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首页> 外文期刊>clinical drug investigation >Pharmacokinetics of Atracurium and Laudanosine in Intensive Care Patients with Acute Respiratory Distress Syndrome Undergoing Mechanical Ventilation
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Pharmacokinetics of Atracurium and Laudanosine in Intensive Care Patients with Acute Respiratory Distress Syndrome Undergoing Mechanical Ventilation

机译：Pharmacokinetics of Atracurium and Laudanosine in Intensive Care Patients with Acute Respiratory Distress Syndrome Undergoing Mechanical Ventilation

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ObjectiveTo determine the pharmacokinetic profiles of atracurium and its main metabolite (laudanosine) in patients with acute respiratory distress syndrome undergoing mechanical ventilation.Patients and Methods: Plasma pharmacokinetic profiles of atracurium and laudanosine were studied in eight critically ill patients with acute respiratory distress syndrome who required a neuromuscular blocking drug to assist mechanical 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 concentrations in plasma were determined by high performance liquid chromatography. A single-compartment pharmacokinetic model was fitted to plasma concentrations of atracurium and laudanosine.ResultsFor atracurium, the median elimination half-life value was 20.7 minutes (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 approximately 2 to 21 hours and the maximum plasma concentration ranged from 0.86 to 16 mg/L. For all patients, the train-of-four (TOF) count was recorded to 4 at baseline. Within 1 hour after the beginning of infusion, 7 of 8 patients had a TOF count of le;1. The neuromuscular recovery ranged from 32 to 67 minutes.ConclusionThe 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 studyprovided sufficient neuromuscular blockage for adequate ventilation, anddoes not require monitoring of neuromuscular function, a procedure that does not seem to eliminate prolonged weakness and myopathy.

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