Skip to main content
SpringerLink
Log in

Pain Assessment and Management

  • Chapter
  • First Online:
Neonatal Anesthesia

  • 2046 Accesses

Abstract

The neonate shows unique responses to nociceptive inputs that are a result of immature sensory and motor systems. In addition, physical development and the maturation of drug metabolism and elimination pathways can profoundly impact the efficacy, toxicity and side effects of analgesics. Important functional differences in pain processing mechanisms are present at the site of pain and in the CNS that lead to profound differences in pain signalling in the neonate compared with the adult. Immature and uncoordinated motor systems change and restrict the range of possible behavioural responses to pain, and postnatal changes in the expression, distribution and function of transmitters and receptors involved in the actions of analgesics influence their effects. The neonatal period is characterised by profound neuroplasticity, and it appears that as a consequence both painful events and exposure to certain compounds, notably some analgesics, have the potential to cause long-term adverse effects in this age group that would not occur at older ages. Therefore, the planning and implementation of safe and effective analgesia for neonates cannot simply be extrapolated from scaled-down versions of techniques used in older children and adults. Rather, they must be carefully constructed and implemented on the basis of a clear understanding of developmental neurobiology and pharmacology. In this chapter, the development of nociception, the assessment of pain in the preterm and term infant and the principles of perioperative and procedure-related pain management will be discussed.

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

Access this chapter

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 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
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

Institutional subscriptions

References

  1. Maxwell LG, Malavolta CP, Fraga MV. Pain management in the peripartum period assessment of pain in the neonate. Clin Perinatol. 2013;40:457–69.

    PubMed  Google Scholar 

  2. Fitzgerald M, Howard RF. The neurobiologic basis of paediatric pain. In: Schechter NL, Berde CB, Yaster M, editors. Second Edition. Philadelphia, PA: Lippincott Williams and Wilkins; 2003. p. 19–42.

    Google Scholar 

  3. Andrews K, Desai D, Dhillon H, Wilcox D, Fitzgerald M. Abdominal sensitivity in the first year of life: comparison of infants with and without prenatally diagnosed unilateral hydronephrosis. Pain. 2002;100:35–46.

    CAS  PubMed  Google Scholar 

  4. Anand K, Hansen D, Hickey P. Hormonal-metabolic stress responses in neonates undergoing cardiac surgery. Anaesthesiology. 1990;73(4):661–70.

    CAS  Google Scholar 

  5. Anand K, Hickey P. Halothane-morphine compared with high-dose sufentanil for anaesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med. 1992;326(1):1–9.

    CAS  PubMed  Google Scholar 

  6. Fitzgerald M, Walker SM. Infant pain management: a developmental neurobiological approach. Nat Clin Pract Neurol. 2009;5(1):35–50.

    PubMed  Google Scholar 

  7. Peters J, Schouw R, Anand K, van Dijk M, Duivenvoorden H, Tibboel D. Does neonatal surgery lead to increased pain sensitivity in later childhood? Pain. 2005;114(3):444–54.

    PubMed  Google Scholar 

  8. Walker SM, Franck LS, Fitzgerald M, Myles J, Stocks J, Marlow N. Long-term impact of neonatal intensive care and surgery on somatosensory perception in children born extremely preterm. Pain. 2009;141(1–2):79–87.

    PubMed  Google Scholar 

  9. Fitzgerald M. The post-natal development of cutaneous afferent fiber input and receptive field organization in the rat dorsal horn. J Physiol. 1985;364:1–18.

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Slater R, Worley A, Fabrizi L, et al. Evoked potentials generated by noxious stimulation in the human infant brain. Eur J Pain. 2010;14(3):321–6.

    PubMed  Google Scholar 

  11. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3):S2–15.

    PubMed Central  PubMed  Google Scholar 

  12. Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron. 2006;52(1):77–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Taddio A, Shah V, Gilbert-MacLeod C, Katz J. Conditioning and hyperalgesia in newborns exposed to repeated heel lances. JAMA. 2002;288:857–61.

    PubMed  Google Scholar 

  14. Walker SM, Meredith-Middleton J, Lickiss T, Moss A, Fitzgerald M. Primary and secondary hyperalgesia can be differentiated by postnatal age and ERK activation in the spinal dorsal horn of the rat pup. Pain. 2007;128(1–2):157–68.

    CAS  PubMed  Google Scholar 

  15. Anand P, Birch R. Restoration of sensory function and lack of long-term chronic pain syndromes after brachial plexus injury in human neonates. Brain. 2002;125(Pt 1):113–22.

    CAS  PubMed  Google Scholar 

  16. Howard RF, Walker SM, Mota PM, Fitzgerald M. The ontogeny of neuropathic pain: postnatal onset of mechanical allodynia in rat spared nerve injury (SNI) and chronic constriction injury (CCI) models. Pain. 2005;115(3):382–9.

    PubMed  Google Scholar 

  17. Moss A, Beggs S, Vega-Avelaira D, et al. Spinal microglia and neuropathic pain in young rats. Pain. 2007;128(3):215–24.

    CAS  PubMed  Google Scholar 

  18. Costigan M, Moss A, Latremoliere A, et al. T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J Neurosci. 2009;29(46):14415–22.

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Taddio A, Katz J, Ilersich A, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination [see comments]. Lancet. 1997;349(9052):599–603.

    CAS  PubMed  Google Scholar 

  20. Carbajal R, Rousset A, Danan C, et al. Epidemiology and treatment of painful procedures in neonates in intensive care units. JAMA. 2008;300(1):60–70.

    CAS  PubMed  Google Scholar 

  21. Anand K, Scalzo F. Can adverse neonatal experiences alter brain development and subsequent behavior? Biol Neonate. 2000;77:69–82.

    CAS  PubMed  Google Scholar 

  22. Schmelzle-Lubiecki BM, Campbell KA, Howard RH, Franck L, Fitzgerald M. Long-term consequences of early infant injury and trauma upon somatosensory processing. Eur J Pain. 2007;11(7):799–809.

    CAS  PubMed  Google Scholar 

  23. Hermann C, Hohmeister J, Demirakca S, Zohsel K, Flor H. Long-term alteration of pain sensitivity in school-aged children with early pain experiences. Pain. 2006;125(3):278–85.

    PubMed  Google Scholar 

  24. Waldenstrom A, Thelin J, Thimansson E, Levinsson A, Schouenborg J. Developmental learning in a pain-related system: evidence for a cross-modality mechanism. J Neurosci. 2003;23(20):7719–25.

    PubMed  Google Scholar 

  25. Beggs S, Torsney C, Drew L, Fitzgerald M. The postnatal reorganization of primary afferent input and dorsal horn cell receptive fields in the rat spinal cord is an activity-dependent process. Eur J Neurosci. 2002;16(7):1249–58.

    PubMed  Google Scholar 

  26. Brummelte S, Grunau RE, Chau V, et al. Procedural pain and brain development in premature newborns. Ann Neurol. 2012;71:385–96.

    PubMed Central  PubMed  Google Scholar 

  27. Vinall J, Miller SP, Chau V, et al. Neonatal pain in relation to postnatal growth in infants born very preterm. Pain. 2012;153:1374–81.

    PubMed  Google Scholar 

  28. Finley GA, Franck L, Grunau R, von Baeyer CL. Why Children's Pain Matters. Pain – Clinical Updates. 2005;13(4):1–6.

    Google Scholar 

  29. Hummel P, van Dijk M. Pain assessment: current status and challenges. Semin Fetal Neonatal Med. 2006;11(4):237–45.

    PubMed  Google Scholar 

  30. Franck L, Greenberg C, Stevens B. Pain assessment in infants and children. Paediatr Clin North Am. 2000;47(3):487–512.

    CAS  Google Scholar 

  31. Clinical Guidelines for the Recognition and Assessment of Acute Pain in Children. 2009. http://www.rcn.org.uk/__data/assets/pdf_file/0004/269185/003542.pdf. Accessed Sep 2013)

  32. Howard R, Carter B, Curry J, et al. Good practice in postoperative and procedural pain management: guidelines from the Association of Paediatric Anaesthetists. Paediatr Anaesth. 2008;18(1):1–81.

    PubMed  Google Scholar 

  33. Pokela M. Pain relief can reduce hypoxaemia in distressed neonates during routine treatment procedures. Paediatrics. 1994;93:379.

    CAS  Google Scholar 

  34. Buttner W, Fincke W. Analysis of behavioural and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young children. Paediatr Anaesth. 2000;10:303–18.

    CAS  PubMed  Google Scholar 

  35. van Dijk M, de Boer J, Koot H, Tibboel D, Passchier J, Duivenvoorden H. The reliability and validity of the COMFORT scale as a postoperative pain instrument in 0 to 3-year-old infants. Pain. 2000;84(2–3):367–77.

    PubMed  Google Scholar 

  36. Ambuel B, Hamlett K, Marx C, Blumer J. Assessing distress in paediatric intensive care environments: the COMFORT scale. J Paediatr Psychol. 1992;17(1):95–109.

    CAS  Google Scholar 

  37. Krechel SW, Bildner J. CRIES: a new neonatal postoperative pain measurement score. Initial testing of validity and reliability. Paediatr Anaesth. 1995;5(1):53–61.

    CAS  PubMed  Google Scholar 

  38. Barrier G, Attia J, Mayer M, Amiel-Tilson C. Measurement of postoperative pain and narcotic administration in infants usind a new clinical scoring system. Intensive Care Med. 1989;15S:37–9.

    Google Scholar 

  39. Sparshott M. The development of a clinical distresss scale for ventilated newborn infants: Identification of pain and distress based on validated behaivoural scores. J Neonatal Nurs. 1996;2:5.

    Google Scholar 

  40. Horgan M, Choonara I. Measuring pain in neonates: an objective score. J Paediatr Nurs. 1996;8:24–8.

    CAS  Google Scholar 

  41. Grunau R, Craig K. Pain expression in neonates: facial action and cry. Pain. 1987;28(3):395–410.

    CAS  PubMed  Google Scholar 

  42. Lawrence J, Alcock D, McGrath P. The development of a tool to assess neonatal pain. Neonatal Netw. 1993;12:59–66.

    CAS  PubMed  Google Scholar 

  43. Hodgkinson K, Bear M, Thorn J. Measuring pain in neonates: evaluating an instrument and developing a common language. Aust J Adv Nurs. 1994;12:17–22.

    CAS  PubMed  Google Scholar 

  44. Ballantyne M, Stevens B, McAllister M, Dionne K, Jack A. Validation of the premature infant pain profile in the clinical setting. Clin J Pain. 1999;15(4):297–303.

    CAS  PubMed  Google Scholar 

  45. Blauer T, Gerstmann D. A simultaneous comparion of three neonatal pain scales during common NICU procedures. Clin J Pain. 1988;14:39–47.

    Google Scholar 

  46. Karling M. RenstrC6m M, Ljungman G. Acute and postoperative pain in children: A Swedish nationwide survey. Acta Paediatrica. 2002;91(6):660–6.

    CAS  PubMed  Google Scholar 

  47. Broome ME, Richtsmeier A, Maikler V, Alexander M. Paediatric pain practices: A national survey of health professionals. J Pain Symptom Manage. 1996;11.

    Google Scholar 

  48. Simons J, MacDonald LM. Changing practice: implementing validated paediatric pain assessment tools. J Child Health Care. 2006;10:160–76.

    PubMed  Google Scholar 

  49. Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anaesth Analg. 1993;77(5):1048–56.

    CAS  Google Scholar 

  50. McAnulty GB, Duffy FH, Butler SC, Bernstein JH, Zurakowski D, Als H. Effects of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) at age 8 years: preliminary data. Clin Paediatr (Phila). 2010;49(3):258–70.

    Google Scholar 

  51. McAnulty G, Duffy FH, Butler S, et al. Individualized developmental care for a large sample of very preterm infants: health, neurobehaviour and neurophysiology. Acta Paediatr. 2009;98(12):1920–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Symington A, Pinelli J. Developmental care for promoting development and preventing morbidity in preterm infants. Cochrane Database Syst Rev. 2006;19(2):CD001814. Online.

    Google Scholar 

  53. Ceelie I, de Wildt SN, van Dijk M, et al. Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery. JAMA. 2013;309:149–54.

    CAS  PubMed  Google Scholar 

  54. van der Marel CD, Peters JW, Bouwmeester NJ, Jacqz-Aigrain E, van den Anker JN, Tibboel D. Rectal acetaminophen does not reduce morphine consumption after major surgery in young infants. Br J Anaesth. 2007;98(3):372–9.

    PubMed  Google Scholar 

  55. Koppert W, Wehrfritz A, Korber N, et al. The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans. Pain. 2004;108(1–2):148–53.

    CAS  PubMed  Google Scholar 

  56. Anderson B. What we don't know about paracetamol in children. Paediatr Anaesth. 1998;8(6):451–60.

    CAS  PubMed  Google Scholar 

  57. Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A. The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. Eur J Pharmacol. 2006;531(1–3):280–1.

    CAS  PubMed  Google Scholar 

  58. Anderson B, van Lingen R, Hansen T, Lin Y, Holford N. Acetaminophen developmental pharmacokinetics in premature neonates and infants: a pooled population analysis. Anaesthesiology. 2002;96(6):1336–45.

    CAS  Google Scholar 

  59. Cuzzolin L, Antonucci R, Fanos V. Paracetamol (acetaminophen) efficacy and safety in the newborn. Curr Drug Metab. 2013;14:178–81.

    CAS  PubMed  Google Scholar 

  60. Allegaert K, Murat I, Anderson BJ. Not all intravenous paracetamol formulations are created equal. Paediatr Anaesth. 2007;17(8):811–2.

    PubMed  Google Scholar 

  61. Anderson B, Woollard G, Holford N. Acetaminophen analgesia in children: placebo effect and pain resolution after tonsillectomy. Eur J Clin Pharmacol. 2001;57:559–69.

    CAS  PubMed  Google Scholar 

  62. Murat I, Baujard C, Foussat C, et al. Tolerance and analgesic efficacy of a new i.v. paracetamol solution in children after inguinal hernia repair. Paediatr Anaesth. 2005;15(8):663–70.

    CAS  PubMed  Google Scholar 

  63. Anderson B, Pons G, Autret-Leca E, Allegaert K, Boccard E. Paediatric intravenous paracetamol (propacetamol) pharmacokinetics: a population analysis. Paediatr Anaesth. 2005;15(4):282–92.

    PubMed  Google Scholar 

  64. Barbaud A, Reichert-Penetrat S, Trechot P, Cuny J, Weber M, Schmutz J. Occupational contact dermatitis to propacetamol. Allergological and chemical investigations in two new cases. Dermatology. 1997;195(4):329–31.

    CAS  PubMed  Google Scholar 

  65. Niemi T, Backman J, Syrjala M, Viinikka L, Rosenberg P. Platelet dysfunction after intravenous ketorolac or propacetamol. Acta Anaesthesiol Scand. 2000;44(1):69–74.

    CAS  PubMed  Google Scholar 

  66. de la Pinitiere A, Beuchée A, Bétrémieux PE. Intravenous propacetamol overdose in a term newborn. Arch Dis Child Fetal Neonatal Ed. 2003;88:F351–266.

    Google Scholar 

  67. Niven DG, Shung J. Intravenous paracetamol overdose in a preterm infant during anaesthesia. Paediatr Anaesth. 2010;20:105–7.

    Google Scholar 

  68. Beringer RM, Thompson JP, Parry S, Stoddart PA. Intravenous paracetamol overdose: two case reports and a change to national treatment guidelines. Arch Dis Child. 2011;96:307–8.

    PubMed  Google Scholar 

  69. Morris JL, Rosen DA, Rosen KR. Nonsteroidal anti-inflammatory agents in neonates. Paediatr Drugs. 2003;5(6):385–405.

    PubMed  Google Scholar 

  70. Ririe D, Prout H, Barclay D, Tong C, Lin M, Eisenach J. Developmental differences in spinal cyclooxygenase 1 expression after surgical incision. Anaesthesiology. 2006;104(3):426–31.

    CAS  Google Scholar 

  71. Ista E, van Dijk M, Gamel C, Tibboel D, de Hoog M. Withdrawal symptoms in children after long-term administration of sedatives and/or analgesics: a literature review. "Assessment remains troublesome". Intensive Care Med. 2007;33(8):1396–406.

    CAS  PubMed  Google Scholar 

  72. Howard RF, Lloyd-Thomas A, Thomas M, et al. Nurse-controlled analgesia (NCA) following major surgery in 10,000 patients in a children's hospital. Paediatr Anaesth. 2010;20(2):126–34.

    PubMed  Google Scholar 

  73. Kart T, Christrup L, Rasmussen M. Recommended use of morphine in neonates, infants and children based on a literature review: part 1–Pharmacokinetics. Paediatr Anaesth. 1997;7(1):5–11.

    CAS  PubMed  Google Scholar 

  74. Kart T, Christrup L, Rasmussen M. Recommended use of morphine in neonates, infants and children based on a literature review: part 2–Clinical use. Paediatr Anaesth. 1997;7(2):93–101.

    CAS  PubMed  Google Scholar 

  75. Bouwmeester N, Anderson B, Tibboel D, Holford N. Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. Br J Anaesth. 2004;92(2):208–17.

    CAS  PubMed  Google Scholar 

  76. Berde CB, Sethna NF. Analgesics for the treatment of pain in children. N Engl J Med. 2002;347(14):1094–103.

    CAS  PubMed  Google Scholar 

  77. Anderson BJ, Meakin GH. Scaling for size: some implications for paediatric anaesthesia dosing. Paediatr Anaesth. 2002;12:205–19.

    PubMed  Google Scholar 

  78. Taylor J, Liley A, Anderson BJ. The relationship between age and morphine infusion rate in children. Paediatr Anaesth. 2013;23:40–4.

    PubMed  Google Scholar 

  79. Lynn A, Nespeca M, Opheim K, Slattery J. Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery. Anaesth Analg. 1993;77(4):695–701.

    CAS  Google Scholar 

  80. Lynn A, Nespeca M, Bratton S, Shen D. Intravenous morphine in postoperative infants: intermittent bolus dosing versus targeted continuous infusions. Pain. 2000;88(1):89–95.

    CAS  PubMed  Google Scholar 

  81. van Dijk M, Bouwmeester N, Duivenvoorden H, et al. Efficacy of continuous versus intermittent morphine administration after major surgery in 0-3-year-old infants; a double-blind randomized controlled trial. Pain. 2002;98(3):305–13.

    PubMed  Google Scholar 

  82. Niesters M, Overdyk F, Smith T, Aarts L, Dahan A. Opioid-induced respiratory depression in paediatrics: a review of case reports. Br J Anaesth. 2013;110:175–82.

    CAS  PubMed  Google Scholar 

  83. Ginsberg B, Howell S, Glass PS, et al. Pharmacokinetic model-driven infusion of fentanyl in children. Anaesthesiology. 1996;85(6):1268–75.

    CAS  Google Scholar 

  84. Fahnenstich H, Steffan J, Kau N, Bartmann P. Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants. Crit Care Med. 2000;28:836–9.

    CAS  PubMed  Google Scholar 

  85. Murrell D, Gibson P, Cohen R. Continuous epidural analgesia in newborn infants undergoing major surgery. J Paediatr Surg. 1993;28(4):548–52. discussion 552-543.

    CAS  Google Scholar 

  86. Lejus C, Surbled M, Schwoerer D, et al. Postoperative epidural analgesia with bupivacaine and fentanyl: hourly pain assessment in 348 paediatric cases. Paediatr Anaesth. 2001;11:327–32.

    CAS  PubMed  Google Scholar 

  87. Tibboel D, Anand KJS, van den Anker JN. The pharmacological treatment of neonatal pain. Semin Fetal Neonatal Med. 2005;10(2):195–205.

    CAS  PubMed  Google Scholar 

  88. Anand KJ, Hall RW. Pharmacological therapy for analgesia and sedation in the newborn. Arch Dis Child Fetal Neonatal Ed. 2006;91(6):F448–453.

    PubMed Central  CAS  PubMed  Google Scholar 

  89. Saarenmaa E, Huttunen P, Leppaluoto J, Fellman V. Alfentanil as procedural pain relief in newborn infants. Arch Dis Child Fetal Neonatal Ed. 1996;75(2):F103–107.

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Penido MG, Garra R, Sammartino M, Pereira e Silva Y. Remifentanil in neonatal intensive care and anaesthesia practice. Acta Paediatr. 2010;99(10):1454–63.

    CAS  PubMed  Google Scholar 

  91. Steinmetz J, Holm-Knudsen R, Sorensen MK, Eriksen K, Rasmussen LS. Hemodynamic differences between propofol-remifentanil and sevoflurane anaesthesia for repair of cleft lip and palate in infants. Paediatr Anaesth. 2007;17(1):32–7.

    PubMed  Google Scholar 

  92. Williams D, Hatch D, Howard R. Codeine phosphate in paediatric medicine. Br J Anaesth. 2001;86:421–7.

    Google Scholar 

  93. Williams D, Patel A, Howard R. Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Br J Anaesth. 2002;89:839–45.

    CAS  PubMed  Google Scholar 

  94. Williams D, Dickenson A, Fitzgerald M, Howard R. Developmental regulation of codeine analgesia in the rat. Anaesthesiology. 2004;100(1):92–7.

    CAS  Google Scholar 

  95. Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879–923.

    CAS  PubMed  Google Scholar 

  96. Allegaert K, Anderson B, Verbesselt R, et al. Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity. Br J Anaesth. 2005;95(2):231–9.

    CAS  PubMed  Google Scholar 

  97. Allegaert K, Van den Anker J, Verbesselt R, et al. O-demethylation of tramadol in the first months of life. Eur J Clin Pharmacol. 2005;61(11):837–42.

    CAS  PubMed  Google Scholar 

  98. Ozalevli M, Unlugenc H, Tuncer U, Gunes Y, Ozcengiz D. Comparison of morphine and tramadol by patient-controlled analgesia for postoperative analgesia after tonsillectomy in children. Paediatr Anaesth. 2005;15(11):979–84.

    PubMed  Google Scholar 

  99. Suresh S, Anand K. Opioid tolerance in neonates: mechanisms, diagnosis, assessment, and management. Semin Perinatol. 1998;22:425–33.

    CAS  PubMed  Google Scholar 

  100. Lonnqvist PA, Bergendahl HT, Eksborg S. Pharmacokinetics of clonidine after rectal administration in children. Anaesthesiology. 1994;81(5):1097–101.

    CAS  Google Scholar 

  101. Ivani G, Bergendahl H, Lampugnani E, et al. Plasma levels of clonidine following epidural bolus injection in children. Acta Anaesthesiol Scand. 1998;42(3):306–11.

    CAS  PubMed  Google Scholar 

  102. Dalens B. Some current controversies in paediatric regional anaesthesia. Curr Opin Anaesthesiol. 2006;19(3):301–8.

    PubMed  Google Scholar 

  103. Breschan C, Krumpholz R, Likar R, Kraschl R, Schalk H. Can a dose of 2microg.kg(-1) caudal clonidine cause respiratory depression in neonates? Paediatr Anaesth. 1999;9(1):81–3.

    CAS  PubMed  Google Scholar 

  104. Breschan C, Jost R, Krumpholz R, et al. A prospective study comparing the analgesic efficacy of levobupivacaine, ropivacaine and bupivacaine in paediatric patients undergoing caudal blockade. Paediatr Anaesth. 2005;15(4):301–6.

    PubMed  Google Scholar 

  105. Peutrell JM, Lonnqvist PA. Neuraxial blocks for anaesthesia and analgesia in children. Curr Opin Anaesthesiol. 2003;16(5):461–70.

    PubMed  Google Scholar 

  106. Walker S, Howard R, Keay K, Fitzgerald M. Developmental age influences the effect of epidural dexmedetomidine on inflammatory hyperalgesia in rat pups. Anaesthesiology. 2005;102(6):1226–34.

    CAS  Google Scholar 

  107. Elia N, Tramer M. Ketamine and postoperative pain–a quantitative systematic review of randomised trials. Pain. 2005;113(1–2):61–70.

    CAS  PubMed  Google Scholar 

  108. Fitzgerald M. The development of nociceptive circuits. Nat Rev Neurosci. 2005;6(7):507–20.

    CAS  PubMed  Google Scholar 

  109. Haberny KA, Paule MG, Scallet AC, et al. Ontogeny of the N-methyl-D-aspartate (NMDA) receptor system and susceptibility to neurotoxicity. Toxicol Sci. 2002;68(1):9–17.

    CAS  PubMed  Google Scholar 

  110. Young C, Jevtovic-Todorovic V, Qin Y, et al. Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain. Br J Pharmacol. 2005;146(2):189–97.

    PubMed Central  CAS  PubMed  Google Scholar 

  111. Mellon RD, Simone AF, Rappaport BA. Use of anaesthetic agents in neonates and young children. Anaesth Analg. 2007;104(3):509–20.

    CAS  Google Scholar 

  112. Slikker Jr W, Zou X, Hotchkiss CE, et al. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci. 2007;98(1):145–58.

    CAS  PubMed  Google Scholar 

  113. Walker SM, Westin BD, Deumens R, Grafe M, Yaksh TL. Effects of intrathecal ketamine in the neonatal rat: evaluation of apoptosis and long-term functional outcome. Anaesthesiology. 2010;113(1):147–59.

    CAS  Google Scholar 

  114. Mazoit J, Dalens B. Pharmacokinetics of local anaesthetics in infants and children. Clin Pharmacokinet. 2004;43(1):17–32.

    CAS  PubMed  Google Scholar 

  115. Foster R, Markham A. Levobupivacaine: a review of its pharmacology and use as a local anaesthetic [In Process Citation]. Drugs. 2000;59(3):551–79.

    CAS  PubMed  Google Scholar 

  116. Morrison S, Dominguez J, Frascarolo P, Reiz S. A comparison of the electrocardiographic cardiotoxic effects of racemic bupivacaine, levobupivacaine, and ropivacaine in anaesthetized swine [In Process Citation]. Anaesth Analg. 2000;90(6):1308–14.

    CAS  Google Scholar 

  117. Dalens B, Mazoit J. Adverse effects of regional anaesthesia in children. Drug Saf. 1998;19(4):251–68.

    CAS  PubMed  Google Scholar 

  118. Luz G, Wieser C, Innerhofer P, Frischhut B, Ulmer H, Benzer A. Free and total bupivacaine plasma concentrations after continuous epidural anaesthesia in infants and children. Paediatr Anaesth. 1998;8(6):473–8.

    CAS  PubMed  Google Scholar 

  119. Lerman J, Strong HA, Ledez KM, Swartz J, Reider MJ, Burrows FA. Effects of age on the serum concentrations of alpha1 acid glycoprotein and the binding of lidocaine in paediatric patients. Clin Pharmacol Ther. 1989;46:219–25.

    CAS  PubMed  Google Scholar 

  120. Mevorach D, Perkins F, Isaacson S. Bupivacaine toxicity secondary to continuous caudal epidural infusion in children [letter; comment]. Anaesth Analg. 1993;77(6):1305–6.

    CAS  Google Scholar 

  121. Berde CB. Convulsions associated with paediatric regional anaesthesia. Anaesth Analg. 1992;75:164–6.

    CAS  Google Scholar 

  122. Larsson BA, Lonnqvist PA, Olsson GL. Plasma concentrations of bupivacaine in neonates after continuous epidural infusion. Anaesth Analg. 1997;84:501–5.

    CAS  Google Scholar 

  123. Bosenberg AT, Thomas J, Cronje L, et al. Pharmacokinetics and efficacy of ropivacaine for continuous epidural infusion in neonates and infants. Paediatr Anaesth. 2005;15(9):739–49.

    PubMed  Google Scholar 

  124. Eidelman A, Weiss JM, Lau J, Carr DB. Topical anaesthetics for dermal instrumentation: a systematic review of randomized, controlled trials. Ann Emerg Med. 2005;46(4):343–51.

    PubMed  Google Scholar 

  125. Larson A, Stidman T, Banerji S, et al. Seizures and methemoglobinemia in an infant after excessive EMLA application. Paediatr Emerg Care. 2013;29:377–9.

    Google Scholar 

  126. Essink-Tjebbes C, Hekster Y, Liem K, van Dongen R. Topical use of local anaesthetics in neonates. Pharm World Sci. 1999;21(4):173–6.

    CAS  PubMed  Google Scholar 

  127. Taddio A, Ohlsson A, Einarson TR, Stevens B, Koren G. A systematic review of lidocaine-prilocaine cream (EMLA) in the treatment of acute pain in neonates. Paediatrics. 1998;101(2):E1.

    CAS  Google Scholar 

  128. Nilsson A, Engberg G, Henneberg S, Danielson K, De Verdier C. Inverse relationship between age-dependent erythrocyte activity of methemoglobin reductase and prilocaine-induced methemoglobinaemia during infancy. Br J Anaesth. 1990;64(1):72–6.

    CAS  PubMed  Google Scholar 

  129. Jain A, Rutter N. Does topical amethocaine gel reduce the pain of venepuncture in newborn infants? A randomised double blind controlled trial. Arch Dis Child Fetal Neonatal Ed. 2000;83(3):F207–210.

    PubMed Central  CAS  PubMed  Google Scholar 

  130. Long CP, McCafferty DF, Sittlington NM, et al. Randomized trail of novel tetracaine patch to provide local anaesthesia in enonates undergoing venepuncture. Br J Anaesth. 2003;91:514–8.

    CAS  PubMed  Google Scholar 

  131. Patel A, Czemiawski B, Gray S, Lui E. Does topical amethocaine gel reduce pain from heel prick blood sampling in premature infants? A randomized double-blind cross-over controlled study. Paediatr Child Health. 2003;8:222–5.

    PubMed Central  PubMed  Google Scholar 

  132. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev (Online). 2010; (1):CD001069 (pub 3).

    Google Scholar 

  133. Anseloni VC, Ren K, Dubner R, Ennis M. A brainstem substrate for analgesia elicited by intraoral sucrose. Neuroscience. 2005;133(1):231–43.

    CAS  PubMed  Google Scholar 

  134. Lefrak L, Burch K, Caravantes R, et al. Sucrose analgesia: identifying potentially better practices. Paediatrics. 2006;118(2):S197–202.

    Google Scholar 

  135. Stevens B, Yamada J, Lee GY, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures.[update of Cochrane Database Syst Rev. 2013;(Jan 31 (1):CD001069; PMID: 23440783). Cochrane Database Syst Rev. 2010;1, CD001069.

    PubMed  Google Scholar 

  136. Johnston CC, Filion F, Snider L, et al. How much sucrose is too much sucrose? Paediatrics. 2007;119(1):226.

    Google Scholar 

  137. Johnston CCFF, Snider L, Majnamer A, Limperopoulos C, Walker CD, Veilleux A, Pelausa E, Cake H, Stone S, Sherrard A, Boyer K. Routine sucrose analgesia during the first week of life in neonates younger than 31 weeks post conceptual age. Paediatrics. 2002;110(3):523–8.

    Google Scholar 

  138. A guideline from the Association of Paediatric Anaesthetists of Great Britain and Ireland. Good Practice in Postoperative and Procedural Pain Management. 2nd Edition. Paediatr Anaesth. 2012;22(1):1–79.

    Google Scholar 

  139. Hammer GB, Golianu B. Opioid analgesia in neonates following cardiac surgery. Semin Cardiothorac Vasc Anaesth. 2007;11(1):47–58.

    Google Scholar 

  140. Anand KJ, Barton BA, McIntosh N, et al. Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates. Arch Paediatr Adolesc Med. 1999;153(4):331–8.

    CAS  Google Scholar 

  141. Anand KJ, Hall RW, Desai N, et al. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. Lancet. 2004;363(9422):1673–82.

    CAS  PubMed  Google Scholar 

  142. Hall RW, Kronsberg SS, Barton BA, Kaiser JR, Anand KJ. Morphine, hypotension, and adverse outcomes among preterm neonates: who's to blame? Secondary results from the NEOPAIN trial. Paediatrics. 2005;115(5):1351–9.

    Google Scholar 

  143. de Graaf J, van Lingen RA, Valkenburg AJ, et al. Does neonatal morphine use affect neuropsychological outcomes at 8 to 9 years of age? Pain. 2013;154:449–58.

    PubMed  Google Scholar 

  144. de Graaf J, van Lingen RA, Simons SH, et al. Long-term effects of routine morphine infusion in mechanically ventilated neonates on children’s functioning: Five-year follow-up of a randomized controlled trial. Pain. 2011;152:1391–7.

    PubMed  Google Scholar 

  145. Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Syst Rev. 2003;1, CD002052.

    PubMed  Google Scholar 

  146. Bellu R, de Waal KA, Zanini R. Opioids for neonates receiving mechanical ventilation. Cochrane Database Syst Rev. 2008;1:CD004212. pub 3.

    PubMed  Google Scholar 

  147. Anand KJ, Johnston CC, Oberlander TF, Taddio A, Lehr VT, Walco GA. Analgesia and local anaesthesia during invasive procedures in the neonate. Clin Ther. 2005;27(6):844–76.

    CAS  PubMed  Google Scholar 

  148. Lago P, Garetti E, Merazzi D, et al. Guidelines for procedural pain in the newborn. Acta Paediatr. 2009;98(6):932–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  149. Carbajal R, Veerapen S, Couderc S, Jugie M, Ville Y. Analgesic effect of breast feeding in term neonates: randomised controlled trial. BMJ. 2003;326(7379):13.

    PubMed Central  PubMed  Google Scholar 

  150. Shah PS, Herbozo C, Aliwalas LL, Shah VS. Breastfeeding or breast milk for procedural pain in neonates. Cochrane Database Syst Rev. 2012;12:CD004950. pub3.

    PubMed  Google Scholar 

  151. Shah V, Taddio A, Rieder MJ. Effectiveness and tolerability of pharmacologic and combined interventions for reducing injection pain during routine childhood immunizations: systematic review and meta-analyses. Clin Ther. 2009;31(2):S104–151.

    CAS  PubMed  Google Scholar 

  152. Johnston CC, Filion F, Campbell-Yeo M, et al. Enhanced kangaroo mother care for heel lance in preterm neonates: a crossover trial. J Perinatol. 2009;29(1):51–6.

    CAS  PubMed  Google Scholar 

  153. Harrison D, Yamada J, Stevens B. Strategies for the prevention and management of neonatal and infant pain. Curr Pain Headache Rep. 2010;14(2):113–23.

    PubMed  Google Scholar 

  154. Mackenzie A, Acworth J, Norden M, Jeffery H, Dalziel S, Munro J. Guideline Statement: Management of Procedure-related Pain in Neonates. Paediatrics and Child Health Division RACP: Sydney, NSW, Australia; 2005.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesia and Pain Medicine, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, WC1N3JH, UK

    Richard F. Howard BSc, MB, ChB, FRCA, FFPM

Authors
  1. Richard F. Howard BSc, MB, ChB, FRCA, FFPM
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard F. Howard BSc, MB, ChB, FRCA, FFPM .

Editor information

Editors and Affiliations

  1. Department of Anesthesia, Women & Children's Hospital of Buffalo, Buffalo, New York, USA

    Jerrold Lerman

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Howard, R.F. (2015). Pain Assessment and Management. In: Lerman, J. (eds) Neonatal Anesthesia. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6041-2_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-6041-2_14

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-6040-5

  • Online ISBN: 978-1-4419-6041-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation