Clearance of Atracurium and Laudanosine in the Urine and by Continuous Venovenous Haemofiltration

Abstract

We have measured the steady state urinary clearances of atracurium, given by constant infusion, and laudanosine in eight patients undergoing artificial ventilation; all had normal renal function (mean creatinine clearance 81 ml min-1). Mean (SD) urinary clearance of atracurium was 0.55 (0.5) ml kg-1 min-1; that of laudanosine was 0.33 (0.2) ml kg-1 min-1. Simultaneous plasma clearances were 7.1 (1.4) ml kg-1 min-1 and 3.8 (1.5) ml kg-1 min-1, respectively. Notional haemofiltration clearances of the two substances were measured also in seven critically ill patients with renal and respiratory failure undergoing continuous venovenous haemofiltration. Mean (SD) clearances of atracurium and laudanosine in the haemofiltrate fluid were 0.11 (0.06) ml kg-1 min-1 and 0.09 (0.02) ml kg-1 min-1, respectively whilst plasma clearances were atracurium 6.7 (1.8) ml kg-1 min-1 and laudanosine 4.5 (1.8) ml kg-1 min-1. There were no significant differences between the plasma clearances of the drugs in the two groups, despite the difference in severity of sickness. Urinary clearance rates of atracurium and laudanosine were approximately 8 and 9% of that in the plasma, but the haemofiltration clearance of both substances was only 2%.

New Neuromuscular Blocking Drugs

“…53 It is excreted in part in the urine. 45 A plasma *Unpublished data. laudanosine concentration of 17 mg per milliliter causes convulsions in dogs.…”

“…82 There are multiple pathways for the elimination of atracurium, and only about 10 percent of a dose of the drug is excreted in the urine in 24 hours. 45 Therefore, the risk of residual neuromuscular blockade is low.…”

Cisatracurium dose–response relationship in patients with chronic liver disease

“…Similar findings have been published for atracurium. In fact, renal clearance and renal elimination of unchanged drug may be slightly greater for cisatracurium than for atracurium [25][26][27]. This may be related to the fact that atracurium contains short-acting isomers that are less likely to appear in the urine [13].…”

Neuromuscular blocking drugs and their antagonists in patients with organ disease

“…Atracurium undergoes Hofmann degradation, a process of spontaneous breakdown at body temperature and pH (45%), as well as metabolism by non‐specific esterases in the plasma (45%). Only about 10% of a bolus dose is excreted in the urine over 24 h in healthy patients [18]. The pharmacokinetics and pharmacodynamics of atracurium are not altered by chronic kidney disease (Tables 1 and 2) [19].…”