Pharmacokinetics of atracurium and laudanosine in intensive care patients with acute respiratory distress syndrome undergoing mechanical ventilation

Objective: To determine the pharmacokinetic profiles of atracurium and its main metabolite (laudanosine) in patients with acute respiratory distress s yndrome undergoing mechanical ventilation. Patients and Methods: Plasma pharmacokinetic profiles of atracurium and lau danosine were studied in eight critically ill patients with acute respirato ry distress syndrome who required a neuromuscular blocking drug to assist m echanical ventilation. Patients received an infusion of atracurium (1 mg/kg per hour) for 72 hours after an initial intravenous bolus dose of 1 mg/kg. Neuromuscular blockade was monitored using an accelerograph. Blood samples were obtained over a 96-hour period. Atracurium and laudanosine concentrat ions in plasma were determined by high performance liquid chromatography. A single-compartment pharmacokinetic model was fitted to plasma concentratio ns of atracurium and laudanosine. Results: For atracurium, the median elimination half-life value was 20.7 mi nutes (0.35h); the steady-state volume of distribution ranged from 0.148 to 0.327 L/kg and the total clearance from 0.27 to 0.67 L/h/kg (4.5 to 11 ml/ min/kg). For laudanosine, the elimination half-life ranged from approximate ly 2 to 21 hours and the maximum plasma concentration ranged from 0.86 to 1 6 mg/L. For all patients, the train-of-four (TOF) count was recorded to 4 a t baseline. Within 1 hour after the beginning of infusion, 7 of 8 patients had a TOF count of less than or equal to 1. The neuromuscular recovery rang ed from 32 to 67 minutes. Conclusion: The pharmacokinetic properties of atracurium in intensive care unit patients with acute respiratory distress syndrome are similar to those in patients during anaesthesia. Moreover, the dosage regimen administered to the patients in this study (i) provided sufficient neuromuscular blockag e for adequate ventilation, and (ii) does not require monitoring of neuromu scular function, a procedure that does not seem to eliminate prolonged weak ness and myopathy.