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Pediatric Drugs

, Volume 21, Issue 6, pp 439–449 | Cite as

A Review of Regional Anesthesia in Infants

  • Karen R. BoretskyEmail author
Review Article
  • 54 Downloads

Abstract

Regional anesthesia provides effective anesthesia and pain relief in infants with age-specific data attesting to safety and efficacy. Regional anesthesia decreases exposure to opioids and general anesthetic agents and associated adverse drug effects, suppresses the stress response, and provides better hemodynamic stability compared to general anesthesia. Regional anesthesia can prevent long-term behavioral responses to pain. As a result, the overall number and variety of nerve blocks being used in infants is increasing. While neuraxial blocks are the most common blocks performed in infants, the introduction of ultrasound imaging and a better safety profile has advanced the use of peripheral nerve blocks. Infant-specific pharmacokinetic and pharmacodynamic data of local anesthetic medications are reviewed including risk factors for the accumulation of high serum levels of unbound, pharmacologically active drug. Bupivacaine accumulates with continuous infusion and 2-chloroprocaine can be used as an alternative. Local anesthetic systemic toxicity has the highest incidence in infants less than 6 months of age and is associated with bolus dosing and penile nerve blocks. Local anesthetic toxicity is treated by securing the airway, suppression of seizure activity and implementation of cardiopulmonary resuscitation. Administration of intralipid (intravenous lipid emulsion) is initiated at the first sign of toxicity. A high level of expertise in regional anesthesia is needed when treating infants due to their unique development.

Notes

Author Contributions

KB wrote and revised the manuscript and approved of the final version.

Compliance with Ethical Standards

Funding

Support was provided solely from Department sources.

Conflict of interest

KB declares no conflicts of interest.

References

  1. 1.
    Bösenberg AT, Jöhr M, Wolf AR. Pro con debate: the use of regional vs systemic analgesia for neonatal surgery. Paediatr Anaesth. 2011;21(12):1247–58.  https://doi.org/10.1111/j.1460-9592.2011.03638.x.CrossRefPubMedGoogle Scholar
  2. 2.
    Berde CB, Jaksic T, Lynn AM, Maxwell LG, Soriano SG, Tibboel D. Anesthesia and analgesia during and after surgery in neonates. Clin Ther. 2005;27(6):900–21.  https://doi.org/10.1016/j.clinthera.2005.06.020.CrossRefPubMedGoogle Scholar
  3. 3.
    Bösenberg AT, Bland BA, Schulte-Steinberg O, Downing JW. Thoracic epidural anesthesia via caudal route in infants. Anesthesiology. 1988;69(2):265–9.CrossRefGoogle Scholar
  4. 4.
    Murrell D, Gibson PR, Cohen RC. Continuous epidural analgesia in newborn infants undergoing major surgery. J Pediatr Surg. 1993;4:548–52.  https://doi.org/10.1016/0022-3468(93)90614-q.CrossRefGoogle Scholar
  5. 5.
    Jöhr M, Berger TM. Regional anaesthetic techniques for neonatal surgery: indications and selection of techniques. Best Pract Res Clin Anaesthesiol. 2004;2:357–75.  https://doi.org/10.1016/j.bpa.2003.11.004.CrossRefGoogle Scholar
  6. 6.
    Abouleish AE, Chung DH, Cohen M. Caudal anesthesia for vascular access procedures in two extremely small premature neonates. Pediatr Surg Int. 2005;21(9):749–51.  https://doi.org/10.1007/s00383-005-1474-x.CrossRefPubMedGoogle Scholar
  7. 7.
    Frenkel O, Mansour K, Fischer JWJ. Ultrasound-guided femoral nerve block for pain control in an infant with a femur fracture due to nonaccidental trauma. Pediatr Emerg Care. 2012;28(2):183–4.  https://doi.org/10.1097/pec.0b013e3182447ea3.CrossRefPubMedGoogle Scholar
  8. 8.
    Bairdain S, Dodson B, Zurakowski D, Waisel DB, Jennings RW, Boretsky KR. Paravertebral nerve block catheters using chloroprocaine in infants with prolonged mechanical ventilation for treatment of long-gap esophageal atresia. Pediatr Anesth. 2015;25(11):1151–7.  https://doi.org/10.1111/pan.12736.CrossRefGoogle Scholar
  9. 9.
    Lönnqvist PA. Regional anaesthesia and analgesia in the neonate. Best Pract Res Clin Anaesthesiol. 2010;3:309–21.  https://doi.org/10.1016/j.bpa.2010.02.012.CrossRefGoogle Scholar
  10. 10.
    Bösenberg AT. Epidural analgesia for major neonatal surgery. Paediatr Anaesth. 1998;8(6):479–83.CrossRefGoogle Scholar
  11. 11.
    Kandiah N, Walker K, Boretsky K. Ultrasound-guided paravertebral block facilitated tracheal extubation in a 5-week-old infant with rib fractures and respiratory failure. A A Case Rep. 2014;2(10):131–2.  https://doi.org/10.1213/xaa.0000000000000023.CrossRefPubMedGoogle Scholar
  12. 12.
    Williams RK, Adams DC, Aladjem EV, et al. The safety and efficacy of spinal anesthesia for surgery in infants: the Vermont infant spinal registry. Anesth Analg. 2006;102(1):67–71.  https://doi.org/10.1213/01.ane.0000159162.86033.21.CrossRefPubMedGoogle Scholar
  13. 13.
    Fredrickson MJ, Seal P. Ultrasound-guided transversus abdominis plane block for neonatal abdominal surgery. Anaesth Intensive Care. 2009;37(3):469–72.  https://doi.org/10.1016/j.envint.2006.11.017.CrossRefPubMedGoogle Scholar
  14. 14.
    Breschan C, Kraschl R, Jost R, Marhofer P, Likar R. Axillary brachial plexus block for treatment of severe forearm ischemia after arterial cannulation in an extremely low birth-weight infant. Paediatr Anaesth. 2004;14(8):681–4.  https://doi.org/10.1111/j.1460-9592.2004.01282.x.CrossRefPubMedGoogle Scholar
  15. 15.
    Anand KJ, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet. 1987;1(8524):62–6.CrossRefGoogle Scholar
  16. 16.
    Anand KJ, Hansen DD, Hickey PR. Hormonal-metabolic stress responses in neonates undergoing cardiac surgery. Anesthesiology. 1990;73(4):661–70.CrossRefGoogle Scholar
  17. 17.
    Wolf AR, Doyle E, Thomas E. Modifying infant stress responses to major surgery: spinal vs extradural vs opioid analgesia. Paediatr Anaesth. 1998;8(4):305.  https://doi.org/10.1046/j.1460-9592.1998.00239.x.CrossRefPubMedGoogle Scholar
  18. 18.
    Wolf AR. Effects of regional analgesia on stress responses to pediatric surgery. Paediatr Anaesth. 2012;22(1):19–24.  https://doi.org/10.1111/j.1460-9592.2011.03714.x.CrossRefPubMedGoogle Scholar
  19. 19.
    Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997;349(9052):599–603.  https://doi.org/10.1016/s0140-6736(96)10316-0.CrossRefPubMedGoogle Scholar
  20. 20.
    Peters JWB, Koot HM, de Boer JB, et al. Major surgery within the first 3 months of life and subsequent biobehavioral pain responses to immunization at later age: a case comparison study. Pediatrics. 2003;111(1):129–35.CrossRefGoogle Scholar
  21. 21.
    Peters JWB, Schouw R, Anand KJS, Van Dijk M, Duivenvoorden HJ, Tibboel D. Does neonatal surgery lead to increased pain sensitivity in later childhood? Pain. 2005;114(3):444–54.  https://doi.org/10.1016/j.pain.2005.01.014.CrossRefPubMedGoogle Scholar
  22. 22.
    Walker SM, Fitzgerald M, Hathway GJ. Surgical injury in the neonatal rat alters the adult pattern of descending modulation from the rostroventral medulla. Anesthesiology. 2015;122(6):1391–400.  https://doi.org/10.1097/aln.0000000000000658.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Walker SM, Tochiki KK, Fitzgerald M. Hindpaw incision in early life increases the hyperalgesic response to repeat surgical injury: critical period and dependence on initial afferent activity. Pain. 2009;147(1–3):99–106.  https://doi.org/10.1016/j.pain.2009.08.017.CrossRefPubMedGoogle Scholar
  24. 24.
    Morton NS, Errera A. APA national audit of pediatric opioid infusions. Paediatr Anaesth. 2010;20(2):119–25.  https://doi.org/10.1111/j.1460-9592.2009.03187.x.CrossRefPubMedGoogle Scholar
  25. 25.
    Chidambaran V, Olbrecht V, Hossain M, Sadhasivam S, Rose J, Meyer MJ. Risk predictors of opioid-induced critical respiratory events in children: naloxone use as a quality measure of opioid safety. Pain Med. 2014;15(12):2139–49.  https://doi.org/10.1111/pme.12575.CrossRefPubMedGoogle Scholar
  26. 26.
    Martin LD, Jimenez N, Lynn AM. A review of perioperative anesthesia and analgesia for infants: updates and trends to watch. F1000Research. 2017;6:120.  https://doi.org/10.12688/f1000research.10272.1.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Bouwmeester NJ, Anderson BJ, Tibboel D, Holford NHG. Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. Br J Anaesth. 2004;92(2):208–17.CrossRefGoogle Scholar
  28. 28.
    McRorie TI, Lynn AM, Nespeca MK, Opheim KE, Slattery JT. The maturation of morphine clearance and metabolism. Am J Dis Child. 1992;146(8):972–6.PubMedGoogle Scholar
  29. 29.
    Lynn A, Nespeca MK, Bratton SL, Strauss SG, Shen DD. Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery. Anesth Analg. 1998;86(5):958–63.CrossRefGoogle Scholar
  30. 30.
    Bardo MT, Hughes RA. Single-dose tolerance to morphine-induced analgesic and hypoactive effects in infant rats. Dev Psychobiol. 1981;14(5):415–23.  https://doi.org/10.1002/dev.420140504.CrossRefPubMedGoogle Scholar
  31. 31.
    Arnold JH, Truog RD, Orav EJ, Scavone JM, Hershenson MB. Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology. 1990;73(6):1136–40.CrossRefGoogle Scholar
  32. 32.
    Krekels EHJ, Tibboel D, de Wildt SN, et al. Evidence-based morphine dosing for postoperative neonates and infants. Clin Pharmacokinet. 2014;53(6):553–63.  https://doi.org/10.1007/s40262-014-0135-4.CrossRefPubMedGoogle Scholar
  33. 33.
    Hoehn T, Jetzek-Zader M, Blohm M, Mayatepek E. Early peristalsis following epidural analgesia during abdominal surgery in an extremely low birth weight infant. Paediatr Anaesth. 2007;17(2):176–9.  https://doi.org/10.1111/j.1460-9592.2006.02038.x.CrossRefPubMedGoogle Scholar
  34. 34.
    Hohn A, Trieschmann U, Franklin J, et al. Incidence of peri-operative paediatric cardiac arrest: influence of a specialised paediatric anaesthesia team. Eur J Anaesthesiol. 2018;36(1):55–63.  https://doi.org/10.1097/eja.0000000000000863.CrossRefGoogle Scholar
  35. 35.
    Tiret L, Nivoche Y, Hatton F, Desmonts JM, Vourc’h G. Complications related to anaesthesia in infants and children. A prospective survey of 40,240 anaesthetics. Br J Anaesth. 1988;61(3):263–9.CrossRefGoogle Scholar
  36. 36.
    Westerkamp AC, De Geus AF, Molenbuur B, et al. Comparing peri-operative complications of paediatric and adult anaesthesia. Eur J Anaesthesiol. 2018;35(4):280–8.  https://doi.org/10.1097/eja.0000000000000769.CrossRefPubMedGoogle Scholar
  37. 37.
    Gregory GA, Steward DJ. Life-threatening perioperative apnea in the ex-”premie”. Anesthesiology. 1983;59(6):495–8.CrossRefGoogle Scholar
  38. 38.
    Habre W, Disma N, Virag K, et al. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe. Lancet Respir Med. 2017;5(5):412–25.  https://doi.org/10.1016/s2213-2600(17)30116-9.CrossRefPubMedGoogle Scholar
  39. 39.
    Mamie C, Habre W, Delhumeau C, Argiroffo CB, Morabia A. Incidence and risk factors of perioperative respiratory adverse events in children undergoing elective surgery. Paediatr Anaesth. 2004;14(3):218–24.  https://doi.org/10.1111/j.1460-9592.2004.01169.x.CrossRefPubMedGoogle Scholar
  40. 40.
    Drake-Brockman TFE, Ramgolam A, Zhang G, Hall GL, von Ungern-Sternberg BS. The effect of endotracheal tubes versus laryngeal mask airways on perioperative respiratory adverse events in infants: a randomised controlled trial. Lancet. 2017;389(10070):701–8.  https://doi.org/10.1016/s0140-6736(16)31719-6.CrossRefPubMedGoogle Scholar
  41. 41.
    Subramanyam R, Yeramaneni S, Hossain MM, Anneken AM, Varughese AM. Perioperative respiratory adverse events in pediatric ambulatory anesthesia: development and validation of a risk prediction tool. Anesth Analg. 2016;122(5):1578–85.  https://doi.org/10.1213/ane.0000000000001216.CrossRefPubMedGoogle Scholar
  42. 42.
    Davidson AJ, Disma N, De Graaff JC, et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016;387(10015):239–50.  https://doi.org/10.1016/s0140-6736(15)00608-x.CrossRefPubMedGoogle Scholar
  43. 43.
    Ecoffey C, Lacroix F, Giaufré E, Orliaguet G, Courrèges P. Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF). Paediatr Anaesth. 2010;20(12):1061–9.  https://doi.org/10.1111/j.1460-9592.2010.03448.x.CrossRefPubMedGoogle Scholar
  44. 44.
    Walker BJ, Long JB, Sathyamoorthy M, et al. Complications in pediatric regional anesthesia: an analysis of more than 100,000 blocks from the pediatric regional anesthesia network. Anesthesiology. 2018;129(4):721–32.  https://doi.org/10.1097/aln.0000000000002372.CrossRefPubMedGoogle Scholar
  45. 45.
    Bosenberg AT. Innovative peripheral nerve blocks facilitated by ultrasound guidance. Paediatr Anaesth. 2018;28(8):684–5.  https://doi.org/10.1111/pan.13424.CrossRefPubMedGoogle Scholar
  46. 46.
    Visoiu M, Boretsky KR, Goyal G, Cladis FP, Cassara A. Postoperative analgesia via transversus abdominis plane (TAP) catheter for small weight children-our initial experience. Paediatr Anaesth. 2012;22(3):281–4.  https://doi.org/10.1111/j.1460-9592.2011.03783.x.CrossRefPubMedGoogle Scholar
  47. 47.
    Öksüz G, Bilal B, Gürkan Y, et al. Quadratus lumborum block versus transversus abdominis plane block in children undergoing low abdominal surgery: a randomized controlled trial. Reg Anesth Pain Med. 2017;42(5):674–9.  https://doi.org/10.1097/aap.0000000000000645.CrossRefPubMedGoogle Scholar
  48. 48.
    Boretsky K, Visoiu M, Bigeleisen P. Ultrasound-guided approach to the paravertebral space for catheter insertion in infants and children. Paediatr Anaesth. 2013;23(12):1193–8.  https://doi.org/10.1111/pan.12238.CrossRefPubMedGoogle Scholar
  49. 49.
    Munshey F, Rodriguez S, Diaz E, Tsui B. Continuous erector spinae plane block for an open pyeloplasty in an infant. J Clin Anesth. 2018;47:47–9.  https://doi.org/10.1016/j.jclinane.2018.03.015.CrossRefPubMedGoogle Scholar
  50. 50.
    Tognù A, Cauli V, De Simone N, Aurini L, Manfrini M, Bonarelli S. In-plane ultrasound- guided lumbar plexus block using catheter-over-needle technique in a 14-month-old baby. Reg Anesth Pain Med. 2016;41(4):538–41.  https://doi.org/10.1097/aap.0000000000000417.CrossRefPubMedGoogle Scholar
  51. 51.
    Willschke H, Marhofer P, B̈senberg A, et al. Epidural catheter placement in children: comparing a novel approach using ultrasound guidance and a standard loss-of-resistance technique. Br J Anaesth. 2006;97(2):200–7.  https://doi.org/10.1093/bja/ael121.CrossRefPubMedGoogle Scholar
  52. 52.
    Mueller CM, Sinclair TJ, Stevens M, Esquivel M, Gordon N. Regional block via continuous caudal infusion as sole anesthetic for inguinal hernia repair in conscious neonates. Pediatr Surg Int. 2017;33(3):341–5.  https://doi.org/10.1007/s00383-016-4027-6.CrossRefPubMedGoogle Scholar
  53. 53.
    Jones LJ, Craven PD, Lakkundi A, Foster JP, Badawi N. Regional (spinal, epidural, caudal) versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy. Cochrane Database Syst Rev. 2015;9(6):CD003669.  https://doi.org/10.1002/14651858.cd003669.pub2.CrossRefGoogle Scholar
  54. 54.
    Ebert KM, Jayanthi VR, Alpert SA, et al. Benefits of spinal anesthesia for urologic surgery in the youngest of patients. J Pediatr Urol. 2019;15(1):49.e1–5.  https://doi.org/10.1016/j.jpurol.2018.08.011.CrossRefGoogle Scholar
  55. 55.
    Neal JT, Kaplan SL, Woodford AL, Desai K, Zorc JJ, Chen AE. The effect of bedside ultrasonographic skin marking on infant lumbar puncture success: a randomized controlled trial. Ann Emerg Med. 2017;69(5):610–9.  https://doi.org/10.1016/j.annemergmed.2016.09.014.CrossRefPubMedGoogle Scholar
  56. 56.
    Kelleher S, Boretsky K, Alrayashi W. Images in anesthesiology: use of ultrasound to facilitate neonatal spinal anesthesia. Anesthesiology. 2017.  https://doi.org/10.1097/aln.0000000000001468.CrossRefPubMedGoogle Scholar
  57. 57.
    Cristiani F, Henderson R, Lauber C, Boretsly K. Success of bedside ultrasound to identify puncture site for spinal anesthesia in neonates and infants. Reg Anesth Pain Med. 2019;78:89.  https://doi.org/10.1136/rapm-2019-100672. (Epub ahead of print).CrossRefGoogle Scholar
  58. 58.
    McCann ME, Withington DE, Arnup SJ, et al. Differences in blood pressure in infants after general anesthesia compared to awake regional anesthesia (GAS study—a prospective randomized trial). Anesth Analg. 2017;125(3):837–45.  https://doi.org/10.1213/ane.0000000000001870.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Oberlander TF, Berde CB, Lam KH, Rappaport LA, Saul JP. Infants tolerate spinal anesthesia with minimal overall autonomic changes: analysis of heart rate variability in former premature infants undergoing hernia repair. Anesth Analg. 1995;80(1):20–7.PubMedGoogle Scholar
  60. 60.
    Kachko L, Birk E, Simhi E, Tzeitlin E, Freud E, Katz J. Spinal anesthesia for noncardiac surgery in infants with congenital heart diseases. Paediatr Anaesth. 2012;22(7):647–53.CrossRefGoogle Scholar
  61. 61.
    Shenkman Z, Johnson VM, Zurakowski D, Arnon S, Sethna NF. Hemodynamic changes during spinal anesthesia in premature infants with congenital heart disease undergoing inguinal hernia correction. Paediatr Anaesth. 2012;22(9):865–70.  https://doi.org/10.1111/j.1460-9592.2012.03873.x.CrossRefPubMedGoogle Scholar
  62. 62.
    Razlevice I, Rugyte DC, Strumylaite L, Macas A. Assessment of risk factors for cerebral oxygen desaturation during neonatal and infant general anesthesia: an observational, prospective study. BMC Anesthesiol. 2016;16(1):107.  https://doi.org/10.1186/s12871-016-0274-2.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    López T, Sánchez FJ, Garzón JC, Muriel C. Spinal anesthesia in pediatric patients. Minerva Anesthesiol. 2012;78(1):78–87.  https://doi.org/10.1111/j.1460-9592.2011.03769.x.CrossRefGoogle Scholar
  64. 64.
    Trifa M, Tumin D, Whitaker EE, Bhalla T, Jayanthi VR, Tobias JD. Spinal anesthesia for surgery longer than 60 min in infants: experience from the first 2 years of a spinal anesthesia program. J Anesth. 2018;32(4):637–40.  https://doi.org/10.1007/s00540-018-2517-5.CrossRefPubMedGoogle Scholar
  65. 65.
    Rochette A, Raux O, Troncin R, Dadure C, Verdier R, Capdevila X. Clonidine prolongs spinal anesthesia in newborns: a prospective dose-ranging study. Anesth Analg. 2004;98(1):56–9.  https://doi.org/10.1213/01.ane.0000093229.17729.6c.CrossRefPubMedGoogle Scholar
  66. 66.
    Bouchut JC, Dubois R, Godard J. Clonidine in preterm-infant caudal anesthesia may be responsible for postoperative apnea. Reg Anesth Pain Med. 2001;26(1):83–5.  https://doi.org/10.1053/rapm.2001.20455.CrossRefPubMedGoogle Scholar
  67. 67.
    Henderson K, Sethna NF, Berde CB. Continuous caudal anesthesia for inguinal hernia repair in former preterm infants. J Clin Anesth. 1993;5(2):129–33.CrossRefGoogle Scholar
  68. 68.
    Sinskey JL, Vecchione TM, Ekstrom BG, Boretsky K. Benefits of ultrasound imaging for placement of caudal epidural blockade in 3 pediatric patients. A A Pract. 2018;10(11):307–9.  https://doi.org/10.1213/xaa.0000000000000693.CrossRefPubMedGoogle Scholar
  69. 69.
    Lönnqvist PA. Continuous paravertebral block in children: initial experience. Anaesthesia. 1992;47(7):607–9.  https://doi.org/10.1111/j.1365-2044.1992.tb02336.x.CrossRefPubMedGoogle Scholar
  70. 70.
    Støving K, Rothe C, Rosenstock CV, Aasvang EK, Lundstrøm LH, Lange KHW. Cutaneous sensory block area, muscle-relaxing effect, and block duration of the transversus abdominis plane block: a randomized, blinded, and placebo-controlled study in healthy volunteers. Reg Anesth Pain Med. 2015;40(4):355–62.  https://doi.org/10.1097/aap.0000000000000252.CrossRefPubMedGoogle Scholar
  71. 71.
    Hernandez MA, Vecchione T, Boretsky K. Dermatomal spread following posterior transversus abdominis plane block in pediatric patients: our initial experience. Pediatr Anesth. 2017;27(3):300–4.  https://doi.org/10.1111/pan.13034.CrossRefGoogle Scholar
  72. 72.
    Murouchi T, Iwasaki S, Yamakage M. Quadratus lumborum block: analgesic effects and chronological ropivacaine concentrations after laparoscopic surgery. Reg Anesth Pain Med. 2016;41(2):146–50.  https://doi.org/10.1097/aap.0000000000000349.CrossRefPubMedGoogle Scholar
  73. 73.
    Zaidi RH, Casanova NF, Haydar B, Voepel-Lewis T, Wan JH. Urethrocutaneous fistula following hypospadias repair: regional anesthesia and other factors. Paediatr Anaesth. 2015;25(11):1144–50.  https://doi.org/10.1111/pan.12719.CrossRefPubMedGoogle Scholar
  74. 74.
    Kundra P, Yuvaraj K, Agrawal K, Krishnappa S, Kumar LT. Surgical outcome in children undergoing hypospadias repair under caudal epidural vs penile block. Pediatr Anesth. 2012;22(7):707–12.  https://doi.org/10.1111/j.1460-9592.2011.03702.x.CrossRefGoogle Scholar
  75. 75.
    Taicher BM, Routh JC, Eck JB, Ross SS, Wiener JS, Ross AK. The association between caudal anesthesia and increased risk of postoperative surgical complications in boys undergoing hypospadias repair. Paediatr Anaesth. 2017;27(7):688–94.  https://doi.org/10.1111/pan.13119.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Hecht S, Piñeda J, Bayne A. Ultrasound-guided pudendal block is a viable alternative to caudal block for hypospadias surgery: a single-surgeon pilot study. Urology. 2018;113:192–6.  https://doi.org/10.1016/j.urology.2017.11.006.CrossRefPubMedGoogle Scholar
  77. 77.
    Kendigelen P, Tutuncu AC, Emre S, Altindas F, Kaya G. Pudendal versus caudal block in children undergoing hypospadias surgery a randomized controlled trial. Reg Anesth Pain Med. 2016;41(5):610–5.  https://doi.org/10.1097/aap.0000000000000447.CrossRefPubMedGoogle Scholar
  78. 78.
    Naja ZM, Ziade FM, Kamel R, El-Kayali S, Daoud N, El-Rajab MA. The effectiveness of pudendal nerve block versus caudal block anesthesia for hypospadias in children. Anesth Analg. 2013;117(6):1401–7.  https://doi.org/10.1213/ane.0b013e3182a8ee52.CrossRefPubMedGoogle Scholar
  79. 79.
    Kaplan I, Jiao Y, AuBuchon JD, Moore RP. Continuous erector spinae plane catheter for analgesia after infant thoracotomy: a case report. A A Pract. 2018;11(9):250–2.  https://doi.org/10.1213/xaa.0000000000000799.CrossRefPubMedGoogle Scholar
  80. 80.
    Kaushal B, Chauhan S, Saini K, et al. Comparison of the efficacy of ultrasound-guided serratus anterior plane block, pectoral nerves II block, and intercostal nerve block for the management of postoperative thoracotomy pain after pediatric cardiac surgery. J Cardiothorac Vasc Anesth. 2019;33(2):418–25.  https://doi.org/10.1053/j.jvca.2018.08.209.CrossRefPubMedGoogle Scholar
  81. 81.
    Suresh S, Ecoffey C, Bosenberg A, et al. The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine recommendations on local anesthetics and adjuvants dosage in pediatric regional anesthesia. Reg Anesth Pain Med. 2018;43(2):211–6.  https://doi.org/10.1097/aap.0000000000000702.CrossRefPubMedGoogle Scholar
  82. 82.
    Vittinghoff M, Lönnqvist PA, Mossetti V, et al. Postoperative pain management in children: guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative). Paediatr Anaesth. 2018;28(6):493–506.  https://doi.org/10.1111/pan.13373.CrossRefPubMedGoogle Scholar
  83. 83.
    Sethna NF, Clendenin D, Athiraman U, Solodiuk J, Rodriguez DP, Zurakowski D. Incidence of epidural catheter-associated infections after continuous epidural analgesia in children. Anesthesiology. 2010;113(1):224–32.  https://doi.org/10.1097/aln.0b013e3181de6cc5.CrossRefPubMedGoogle Scholar
  84. 84.
    Taenzer AH, Clark C, Kovarik WD. Experience with 724 epidurograms for epidural catheter placement in pediatric anesthesia. Reg Anesth Pain Med. 2010;35(5):432–5.  https://doi.org/10.1097/aap.0b013e3181ef4b76.CrossRefPubMedGoogle Scholar
  85. 85.
    Tsui BCH, Wagner A, Cave D, Kearney R. Thoracic and lumbar epidural analgesia via the caudal approach using electrical stimulation guidance in pediatric patients: a review of 289 patients. Anesthesiology. 2004;100(3):683–9.  https://doi.org/10.1097/00000542-200403000-00032.CrossRefPubMedGoogle Scholar
  86. 86.
    Ponde VC, Bedekar VV, Desai AP, Puranik KA. Does ultrasound guidance add accuracy to continuous caudal-epidural catheter placements in neonates and infants? Paediatr Anaesth. 2017;27(10):1010–4.  https://doi.org/10.1111/pan.13212.CrossRefPubMedGoogle Scholar
  87. 87.
    Willschke H, Sitzwohl C, Cox SG, et al. Ultrasonography for ilioinguinal/iliohypogastric nerve blocks in children††. This study was performed at the Red Cross Children Hospital, Klipfontein Road, Rondebosch 7700, Cape Town, South Africa. Br J Anaesth. 2005;95(2):226–30.  https://doi.org/10.1093/bja/aei157.CrossRefPubMedGoogle Scholar
  88. 88.
    Vecchione TM, Boretsky KR. Ultrasound images of the epidural space through the acoustic window of the infant. Anesthesiology. 2017;126(3):562.  https://doi.org/10.1097/aln.0000000000001447.CrossRefPubMedGoogle Scholar
  89. 89.
    Lowe LH, Johanek AJ, Moore CW. Sonography of the neonatal spine: part I, normal anatomy, imaging pitfalls, and variations that may simulate disorders. Am J Roentgenol. 2007;188(3):733–8.  https://doi.org/10.2214/ajr.05.2159.CrossRefGoogle Scholar
  90. 90.
    Oberndorfer U, Marhofer P, Bösenberg A, et al. Ultrasonographic guidance for sciatic and femoral nerve blocks in children. Br J Anaesth. 2007;98(6):797–801.  https://doi.org/10.1093/bja/aem092.CrossRefPubMedGoogle Scholar
  91. 91.
    Lam DKM, Corry GN, Tsui BCH. Evidence for the use of ultrasound imaging in pediatric regional anesthesia: a systematic review. Reg Anesth Pain Med. 2016;41(2):229–41.  https://doi.org/10.1097/aap.0000000000000208.CrossRefPubMedGoogle Scholar
  92. 92.
    Weintraud M, Marhofer P, Bösenberg A, et al. Ilioinguinal/iliohypogastric blocks in children: where do we administer the local anesthetic without direct visualization? Anesth Analg. 2008;106(1):89–93.  https://doi.org/10.1213/01.ane.0000287679.48530.5f.CrossRefPubMedGoogle Scholar
  93. 93.
    Mazoit JX, Dalens BJ. Pharmacokinetics of local anaesthetics in infants and children. Clin Pharmacokinet. 2004;43(1):17–32.  https://doi.org/10.2165/00003088-200443010-00002.CrossRefPubMedGoogle Scholar
  94. 94.
    Mazoit JX. Local anesthetics and their adjuncts. Paediatr Anaesth. 2012;22(1):31–8.  https://doi.org/10.1111/j.1460-9592.2011.03692.x.CrossRefPubMedGoogle Scholar
  95. 95.
    Gunter JB. Benefit and risks of local anesthetics in infants and children. Pediatr Drugs. 2002;4(10):649–72.  https://doi.org/10.2165/00128072-200204100-00003.CrossRefGoogle Scholar
  96. 96.
    Lerman J, Strong HA, LeDez KM, Swartz J, Rieder MJ, Burrows FA. Effects of age on the serum concentration of alpha 1-acid glycoprotein and the binding of lidocaine in pediatric patients. Clin Pharmacol Ther. 1989;46(2):219–25.CrossRefGoogle Scholar
  97. 97.
    Aarons L, Sadler B, Pitsiu M, Sjövall J, Henriksson J, Molnár V. Population pharmacokinetic analysis of ropivacaine and its metabolite 2′,6′-pipecoloxylidide from pooled data in neonates, infants, and children. Br J Anaesth. 2011;107(3):409–24.  https://doi.org/10.1093/bja/aer154.CrossRefPubMedGoogle Scholar
  98. 98.
    Booker PD, Taylor C, Saba G. Perioperative changes in alpha 1-acid glycoprotein concentrations in infants undergoing major surgery. Br J Anaesth. 1996;76(3):365–8.CrossRefGoogle Scholar
  99. 99.
    Rapp HJ, Molnár V, Austin S, et al. Ropivacaine in neonates and infants: a population pharmacokinetic evaluation following single caudal block. Paediatr Anaesth. 2004;14(9):724–32.  https://doi.org/10.1111/j.1460-9592.2004.01373.x.CrossRefPubMedGoogle Scholar
  100. 100.
    Anderson BJ, Hansen TG. Getting the best from pediatric pharmacokinetic data. Paediatr Anaesth. 2004;14(9):713–5.  https://doi.org/10.1111/j.1460-9592.2004.01374.x.CrossRefPubMedGoogle Scholar
  101. 101.
    Hansen TG, Ilett KF, Reid C, Im Lim S, Peter Hackett L, Bergesio R. Caudal ropivacaine in infants: population pharmacokinetics and plasma concentrations. Anesthesiology. 2001;94(4):579–84.  https://doi.org/10.1097/00000542-200104000-00009.CrossRefPubMedGoogle Scholar
  102. 102.
    Arlander E, Ekström G, Alm C, et al. Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. Clin Pharmacol Ther. 1998;64(5):484–91.  https://doi.org/10.1016/s0009-9236(98)90131-x.CrossRefPubMedGoogle Scholar
  103. 103.
    Calder A, Bell GT, Andersson M, Thomson AH, Watson DG, Morton NS. Pharmacokinetic profiles of epidural bupivacaine and ropivacaine following single-shot and continuous epidural use in young infants. Paediatr Anaesth. 2012;22(5):430–7.  https://doi.org/10.1111/j.1460-9592.2011.03771.x.CrossRefPubMedGoogle Scholar
  104. 104.
    Bösenberg AT, Thomas J, Cronje L, et al. Pharmacokinetics and efficacy of ropivacaine for continuous epidural infusion in neonates and infants. Paediatr Anaesth. 2005;15(9):739–49.  https://doi.org/10.1111/j.1460-9592.2004.01550.x.CrossRefPubMedGoogle Scholar
  105. 105.
    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.CrossRefGoogle Scholar
  106. 106.
    Suresh S, De Oliveira GS. Blood bupivacaine concentrations after transversus abdominis plane block in neonates: a prospective observational study. Anesth Analg. 2016;122(3):814–7.  https://doi.org/10.1213/ane.0000000000001088.CrossRefPubMedGoogle Scholar
  107. 107.
    Kokki H. Spinal blocks. Paediatr Anaesth. 2012;22(1):56–64.  https://doi.org/10.1111/j.1460-9592.2011.03693.x.CrossRefPubMedGoogle Scholar
  108. 108.
    Kokki H, Tuovinen K, Hendolin H. Spinal anaesthesia for paediatric day-case surgery: a double-blind, randomized, parallel group, prospective comparison of isobaric and hyperbaric bupivacaine. Br J Anaesth. 1998;81(4):502–6.  https://doi.org/10.1093/bja/81.4.502.CrossRefPubMedGoogle Scholar
  109. 109.
    Tsui BCH, Boretsky K, Berde C. Maximum recommended dosage of ropivacaine and bupivacaine for pediatric regional anesthesia. Reg Anesth Pain Med. 2018;43(8):895–6.  https://doi.org/10.1097/aap.0000000000000855.CrossRefPubMedGoogle Scholar
  110. 110.
    Muhly WT, Gurnaney HG, Kraemer FW, Ganesh A, Maxwell LG. A retrospective comparison of ropivacaine and 2-chloroprocaine continuous thoracic epidural analgesia for management of postthoracotomy pain in infants. Paediatr Anaesth. 2015;25(11):1162–7.  https://doi.org/10.1111/pan.12745.CrossRefPubMedGoogle Scholar
  111. 111.
    Veneziano G, Tobias J. Chloroprocaine for epidural anesthesia in infants and children. Pediatr Anesthesiol. 2017;27:581–90.  https://doi.org/10.1111/pan.13134.CrossRefGoogle Scholar
  112. 112.
    Hernandez MA, Boretsky K. Chloroprocaine: local anesthetic systemic toxicity in a 9-month infant with paravertebral catheter. Paediatr Anaesth. 2016;26(6):665–6.  https://doi.org/10.1111/pan.12912.CrossRefPubMedGoogle Scholar
  113. 113.
    Cladis FP, Litman RS. Transient cardiovascular toxicity with unintentional intravascular injection of 3% 2-chloroprocaine in a 2-month-old infant. Anesthesiology. 2004;100(1):181–3.  https://doi.org/10.1097/00000542-200401000-00030.CrossRefPubMedGoogle Scholar
  114. 114.
    AAP Pharmaceuticals. LLC, Shaumburg IL, Nesacaine (Chlorprocaine hydrochloride), US Food and Drug Website. Revised Nov. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/009435s044lbl.pdf. Accessed 24 June 2019.
  115. 115.
    Toulon P. Developmental hemostasis: laboratory and clinical implications. Int J Lab Hematol. 2016;38(Suppl 1):66–77.  https://doi.org/10.1111/ijlh.12531.CrossRefPubMedGoogle Scholar
  116. 116.
    Lippi G, Salvagno GL, Rugolotto S, et al. Routine coagulation tests in newborn and young infants. J Thromb Thrombolysis. 2007;24(2):153–5.  https://doi.org/10.1007/s11239-007-0046-4.CrossRefPubMedGoogle Scholar
  117. 117.
    Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979–2009. Reg Anesth Pain Med. 1979;35(2):181–7.CrossRefGoogle Scholar
  118. 118.
    Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med. 2002;27(6):556–61.CrossRefGoogle Scholar
  119. 119.
    Gitman M, Barrington MJ. Local anesthetic systemic toxicity: a review of recent case reports and registries. Reg Anesth Pain Med. 2018;43(2):124–30.  https://doi.org/10.1097/aap.0000000000000721.CrossRefPubMedGoogle Scholar
  120. 120.
    Buck D, Kreeger R, Spaeth J. Case discussion and root cause analysis: bupivacaine overdose in an infant leading to ventricular tachycardia. Anesth Analg. 2014;119(1):137–40.  https://doi.org/10.1213/ane.0000000000000275.CrossRefPubMedGoogle Scholar
  121. 121.
    Groban L. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med. 2003;28(1):3–11.  https://doi.org/10.1053/rapm.2003.50014.CrossRefPubMedGoogle Scholar
  122. 122.
    Stewart J, Kellett N, Castro D. The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy volunteers. Anesth Analg. 2003;97(2):412–6.  https://doi.org/10.1016/b978-0-12-409547-2.12548-x.CrossRefPubMedGoogle Scholar
  123. 123.
    Groban L, Deal DD, Vernon JC, James RL, Butterworth J. Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg. 2001;92(1):37–43.  https://doi.org/10.1097/00000539-200101000-00008.CrossRefPubMedGoogle Scholar
  124. 124.
    McLeod GA, Burke D. Levobupivacaine. Anaesthesia. 2001;56(4):331–41.  https://doi.org/10.1046/j.1365-2044.2001.01964.x.CrossRefPubMedGoogle Scholar
  125. 125.
    Graf BM, Abraham I, Eberbach N, Kunst G, Stowe DF, Martin E. Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology. 2002;96(6):1427–34.  https://doi.org/10.1097/00000542-200206000-00023.CrossRefPubMedGoogle Scholar
  126. 126.
    Yu RN, Houck CS, Casta A, Blum RH. Institutional policy changes to prevent cardiac toxicity associated with bupivacaine penile blockade in infants. A A Case Rep. 2016;7(3):71–5.  https://doi.org/10.1213/xaa.0000000000000347.CrossRefPubMedGoogle Scholar
  127. 127.
    Neal JM, Barrington MJ, Fettiplace MR, et al. The third American Society of Regional Anesthesia and Pain Medicine practice advisory on local anesthetic systemic toxicity: executive summary 2017. Reg Anesth Pain Med. 2018;43(2):113–23.  https://doi.org/10.1097/aap.0000000000000720.CrossRefPubMedGoogle Scholar
  128. 128.
    Hiller DB, Di Gregorio G, Ripper R, et al. Epinephrine impairs lipid resuscitation from bupivacaine overdose: a threshold effect. Anesthesiology. 2009;111(3):498–505.  https://doi.org/10.1097/aln.0b013e3181afde0a.CrossRefPubMedGoogle Scholar
  129. 129.
    Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105(1):217–8.CrossRefGoogle Scholar
  130. 130.
    Fettiplace MR, Weinberg G. The mechanisms underlying lipid resuscitation therapy. Reg Anesth Pain Med. 2018;43(2):138–49.  https://doi.org/10.1097/aap.0000000000000719.CrossRefPubMedGoogle Scholar
  131. 131.
    Presley JD, Chyka PA. Intravenous lipid emulsion to reverse acute drug toxicity in pediatric patients. Ann Pharmacother. 2013;47(5):735–43.  https://doi.org/10.1345/aph.1r666.CrossRefPubMedGoogle Scholar
  132. 132.
    Fairchild KD, Patterson A, Gumpper KF. Overdose of intravenous fat emulsion in a preterm infant: case report. Nutr Clin Pract. 1999;14(3):116–9.  https://doi.org/10.1177/088453369901400304.CrossRefGoogle Scholar
  133. 133.
    Chuo J, Lambert G, Hicks RW. Intralipid medication errors in the neonatal intensive care unit. Jt Comm J Qual Patient Saf. 2007;33(2):104–11.CrossRefGoogle Scholar
  134. 134.
    Low E, Ryan CA. Overdose of intravenous intralipid in a premature neonate. Jt Comm J Qual Patient Saf. 2007;33(10):588–9.CrossRefGoogle Scholar
  135. 135.
    Pacira Pharmaceuticals, Inc., EXPAREL, US Food and Drug Administration Website. Revised 4/2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022496s9lbl.pd. Accessed 24 June 2019.
  136. 136.
    Hu D, Onel E, Singla N, Kramer WG, Hadzic A. Pharmacokinetic profile of liposome bupivacaine injection following a single administration at the surgical site. Clin Drug Investig. 2013;33(2):109–15.  https://doi.org/10.1007/s40261-012-0043-z.CrossRefPubMedGoogle Scholar
  137. 137.
    Haas E, Onel E, Miller H, Ragupathi M, White PF. A double-blind, randomized, active-controlled study for post-hemorrhoidectomy pain management with liposome bupivacaine, a novel local analgesic formulation. Am Surg. 2012;78(5):574–81.PubMedGoogle Scholar
  138. 138.
    Bramlett K, Onel E, Viscusi ER, Jones K. A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee. 2012;19(5):530–6.  https://doi.org/10.1016/j.knee.2011.12.004.CrossRefPubMedGoogle Scholar
  139. 139.
    Balocco AL, Van Zundert PGE, Gan SS, Gan TJ, Hadzic A. Extended release bupivacaine formulations for postoperative analgesia: an update. Curr Opin Anaesthesiol. 2018;31(5):636–42.  https://doi.org/10.1097/aco.0000000000000648.CrossRefPubMedGoogle Scholar
  140. 140.
    Viscusi E, Gimbel JS, Pollack RA, Hu J, Lee G-C. HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCL in bunionectomy: phase III results from the randomized EPOCH 1 study. Reg Anesth Pain Med. 2019.  https://doi.org/10.1136/rapm-2019-100531.CrossRefPubMedGoogle Scholar
  141. 141.
    Catterall WA. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Annu Rev Pharmacol Toxicol. 1980;20(1):15–43.  https://doi.org/10.1146/annurev.pa.20.040180.000311.CrossRefPubMedGoogle Scholar
  142. 142.
    Padera R, Bellas E, Tse JY, Hao D, Kohane DS. Local myotoxicity from sustained release of bupivacaine from microparticles. Anesthesiology. 2008;108(5):921–8.  https://doi.org/10.1097/aln.0b013e31816c8a48.CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Lobo K, Donado C, Cornelissen L, et al. A phase 1, dose-escalation, double-blind, block-randomized, controlled trial of safety and efficacy of neosaxitoxin alone and in combination with 0.2% bupivacaine, with and without epinephrine, for cutaneous anesthesia. Anesthesiology. 2015;123(4):873–85.  https://doi.org/10.1097/ALN.0000000000000831.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Anesthesiology, Critical Care and Pain MedicineBoston Children’s HospitalBostonUSA

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