Skip to main content
SpringerLink
Log in
Book cover

Pediatric Anesthesia, Intensive Care and Pain: Standardization in Clinical Practice pp 131–144Cite as

Drugs and Clinical Pharmacology of Central Blocks in Infants and Children

  • Chapter

  • 2222 Accesses

Abstract

Even though more than 100 years have passed since the first description of the use of central blocks in children (Bier, 1899, Tyrell-Gray, 1909), there are still new and important things to learn within this particular field of anesthesia. Therefore, to perform safe and effective regional anesthesia in infants and children, a solid knowledge of the age-related pharmacology of both local anesthetics and their adjuncts is an absolute prerequisite. Although not as extensive as in adults, the published literature within the field of clinical pharmacology of local anesthetics and their adjuncts in infants and children is quite substantial at this point in time.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Notes

  1. 1.

    Because compartmental pharmacokinetics are based on the assumption of linearity, concentration is described by a sum of exponentials with the assumption that absorption is faster than distribution and distribution is faster than elimination. If absorption is longer than elimination, it is not possible to distinguish between the phases. In other words, if absorption continues during elimination, the terminal phase appears falsely prolonged.

References

  1. Lönnqvist PA (2012) Toxicity of local anesthetic drugs: a pediatric perspective. Paediatr Anaesth 22:39–43

    Article  PubMed  Google Scholar 

  2. Walker SM, Westin BD, Deumens R et al. (2010) Effects of Intrathecal Ketamine in the Neonatal Rat: Evaluation of Apoptosis and Long-term Functional Outcome. Anesthesiology 113:147159

    Article  Google Scholar 

  3. Westin BD, Walker SM, Deumens R et al. (2010) Validation of a Preclinical Spinal Safety Model: Effects of Intrathecal Morphine in the Neonatal Rat. Anesthesiology 113:183–199

    Article  PubMed  CAS  Google Scholar 

  4. Walker SM, Grafe M, Yaksh TL (2012) Intrathecal clonidine in the neonatal rat: dose-dependent analgesia and evaluation of spinal apoptosis and toxicity. Anest Analg 2012; in press

    Google Scholar 

  5. Lonnqvist PA, Walker SM (2012) Ketamine as an adjunct to caudal blockade in neonates and infants: is it time to re-evaluate? Br J Anaesth 2012; in press

    Google Scholar 

  6. Lonnqvist PA, Ivani G, Moriarty T (2002) Use of caudal-epidural opioids in children: still state of the art or the beginning of the end? Paediatr Anaesth 12:747–749.

    Article  PubMed  CAS  Google Scholar 

  7. Lonnqvist PA (2012) Alpha-2 adrenoceptor agonists as adjuncts to Peripheral Nerve Blocks in Children-is there a mechanism of action and should we use them? Paediatr Anaesth 22:421–424

    Article  PubMed  Google Scholar 

  8. Lonnqvist PA(2005) Adjuncts to caudal block in children — Quo vadis? Br J Anaesth 95:431–433

    Article  PubMed  CAS  Google Scholar 

References of the Review Article

  1. Catterall WA (2002) Molecular mechanisms of gating and drug block of sodium channels. Novartis Found Symp 241:206–218

    Article  PubMed  CAS  Google Scholar 

  2. Mazoit JX, Dalens BJ (2004) Pharmacokinetics of local anaesthetics in infants and children. Clin Pharmacokinet 43:17–32

    Article  PubMed  CAS  Google Scholar 

  3. Nau C, Strichartz GR (2002) Drug chirality in anesthesia. Anesthesiology 97:497–502

    Article  PubMed  CAS  Google Scholar 

  4. Cartwright PD, Fyhr P (1988) The manufacture and storage of local anesthetics. Reg Anesth 13:1–12

    CAS  Google Scholar 

  5. Mazoit JX, Denson DD, Samii K (1988) Pharmacokinetics of bupivacaine following caudal anesthesia in infants. Anesthesiology 68:387–391

    Article  PubMed  CAS  Google Scholar 

  6. Mazoit JX, Denson DD, Samii K (1996) Pharmaisolated albumin and isolated alpha-1-acid glycoprotein. Differences between the two enantiomers are partly due to cooperativity. J Pharmacol Exp Ther 276:109–115

    CAS  Google Scholar 

  7. Meunier JF, Goujard E, Dubousset AM et al. (2001) Pharmacokinetics of bupivacaine after continuous epidural infusion in infants with and without biliary atresia. Anesthesiology 95:87–95

    Article  PubMed  CAS  Google Scholar 

  8. Sitbon P, Laffon M, Lesage V et al. (1997) Lidocaine plasma concentrations in pediatric patients after providing airway topical anesthesia from a calibrated device. Anesth Russell SC, Doyle E. A risk-benefit assessment of topical percutaneous local anaesthetics in children. Drug Saf 16:279–287

    Article  Google Scholar 

  9. Taddio A, Ohlsson A, Einarson TR et al. (1998) A systematic review of lidocaine-prilocaine cream (EMLA) in the treatment of acute pain in neonates. Pediatrics 101:E1

    Article  PubMed  CAS  Google Scholar 

  10. Russell SC, Doyle E (1997) A risk-benefit assessment of topical percutaneous local anaesthetics in children. Drug Saf 16:279–287

    Article  PubMed  CAS  Google Scholar 

  11. Burm AGL (1989) Clinical pharmacokinetics of epidural and spinal anesthesia. Clin Pharmacokinet 16:283–311

    Article  PubMed  CAS  Google Scholar 

  12. Ecoffey C, Desparmet J, Berdeaux A et al. (1984) Pharmacokinetics of lidocaine in children following caudal anaesthesia. Br J Anaesth 56:1399–1402

    Article  PubMed  CAS  Google Scholar 

  13. Ecoffey C, Desparmet J, Berdeaux A et al. (2004) Bupivacaine in children: pharmacokinetics children under 2 years of age. Br J Anaesth 92:218–222

    Article  Google Scholar 

  14. Chalkiadis GA, Eyres RL, Cranswick N et al. (2004) Pharmacokinetics of levobupivacaine 0.25% following caudal administration in children under 2 years of age. Br J Anaesth 92:218–222

    Article  PubMed  CAS  Google Scholar 

  15. Cortinez LI, Fuentes R, Solari S et al. (2008) Pharmacokinetics of levobupivacaine (2.5 mg/kg) after caudal administration in children younger than 3 years. Anesth Analg 107:11821184

    Google Scholar 

  16. Desparmet J, Meistelman C, Barre J et al. (1987) Continuous epidural infusion of bupiva- caine for postoperative pain relief in children. Anesthesiology 67:108–110

    Article  PubMed  CAS  Google Scholar 

  17. Lerman J, Nolan J, Eyres R et al. (2003) Efficacy, safety, and pharmacokinetics of levobupivacaine with and without fentanyl after continuous epidural infusion in children: a multicenter trial. Anesthesiology 99:1166–1174

    Article  PubMed  CAS  Google Scholar 

  18. Ala-Kokko TI, Partanen A, Karinen J et al. (2000) Pharmacokinetics of 0.2% ropivacaine and 0.2% bupivacaine following caudal blocks in children. Acta Anaesthesiol Scand 44:1099–1102

    Article  PubMed  CAS  Google Scholar 

  19. Lonnqvist PA, Westrin P, Larsson BA et al. (2000) Ropivacaine pharmacokinetics after caudal block in 1–8 year old children. Br J Anaesth 85:506–511

    Article  PubMed  CAS  Google Scholar 

  20. Emanuelsson BM, Persson J, Sandin S et al. (1997) Intraindividual and interindividual variability in the disposition of the local anesthetic ropivacaine in healthy subjects. Ther Drug Monit 19:126–131

    Article  PubMed  CAS  Google Scholar 

  21. Hansen TG, Ilett KF, Reid C et al. (2001) Caudal ropivacaine in infants: population phar- macokinetics and plasma concentrations. Anesthesiology 94:579–584

    Article  PubMed  CAS  Google Scholar 

  22. McCann ME, Sethna NF, Mazoit JX et al. (2001) The pharmacokinetics of epidural ropiva- caine in infants and young children. Anesth Analg 93:893–897

    Article  PubMed  CAS  Google Scholar 

  23. Bosenberg AT, Thomas J, Cronje L et al. (1998) Pharmacokinetics and efficacy of ropi- vavoxamine and ketoconazole as in vivo inhibitors. Clin Pharmacol Ther 64:484–491

    Article  Google Scholar 

  24. Rapp HJ, Molnar V, Austin S et al. (2004) Ropivacaine in neonates and infants: a population pharmacokinetic evaluation following single caudal block. Pediatr Anesth 14:724–732

    Article  Google Scholar 

  25. Berde CB, Yaster M, Meretoja O et al. (2008) Stable plasma concentrations of unbound ropi- vacaine during postoperative epidural infusion for 24–72 hours in children. Eur J Anaesthe- siol 25:410–417

    Article  CAS  Google Scholar 

  26. Dalens B, Ecoffey C, Joly A et al. (2001) Pharmacokinetics and analgesic effect of ropivacaine following ilioinguinal/iliohypogastric nerve block in children. Paediatr Anaesth 11:415–420

    Article  PubMed  CAS  Google Scholar 

  27. Arlander E, Ekstrom G, Alm C et al. (1998) Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. Clin Pharmacol Ther 64:484–491

    Article  PubMed  CAS  Google Scholar 

  28. Gantenbein M, Attolini L, Bruguerolle B et al. (2000) Oxidative metabolism of bupivacaine into pipecolylxylidine in humans is mainly catalyzed by CYP3A. Drug Metab Dispos 28:383–385

    PubMed  CAS  Google Scholar 

  29. Burm AG, van der Meer AD, van Kleef JW et al. (1994) Pharmacokinetics of the enantiomers of bupivacaine following intravenous administration of the racemate. Br J Clin Pharmacol 38:125–129

    Article  PubMed  CAS  Google Scholar 

  30. Burm AGL, Vermeulen NPE, Van Kleef JW et al. (1987) Pharmacokinetics of lidocaine and bupivacaine in surgical patients following epidural administration. Simultaneous investigation of absorption and disposition kinetics using stable isotopes. Clin Pharmacokinet 13:191–203

    CAS  Google Scholar 

  31. Burm AG, Stienstra R, Brouwer RP et al. (2000) Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery: pharmacokinetic evaluation. Anesthesi- ology 93:395–403

    Article  CAS  Google Scholar 

  32. Scott DB, Lee A, Fagan D et al. (1989) Acute toxic ity of ropivacaine compared with that of bupivacaine. Anesth Analg 69:563–569

    PubMed  CAS  Google Scholar 

  33. Knudsen K, Beckman Suurküla M, Blomberg S et al. (1997) Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 78:507–514

    Article  PubMed  CAS  Google Scholar 

  34. Bardsley H, Gristwood R, Baker H et al. (1998) A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 46:245–249

    Article  PubMed  CAS  Google Scholar 

  35. Stewart J, Kellett N, Castro D (1995) The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy tricular myocytes. Circulation 92:3014–3024

    Article  Google Scholar 

  36. Maxwell LG, Martin LD, Yaster M (1994) Bupivacaine-induced cardiac toxicity in neonates:successful treatment with intravenous phenytoin. Anesthesiology 80:682–686

    Article  PubMed  CAS  Google Scholar 

  37. Hubler M, Gabler R, Ehm B et al. (2010) Successful resuscitation following opivacaine-in- duced systemic toxicity in a neonate. Anaesthesia 65:1137–1140

    Article  PubMed  CAS  Google Scholar 

  38. Longobardo M, Delpon E, Caballero R et al. (1998) Structural determinants of potency and stereoselective block of hKv1.5 channels induced by local anesthetics. Mol Pharmacol 54:162–169

    PubMed  CAS  Google Scholar 

  39. Gonzalez T, Arias C, Caballero R et al. (2002) Effects of levobupivacaine, ropivacaine and bupivacaine on HERG channels: stereoselective bupivacaine block. Br J Pharmacol 137:1269–1279

    Article  PubMed  CAS  Google Scholar 

  40. Valenzuela C, Snyders DJ, Bennett PB et al. (1995) Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation 92:3014–3024

    Article  PubMed  CAS  Google Scholar 

  41. Komai H, Lokuta AJ (1999) Interaction of bupivacaine and tetracaine with the sarcoplasmic reticulum Ca2+ release channel of skeletal and cardiac muscles. Anesthesi- ology 90:835–843

    Article  CAS  Google Scholar 

  42. Zapata-Sudo G, Trachez MM, Sudo RT et al. (2001) Is comparative cardiotoxicity of S()) and R(+) bupivacaine related to enantio- mer-selective inhibition of L-type Ca(2+) channels? Anesth Analg 92:496–501

    Article  PubMed  CAS  Google Scholar 

  43. Raymond SA, Thalhammer JG, Strichartz GR (1989) Axonal excitability: endogenous and exogenous modulation, in Dimitrijevic Ed Altered sensation and Pain. Recent Achievement in Restorative Neurology, Vol 3, Karger Basel 1990, cited by Raymond SA and Strichartz GR. The long and short of differential block (Editorial). Anesthesiology 70:725–728

    Article  PubMed  CAS  Google Scholar 

  44. Vabnick I, Novakovic SD, Levinson SR et al. (1996) The clustering of axonal sodium channels during development of the peripheral nervous system. J Neurosci 16:4914–4922

    PubMed  CAS  Google Scholar 

  45. Rasband MN, Trimmer JS (2001) Developmental clustering of ion channels at and near the node of Ranvier. Dev Biol 236:5–16

    Article  PubMed  CAS  Google Scholar 

  46. Kohane DS, Sankar WN, Shubina M et al. (1998) Sciatic nerve blockade in infant, adolescent, and adult rats: a comparison of ropivacaine with bupivacaine. Anesthesiology 89:1199–1208

    Article  PubMed  CAS  Google Scholar 

  47. Greitz D, Hannerz J (1996) A proposed model of cerebrospinal fluid circulation: observations with radionuclide cisternography. AJNR Am J Neuroradiol 17:431–438

    PubMed  CAS  Google Scholar 

  48. Wachi A, Kudo S, Sato K (1989) Characteristics of cerebrospinal fluid circulation in infants as detected with MR velocity imaging. Acta Anaesthesiol Scand 33:385–388

    Article  Google Scholar 

  49. Booth D, Evans DJ (2004) Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev 4:CD004218

    PubMed  Google Scholar 

  50. de La Coussaye J, Brugada J, Allessie MA (1992) Electrophysiologic and arrhythmogenic- effects of bupivacaine. A study with high-resolution ventricular epicardial mapping in rabbit hearts. Anesthesiology 77:32–41

    Google Scholar 

  51. Mazoit JX, Decaux A, Bouaziz H et al. (2000) Comparative ventricular electrophysiologic effect of racemic bupivacaine, levobupivacaine, and ropivacaine on the isolated rabbit heart. Anesthesiology 93:784–792

    Article  PubMed  CAS  Google Scholar 

  52. Simon L, Kariya N, Edouard A et al. (2004) Effect of bupivacaine on the isolated rabbit heart: developmental aspect on ventricular conduction and contractility. Anesthesiology 101:937–944

    Article  PubMed  CAS  Google Scholar 

  53. Odoom JA, Sturk A, Dokter PWC et al. (1989) The effects of bupivacaine and pipecoloxy- lidide on platelet function in vitro. Acta Anaesthesiol Scand 33:385–388

    Article  PubMed  CAS  Google Scholar 

  54. Hollmann MW, Gross A, Jelacin N et al. (2001) Local anesthetic effects on priming and activation of human neutrophils. Anesthesiology 95:113–122

    Article  PubMed  CAS  Google Scholar 

  55. Beloeil H, Asehnoune K, Moine P et al. (2005) Bupivacaine’s action on the carrageenan induced inflammatory response in mice: cytokine production by leukocytes after ex-vivo stimulation. Anesth Analg 100:1081–1086

    Article  PubMed  CAS  Google Scholar 

  56. Leduc C, Gentili ME, Estèbe JP et al. (2002) Inhibition of peroxydation by local anesthetic in an inflammatory rat model with carrageenan. Anesth Analg 95:992–996

    PubMed  CAS  Google Scholar 

  57. Rowbotham MC, Reisner-Keller LA, Fields HL (1991) Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 41:1024–1028

    Article  PubMed  CAS  Google Scholar 

  58. Marret E, Rolin M, Beaussier M et al. (2008) Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. Br J Surg 95:1331–1338

    Article  PubMed  CAS  Google Scholar 

  59. Linchitz RM, Raheb JC (1999) Subcutaneous infusion of lidocaine provides effective pain relief for CRPS patients. Clin J Pain 15:67–72

    Article  PubMed  CAS  Google Scholar 

  60. Dadure C, Motais F, Ricard C et al. (2005) Con enantiomers on intracellular Ca2+ regulation in murine skeletal muscle fibers. Anesthesiology 102:793–798

    Article  Google Scholar 

  61. Popitz-Bergez FA, Leeson S, Strichartz GR et al. (1995) Relation between functional deficit and intraneural local anesthetic during peripheral nerve block. A study in the rat sciatic nerve. Anesthesiology 83:583–592

    CAS  Google Scholar 

  62. Zink W, Missler G, Sinner B et al. (2005) Differential effects of bupivacaine and ropivacaine enantiomers on intracellular Ca2+ regulation in murine skeletal muscle fibers. Anesthesiology 102:793–798

    Article  PubMed  CAS  Google Scholar 

  63. Nouette-Gaulain K, Sirvent P, Canal-Raffin M et al. (2007) Effects of intermittent femoral nerve injections of bupivacaine, levobupivacaine, and ropivacaine on mitochondrial energy metabolism and intracellular calcium homeostasis in rat psoas muscle. Anesthesiology 106:1026–1034

    Article  PubMed  CAS  Google Scholar 

  64. Brown DL, Ransom DM, Hall JA et al. (1995) Regional anesthesia and local anesthetic induced systemic toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg 81:321–328

    PubMed  CAS  Google Scholar 

  65. Di Gregorio G, Neal JM, Rosenquist RW et al. (2010) Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med 35:181–187

    Article  PubMed  Google Scholar 

  66. Weinberg GL (2010) Treatment of local anesthetic systemic toxicity (LAST). Reg Anesth Pain Med 35:188–193

    Article  PubMed  CAS  Google Scholar 

  67. Rosenblatt MA, Abel M, Fischer GW et al. (2006) Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 105:217–218

    Article  PubMed  Google Scholar 

  68. Litz RJ, Popp M, Stehr SN et al. (2009) Successful lipid emulsions. Anesthesiology 110:380–386

    Google Scholar 

  69. Ludot H, Tharin JY, Belouadah M et al. (2008) Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. Anesth Analg 106:1572–1574

    Article  PubMed  CAS  Google Scholar 

  70. Mazoit JX, Le Guen R, Beloeil H et al. (2009) Binding of long-lasting local anesthetics to lipid emulsions. Anesthesiology 110:380–386

    PubMed  Google Scholar 

  71. Flandin-Bléty C, Barrier G (1995) Accidents following extradural analgesia in children. The results of a retrospective study. Paediatr Anaesth 5:41–46

    Article  PubMed  Google Scholar 

  72. Jamali S, Monin S, Begon C et al. (1994) Clonidine in pediatric caudal anesthesia. Anesth Analg 78:663–666

    Article  PubMed  CAS  Google Scholar 

  73. Hansen TG, Henneberg SW, Walther Larsen S et al. (2004) Caudal bupivacaine supplemented with caudal or intravenous clonidine in children undergoing hypospadias repair: a doubleblind study. Br J Anaesth 92:223–227

    Article  PubMed  CAS  Google Scholar 

  74. De Negri P, Ivani G, Visconti C et al. (2001) How to prolong postoperative analgesia after caudal anaesthesia with ropivacaine in children: S-ketamine versus clonidine. Paediatr Anaesth 11:679–683

    Article  PubMed  Google Scholar 

  75. Braun S, Gaza N, Werdehausen R et al. (2010) Ketamine induces apoptosis via the mitochondrial pathway in human lymphocytes and neuronal cells. Br J Anaesth 105:347–354

    Article  PubMed  CAS  Google Scholar 

  76. Eisenach JC, Yaksh TL (2003) Epidural ketamine in healthy children - what is the point? Anesth Analg 96:626

    PubMed  Google Scholar 

  77. Lejus C, Surbled M, Schwoerer D et al. (2001) Postoperative epidural analgesia with bupi- vacaine and fentanyl: hourly pain assessment in 348 paediatric cases. Paediatr Anaesth 11:327–332

    Article  PubMed  CAS  Google Scholar 

  78. Luz G, Innerhofer I, Bachmann B et al. (1996) Bupivacaine plasma concentrations during continuous epidural anesthesia in infants and children. Anesth Analg 82:231–234

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Section of Anesthesiology and Intensive Care, The Karolinska Institute, Stockholm, Sweden

    Per-Arne Lönnqvist

Authors
  1. Per-Arne Lönnqvist
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Per-Arne Lönnqvist .

Editor information

Editors and Affiliations

  1. Anesthesia and Intensive Care, Pediatric Anesthesia and Intensive Care Section, and Postgraduate School, University of Catania, AOU Policlinico-Vittorio Emanuele, Catania, Italy

    Marinella Astuto

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Italia

About this chapter

Cite this chapter

Lönnqvist, PA. (2013). Drugs and Clinical Pharmacology of Central Blocks in Infants and Children. In: Astuto, M. (eds) Pediatric Anesthesia, Intensive Care and Pain: Standardization in Clinical Practice. Anesthesia, Intensive Care and Pain in Neonates and Children. Springer, Milano. https://doi.org/10.1007/978-88-470-2685-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-88-470-2685-8_12

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-2684-1

  • Online ISBN: 978-88-470-2685-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation