Pharmacokinetic-pharmacodynamic modeling of atracurium in intensive care patients

The authors have studied 10 critically ill patients with acute respiratory distress syndrome who required a neuromuscular blocking drug to assist mech anical ventilation. patients received a bolus dose of 1 mg/kg of atracurium followed by a constant infusion rate of 1 mg/kg/h of this drug for 72 hear s. Neuromuscular block was monitored using an accelerograph. Blood samples were obtained over a 96-hour period. A preliminary independent analysis was done to estimate the individual pharmacokinetic parameters; data were cons istent with a one-compartment model. The pharmacodynamic data analysis was then performed using the changes in train-of-four (TOF) count as an index o f the therapeutic effect of atracurium. Pharmacokinetic-dynamic variables w ere calculated using the Sheiner model and the Hill equation. The eliminati on half-life of atracurium averaged 22 minutes. Mean volume of distribution and plasma clearance were 217 ml/kg and 550 ml/min, respectively. There wa s a significant hysteresis loop when the TOF count was plotted against pred icted plasma atracurium concentrations. The mean sigmoidicity factor, gamma , was 4.04. The concentration producing 50% of the E-max was 1.36 mug/mL, a nd the mean k(e0) was 0.059 min(-1). Recovery time ranged from 30 to 80 min utes, and none of the patients of this study had residual paralysis. Journa l of Clinical Pharmacology, 2001.;41:44-50 (C) 2001 the American College of Clinical Pharmacology.