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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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References

1.Schechter, NL, Berde, CB, Yaster, M. Pain in Infants, Children, and Adolescents, 2nd edn. Philadelphia: Lippincott Willliams and Wilkins, 2003.Google Scholar
2.Desparmet, JF, Hardart, RA, Yaster, M. Central blocks in children and adolescents. In: Schechter, NL, Berde, CB, Yaster, M, eds. Pain in Infants, Children, and Adolescents. Philadelphia: Lippincott Williams and Wilkins, 2003; 363–395.Google Scholar
3.Golianu, B, Krane, EJ, Galloway, KS et al. Pediatric acute pain management. Pediatr Clin North Am 2000; 47: 559–587.CrossRefGoogle ScholarPubMed
4.Wilder, RT. Local anesthetics for the pediatric patient. Pediatr Clin North Am 2000; 47: 545–558.CrossRefGoogle ScholarPubMed
5.Dalens, B. Some open questions in pediatric regional anesthesia. Minerva Anesthesiol 2003; 69: 451–456.Google ScholarPubMed
6.Mather, LE, Chang, DH. Cardiotoxicity with modern local anaesthetics: is there a safer choice? Drugs 2001; 61: 333–342.CrossRefGoogle Scholar
7.Groban, L, Deal, DD, Vernon, JC et al. Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg 2001; 92: 37–43.CrossRefGoogle ScholarPubMed
8.Knudsen, K, Beckman Suurküla, M et al. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997; 78: 507–514.CrossRefGoogle ScholarPubMed
9.Lönnqvist, PA, Westrin, P, Larsson, BA et al. Ropivacaine pharmacokinetics after caudal block 1–8-year-old children. Br J Anaesth 2000; 85: 506–511.CrossRefGoogle Scholar
10.McCann, ME, Sethna, MF, Mazoit, JX et al. The pharmacokinetics of epidural ropivacaine in infants and young children. Anesth Analg 2001; 93: 893–897.CrossRefGoogle ScholarPubMed
11.Hansen, TG, Ilett, KF, Reid, C et al. Pharmacokinetics and clinical efficacy of long-term epidural ropivacaine infusion in children. Br J Anaesth 2000; 85: 347–353.CrossRefGoogle ScholarPubMed
12.Seow, LT, Lips, FJ, Cousins, MJ. Lidocaine and bupivacaine mixtures before epidural blockade. Anesthesiology 1982; 57: 177–183.CrossRefGoogle Scholar
13.Engman, M, Neidenstrom, P, Norsten-Hoog, C et al. Determination of ropivacaine and [2H3] ropivacaine in biological samples by gas chromatography with nitrogen–phosphorus detection or mass spectrometry. J Chromatogr B Biomed Sci Appl 1998; 709: 57–67.CrossRefGoogle ScholarPubMed
14.Brown, H, Prescott, R. Applied Mixed Models in Medicine. Chichester: John Wiley & Sons, Ltd., 1999: Chapter 1, pp. 1–32.Google Scholar
15.Booker, PD, Taylor, C, Saba, G. Perioperative changes in α1-acid glycoprotein concentrations in infants undergoing major surgery. Br J Anaesth 1996; 76: 365–368.CrossRefGoogle Scholar
16.Halldin, MM, Bredberg, E, Angelin, B et al. Metabolism and excretion of ropivacaine in humans. Drug Metab Dispos 1996; 24: 962–968.Google ScholarPubMed
17.Erichsen, C-J, Sjövall, J, Kehlet, H et al. Pharmacokinetics and analgesic effect of ropivacaine during continuous epidural infusion for postoperative pain relief. Anesthesiology 1996; 84: 834–842.CrossRefGoogle ScholarPubMed
18.Burm, AG, Stienstra, R, Brouwer, RP et al. Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery: pharmacokinetic evaluation. Anesthesiology 2000; 93: 395–403.CrossRefGoogle ScholarPubMed
19.Bösenberg, AT, Thomas, J, Cronje, L et al. Pharmacokinetics and efficacy of ropivacaine for continuous epidural infusion in neonates and infants. Paediatr Anaesth 2005; 15: 739–749.CrossRefGoogle ScholarPubMed
20.Alcorn, J, McNamara, PJ. Ontogeny of hepatic and renal systemic clearance pathways in infants. Part I. Clin Pharmacokinet 2002; 41: 959–998.CrossRefGoogle ScholarPubMed
21.Alcorn, J, McNamara, PJ. Ontogeny of hepatic and renal systemic clearance pathways in infants. Part II. Clin Pharmacokinet 2002; 41: 1077–1094.CrossRefGoogle ScholarPubMed
22.Shafer, AL, Donnelly, AJ. Management of postoperative pain by continuous epidural infusion of analgesics. Clin Pharm 1991; 10: 745–764.Google ScholarPubMed