Pharmacodynamics of Atracurium in Clinical Practice

To determine which factors influenced the pharmacodynamics of atracurium in clinical practice, the steady-state plasma concentration of atracurium for 90% paralysis (Cpss90) was measured in 100 adult patients. Neuromuscular block was maintained at 88%-92% of the control response by adjusting the target concentration being delivered by preprogrammed intravenous atracurium infusion. The Cpss90 was measured empirically from plasma samples taken when the block had been stable for 15 min with no adjustment in the infusion rate for 20 min. To describe how factors influenced the Cpss90 of atracurium, a model was developed by multiple stepwise linear regression analysis. Influencing variables retained in the final model were plasma potassium concentration, intraoperative administration of gentamicin, and premedication with papaveretum and hyoscine. The model predicted that the Cpss90 of atracurium would decrease with decreasing serum potassium according to the relationship log10(Cpss90) = 2.380 + 0.171 x [K mmol/L] (n = 100; ANOVA, P < 0.001). Intraoperative administration of gentamicin modified this relationship resulting in a 25.1% decrease in the predicted Cpss90 (n = 15; ANOVA, P < 0.001). Premedication with papaveretum and hyoscine also modified this relationship resulting in a 21.2% decrease in predicted Cpss90 (n = 30; ANOVA, P < 0.001). The model predicted that administration of both would decrease the Cpss90 by 41.0%. Patients aged > or = 70 yr had a slight, but statistically insignificant, increase in the Cpss90 compared to younger adult patients. No other factor was found to influence the Cpss90, including patient sex, body fluid, and other drugs administered in the perioperative period, including calcium channel antagonists and ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)