Sedation with propofol during regional anaesthesia.

relationship between plasma concentration and effect. We would agree that the assumption of first-order intercompartmental drug transfer is a simplification of what must obtain in the muscle in vivo, and it may be that further refinement of the link model will bring closer agreement between observations and model predictions. Such refinement would add further model parameters, and, in our view, these will require simultaneous justification from both structural and statistical points of view. We are delighted by the interest which Dr Fisher has shown in our work, but we fail to see that there is a flaw in the justification for the threshold model which we have proposed.