustained plasma concentrations reach the peak concentration later, 9-16 min after the bolus intravenous injection. The model allows the interpretation of several observations encountered with the clinical use of the muscle relaxants.