title: Cisatracurium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children.
abstract: BACKGROUND
  Hypothermia potentiates neuromuscular blockade in adults during cardiopulmonary bypass (CPB) but the pediatric literature is sparse. Temperature-dependent Hoffman degradation of cisatracurium may allow reduction in infusion rate (IR) during hypothermia. The effect of hypothermic CPB on the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium has not been described in children.
  
  
  METHODS
  Using neuromuscular monitoring with a Datex Relaxograph, cisatracurium IR was adjusted to obtain a pseudo-steady state during each phase of surgery (pre-CPB, CPB, post-CPB). Paired samples were taken at each phase. Cisatracurium plasma concentrations (Cpss) were determined by HPLC. Core and skin temperatures were recorded.
  
  
  RESULTS
  Data from ten infants were analyzed: Group 1: mean 33.6°C; Group 2: mean 21.9°C. To maintain T1% between 5% and 10% in Group 2, the IR was decreased by a mean of 89% (P < 0.001). IR was not significantly different in Group 1. Post-CPB IR approximated pre-CPB rates in both groups. During CPB, Cpss fell by 27% in Group 1 and by 50% in Group 2 (P = 0.039). Post-CPB Cpss was not significantly different to pre-CPB in either group. Clearance did not change significantly in Group 1 but fell significantly in Group 2 during CPB (P = 0.002). Clearance post-CPB was unchanged from pre-CPB.
  
  
  CONCLUSIONS
  Cisatracurium IR may be decreased by around 60% during CPB with moderate hypothermia but can be maintained at baseline during mild hypothermia.
authors.affiliation: Department of Anesthesia, McGill University, Montreal Children's Hospital, Montreal, QC, Canada. davinia.withington@mcgill.ca
authors.forename: Davinia
authors.initials: D
authors.lastname: Withington
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ménard
authors.forename: France
authors.initials: F
authors.lastname: Varin
mesh_terms: D001279:Atracurium / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D001831:Body Temperature; D002138:Calibration; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004576:Electromyography; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery; D006801:Humans; D007036:Hypothermia, Induced; D007223:Infant; D008297:Male; D016343:Monitoring, Intraoperative; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012881:Skin Temperature
chemical_list: D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; C101584:cisatracurium