Human Dose–Response Curves for Neuromuscular Blocking Drugs

Abstract

The validity of the log-probit method of analyzing dose-response data was demonstrated and the accuracy of the incremental dose method for generating dose-response data for pancuronium and d-tubocurarine, was tested. During balanced general anesthesia, cumulative dose-response data were obtained from 10 patients each for pancuronium and d-tubocurarine. Dose-response data were obtained using a single bolus injection method in 46 patients given pancuronium and 27 patients given d-tubocurarine. Evoked thumb adduction response was measured using an FT-10 force-displacement transducer and recorded on a Grass-7 polygraph. Dose-response data were plotted on log-probit paper and analyzed by the Litchfield-Wilcoxon approximation method to determine mean ED50 and ED95 [dose which was 95% effective] for each muscle relaxant. The dose-response data were plotted on arithmetic scales and analyzed by the linear regression method to determine ED50 and ED95. These results were compared with those obtained by use of the log-probit method. The validity of the incremental dose method of obtaining dose-response curves was determined by comparison with the dose-response curves obtained using the conventional single bolus injection method. For each neuromuscular relaxant studied, the mean dose-response curve obtained by the cumulative dose method was not statistically significantly different from the bolus method dose-response curve. Comparing methods of analysis, the log-probit method yields results that are statistically not different from those obtained by use of conventional linear regression analysis. The log-probit plot is a simple, accurate, appropriate approach for analyzing neuromuscular relaxant dose-response data. The log-probit curve yields results that are not statistically significantly different from those of the linear regression method, and is a better fit to the data at the clinically important extremes (85-99%) of the response scale. For pancuronium and d-tubocurarine, the incremental dose method is efficient and accurate for generating dose-response curves.