Pharmacodynamics and atracurium and laudanosine concentrations during a fixed continuous infusion of atracurium in mechanically ventilated patients with acute respiratory distress syndrome

Abstract

The present study was designed to assess the pharmacodynamics and the plasma levels of atracurium and laudanosine found during a 72-hour fixed rate infusion of atracurium in acute respiratory distress syndrome patients without renal or liver failure. Nine sedated and mechanically ventilated acute respiratory distress syndrome patients without renal or liver failure were paralysed with a bolus of atracurium (1 mg.kg-1)followed by a 72-hour continuous infusion (1 mg·kg-l.h-1). The count of train-of-four (TOF) and TOF ratio were monitored by an accelerograph until full neuromuscular recovery (T4/T1≥ 0.7). Atracurium and laudanosine concentrations were measured from the onset to four days after cessation of the infusion. An electroencephalogram was recorded daily. Analysis showed that TOF count was always ≤ 3 until cessation of the infusion. Following cessation, neuromuscular recovery occurred between 31 and 96 minutes (median value=45 min). The highest atracurium and laudanosine concentrations ranged from 3.3 to 5.8 μg.ml-1 and from 3 to 20 μg.ml-1 respectively. In four patients with renal impairment, the highest laudanosine concentration was >1O μg.ml-1. No seizure was recorded. A fixed infusion rate of atracurium in acute respiratory distress syndrome patients provided an effective muscle paralysis with a rapid neuromuscular recovery but can lead to accumulation of laudanosine in patients with renal impairment.