Cumulative dose-response with infusion: a technique to determine neuromuscular blocking potency of atracurium and vecuronium

Abstract

The ability of cumulative dose-response techniques to obtain accurate data is most likely limited by redistribution and elimination of the drug during the study period. Therefore the usefulness of these techniques would be improved by replacing the amount of drug lost. This hypothesis was assessed for the intermediate-duration neuromuscular blockers vecuronium and atracurium, and calculations were made based on a pharmacokinetic model with an effect compartment. Sixty patients received either single doses (SD) (n = 36), cumulative doses (CD) (n = 12), or CD of vecuronium or atracurium with an infusion (CDI) to replace eliminated or redistributed drug (n = 12). The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade at the adductor pollicis and log dose. The potencies obtained with all three methods were within 20% of each other. For vecuronium the ED90 was (mean +/- SE) 0.034 +/- 0.002 (SD), 0.037 +/- 0.003 (CD), and 0.036 +/- 0.003 mg/kg (CDI). For atracurium the ED90 was 0.175 +/- 0.009 (SD), 0.206 +/- 0.019 (CD), and 0.179 +/- 0.015 mg/kg (CDI). Calculated values corresponded well with measured values. The calculations predicted that the agreement between single- and cumulative-dose techniques would be improved if (1) the dose increment was increased, (2) the elimination half-life was increased above 20 minutes, or (3) an infusion was added.(ABSTRACT TRUNCATED AT 250 WORDS)