title: Pharmacokinetics and dynamics of atracurium infusions after paediatric orthotopic liver transplantation.
abstract: We examined the pharmacokinetics and pharmacodynamics of atracurium besylate and its metabolites in children after orthotopic liver transplantation (OLT), as a suitable model for critically ill children. Ten children were studied after OLT on return to the intensive care unit (ICU). The mean (range) age was 36 (7-78) months, and weight 6-24.2 kg. Atracurium was started at induction of anaesthesia and adjusted in the ICU according to clinical need. Neuromuscular block was measured using accelerometry (TOFguard) and the train-of-four (TOF) ratio or count. Arterial plasma samples for atracurium and metabolites taken before, 12-hourly during, and at frequent intervals after the infusion were analysed by HPLC. The mean (range) maximum infusion rate during steady-state conditions was 1.44 (0.48-3.13) mg kg(-1) h(-1) and the duration of infusion 36.9 (22.5-98.4) h. Tachyphylaxis was not observed. The mean terminal half-life (t1/2) for atracurium was 18.8 (12-32.3) min. The steady-state plasma clearance (CLss) was 13.9 (7.9-20.3) ml min(-1) kg(-1) and the terminal volume of distribution (Vz) 390 (124-551) ml kg(-1); both were higher than in adults after successful OLT. The maximum concentration (Cmax) of laudanosine was 1190 (400-1890) ng ml(-1) and t1/2 was 3.9 (1.1-6.7) h. The renal clearance of laudanosine was 0.9 (0.1-2.5) ml min(-1) kg(-1) and increased with urine flow, but there was no significant relationship with serum creatinine. EEG spikes were confirmed in one child only; the corresponding laudanosine Cmax was 720 ng ml(-1). Monoquaternary alcohol Cmax was 986 (330-1770) ng ml(-1) and t1/2 42.9 (30-57.7) min. Mean recovery time on stopping the atracurium infusion to a TOF ratio >0.75 was 23.6 (12-27) min. Atracurium is an effective and safe neuromuscular blocking agent in this population. Laudanosine concentrations are not excessive if graft function is satisfactory.
authors.affiliation: University Department of Anaesthesia and Intensive Care Medicine, N5 Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: B
authors.initials: B
authors.lastname: Chow
authors.forename: M I
authors.initials: MI
authors.lastname: Bowden
authors.forename: E
authors.initials: E
authors.lastname: Ho
authors.forename: B C
authors.initials: BC
authors.lastname: Weatherley
authors.forename: J F
authors.initials: JF
authors.lastname: Bion
mesh_terms: D001279:Atracurium / Q000008:administration & dosage / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003422:Critical Care / Q000379:methods*; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007546:Isoquinolines / Q000097:blood; D016031:Liver Transplantation; D008297:Male; D019148:Neuromuscular Blockade / Q000379:methods; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000097:blood*; D011182:Postoperative Care / Q000379:methods*
chemical_list: D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; C001522:laudanosine