Skip to main content
SpringerLink
Log in

Sedation in the Neonatal Intensive Care Unit: International Practice

  • Chapter
  • First Online:
Pediatric Sedation Outside of the Operating Room

Abstract

Inadequate pain management in neonatal life impairs neurodevelopmental outcome because it alters pain thresholds, pain- or stress-related behavior, and physiological responses later in life. However, there are also emerging animal experimental and human epidemiological data on the impact of analgo-sedatives on neuro-apoptosis and impaired neurodevelopmental outcome. As a consequence, the management of neonatal pain is in search of a new balance, and these conflicting observations are the main drivers to tailor our pain management in neonates. Adequate pain management is based on prevention, assessment, and treatment with subsequent reassessment. Issues related to prevention and assessment tools are covered. Non-pharmacological (e.g., complementary interventions like facilitated tucking, nonnutritive sucking) and pharmacological (e.g., acetaminophen, opioids, ketamine, propofol) treatment modalities were reviewed and reflect the increased knowledge on neonatal pain management. Each topic ends with some take-home messages that in part also reflect our personal opinion on the current status of this topic.

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 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover 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. Anand KJ, Hickey PR. Pain and its effects in the human neonate and fetus. N Engl J Med. 1987;317:1321–9. https://doi.org/10.1056/NEJM198711193172105.

    Article  CAS  PubMed  Google Scholar 

  2. Walker SM, Franck LS, Fitzgerald M, et al. Long-term impact of neonatal intensive care and surgery on somatosensory perception in children born extremely preterm. Pain. 2009;141:79–87. https://doi.org/10.1016/j.pain.2008.10.012.

    Article  PubMed  Google Scholar 

  3. Morton NS. The pain-free ward: myth or reality. Paediatr Anaesth. 2012;22:527–9. https://doi.org/10.1111/j.1460-9592.2012.03881.x.

    Article  PubMed  Google Scholar 

  4. Johnston CC, Fernandes AM, Campbell-Yeo M. Pain in neonates is different. Pain. 2011;152:S65–73. https://doi.org/10.1016/j.pain.2010.10.008.

    Article  PubMed  Google Scholar 

  5. Walker SM. Long-term effects of neonatal pain. Semin Fetal Neonatal Med. 2019;24:101005. https://doi.org/10.1016/j.siny.2019.04.005.

    Article  PubMed  Google Scholar 

  6. Schiller RM, Allegaert K, Hunfeld M, et al. Analgesics and sedatives in critically ill newborns and infants: the impact on long-term neurodevelopment. J Clin Pharmacol. 2018;58(Suppl 10):140–50. https://doi.org/10.1002/jcph.1139.

    Article  CAS  Google Scholar 

  7. Allegaert K, Tibboel D, van den Anker J. Pharmacological treatment of neonatal pain: in search of a new equipoise. Semin Fetal Neonatal Med. 2013;18:42–7. https://doi.org/10.1016/j.siny.2012.10.001.

    Article  PubMed  Google Scholar 

  8. Durrmeyer X, Vutskits L, Anand KJ, et al. Use of analgesic and sedative drugs in the NICU: integrating clinical trials and laboratory data. Pediatr Res. 2010;67:117–27. https://doi.org/10.1203/PDR.0b013e3181c8eef3.

    Article  PubMed  Google Scholar 

  9. Davidson AJ. Anesthesia and neurotoxicity to the developing brain: the clinical relevance. Paediatr Anaesth. 2011;21:716–21. https://doi.org/10.1111/j.1460-9592.2010.03506.x.

    Article  PubMed  Google Scholar 

  10. Davidson A, Flick RP. Neurodevelopmental implications of the use of sedation and analgesia in neonates. Clin Perinatol. 2013;40:559–73. https://doi.org/10.1016/j.clp.2013.05.009.

    Article  PubMed  Google Scholar 

  11. Nemergut ME, Aganga D, Flick RP. Anesthetic neurotoxicity: what to tell the parents? Paediatr Anaesth. 2014;24:120–6. https://doi.org/10.1111/pan.12325.

    Article  PubMed  Google Scholar 

  12. Marlow N. Anesthesia and long-term outcomes after neonatal intensive care unit. Paediatr Anaesth. 2014;24:60–7. https://doi.org/10.1111/pan.12304.

    Article  PubMed  Google Scholar 

  13. Hohmeister J, Kroll A, Wollgarten-Hadamek I, et al. Cerebral processing of pain in school-aged children with neonatal nociceptive input: an exploratory fMRI study. Pain. 2010;150:257–67. https://doi.org/10.1016/j.pain.2010.04.004.

    Article  PubMed  Google Scholar 

  14. Walker SM. Neonatal pain. Paediatr Anaesth. 2014;24:39–48. https://doi.org/10.1111/pan.12293.

    Article  PubMed  Google Scholar 

  15. McCann ME, de Graaff JC, Dorris L, et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet. 2019;393:664–77. https://doi.org/10.1016/S0140-6736(18)32485-1.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Thewissen L, Allegaert K. Analgosedation in neonates: do we still need additional tools after 30 years of clinical research? Arch Dis Child Educ Pract Ed. 2011;96:112–8. https://doi.org/10.1136/adc.2008.145565.

    Article  PubMed  Google Scholar 

  17. Lago P, Garetti E, Boccuzzo G, et al. Procedural pain in neonates: the state of the art in the implementation of national guidelines in Italy. Paediatr Anaesth. 2013;23:407–14. https://doi.org/10.1111/pan.12107.

    Article  PubMed  Google Scholar 

  18. Bellieni C, Buonocore G. Improve the struggle against babies’ pain. Lancet. 2011;377:1315–6. https://doi.org/10.1016/S0140-6736(11)60535-7.

    Article  PubMed  Google Scholar 

  19. Guimaraes H, Sanchez-Luna M, Bellieni CV, et al. Ethical charter of Union of European Neonatal and Perinatal Societies. J Matern Fetal Neonatal Med. 2011;24:855–8. https://doi.org/10.3109/14767058.2010.531314.

    Article  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;300:60–70. https://doi.org/10.1001/jama.300.1.60.

    Article  CAS  PubMed  Google Scholar 

  21. Simons SH, van Dijk M, Anand KS, et al. Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates. Arch Pediatr Adolesc Med. 2003;157:1058–64. https://doi.org/10.1001/archpedi.157.11.1058.

    Article  PubMed  Google Scholar 

  22. Lago P, Boccuzzo G, Garetti E, et al. Pain management during invasive procedures at Italian NICUs: has anything changed in the last five years? J Matern Fetal Neonatal Med. 2013;26:303–5. https://doi.org/10.3109/14767058.2012.733783.

    Article  CAS  PubMed  Google Scholar 

  23. Carbajal R, Eriksson M, Courtois E, et al. Sedation and analgesia practices in neonatal intensive care units (EUROPAIN): results from a prospective cohort study. Lancet Respir Med. 2015;3:796–812. https://doi.org/10.1016/S2213-2600(15)00331-8.

    Article  PubMed  Google Scholar 

  24. Allegaert K, Mian P, van den Anker JN. Developmental pharmacokinetics in neonates: maturational changes and beyond. Curr Pharm Des. 2017;23:5769–78. https://doi.org/10.2174/1381612823666170926121124.

    Article  CAS  PubMed  Google Scholar 

  25. van den Hoogen NJ, de Kort AR, Allegaert KM, et al. Developmental neurobiology as a guide for pharmacological management of pain in neonates. Semin Fetal Neonatal Med. 2019;24:101012. https://doi.org/10.1016/j.siny.2019.05.004.

    Article  PubMed  Google Scholar 

  26. Van Dijk M, Tibboel D. Update on pain assessment in sick neonates and infants. Pediatr Clin North Am. 2012;59:1167–81. https://doi.org/10.1016/j.pcl.2012.07.012.

    Article  PubMed  Google Scholar 

  27. Stevens B, Johnston C, Taddio A, et al. The premature infant pain profile: evaluation 13 years after development. Clin J Pain. 2010;26:813–30. https://doi.org/10.1097/AJP.0b013e3181ed1070.

    Article  PubMed  Google Scholar 

  28. Gibbins S, Stevens BJ, Yamada J, et al. Validation of the premature infant pain profile-revised (PIPP-R). Early Hum Dev. 2014;90:189–93. https://doi.org/10.1016/j.earlhumdev.2014.01.005.

    Article  PubMed  Google Scholar 

  29. Carbajal R, Paupe A, Hoenn E, et al. APN: evaluation behavioral scale of acute pain in newborn infants. Arch Pediatr. 1997;4:623–8. https://doi.org/10.1016/s0929-693x(97)83360-x.

    Article  CAS  PubMed  Google Scholar 

  30. Taddio A, Hogan ME, Moyer P, et al. Evaluation of the reliability, validity and practicality of 3 measures of acute pain in infants undergoing immunization injections. Vaccine. 2011;29:1390–4. https://doi.org/10.1016/j.vaccine.2010.12.051.

    Article  PubMed  Google Scholar 

  31. Van Dijk M, Peters JW, van Deventer P, et al. The COMFORT Behavior Scale: a tool for assessing pain and sedation in infants. Am J Nurs. 2005;105:33–6. https://doi.org/10.1097/00000446-200501000-00019.

    Article  PubMed  Google Scholar 

  32. Van Dijk M, Roofthooft DW, Anand KJ, et al. Taking up the challenge of measuring prolonged pain in (premature) neonates: the COMFORTneo scale seems promising. Clin J Pain. 2009;25:607–16. https://doi.org/10.1097/AJP.0b013e3181a5b52a.

    Article  PubMed  Google Scholar 

  33. Krechel SW, Bildner J. CRIES: a new neonatal postoperative pain measurement score. Initial testing of validity and reliability. Paediatr Anaesth. 1995;5:53–61. https://doi.org/10.1111/j.1460-9592.1995.tb00242.x.

    Article  CAS  PubMed  Google Scholar 

  34. Manworren RC, Hynan LS. Clinical validation of FLACC: preverbal patient pain scale. Pediatr Nurs. 2003;29:140–6.

    PubMed  Google Scholar 

  35. Hummel P, Lawlor-Klean P, Weiss MG. Validity and reliability of the N-PASS assessment tool with acute pain. J Perinatol. 2010;30:474–8. https://doi.org/10.1038/jp.2009.185.

    Article  CAS  PubMed  Google Scholar 

  36. Spasojevic S, Bregun-Doronjski A. A simultaneous comparison of four neonatal pain scales in clinical settings. J Matern Fetal Neonatal Med. 2011;24:590–4. https://doi.org/10.3109/14767058.2010.511342.

    Article  PubMed  Google Scholar 

  37. Debillon T, Zupan V, Ravault N, et al. Development and initial validation of the EDIN scale, a new tool for assessing prolonged pain in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2001;85:F36–41. https://doi.org/10.1136/fn.85.1.f36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Grunau RE, Oberlander T, Holsti L, et al. Bedside application of the Neonatal Facial Coding System in pain assessment of premature neonates. Pain. 1998;76:277–86. https://doi.org/10.1016/s0304-3959(98)00046-3.

    Article  PubMed  Google Scholar 

  39. Cignacco E, Mueller R, Hamers JP, et al. Pain assessment in the neonate using the Bernese Pain Scale for neonates. Early Hum Dev. 2004;78:125–31. https://doi.org/10.1016/j.earlhumdev.2004.04.001.

    Article  PubMed  Google Scholar 

  40. Slater R, Cantarella A, Franck L, et al. How well do clinical pain assessment tools reflect pain in infants ? PLoS Med. 2008;24:e129. https://doi.org/10.1371/journal.pmed.0050129.

    Article  Google Scholar 

  41. Slater R, Cornelissen L, Fabrizi L, et al. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Lancet. 2010;376:1225–32. https://doi.org/10.1016/S0140-6736(10)61303-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Green G, Hartley C, Hoskin A, et al. Behavioural discrimination of noxious stimuli in infants is dependent on brain maturation. Pain. 2019;160:493–500. https://doi.org/10.1097/j.pain.0000000000001425.

    Article  PubMed  Google Scholar 

  43. Maxwell LG, Fraga MV, Malavolta CP. Assessment of pain in the newborn: an update. Clin Perinatol. 2019;46:693–707. https://doi.org/10.1016/j.clp.2019.08.005.

    Article  PubMed  Google Scholar 

  44. Gursul D, Hartley C, Slater R. Nociception and the neonatal brain. Semin Fetal Neonatal Med. 2019;24:101016. https://doi.org/10.1016/j.siny.2019.05.008.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Hyttel-Sorensen S, Austin T, van Bel F, et al. Clinical use of cerebral oximetry in extremely preterm infants is feasible. Dan Med J. 2013;60:A4533.

    PubMed  Google Scholar 

  46. Munsters J, Wallström L, Agren J, et al. Skin conductance measurements as pain assessment in newborn infants born at 22–27 weeks gestational age at different postnatal age. Early Hum Dev. 2012;88:21–6. https://doi.org/10.1016/j.earlhumdev.2011.06.010.

    Article  PubMed  Google Scholar 

  47. Valkenburg AJ, Niehof SP, van Dijk M, et al. Skin conductance peaks could result from changes in vital parameters unrelated to pain. Pediatr Res. 2012;71:375–9. https://doi.org/10.1038/pr.2011.72.

    Article  PubMed  Google Scholar 

  48. Ballantyne M, Stevens B, McAllister M, et al. Validation of the premature infant pain profile in the clinical setting. Clin J Pain. 1999;15:297–303. https://doi.org/10.1097/00002508-199912000-00006.

    Article  CAS  PubMed  Google Scholar 

  49. Maaskant J, Raymakers-Janssen P, Veldhoen E, et al. The clinimetric properties of the COMFORT scale: a systematic review. Eur J Pain. 2016;20:1587–611. https://doi.org/10.1002/ejp.880.

    Article  CAS  PubMed  Google Scholar 

  50. Ista E, van Dijk M, van Achterberg T. Do implementation strategies increase adherence to pain assessment in hospitals? A systematic review. Int J Nurs Stud. 2013;50:552–68. https://doi.org/10.1016/j.ijnurstu.2012.11.003.

    Article  PubMed  Google Scholar 

  51. Foster J, Spence K, Henderson-Smart D, et al. Procedural pain in neonates in Australian hospitals: a survey update of practices. J Paediatr Child Health. 2013;49:E35–9. https://doi.org/10.1111/jpc.12064.

    Article  PubMed  Google Scholar 

  52. Ceelie I, de Wildt SN, de Jong M, et al. Protocolized post-operative pain management in infants; do we stick to it ? Eur J Pain. 2012;16:760–6. https://doi.org/10.1002/j.1532-2149.2011.00056.x.

    Article  CAS  PubMed  Google Scholar 

  53. Anand KJS, Eriksson M, Boyle EM, et al. Assessment of continuous pain in newborns admitted to NICUs in 18 European countries. Acta Paediatr. 2017;106:1248–59. https://doi.org/10.1111/apa.13810.

    Article  PubMed  Google Scholar 

  54. Allegaert K, Casteels I, Tibboel D. Pain management during eye examinations for retinopathy of prematurity: what about procedural adaptations to blunt the pain response ? Acta Paediatr. 2010;99:488–9. https://doi.org/10.1111/j.1651-2227.2009.01672.x.

    Article  CAS  PubMed  Google Scholar 

  55. Huhn EA, Visca E, Vogt DR, et al. Decreased neonatal pain response after vaginal-operative delivery with Kiwi OmniCup versus metal ventouse. BMC Pregnancy Childbirth. 2017;17:47. https://doi.org/10.1186/s12884-017-1231-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cordero L, Sananes M, Leona W. Mechanically ventilated VLBW infants: a comparison of two airway suctioning frequencies. Pediatr Res. 2001;49:273A.

    Google Scholar 

  57. Dunbar AE 3rd, Sharek PJ, Mickas NA, et al. Implementation and case-study results of potentially better practices to improve pain management of neonates. Pediatrics. 2006;118(Suppl 2):87–94. https://doi.org/10.1542/peds.2006-0913E.

    Article  Google Scholar 

  58. Cone S, Pickler RH, Grap MJ, et al. Endotracheal suctioning in preterm infants using four-handed versus routine care. J Obstet Gynecol Neonatal Nurs. 2013;42:92–104. https://doi.org/10.1111/1552-6909.12004.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Taylor JE, Hawley G, Flenady V, et al. Tracheal suctioning without disconnection in intubated ventilated neonates. Cochrane Database Syst Rev. 2011:CD003065. https://doi.org/10.1002/14651858.CD003065.pub2.

  60. Gillies D, Spence K. Deep versus shallow suction of endotracheal tubes in ventilated neonates and young infants. Cochrane Database Syst Rev. 2011:CD003309. https://doi.org/10.1002/14651858.CD003309.pub2.

  61. Larsson BA, Tannfeldt G, Lagercrantz H, et al. Venipuncture is more effective and less painful than heel lancing for blood tests in neonates. Pediatrics. 1998;101:882–6. https://doi.org/10.1542/peds.101.5.882.

    Article  CAS  PubMed  Google Scholar 

  62. Ogawa S, Ogihara T, Fujiwara E, et al. Venepuncture is preferable to heel lance for blood sampling in term neonates. Arch Dis Child Fetal Neonatal Ed. 2005;90:F432–6. https://doi.org/10.1136/adc.2004.069328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hwang MJ, Seol GH. Cerebral oxygenation and pain of heel blood sampling using manual and automatic lancets in premature infants. J Perinat Neonatal Nurs. 2015;29:356–62. https://doi.org/10.1097/JPN.0000000000000138.

    Article  PubMed  Google Scholar 

  64. Bellieni CV, Tei M, Coccina F, et al. Sensorial saturation for infants’ pain. J Matern Fetal Neonatal Med. 2012;25(Suppl 1):79–81. https://doi.org/10.3109/14767058.2012.663548.

    Article  PubMed  Google Scholar 

  65. Cignacco E, Hamers JP, Stoffel L, et al. The efficacy of non-pharmacological interventions in the management of procedural pain in preterm and term neonates. A systematic literature review. Eur J Pain. 2007;11:139–52. https://doi.org/10.1016/j.ejpain.2006.02.010.

    Article  PubMed  Google Scholar 

  66. Bucsea O, Pillai RR. Non-pharmacological pain management in the neonatal intensive care unit: managing neonatal pain without drugs. Semin Fetal Neonatal Med. 2019;24:101017. https://doi.org/10.1016/j.siny.2019.05.009.

    Article  PubMed  Google Scholar 

  67. Karp H. The fourth trimester and the calming reflex: novel ideas for nurturing young infants. Midwifery Today Int Midwife. 2012;102:25–6.

    Google Scholar 

  68. Pinelli J, Symington A, Ciliska D. Nonnutritive sucking in high-risk infants: benign intervention or legitimate therapy ? J Obstet Gynecol Neonatal Nurs. 2002;31:582–91. https://doi.org/10.1111/j.1552-6909.2002.tb00084.x.

    Article  PubMed  Google Scholar 

  69. Mangat AK, Oei JL, Chen K, et al. A review of non-pharmacological treatments for pain management in newborn infants. Children. 2018;5:E130. https://doi.org/10.3390/children5100130.

    Article  PubMed  Google Scholar 

  70. Harrison D, Bueno M, Yamada J, et al. Analgesic effects of sweet-tasting solutions for infants: current state of equipoise. Pediatrics. 2010;126:894–902. https://doi.org/10.1542/peds.2010-1593.

    Article  PubMed  Google Scholar 

  71. Naughton KA. The combined use of sucrose and nonnutritive sucking for procedural pain in both term and preterm neonates: an integrative review of the literature. Adv Neonatal Care. 2013;13:9–19. https://doi.org/10.1097/ANC.0b013e31827ed9d3.

    Article  PubMed  Google Scholar 

  72. Carbajal R, Chauvet X, Couderc S, et al. Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates. BMJ. 1999;319:1393–7. https://doi.org/10.1136/bmj.319.7222.1393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Bueno M, Yamada J, Harrison D, et al. A systematic review and meta-analyses of nonsucrose sweet solutions for pain relief in neonates. Pain Res Manag. 2013;18:153–61. https://doi.org/10.1155/2013/956549.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Stevens B, Yamada J, Lee GY, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2013;1:CD001069. https://doi.org/10.1002/14651858.CD001069.pub4.

    Article  Google Scholar 

  75. Marin Gabriel MA, Del Rey Hurtado de Mendoza B, Jiménez Figueroa L, et al. Analgesia with breastfeeding in addition to skin-to-skin contact during heel prick. Arch Dis Child Fetal Neonatal Ed. 2013;98:F499–503. https://doi.org/10.1136/archdischild-2012-302921.

    Article  PubMed  Google Scholar 

  76. Meesters N, Simons S, van Rosmalen J, et al. Waiting 2 minutes after sucrose administration-unnecessary ? Arch Dis Child Fetal Neonatal Ed. 2017;102:F167–9. https://doi.org/10.1136/archdischild-2016-310841.

    Article  PubMed  Google Scholar 

  77. Taddio A, Shah V, Leung E, et al. Knowledge translation of the HELPinKIDS clinical practice guideline for managing childhood vaccination pain: usability and knowledge uptake of educational materials directed to new parents. BMC Pediatr. 2013;13:23. https://doi.org/10.1186/1471-2431-13-23.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Van Sleuwen BE, Engelberts AC, Boere-Boonekamp MM, et al. Swaddling: a systematic review. Pediatrics. 2007;120:e1097–106. https://doi.org/10.1542/peds.2006-2083.

    Article  PubMed  Google Scholar 

  79. Prasopkittikun T, Tilokskulchai F. Management of pain form heel stick in neonates: an analysis of research conducted in Thailand. J Perinat Neonatal Nurs. 2003;17:304–12. https://doi.org/10.1097/00005237-200310000-00009.

    Article  PubMed  Google Scholar 

  80. Liaw JJ, Yang L, Katherine Wang KW, et al. Non-nutritive sucking and facilitated tucking relieve preterm infant pain during heel-stick procedures: a prospective, randomised controlled crossover trial. Int J Nurs Stud. 2012;49:300–9. https://doi.org/10.1016/j.ijnurstu.2011.09.017.

    Article  PubMed  Google Scholar 

  81. Liaw JJ, Yang L, Lee CM, et al. Effects of combined use of non-nutritive sucking, oral sucrose, and facilitated tucking on infant behavioural states across heel-stick procedures: a prospective, randomised controlled trial. Int J Nurs Stud. 2013;50:883–94. https://doi.org/10.1016/j.ijnurstu.2012.08.021.

    Article  PubMed  Google Scholar 

  82. Sundaram B, Shrivatava S, Pandian JS, et al. Facilitated tucking on pain in pre-term newborns during neonatal intensive care: a single blinded randomized controlled cross-over pilot trial. J Pediatr Rehabil Med. 2013;6:19–27. https://doi.org/10.3233/PRM-130233.

    Article  PubMed  Google Scholar 

  83. Hill S, Engle S, Jorgensen J, Kralik A, et al. Effects of facilitated tucking during routine care of infants born preterm. Pediatr Phys Ther. 2005;17:158–63. https://doi.org/10.1097/01.pep.0000163097.38957.ec.

    Article  PubMed  Google Scholar 

  84. Corff KE, Seideman R, Venkataraman PS, et al. Facilitated tucking: a nonpharmacologic comfort measure for pain in preterm neonates. J Obstet Gynecol Neonatal Nurs. 1995;24:143–7. https://doi.org/10.1111/j.1552-6909.1995.tb02456.x.

    Article  CAS  PubMed  Google Scholar 

  85. Cignacco EL, Sellam G, Stoffel L, et al. Oral sucrose and ‘facilitated tucking’ for repeated pain relief in preterms: a randomized controlled trial. Pediatrics. 2012;129:299–308. https://doi.org/10.1542/peds.2011-1879.

    Article  PubMed  Google Scholar 

  86. Axelin A, Salanterä S, Lehtonen L. ‘Facilitated tucking by parents’ in pain management of preterm infants-a randomized crossover trial. Early Hum Dev. 2006;82:241–7. https://doi.org/10.1016/j.earlhumdev.2005.09.012.

    Article  PubMed  Google Scholar 

  87. Ward-Larson C, Horn RA, Gosnell F. The efficacy of facilitated tucking for relieving procedural pain of endotracheal suctioning in very low birth weight infants. MCN: Am J Matern Child Nurs. 2004;29:151–6. https://doi.org/10.1097/00005721-200405000-00004.

    Article  Google Scholar 

  88. Fearon I, Kisilevsky BS, Mains SM, et al. Swaddling after heel lance: age-specific effects on behavioral recovery in preterm infants. J Dev Behav Pediatr. 1997;18:222–32.

    Article  CAS  PubMed  Google Scholar 

  89. Johnston C, Campbell-Yeo M, Rich B, et al. Therapeutic touch is not therapeutic for procedural pain in very preterm neonates: a randomized trial. Clin J Pain. 2013;29:824–9. https://doi.org/10.1097/AJP.0b013e3182757650.

    Article  PubMed  Google Scholar 

  90. Alinejard-Naeini M, Mohagheghi P, Peyrovi H, et al. The effect of facilitated tucking during endotracheal suctioning on procedural pain in preterm neonates: a randomized controlled crossover study. Global J Health Sci. 2014;6:278–84. https://doi.org/10.5539/gjhs.v6n4p278.

    Article  Google Scholar 

  91. Peyrovi H, Alinejad-Naeini M, Mohagheghi P, et al. The effect of facilitated tucking position during endotracheal suctioning on physiological responses and coping with stress in premature infants: a randomized controlled crossover study. J Matern Fetal Neonatal Med. 2014;27:1555–9. https://doi.org/10.3109/14767058.2013.868429.

    Article  PubMed  Google Scholar 

  92. Gautheyrou L, Durand S, Jourdes E, et al. Facilitated tucking during early neonatologist-performed echocardiograpy in very preterm neonates. Acta Paediatr. 2018;107:2079–85. https://doi.org/10.1111/apa.14555.

    Article  PubMed  Google Scholar 

  93. Perroteau A, Nanquette MC, Rousseau A, et al. Efficacy of facilitated tucking combined with non-nutritive sucking on very preterm infants’ pain during the heel-stick procedure: a randomized controlled trial. Int J Nurs Stud. 2018;86:29–35. https://doi.org/10.1016/j.ijnurstu.2018.06.007.

    Article  PubMed  Google Scholar 

  94. Cignacco E, Axelin A, Stoffel L, et al. Facilitated tucking as a non-pharmacological intervention for neonatal pain relief: is it clinically feasible? Acta Paediatr. 2010;99:1763–5. https://doi.org/10.1111/j.1651-2227.2010.01941.x.

    Article  CAS  PubMed  Google Scholar 

  95. Losacco V, Cuttini M, Greisen G, et al. Heel blood sampling in European neonatal intensive care units: compliance with pain management guidelines. Arch Dis Child Fetal Neonatal Ed. 2011;96:F65–8. https://doi.org/10.1136/adc.2010.186429.

    Article  PubMed  Google Scholar 

  96. Johnston CC, Stevens B, Pinelli J, et al. Kangaroo care is effective in diminishing pain response in preterm neonates. Arch Pediatr Adolesc Med. 2003;157:1084–8. https://doi.org/10.1001/archpedi.157.11.1084.

    Article  PubMed  Google Scholar 

  97. Axelin A, Lehtonen L, Pelander T, et al. Mothers’ different styles of involvement in preterm infant pain care. J Obstet Gynecol Neonatal Nurs. 2010;39:415–24. https://doi.org/10.1111/j.1552-6909.2010.01150.x.

    Article  PubMed  Google Scholar 

  98. Lönnqvist PA. Regional anaesthesia and analgesia in the neonate. Best Pract Res Clin Anaesthesiol. 2010;24:309–21. https://doi.org/10.1016/j.bpa.2010.02.012.

    Article  CAS  PubMed  Google Scholar 

  99. Shah VS, Taddio A, Hancock R, et al. Topical amethocaine gel 4% for intramuscular injection in term neonates: a double-blind, placebo-controlled, randomized trial. Clin Ther. 2008;30:166–74. https://doi.org/10.1016/j.clinthera.2008.01.018.

    Article  CAS  PubMed  Google Scholar 

  100. Jain A, Rutter N. Does topical amethocaine gel reduce the pain of venipuncture in newborn infants? A randomised double blind controlled trial. Arch Dis Child Fetal Neonatal Ed. 2000;83:F207–10. https://doi.org/10.1136/fn.83.3.f207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lemyre B, Hogan DL, Gaboury I, et al. How effective is tetracaine 4% gel, before a venipuncture, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial. BMC Pediatr. 2007;7:7. https://doi.org/10.1186/1471-2431-7-7.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Lemyre B, Sherlock R, Hogan D, et al. How effective is tetracaine 4% gel, before a peripherally inserted central catheter, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial. BMC Med. 2006;4:11. https://doi.org/10.1186/1741-7015-4-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Long CP, McCafferty DF, Sittlington NM, et al. Randomized trial of a novel tetracaine patch to provide local anaesthesia in neonates undergoing venipuncture. Br J Anaesth. 2003;91:514–8. https://doi.org/10.1093/bja/aeg216.

    Article  CAS  PubMed  Google Scholar 

  104. Jain A, Rutter N, Ratnayaka M. Topical amethocaine gel for pain relief of heel prick blood sampling: a randomised double blind controlled trial. Arch Dis Child Fetal Neonatal Ed. 2001;84:F56–9. https://doi.org/10.1136/fn.84.1.f56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Bonetto G, Salvatico E, Varela N, et al. Pain prevention in term neonates: randomized trial for three methods. Arch Argent Pediatr. 2008;106:392–6. https://doi.org/10.1590/S0325-00752008000500004.

    Article  PubMed  Google Scholar 

  106. Larsson BA, Jylli L, Lagercrantz H, et al. Does a local anaesthetic cream (EMLA) alleviate pain from heel-lancing in neonates ? Acta Anaesthesiol Scand. 1995;39:1028–31. https://doi.org/10.1111/j.1399-6576.1995.tb04223.x.

    Article  CAS  PubMed  Google Scholar 

  107. Stevens B, Johnston C, Taddio A, et al. Management of pain from heel lance with lidocaine-prilocaine (EMLA) cream: is it safe and efficacious in preterm infants ? J Dev Behav Pediatr. 1999;20:216–21. https://doi.org/10.1097/00004703-199908000-00003.

    Article  CAS  PubMed  Google Scholar 

  108. Kaur G, Gupta P, Kumar A. A randomized trial of eutectic mixture of local anesthetics during lumbar puncture in newborns. Arch Pediatr Adolesc Med. 2003;157:1065–70. https://doi.org/10.1001/archpedi.157.11.1065.

    Article  PubMed  Google Scholar 

  109. Enad D, Salvador A, Brodsky NL, et al. Safety and efficacy of eutectic mixture of local anesthetics (EMLA) for lumbars puncture (LP) in newborns (NB). Pediatr Res. 1995;37:204A (Abstract 1212).

    Google Scholar 

  110. Foster JP, Taylor C, Spence K. Topical anaesthesia for needle-related pain in newborn infants. Cochrane Database Syst Rev. 2017;2:CD010331. https://doi.org/10.1002/14651858.CD010331.pub2.

    Article  PubMed  Google Scholar 

  111. Abad F, Diaz-Gomez NM, Domenech E, et al. Oral sucrose compares favourably with lidocaine-prilocaine cream for pain relief during venepuncture in neonates. Acta Paediatr. 2001;90:160–5.

    Article  CAS  PubMed  Google Scholar 

  112. Gradin M, Eriksson M, Holmqvist G, et al. Pain reduction at venipuncture in newborns: oral glucose compared with local anesthetic cream. Pediatrics. 2002;110:1053–7. https://doi.org/10.1542/peds.110.6.1053.

    Article  PubMed  Google Scholar 

  113. Shahid S, Florez ID, Mbuagbaw L. Efficacy and safety of EMLA cream for pain control due to venipuncture in infants: a meta-analysis. Pediatrics. 2019;143:e20181173. https://doi.org/10.1542/peds.2018-1173.

    Article  PubMed  Google Scholar 

  114. Biran V, Gourrier E, Cimerman P, et al. Analgesic effects of EMLA cream and oral sucrose during venipuncture in preterm infants. Pediatrics. 2011;128:e63–70. https://doi.org/10.1542/peds.2010-1287.

    Article  PubMed  Google Scholar 

  115. Madsen S. Towards evidence based emergency medicine: the BETs from the Manchester Royal Infirmary. BET1. Topical anaesthetic and pain associated with lumbar puncture in neonates. Emerg Med J. 2009;26:57–8. https://doi.org/10.1136/emj.2008.069583.

    Article  PubMed  Google Scholar 

  116. Wang J, Zhao S, Luo L, et al. Dorsal penile nerve block versus eutectic mixture of local anesthetics cream for pain relief in infants during circumcision: a meta-analysis. PLoS One. 2018;13:e0203439. https://doi.org/10.1371/journal.pone.0203439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Sharara-Chami R, Lakissian Z, Charafeddine L, et al. Combination analgesia for neonatal circumcision: a randomized controlled trial. Pediatrics. 2017;140:e20171935. https://doi.org/10.1542/peds.2017-1935.

    Article  PubMed  Google Scholar 

  118. Taddio A, Stevens B, Craig K, et al. Efficacy and safety of lidocaine-prilocaine cream for pain during circumcision. N Engl J Med. 1997;336:1197–201. https://doi.org/10.1056/NEJM199704243361701.

    Article  CAS  PubMed  Google Scholar 

  119. Brady-Fryer B, Weibe N, Lander JA. Pain relief for neonatal circumcision. Cochrane Database Syst Rev. 2004:CD004217. https://doi.org/10.1002/14651858.CD004217.pub2.

  120. Taddio A, Nulman I, Goldbach M, et al. Use of lidocaine-prilocaine cream for vaccination pain in infants. J Pediatr. 1994;124:643–8. https://doi.org/10.1016/s0022-3476(05)83150-6.

    Article  CAS  PubMed  Google Scholar 

  121. Shah V, Taddio A, Rieder MJ, et al. 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(Suppl 2):104–51. https://doi.org/10.1016/j.clinthera.2009.08.001.

    Article  CAS  Google Scholar 

  122. Reis EC, Roth EK, Syphan JL, et al. Effective pain reduction for multiple immunization injections in young infants. Arch Pediatr Adolesc Med. 2003;157:1115–20. https://doi.org/10.1001/archpedi.157.11.1115.

    Article  PubMed  Google Scholar 

  123. Babl FE, Goldfinch C, Mandrawa C, et al. Does nebulized lidocaine reduce the pain and distress of nasogastric tube insertion in young children? A randomized, double-blind, placebo-controlled trial. Pediatrics. 2009;123:1548–55. https://doi.org/10.1542/peds.2008-1897.

    Article  PubMed  Google Scholar 

  124. McCullough S, Halton T, Mowbray D, et al. Lingual sucrose reduces the pain response to nasogastric tube insertion: a randomised clinical trial. Arch Dis Child Fetal Neonatal Ed. 2008;93:F100–3. https://doi.org/10.1136/adc.2006.110338.

    Article  CAS  PubMed  Google Scholar 

  125. Allegaert K. The clinical pharmacology of short acting analgo-sedatives in neonates. Curr Clin Pharmacol. 2011;6:222–6. https://doi.org/10.2174/157488411798375912.

    Article  CAS  PubMed  Google Scholar 

  126. Allegaert K, Peeters MY, Verbesselt R, et al. Inter-individual variability in propofol pharmacokinetics in preterm and term neonates. Br J Anaesth. 2007;99:864–70. https://doi.org/10.1093/bja/aem294.

    Article  CAS  PubMed  Google Scholar 

  127. Welzing L, Kribs A, Eifinger F, et al. Propofol as an induction agent for endotracheal intubation can cause significant arterial hypotension in preterm neonates. Paediatr Anaesth. 2010;20:605–11. https://doi.org/10.1111/j.1460-9592.2010.03330.x.

    Article  PubMed  Google Scholar 

  128. Nauta M, Onland W, De Jaegere A. Propofol as an induction agent for endotracheal intubation can cause significant arterial hypotension in preterm neonates. Paediatr Anaesth. 2011;21:711–2. https://doi.org/10.1111/j.1460-9592.2011.03552.x.

    Article  PubMed  Google Scholar 

  129. Ghanta S, Abdel-Latif ME, Lui K, et al. Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: a randomized, controlled trial. Pediatrics. 2007;119:e1248–55. https://doi.org/10.1542/peds.2006-2708.

    Article  PubMed  Google Scholar 

  130. Papoff P, Mancuso M, Caresta E, et al. Effectiveness and safety of propofol in newborn infants. Pediatrics. 2008;121:448. https://doi.org/10.1542/peds.2007-3132.

    Article  PubMed  Google Scholar 

  131. Penido MG, de Oliveira Silva DF, Tavares EC, et al. Propofol versus midazolam for intubating preterm neonates: a randomized controlled trial. J Perinatol. 2011;31:356–60. https://doi.org/10.1038/jp.2010.135.

    Article  CAS  PubMed  Google Scholar 

  132. Simons SH, van der Lee R, Reiss IK, et al. Clinical evaluation of propofol as sedative for endotracheal intubation in neonates. Acta Paediatr. 2013;102:e487–92. https://doi.org/10.1111/apa.12367.

    Article  CAS  PubMed  Google Scholar 

  133. Smits A, Thewissen L, Caicedo A, et al. Propofol dose-finding to reach optimal effect for (semi)-elective intubation in neonates. J Pediatr. 2016;179:54–60.e9. https://doi.org/10.1016/j.jpeds.2016.07.049.

    Article  CAS  PubMed  Google Scholar 

  134. Durrmeyer X, Breining S, Claris O, et al. Effect of atropine with propofol with atracurium and sufentanil on oxygen desaturation in neonates requiring nonemergency intubation: a randomized clinical trial. JAMA. 2018;319:1790–801. https://doi.org/10.1001/jama.2018.3708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Dekker J, Lopriore E, van Zanten HA, et al. Sedation during minimal invasive surfactant therapy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019;104:F378–83. https://doi.org/10.1136/archdischild-2018-315015.

    Article  PubMed  Google Scholar 

  136. Vanderhaegen J, Naulaers G, Van Huffel S, et al. Cerebral and systemic hemodynamic effects of intravenous bolus administration of propofol in neonates. Neonatology. 2010;98:57–63. https://doi.org/10.1159/000271224.

    Article  CAS  PubMed  Google Scholar 

  137. Massolo AC, Sgrὸ S, Piersigilli F, et al. Propofol formulation affects myocardial function in newborn infants. Pediatr Cardiol. 2019;40:1536–42. https://doi.org/10.1007/s00246-019-02182-4.

    Article  PubMed  Google Scholar 

  138. Thewissen L, Caicedo A, Dereymaeker A, et al. Cerebral autoregulation and activity after propofol for endotracheal intubation in preterm neonates. Pediatr Res. 2018;84:719–25. https://doi.org/10.1038/s41390-018-0160-3.

    Article  CAS  PubMed  Google Scholar 

  139. Piersigilli F, Di Pede A, Catena G, et al. Propofol and fentanyl sedation for laser treatment of retinopathy of prematurity to avoid intubation. J Matern Fetal Neonatal Med. 2019;32:517–21. https://doi.org/10.1080/14767058.2017.1383379.

    Article  CAS  PubMed  Google Scholar 

  140. Morse J, Hannam JA, Cortinez LI, et al. A manual propofol infusion regimen for neonates and infants. Paediatr Anaesth. 2019;29:907–14. https://doi.org/10.1111/pan.13706.

    Article  PubMed  Google Scholar 

  141. Sammartino M, Garra R, Sbaraglia F, et al. Propofol overdose in a preterm baby: may propofol infusion syndrome arise in two hours ? Paediatr Anaesth. 2010;20:973–4. https://doi.org/10.1111/j.1460-9592.2010.03395.x.

    Article  PubMed  Google Scholar 

  142. Michel-Macias C, Morales-Barquet DA, Reyes-Palomino AM, et al. Single dose of propofol causing propofol infusion syndrome in a newborn. Oxf Med Case Reports. 2018;2018:omy023. https://doi.org/10.1093/omcr/omy023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Allegaert K, Peeters MY, Knibbe C. Propofol in (pre)term neonates: consider the extensive interindividual variability in clearance within the neonatal population. Paediatr Anaesth. 2011;21:174–5. https://doi.org/10.1111/j.1460-9592.2010.03482.x.

    Article  PubMed  Google Scholar 

  144. Shah PS, Shah VS. Propofol for procedural sedation/anaesthesia in neonates. Cochrane Database Syst Rev. 2011:CD007248. https://doi.org/10.1002/14651858.CD007248.pub2.

  145. Bhutta AT. Ketamine: a controversial drug for neonates. Semin Perinatol. 2007;31:303–8. https://doi.org/10.1053/j.semperi.2007.07.005.

    Article  PubMed  Google Scholar 

  146. Saarenmaa E, Neuvonen PJ, Huttunen P, et al. Ketamine for procedural pain relief in newborn infants. Arch Dis Child Fetal Neonatal Ed. 2001;85:F53–6. https://doi.org/10.1136/fn.85.1.f53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Lönnqvist PA, Walker SM. Ketamine as an adjunct to caudal block in neonates and infants: is it time to re-evaluate ? Br J Anaesth. 2012;109:138–40. https://doi.org/10.1093/bja/aes228.

    Article  CAS  PubMed  Google Scholar 

  148. Hartvig P, Larsson E, Joachimsson PO. Postoperative analgesia and sedation following pediatric cardiac surgery using a constant infusion of ketamine. J Cardiothorac Vasc Anesth. 1993;7:148–53. https://doi.org/10.1016/1053-0770(93)90207-2.

    Article  CAS  PubMed  Google Scholar 

  149. Bourgoin L, Caeymaex L, Decobert F, et al. Administering atropine and ketamine before less invasive surfactant administration resulted in low pain scores in a prospective study of premature neonates. Acta Paediatr. 2018;107:1184–90. https://doi.org/10.1111/apa.14317.

    Article  CAS  PubMed  Google Scholar 

  150. Milési C, Baleine J, Mura T, et al. Nasal midazolam vs ketamine for neonatal intubation in the delivery room: a randomised trial. Arch Dis Child Fetal Neonatal Ed. 2018;103:F221–6. https://doi.org/10.1136/archdischild-2017-312808.

    Article  PubMed  Google Scholar 

  151. Lyon F, Dabbs T, O’Meara M. Ketamine sedation during treatment of retinopathy of prematurity. Eye. 2008;22:684–6. https://doi.org/10.1038/sj.eye.6702717.

    Article  CAS  PubMed  Google Scholar 

  152. Ulgey A, Güneş I, Bayram A, et al. Decreasing the need for mechanical ventilation after surgery for retinopathy of prematurity: sedoanalgesia vs. general anesthesia. Turk J Med Sci. 2015;45:1292–9. https://doi.org/10.3906/sag-1401-24.

    Article  CAS  PubMed  Google Scholar 

  153. Saroyan JM, Tresgallo ME, Farkouh C, et al. The use of oral ketamine for analgesia with dressing change in an infant with epidermolysis bullosa: report of a case. Pediatr Dermatol. 2009;26:764–6. https://doi.org/10.1111/j.1525-1470.2009.01036.x.

    Article  PubMed  Google Scholar 

  154. Elalouf C, Le Moing AG, Fontaine C, et al. Prospective follow-up of a cohort of preterm infants<33 WG receiving ketamine for tracheal intubation in the delivery room: neurological outcome at 1 and 2 years. Arch Pediatr. 2018;25:295–300. https://doi.org/10.1016/j.arcped.2018.03.001.

    Article  CAS  PubMed  Google Scholar 

  155. Eleveld DJ, Proost JH, Vereecke H, et al. An allometric model of remifentanil pharmacokinetics and pharmacodynamics. Anesthesiology. 2017;126:1005–8. https://doi.org/10.1097/ALN.0000000000001634.

    Article  CAS  PubMed  Google Scholar 

  156. Norman E, Wikström S, Hellström-Westas L, et al. Rapid sequence induction is superior to morphine for intubation of preterm infants: a randomized controlled trial. J Pediatr. 2011;159:893–9.e1. https://doi.org/10.1016/j.jpeds.2011.06.003.

    Article  PubMed  Google Scholar 

  157. Choong K, AlFaleh K, Doucette J, et al. Remifentanil for endotracheal intubation in neonates: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2010;95:F80–4. https://doi.org/10.1136/adc.2009.167338.

    Article  CAS  PubMed  Google Scholar 

  158. Welzing L, Kribs A, Huenseler C, et al. Remifentanil for INSURE in preterm infants: a pilot study for evaluation of efficacy and safety aspects. Acta Paediatr. 2009;98:1416–20. https://doi.org/10.1111/j.0803-5253.2009.01364.x.

    Article  CAS  PubMed  Google Scholar 

  159. Pereira e Silva Y, Gomez RS, Marcatto Jde O, et al. Morphine versus remifentanil for intubating preterm neonates. Arch Dis Child Fetal Neonatal Ed. 2007;92:F293–4. https://doi.org/10.1136/adc.2006.105262.

    Article  PubMed  Google Scholar 

  160. Hume-Smith H, McCormack J, Montgomery C, et al. The effect of age on the dose of remifentanil for tracheal intubation in infants and children. Paediatr Anaesth. 2010;20:19–27. https://doi.org/10.1111/j.1460-9592.2009.03190.x.

    Article  PubMed  Google Scholar 

  161. Avino D, Zhang WH, De Villé A, et al. Remifentanil versus morphine-midazolam premedication on the quality of endotracheal intubation in neonates: a noninferiority randomized trial. J Pediatr. 2014;164:1032–7. https://doi.org/10.1016/j.jpeds.2014.01.030.

    Article  CAS  PubMed  Google Scholar 

  162. de Kort EH, Hanff LM, Roofthooft D, et al. Insufficient sedation and severe side effects after fast administration of remifentanil during INSURE in preterm newborns. Neonatology. 2017;111:172–6. https://doi.org/10.1159/000450536.

    Article  CAS  PubMed  Google Scholar 

  163. Audil HY, Tse S, Pezzano C, et al. Efficacy, safety, and usability of remifentanil as premedication for INSURE in preterm neonates. Children. 2018;5:E63. https://doi.org/10.3390/children5050063.

    Article  PubMed  Google Scholar 

  164. Chollat C, Maroni A, Aubelle MS, et al. Efficacy and safety aspects of remifentanil sedation for intubation in neonates: a retrospective study. Front Pediatr. 2019;7:450. https://doi.org/10.3389/fped.2019.00450.

    Article  PubMed  PubMed Central  Google Scholar 

  165. Crawford MW, Hayes J, Tan JM. Dose-response of remifentanil for tracheal intubation in infants. Anesth Analg. 2005;100:1599–604. https://doi.org/10.1213/01.ANE.0000150940.57369.B5.

    Article  CAS  PubMed  Google Scholar 

  166. Chollat C, Tourrel F, Marret S. Does remifentanil have a place for sedation in the case of endotracheal intubation or minimally invasive surfactant therapy in neonates ? Neonatology. 2017;112:372–3. https://doi.org/10.1159/000479622.

    Article  PubMed  Google Scholar 

  167. Allegaert K, Thewissen L, van den Anker JN. Remifentanil in neonates: a promising compound in search of its indications ? Pediatr Neonatol. 2012;53:387–8. https://doi.org/10.1016/j.pedneo.2012.10.001.

    Article  PubMed  Google Scholar 

  168. Lago P, Tiozzo C, Boccuzzo G, et al. Remifentanil for percutaneous intravenous central catheter placement in preterm infant: a randomized controlled trial. Paediatr Anaesth. 2008;18:736–44. https://doi.org/10.1111/j.1460-9592.2008.02636.x.

    Article  PubMed  Google Scholar 

  169. Sammartino M, Bocci MG, Ferro G, et al. Efficacy and safety of continuous intravenous infusion of remifentanil in preterm infants undergoing laser therapy in retinopathy of prematurity: clinical experience. Paediatr Anaesth. 2003;13:596–602. https://doi.org/10.1046/j.1460-9592.2003.01101.x.

    Article  CAS  PubMed  Google Scholar 

  170. Sammartino M, Garra R, Sbaraglia F. Experience of remifentanil in extremely low-birth-weight babies undergoing laparotomy. Pediatr Neonatol. 2011;52:176–9. https://doi.org/10.1016/j.pedneo.2011.03.013.

    Article  PubMed  Google Scholar 

  171. Giannantonio C, Sammartino M, Valente E, et al. Remifentanil analgosedation in preterm newborns during mechanical ventilation. Acta Paediatr. 2009;98:1111–5. https://doi.org/10.1111/j.1651-2227.2009.01318.x.

    Article  CAS  PubMed  Google Scholar 

  172. Welzing L, Link F, Junghaenel S, et al. Remifentanil-induced tolerance, withdrawal or hyperalgesia in infants: a randomized controlled trial: remifentanil-based analgesia and sedation of paediatric intensive care patients. Neonatology. 2013;104:34–41. https://doi.org/10.1159/000348790.

    Article  CAS  PubMed  Google Scholar 

  173. Trends in narcotics and sedative use during mechanical ventilation of preterm infants in Canadian neonatal intensive care units. Zhongguo Dang Dai Er Ke Za Zhi. 2018;20:5–11.

    Google Scholar 

  174. American Academy of Pediatrics, Committee on Drugs, Committee on Environmental Health. Use of chloral hydrate for sedation in children. Pediatrics. 1993;92:471–3.

    Google Scholar 

  175. Reimche LD, Sankaran K, Hindmarsh KW, et al. Chloral hydrate sedation in neonates and infants–clinical and pharmacologic considerations. Dev Pharmacol Ther. 1989;12:57–64.

    Article  CAS  PubMed  Google Scholar 

  176. Litman RS, Soin K, Salam A. Chloral hydrate sedation in term and preterm infants: an analysis of efficacy and complications. Anesth Analg. 2010;110:739–46. https://doi.org/10.1213/ANE.0b013e3181ca12a8.

    Article  CAS  PubMed  Google Scholar 

  177. Ikbal M, Tastekin A, Dogan H, et al. The assessment of genotoxic effects in lymphocyte cultures of infants treated with chloral hydrate. Mutat Res. 2004;564:159–64. https://doi.org/10.1016/j.mrgentox.2004.08.007.

    Article  CAS  PubMed  Google Scholar 

  178. Cruise S, Tam-Chan D, Harrison D, et al. Prospective clinical audit of chloral hydrate administration practices in a neonatal unit. J Paediatr Child Health. 2012;48:1010–5. https://doi.org/10.1111/j.1440-1754.2012.02586.x.

    Article  PubMed  Google Scholar 

  179. Allegaert K, Daniels H, Naulaers G, et al. Pharmacodynamics of chloral hydrate in former preterm infants. Eur J Pediatr. 2005;164:403–7. https://doi.org/10.1007/s00431-005-1648-5.

    Article  CAS  PubMed  Google Scholar 

  180. Yu XQ, Suguihara C, Navarro H, et al. Effect of chloral hydrate on the cardiorespiratory response to hypoxia in newborn piglets. Biol Neonate. 1996;69:146–52. https://doi.org/10.1159/000244290.

    Article  CAS  PubMed  Google Scholar 

  181. Hershenson M, Brouillette RT, Olsen E, et al. The effect of chloral hydrate on genioglossus and diaphragmatic activity. Pediatr Res. 1984;18:516–9. https://doi.org/10.1203/00006450-198406000-00006.

    Article  CAS  PubMed  Google Scholar 

  182. Heistein LC, Ramaciotti C, Scott WA, et al. Chloral hydrate sedation for pediatric echocardiography: physiologic responses, adverse events, and risk factors. Pediatrics. 2006;117:e434–41. https://doi.org/10.1542/peds.2005-1445.

    Article  PubMed  Google Scholar 

  183. Keidan I, Gozal D, Minuskin T, et al. The effect of fasting practice on sedation with chloral hydrate. Pediatr Emerg Care. 2004;20:805–7. https://doi.org/10.1097/01.pec.0000148027.53598.b8.

    Article  PubMed  Google Scholar 

  184. Beauve B, Dearlove O. Sedation of children under 4 weeks of age for MRI examination. Paediatr Anaesth. 2008;18:892–3. https://doi.org/10.1111/j.1460-9592.2008.02580.x.

    Article  PubMed  Google Scholar 

  185. Van Wezel-Meijler G, Leijser LM, de Bruine FT, et al. Magnetic resonance imaging of the brain in newborn infants: practical aspects. Early Hum Dev. 2009;85:85–92. https://doi.org/10.1016/j.earlhumdev.2008.11.010.

    Article  PubMed  Google Scholar 

  186. Bracken J, Heaslip I, Ryan S. Chloral hydrate sedation in radiology: retrospective audit of reduced dose. Pediatr Radiol. 2012;42:349–54. https://doi.org/10.1007/s00247-011-2279-9.

    Article  PubMed  Google Scholar 

  187. Ibrahim T, Few K, Greenwood R, et al. ‘Feed and wrap’ or sedate and immobilise for neonatal brain MRI ? Arch Dis Child Fetal Neonatal Ed. 2015;100:F465–6. https://doi.org/10.1136/archdischild-2015-308847.

    Article  PubMed  Google Scholar 

  188. Mason KP, Sanborn P, Zurakowski D, et al. Superiority of pentobarbital versus chloral hydrate for sedation in infants during imaging. Radiology. 2004;230:537–42. https://doi.org/10.1148/radiol.2302030107.

    Article  PubMed  Google Scholar 

  189. McCarver-May DG, Kang J, Aouthmany M, et al. Comparison of chloral hydrate and midazolam for sedation of neonates for neuroimaging studies. J Pediatr. 1996;128:573–6. https://doi.org/10.1016/s0022-3476(96)70375-x.

    Article  CAS  PubMed  Google Scholar 

  190. Miller J, Xue B, Hossain M, et al. Comparison of dexmedetomidine and chloral hydrate sedation for transthoracic echocardiography in infants and toddlers: a randomized clinical trial. Paediatr Anaesth. 2016;26:266–72. https://doi.org/10.1111/pan.12819.

    Article  PubMed  Google Scholar 

  191. Clark RH, Bloom BT, Spitzer AR, et al. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics. 2006;117:1979–87. https://doi.org/10.1542/peds.2005-1707.

    Article  PubMed  Google Scholar 

  192. Hsieh EM, Hornik CP, Clark RH, et al. Medication use in the neonatal intensive care unit. Am J Perinatol. 2014;31:811–21. https://doi.org/10.1055/s-0033-1361933.

    Article  PubMed  Google Scholar 

  193. Olkkola KT, Hamunen K, Maunuksela EL. Clinical pharmacokinetics and pharmacodynamics of opioid analgesics in infants and children. Clin Pharmacokinet. 1995;28:385–404. https://doi.org/10.2165/00003088-199528050-00004.

    Article  CAS  PubMed  Google Scholar 

  194. Lam J, Baello S, Iqbal M, et al. The ontogeny of P-glycoprotein in the developing human blood-brain barrier: implication for opioid toxicity in neonates. Pediatr Res. 2015;78:417–21. https://doi.org/10.1038/pr.2015.119.

    Article  CAS  PubMed  Google Scholar 

  195. Taylor J, Liley A, Anderson BJ. The relationship between age an morphine infusion rate in children. Paediatr Anaesth. 2013;23:40–4. https://doi.org/10.1111/j.1460-9592.2012.03917.x.

    Article  PubMed  Google Scholar 

  196. Knibbe CA, Krekels EH, van den Anker JN, et al. Morphine glucuronidation in preterm neonates, infants and children younger than 3 years. Clin Pharmacokinet. 2009;48:371–85. https://doi.org/10.2165/00003088-200948060-00003.

    Article  CAS  PubMed  Google Scholar 

  197. Krekels EH, DeJongh J, van Lingen RA, et al. Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children. Clin Pharmacokinet. 2011;50:51–63. https://doi.org/10.2165/11536750-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  198. Roka A, Melinda KT, Vasarhelyi B, et al. Elevated morphine concentrations in neonates treated with morphine and prolonged hypothermia for hypoxic ischemic encephalopathy. Pediatrics. 2008;121:e844–9. https://doi.org/10.1542/peds.2007-1987.

    Article  PubMed  Google Scholar 

  199. Lynn A, Nespeca MK, Bratton SL, et al. Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery. Anesth Analg. 1998;86:958–63. https://doi.org/10.1097/00000539-199805000-00008.

    Article  CAS  PubMed  Google Scholar 

  200. Völler S, Flint RB, Andriessen P, et al. Rapidly maturing fentanyl clearance in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 2019;104:F598–603. https://doi.org/10.1136/archdischild-2018-315920.

    Article  PubMed  Google Scholar 

  201. Walter-Nicolet E, Annequin D, Biran V, et al. Pain management in newborns: from prevention to treatment. Paediatr Drugs. 2010;12:353–65. https://doi.org/10.2165/11318900-000000000-00000.

    Article  PubMed  Google Scholar 

  202. Rana D, Bellflower B, Sahni J, et al. Reduced narcotic and sedative utilization in a NICU after implementation of pain management guidelines. J Perinatol. 2017;37:1038–42. https://doi.org/10.1038/jp.2017.88.

    Article  CAS  PubMed  Google Scholar 

  203. Van Dijk M, Bouwmeester NJ, Duivenvoorden HJ, 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;98:305–13. https://doi.org/10.1016/s0304-3959(02)00031-3.

    Article  PubMed  Google Scholar 

  204. 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: a randomized controlled trial. JAMA. 2013;309:149–54. https://doi.org/10.1001/jama.2012.148050.

    Article  CAS  PubMed  Google Scholar 

  205. Ancora G, Lago P, Garetti E, et al. Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation. J Pediatr. 2013;163:645–51.e1. https://doi.org/10.1016/j.jpeds.2013.02.039.

    Article  CAS  PubMed  Google Scholar 

  206. Cignacco E, Hamers JP, van Lingen RA, et al. Pain relief in ventilated preterms during endotracheal suctioning: a randomized controlled trial. Swiss Med Wkly. 2008;138:635–45. https://doi.org/2008/43/smw-12288

    PubMed  Google Scholar 

  207. Bellu R, de Waal K, Zanini R. Opioids for neonates receiving mechanical ventilation: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2010;95:F241–51. https://doi.org/10.1136/adc.2008.150318.

    Article  CAS  PubMed  Google Scholar 

  208. Bhandari V, Bergqvist LL, Kronsberg SS, et al. Morphine administration and short-term pulmonary outcomes among ventilated preterm infants. Pediatrics. 2005;116:352–9. https://doi.org/10.1542/peds.2004-2123.

    Article  PubMed  Google Scholar 

  209. Hartley C, Moultrie F, Hoskin A, et al. Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial. Lancet. 2018;392:2595–605. https://doi.org/10.1016/S0140-6736(18)31813-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. 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. https://doi.org/10.1016/j.pain.2011.02.017.

    Article  CAS  PubMed  Google Scholar 

  211. 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. https://doi.org/10.1016/j.pain.2012.12.006.

    Article  CAS  PubMed  Google Scholar 

  212. Hall RW. Anesthesia and analgesia in the NICU. Clin Perinatol. 2012;39:239–54. https://doi.org/10.1016/j.clp.2011.12.013.

    Article  PubMed  PubMed Central  Google Scholar 

  213. Anderson BJ, Larsson P. A maturation model for midazolam clearance. Paediatr Anaesth. 2011;21:302–8. https://doi.org/10.1111/j.1460-9592.2010.03364.x.

    Article  PubMed  Google Scholar 

  214. Völler S, Flint RB, Beggah F, et al. Recently registered midazolam doses for preterm neonates do not lead to equal exposure: a population pharmacokinetic model. J Clin Pharmacol. 2019;59:1300–8. https://doi.org/10.1002/jcph.1429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Ince I, de Wildt SN, Wang C, et al. A novel maturation function for clearance of the cytochrome P450 3A substrate midazolam from preterm neonates to adults. Clin Pharmacokinet. 2013;52:555–65. https://doi.org/10.1007/s40262-013-0050-0.

    Article  CAS  PubMed  Google Scholar 

  216. Vet NJ, Brussee JM, de Hoog M, et al. Inflammation and organ failure severely affect midazolam clearance in critically ill children. Am J Respir Crit Care Med. 2016;194:58–66. https://doi.org/10.1164/rccm.201510-2114OC.

    Article  CAS  PubMed  Google Scholar 

  217. 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 Pediatr Adolesc Med. 1999;153:331–8. https://doi.org/10.1001/archpedi.153.4.331.

    Article  CAS  PubMed  Google Scholar 

  218. Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Syst Rev. 2017;1:CD002052. https://doi.org/10.1002/14651858.CD002052.pub3.

    Article  PubMed  Google Scholar 

  219. Welzing L, Oberthuer A, Junghaenel S, et al. Remifentanil/midazolam versus fentanyl/midazolam for analgesia and sedation of mechanically ventilated neonates and young infants: a randomized controlled trial. Intensive Care Med. 2012;38:1017–24. https://doi.org/10.1007/s00134-012-2532-1.

    Article  CAS  PubMed  Google Scholar 

  220. Burtin P, Daoud P, Jacqz-Aigrain E, et al. Hypotension with midazolam and fentanyl in the newborn. Lancet. 1991;337:1545–6. https://doi.org/10.1016/s0140-6736(94)92085-0.

    Article  CAS  PubMed  Google Scholar 

  221. Attardi DM, Paul DA, Tuttle DJ, et al. Premedication for intubation in neonates. Arch Dis Child Fetal Neonatal Ed. 2000;83:F61. https://doi.org/10.1136/fn.83.2.f160c.

    Article  Google Scholar 

  222. McPherson C. Premedication for endotracheal intubation in the neonate. Neonatal Netw. 2018;37:238–47. https://doi.org/10.1891/0730-0832.37.4.238.

    Article  PubMed  Google Scholar 

  223. Wildschut ED, Hanekamp MN, Vet NJ, et al. Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation. Intensive Care Med. 2010;36:1587–91. https://doi.org/10.1007/s00134-010-1931-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. van Hoorn CE, Hoeks SE, Essink H, et al. A systematic review and narrative synthesis on the histological and neurobehavioral long-term effects of dexmedetomidine. Paediatr Anaesth. 2019;29:125–36. https://doi.org/10.1111/pan.13553.

    Article  PubMed  PubMed Central  Google Scholar 

  225. Chrysostomou C, Schulman SR, Herrera Castellanos M, et al. A Phase II/III multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates. J Pediatr. 2014;164:276–82. https://doi.org/10.1016/j.jpeds.2013.10.002.

    Article  CAS  PubMed  Google Scholar 

  226. Dilek O, Yasemin G, Atci M. Preliminary experience with dexmedetomidine in neonatal anesthesia. J Anaesthesiol Clin Pharmacol. 2011;27:17–22.

    PubMed  PubMed Central  Google Scholar 

  227. Franciscovich CD, Monk HM, Brodecki D, et al. Sedation practices of neonates receiving extracorporeal membrane oxygenation. ASAIO J. 2019. https://doi.org/10.1097/MAT.0000000000001043.

  228. Bua J, Massaro M, Cossovel F, et al. Intranasal dexmedetomidine, a midazolam-sparing drug, for MRI in preterm neonates. Paediatr Anaesth. 2018;28:747–8. https://doi.org/10.1111/pan.13454.

    Article  PubMed  Google Scholar 

  229. van Dijkman SC, De Cock PAJG, Smets K, et al. Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimization. Eur J Clin Pharmacol. 2019;75:1393–404. https://doi.org/10.1007/s00228-019-02708-y.

    Article  CAS  PubMed  Google Scholar 

  230. Shukry M, Kennedy K. Dexmedetomidine as a total intravenous anesthetic in infants. Paediatr Anaesth. 2007;17:581–3. https://doi.org/10.1111/j.1460-9592.2006.02171.x.

    Article  PubMed  Google Scholar 

  231. Shiota M, Oda Y, Taniguchi M, et al. Dexmedetomidine infusion for sedation in the intensive care setting in an infant with airway compromise due to congenital mediastinal neuroblastoma. Paediatr Anaesth. 2012;22:603–5. https://doi.org/10.1111/j.1460-9592.2012.03865.x.

    Article  PubMed  Google Scholar 

  232. Sellas MN, Kyllonen KC, Lepak MR, et al. Dexmedetomidine for the management of postoperative pain and sedation in newborns. J Pediatr Pharmacol Ther. 2019;24:227–33. https://doi.org/10.5863/1551-6776-24.3.227.

    Article  PubMed  PubMed Central  Google Scholar 

  233. Bong CL, Tan J, Lim S, et al. Randomised controlled trial of dexmedetomidine sedation vs general anaesthesia for inguinal hernia surgery on perioperative outcomes in infants. Br J Anaesth. 2019;122:662–70. https://doi.org/10.1016/j.bja.2018.12.027.

    Article  CAS  PubMed  Google Scholar 

  234. Kubota T, Fukasawa T, Kitamura E, et al. Epileptic seizures induced by dexmedetomidine in a neonate. Brain Dev. 2013;35:360–2. https://doi.org/10.1016/j.braindev.2012.05.011.

    Article  PubMed  Google Scholar 

  235. Reinoso-Barbero F, Pascual-Pascual SI, de Lucas R, et al. Equimolar nitrous oxide/oxygen versus placebo for procedural pain in children: a randomized trial. Pediatrics. 2011;127:e1464–70. https://doi.org/10.1542/peds.2010-1142.

    Article  PubMed  Google Scholar 

  236. Mandel R, Ali N, Chen J, et al. Nitrous oxide analgesia during retinopathy screening: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2012;97:F83–7. https://doi.org/10.1136/adc.2011.210740.

    Article  PubMed  Google Scholar 

  237. Carbajal R, Biran V, Lenclen R, et al. EMLA cream and nitrous oxide to alleviate pain induced by palivizumab (Synagis) intramuscular injections in infants and young children. Pediatrics. 2008;121:e1591–8. https://doi.org/10.1542/peds.2007-3104.

    Article  PubMed  Google Scholar 

  238. Allegaert K, Devlieger H, Bulckaert D, et al. Variability in pain expression characteristics in former preterm infants. J Perinat Med. 2005;33:442–8. https://doi.org/10.1515/JPM.2005.078.

    Article  PubMed  Google Scholar 

  239. Vialet R, Michel F, Hassid S, et al. Sevoflurane for central venous catheterization in non-intubated neonates. Indian J Pediatr. 2009;76:273–7. https://doi.org/10.1007/s12098-009-0012-6.

    Article  PubMed  Google Scholar 

  240. Michel F, Vialet R, Hassid S, et al. Sevoflurane for central catheter placement in neonatal intensive care: a randomized trial. Paediatr Anaesth. 2010;20:712–9. https://doi.org/10.1111/j.1460-9592.2010.03334.x.

    Article  PubMed  Google Scholar 

  241. Hassid S, Nicaise C, Michel F, et al. Randomized controlled trial of sevoflurane for intubation in neonates. Paediatr Anaesth. 2007;17:1053–8. https://doi.org/10.1111/j.1460-9592.2007.02214.x.

    Article  PubMed  Google Scholar 

  242. Lerman J, Robinson S, Willis MM, et al. Anesthetic requirements for halothane in young children 0–1 month and 1–6 months of age. Anesthesiology. 1983;59:421–4. https://doi.org/10.1097/00000542-198311000-00010.

    Article  CAS  PubMed  Google Scholar 

  243. Cuzzolin L, Antonucci R, Fanos V. Paracetamol (acetaminophen) efficacy and safety in the newborn. Curr Drug Metab. 2013;14:178–85.

    CAS  PubMed  Google Scholar 

  244. Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2009;18:915–21. https://doi.org/10.1111/j.1460-9592.2008.02764.x.

    Article  Google Scholar 

  245. Langhendries JP, Allegaert K, Van Den Anker JN, et al. Possible effects of repeated exposure to ibuprofen and acetaminophen on the intestinal immune response in young infants. Med Hypotheses. 2016;87:90–6. https://doi.org/10.1016/j.mehy.2015.11.012.

    Article  CAS  PubMed  Google Scholar 

  246. van den Anker JN, Allegaert K. Acetaminophen in the neonatal intensive care unit: shotgun approach or silver bullet. J Pediatr. 2018;198:10–1. https://doi.org/10.1016/j.jpeds.2018.02.046.

    Article  PubMed  Google Scholar 

  247. Gibb IA, Anderson BJ. Paracetamol (acetaminophen) pharmacodynamics: interpreting the plasma concentration. Arch Dis Child. 2008;93:241–7. https://doi.org/10.1136/adc.2007.126896.

    Article  CAS  PubMed  Google Scholar 

  248. Cook SF, Roberts JK, Samiee-Zafarghandy S, et al. Population pharmacokinetics of intravenous paracetamol (acetaminophen) in preterm and term neonates: model development and external evaluation. Clin Pharmacokinet. 2016;55:107–19. https://doi.org/10.1007/s40262-015-0301-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Krekels EH, van Ham S, Allegaert K, et al. Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants. Eur J Clin Pharmacol. 2015;71:1075–82. https://doi.org/10.1007/s00228-015-1887-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Cook SF, Stockmann C, Samiee-Zafarghandy S, et al. Neonatal maturation of paracetamol (acetaminophen) glucuronidation, sulfation, and oxidation based on a parent-metabolite population pharmacokinetic model. Clin Pharmacokinet. 2016;55:1395–411. https://doi.org/10.1007/s40262-016-0408-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Anderson BJ, Van Lingen RA, Hansen TG, et al. Acetaminophen developmental pharmacokinetics in premature neonates and infants: a pooled population analysis. Anesthesiology. 2002;96:1336–45. https://doi.org/10.1097/00000542-200206000-00012.

    Article  CAS  PubMed  Google Scholar 

  252. Allegaert K, Palmer GM, Anderson BJ. The pharmacokinetics of intravenous paracetamol in neonates: size matters most. Arch Dis Child. 2011;96:575–60. https://doi.org/10.1136/adc.2010.204552.

    Article  PubMed  Google Scholar 

  253. Härmä A, Aikio O, Hallman M, et al. Intravenous paracetamol decreases requirements of morphine in very preterm infants. J Pediatr. 2016;168:36–40. https://doi.org/10.1016/j.jpeds.2015.08.003.

    Article  CAS  PubMed  Google Scholar 

  254. Shah V, Taddio A, Ohlsson A. Randomised controlled trial of paracetamol for heel prick pain in neonates. Arch Dis Child Fetal Neonatal Ed. 1998;79:F209–11. https://doi.org/10.1136/fn.79.3.f209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Roofthooft DWE, Simons SHP, van Lingen RA, et al. Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants. Neonatology. 2017;112:150–8. https://doi.org/10.1159/000468975.

    Article  CAS  PubMed  Google Scholar 

  256. Hedén L, von Essen L, Ljungman G. Effect of high-dose paracetamol on needle procedures in children with cancer--an RCT. Acta Paediatr. 2014;103:314–9. https://doi.org/10.1111/apa.12509.

    Article  CAS  PubMed  Google Scholar 

  257. Howard CR, Howard FM, Weitzman ML. Acetaminophen analgesia in neonatal circumcision: the effect on pain. Pediatrics. 1994;93:641–6.

    CAS  PubMed  Google Scholar 

  258. Van Lingen RA, Quak CM, Deinum HT, et al. Effects of rectally administered paracetamol on infants delivered by vacuum extraction. Eur J Obstet Gynecol Reprod Biol. 2001;94:73–8. https://doi.org/10.1016/s0301-2115(00)00336-5.

    Article  PubMed  Google Scholar 

  259. Tinner EM, Hoesli I, Jost K, et al. Rectal paracetamol in newborn infants after assisted vaginal delivery may increase pain response. J Pediatr. 2013;162:62–6. https://doi.org/10.1016/j.jpeds.2012.06.020.

    Article  CAS  PubMed  Google Scholar 

  260. Allegaert K, Naulaers G, Vanhaesebrouck S, et al. The paracetamol concentration-effect relation in neonates. Paediatr Anaesth. 2013;23:45–50. https://doi.org/10.1111/pan.12076.

    Article  PubMed  Google Scholar 

  261. Allegaert K, Anderson B, Simons S, et al. Paracetamol to induce ductus arteriosus closure: is it valid ? Arch Dis Child. 2013;98:462–6. https://doi.org/10.1136/archdischild-2013-303688.

    Article  PubMed  Google Scholar 

  262. Wickens K, Beasley R, Town I, et al. The effects of early and late paracetamol exposure on asthma and atopy: a birth cohort. Clin Exp Allergy. 2011;41:399–406. https://doi.org/10.1111/j.1365-2222.2010.03610.x.

    Article  CAS  PubMed  Google Scholar 

  263. Montirosso R, Del Prete A, Bellu R, et al. Level of NICU quality of developmental care and neurobehavioral performance in very preterm infants. Pediatrics. 2012;129:e1129–37. https://doi.org/10.1542/peds.2011-0813.

    Article  PubMed  PubMed Central  Google Scholar 

  264. Ozawa M, Yokoo K, Funaba Y, et al. A quality improvement collaborative program for neonatal pain management in Japan. Adv Neonatal Care. 2017;17:184–91. https://doi.org/10.1097/ANC.0000000000000382.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Development and Regeneration, and Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium

    Karel Allegaert

  2. Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

    Karel Allegaert

  3. Department of Development and Regeneration, KU Leuven, Neonatal Intensive Care Unit, Leuven, Belgium

    Karel Allegaert

  4. Department of Pediatrics, Pharmacology and Physiology, Children’s National Medical Center, Washington, DC, USA

    John van den Anker

  5. Intensive Care, Erasmus Medical Center-Sophia Children’s Hospital, Rotterdam, The Netherlands

    John van den Anker

  6. Department of Pediatric Pharmacology, University Children’s Hospital Basel, Basel, Switzerland

    John van den Anker

Authors
  1. Karel Allegaert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John van den Anker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karel Allegaert .

Editor information

Editors and Affiliations

  1. Department of Anesthesiology, Harvard Medical School, Boston, MA, USA

    Keira P. Mason, MD

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Allegaert, K., van den Anker, J. (2021). Sedation in the Neonatal Intensive Care Unit: International Practice. In: Mason, MD, K.P. (eds) Pediatric Sedation Outside of the Operating Room. Springer, Cham. https://doi.org/10.1007/978-3-030-58406-1_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-58406-1_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-58405-4

  • Online ISBN: 978-3-030-58406-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation