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Stable plasma concentrations of unbound ropivacaine during postoperative epidural infusion for 24–72 hours in children

Published online by Cambridge University Press:  01 May 2008

C. B. Berde ,
M. Yaster ,
O. Meretoja ,
M. E. McCann ,
G. Huledal ,
U. Gustafsson  and
L. E. Larsson
C. B. Berde
Affiliation:
Children’s Hospital, Boston, MA, USA
M. Yaster
Affiliation:
Johns Hopkins University, Baltimore, MD, USA
O. Meretoja
Affiliation:
University of Helsinki, Hospital for Children and Adolescents, Helinski, Finland
M. E. McCann
Affiliation:
Children’s Hospital, Boston, MA, USA
G. Huledal*
Affiliation:
AstraZeneca R&D, Clinical Development, Södertälje, Sweden
U. Gustafsson
Affiliation:
AstraZeneca R&D, Clinical Development, Södertälje, Sweden
L. E. Larsson
Affiliation:
AstraZeneca R&D, Clinical Development, Södertälje, Sweden
*
Clinical Development, AstraZeneca R&D, Södertälje, SE-151 85 Södertälje, Sweden. E-mail: gunilla.huledal@astrazeneca.com; Tel: +46 8 553 28383; Fax: +46 8 553 28896
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Summary

Background and objectives

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 α1-acid-glucoprotein (mean 13 and 25 μmol 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.

Conclusion

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.

Keywords

ANAESTHESIA CONDUCTION, epidural blockPOSTOPERATIVE PERIODANAESTHETICS LOCAL, ropivacainePHARMACOKINETICS, plasma concentrationsANALGESIA, postoperativeNERVE BLOCK, continuous epidural infusion
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 5 , May 2008 , pp. 410 - 417
Copyright
Copyright © European Society of Anaesthesiology 2008

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