DISPOSITION OF INFUSIONS OF ATRACURIUM AND ITS METABOLITE, LAUDANOSINE, IN PATIENTS IN RENAL AND RESPIRATORY FAILURE IN AN ITU

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Abstract
A study of plasma atracurium and laudanosine concentrations was undertaken in 14 critically ill patients who received a bolus dose of atracurium 0.6 mg kg−1 followed by an infusion of 0.6mg kg−1 h−1 for a period of 11–47 h. Seven of the patients had normal renal function and seven were in acute renal failure. In both groups plasma concentrations of atracurium reached a plateau of approximately 1300 ng ml−1within 30 min of the bolus dose. The drug disappeared from the plasma within 120 min after discontinuation of the infusion. There was no difference between the two groups with respect to the pharmacokinetic parameters derived for atracurium. In the patients with normal renal function, plasma laudanosine concentration reached a plateau of apprpximately 1200ng ml−1 within 10h. In patients with renal failure there was a greater variation in the plasma laudanosine concentration: the highest value recorded was 4300 ng ml−1. Patients with renal failure had a significantly longer mean elimination half-life for laudanosine (1418 min v. 375min; P < 0.05) and Vd (4.52 litre kg−1 v. 240 litre kg−1; P < 0.01) than the patients with normal renal function.