title: Stable plasma concentrations of unbound ropivacaine during postoperative epidural infusion for 24-72 hours in children.
abstract: OBJECTIVE
  The aim of this open, non-controlled, multi-centre study was to evaluate the pharmacokinetics and safety of a 24-72 h continuous epidural ropivacaine infusion in children aged 1-9 yr.
  
  
  METHODS
  After induction of general anaesthesia, 29 ASA I-II children, scheduled for major surgery in dermatomes below T10 had lumbar epidural catheters placed. A bolus of ropivacaine, 2 mg kg(-1), was given over 4 min, followed immediately by an infusion of 2 mg mL(-1) ropivacaine 0.4 mg kg(-1) h(-1) for the next 24-72 h.
  
  
  RESULTS
  Plasma concentrations of total ropivacaine (mean 0.83 and 1.06 mg L(-1) at 16-31 and 59-72 h, respectively) and alpha1-acid-glucoprotein (mean 13 and 25 micromol L(-1) at baseline and 59-72 h) increased over the course of the infusion. Plasma concentrations of unbound ropivacaine were stable throughout the epidural infusion (mean 0.021 range 0.011-0.068 and mean 0.016 range 0.009-0.023 mg L(-1) at 16-31 and 59-72 h, respectively) and were well below threshold levels associated with central nervous system toxicity in adults (0.35 mg L(-1)). Apparent unbound clearance (mean 346, range 86-555 mL min(-1) kg(-1)) showed no age-dependency. No signs of systemic toxicity or cardiovascular effects were observed. All patients received additional analgesics with morphine.
  
  
  CONCLUSIONS
  Following a 24-72 h epidural infusion of ropivacaine 0.4 mg kg(-1) h(-1) in 1-9-yr-old children, the plasma concentrations of unbound ropivacaine were stable over time with no age-dependency.
authors.affiliation: Children's Hospital, Boston, MA, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Berde
authors.forename: M
authors.initials: M
authors.lastname: Yaster
authors.forename: O
authors.initials: O
authors.lastname: Meretoja
authors.forename: M E
authors.initials: ME
authors.lastname: McCann
authors.forename: G
authors.initials: G
authors.lastname: Huledal
authors.forename: U
authors.initials: U
authors.lastname: Gustafsson
authors.forename: L E
authors.initials: LE
authors.lastname: Larsson
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016058:Analgesia, Patient-Controlled; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007268:Injections, Epidural; D008297:Male; D009961:Orosomucoid / Q000032:analysis*; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000188:drug therapy*; D011184:Postoperative Period; D000077212:Ropivacaine; D013223:Statistics as Topic; D013997:Time Factors; D013520:Urologic Surgical Procedures
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D009961:Orosomucoid; D000077212:Ropivacaine