Volume of the effect compartment in simulations of neuromuscular block

BACKGROUND: The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants. METHODS: The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent receptor concentration in the effect compartment is the ratio of this amount and the volume arbitrarily assigned to the effect compartment. The muscle relaxants were postulated to diffuse between the central and the effect compartment and to bind to the postsynaptic receptors. NMB was calculated from the free concentration of the muscle relaxant in the effect compartment. RESULTS: The simulations suggest that the time profiles of NMB and the derived pharmacokinetic and pharmacodynamic variables are dependent on the apparent receptor concentration in the effect compartment. For small, but not for large, volumes, times to peak submaximal NMB are projected to depend on the magnitude of NMB and on the binding affinities. CONCLUSION: An experimental design to estimate the volume of the effect compartment is suggested.