A new four-parameter threshold model for the plasma atracurium concentration-response relationship.

The plasma concentration of atracurium and the electromyographic depression of the first response of the train-of-four (T1:T0) were measured during and after recovery from a 10-min infusion of atracurium 0.25 mg kg-1 in 14 patients anaesthetized with 66% nitrous oxide and 0.9% isoflurane (end-tidal) in oxygen. A standard pharmaco-dynamic model was fitted to the data; a small but consistent discrepancy was found between the time and rate of onset of depression of the ratio T1:T0 and the predictions of the standard biophase model of best fit to the data. This discrepancy is reduced by the inclusion of a threshold term (CPss theta) in the model to represent the greatest steady state plasma concentration which would just fail to evoke an effect. The values of CPss theta correlated significantly with the values of CPss50 (r = +0.627; P less than 0.02). The estimates of CPss50 and keo from the two models are very similar; the estimate of gamma, the slope of the concentration-response curve, was less in the threshold model. The relationship of the present threshold model to existing knowledge of neuromuscular physiology is discussed.