Abstract
A cumulative dose response curve for loss of consciousness was obtained using 48 unselected premedicated patients presenting for elective surgery. Dosage was administered on the basis of lean tissue mass (LTM) using a simple nomogram. The end point for loss of consciousness was the failure of the patient to grasp a light object. Using probit analysis an ED50 for thiopentone in premedicated patients was found to be 2.63 mg/kg LTM. The sequential up-and-down technique was then used to determine ED50 values for thiopentone (2.70 mg/kg LTM), methohexitone (1.1 mg/kg LTM), propanidid (3.66 mg/kg LTM) and Alfathesin (0.014 ml/kg LTM).
The experimental methods and, in particular, the administration of doses to patients on the basis of LTM, would appear to be responsible for a high level of predictability of response in an apparently heterogeneous patient population.
The ED50 values compared favourably with clinically recommended doses for induction of anaesthesia, except the ED50 for Alfathesin which was approximately one quarter of that recommended.
An appendix provides some of the mathematical background of the up-and-down sequential technique together with a table of maximum likelihood solutions for different sequences and an example of the calculation of an ED50 and its confidence limits