Advertisement

Journal of Anesthesia

, Volume 30, Issue 3, pp 449–460 | Cite as

Remifentanil: applications in neonates

  • Mineto Kamata
  • Joseph D. TobiasEmail author
Review Article

Abstract

Remifentanil is a synthetic opioid derivative that was introduced into clinical practice in the United States in 1996. The unique modification of its chemical structure to include a methyl-ester ring allows its hydrolysis by non-specific plasma and tissue esterases. This molecular configuration results in its rapid metabolism thereby providing a rapid onset, easy titration by continuous infusion, and a short context-sensitive half-life with rapid elimination. These principles are stable and consistent across all age groups regardless of the infusion characteristics. Owing to these pharmacokinetic characteristics, it is an effective agent in the neonatal population allowing the provision of intense analgesia and anesthesia with a rapid recovery profile in various clinical scenarios. Here, we review the pharmacokinetics of remifentanil in neonates, discuss its clinical applications including intraoperative administration for anesthetic care, unique applications for procedural sedation including endotracheal intubation, and its potential use for sedation in the Intensive Care Unit setting during mechanical ventilation.

Keywords

Remifentanil Neonatal anesthesia Sedation 

Notes

Compliance with ethical standards

Conflict of interest

This review was not sponsored, and there are no conflicts of interests known at the time of submission.

References

  1. 1.
    Egan TD, Kern SE, Muir KT, White J. Remifentanil by bolus injection: a safety, pharmacokinetic, pharmacodynamic, and age effect investigation in human volunteers. Br J Anaesth. 2004;92:335–43.CrossRefPubMedGoogle Scholar
  2. 2.
    Glass PS, Gan TJ, Howell S. A review of the pharmacokinetics and pharmacodynamics of remifentanil. Anesth Analg. 1999;89(4 Suppl):S7–14.CrossRefPubMedGoogle Scholar
  3. 3.
    Gelberg J, Jonmarker C, Stenqvist O, Werner O. Intravenous boluses of fentanyl, 1 μg kg−1, and remifentanil, 0.5 μg kg−1, give similar maximum ventilatory depression in awake volunteers. Br J Anaesth. 2012;108:1028–34.CrossRefPubMedGoogle Scholar
  4. 4.
    Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE. Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. J Pharmacol Exp Ther. 1997;281:226–32.PubMedGoogle Scholar
  5. 5.
    Davis PJ, Stiller RL, Wilson AS, McGowan FX, Egan TD, Muir KT. In vitro remifentanil metabolism: the effects of whole blood constituents and plasma butyrylcholinesterase. Anesth Analg. 2002;95:1305–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Kapila A, Glass PS, Jacobs JR, Muir KT, Hermann DJ, Shiraishi M, Howell S, Smith RL. Measured context-sensitive half-times of remifentanil and alfentanil. Anesthesiology. 1995;83:968–75.CrossRefPubMedGoogle Scholar
  7. 7.
    Egan TD, Minto CF, Hermann DJ, Barr J, Muir KT, Shafer SL. Remifentanil versus alfentanil. Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers. Anesthesiology. 1996;84:821–33.CrossRefPubMedGoogle Scholar
  8. 8.
    Welzing L, Roth B. Experience with remifentanil in neonates and infants. Drugs. 2006;66:1339–50.CrossRefPubMedGoogle Scholar
  9. 9.
    Dershwitz M, Hoke JF, Rosow CE, Michałowski P, Connors PM, Muir KT, Dienstag JL. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology. 1996;84:812–20.CrossRefPubMedGoogle Scholar
  10. 10.
    Hoke JF, Shlugman D, Dershwitz M, Michałowski P, Malthouse-Dufore S, Connors PM, Martel D, Rosow CE, Muir KT, Rubin N, Glass PS. Pharmacokinetics and pharmacodynamics of remifentanil in persons with renal failure compared with healthy volunteers. Anesthesiology. 1997;87:533–41.CrossRefPubMedGoogle Scholar
  11. 11.
    Kapila A, Glass PS, Jacobs JR, Muir KT, Hermann DJ, Shiraishi M, Howell S, Smith RL. Measured context-sensitive half-times of remifentanil and alfentanil. Anesthesiology. 1995;83:968–75.CrossRefPubMedGoogle Scholar
  12. 12.
    Ross AK, Davis PJ. Dear Gd GL, Ginsberg B, McGowan FX, Stiller RD, Henson LG, Huffman C, Muir KT. Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures. Anesth Analg. 2001;93:1393–401.CrossRefPubMedGoogle Scholar
  13. 13.
    Davis PJ, Galinkin J, McGowan FX, Lynn AM, Yaster M, Rabb MF, Krane EJ, Kurth CD, Blum RH, Maxwell L, Orr R, Szmuk P, Hechtman D, Edwards S, Henson LG. A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles. Anesth Analg 2001;93:1380–6.Google Scholar
  14. 14.
    Lynn AM, Rabb MF, Yaster M, Henson LG, Blum R, Hechtman D, Maxwell L, Szmuk P, Orr R, Krane EJ, Edwards S, Kurth CD. A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis. Anesth Analg. 2001;93:1387–92.CrossRefPubMedGoogle Scholar
  15. 15.
    Ben Khalifa S, Blidi S, Trifa M, Skhiri A, Drira M, Regaya T, Fekih Hassen A. Time to extubation in infants undergoing pyloromyotomy—isoflurane inhalation vs remifentanil infusion. Middle East J Anaesthesiol 2009;20:277-80.Google Scholar
  16. 16.
    Michel F, Lando A, Aubry C, Arnaud S, Merrot T, Martin C. Experience with remifentanil-sevoflurane balanced anesthesia for abdominal surgery in neonates and children less than 2 years. Paediatr Anaesth. 2008;18:532–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Wee LH, Moriarty A, Cranston A, Bagshaw O. Remifentanil infusion for major abdominal surgery in small infants. Paediatr Anaesth. 1999;9:415–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Chambers N, Lopez T, Thomas J, James MF. Remifentanil and the tunnelling phase of paediatric ventriculoperitoneal shunt insertion. A double-blind, randomised, prospective study. Anaesthesia. 2002;57:133–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Gharavi-Fard M, Taghavi-Gilani M, Kazemi S, Razavi M. Apneas in infants with postconceptional age below 60 weeks undergoing herniorrhaphy. Iran J Pediatr. 2014;24:179–83.Google Scholar
  20. 20.
    Mausser G, Friedrich G, Schwarz G. Airway management and anesthesia in neonates, infants and children during endolaryngotracheal surgery. Paediatr Anaesth. 2007;17:942–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Eck JB, Lynn AM. Use of remifentanil in infants. Paediatr Anaesth. 1998;8:437–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Wee L, Stokes MA. Bladder exstrophy in a neonate at risk of transient myasthenia gravis: a role for remifentanil and epidural analgesia. Br J Anaesth. 1999;82:774–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Sommer M, Riedel J, Fusch C, Fetsge PA, Hachenberg T. Intravenous anaesthesia with remifentanil in a preterm infant. Paediatr Anaesth. 2001;2:252–4.CrossRefGoogle Scholar
  24. 24.
    Fernández A, Jerez A, Falcone N. Anaesthetic management in a case of a type IV laryngotracheo-oesophageal cleft. Paediatr Anaesth. 2003;13:270–3.CrossRefPubMedGoogle Scholar
  25. 25.
    Krosnar S, Baxter A. Thoracoscopic repair of esophageal atresia with tracheoesophageal fistula: anesthetic and intensive care management of a series of eight neonates. Paediatr Anaesth. 2005;15:541–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Koomen E, Poortmans G, Anderson BJ, Janssens MM. Jet ventilation for laryngotracheal surgery in an ex-premature infant. Paediatr Anaesth. 2005;15:786–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Guruswamy V, Roberts S, Arnold P, Potter F. Anaesthetic management of a neonate with congenital cyst adenoid malformation. Br J Anaesth. 2005;95:240–2.CrossRefPubMedGoogle Scholar
  28. 28.
    Gerçek A, Dagcinar A, Ozek MM. Anesthetic management of a newborn with Mohr (oro-facial-digital type II) syndrome. Paediatr Anaesth. 2007;17:603–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Arai LR, Dicindio S, Cook SP, Davis DA. Anesthesia management of a patient with a laryngotracheo-esophageal cleft. Paediatr Anaesth. 2007;17:171–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Pickard A, Chen J. Petty syndrome–implications for anesthesia. Paediatr Anaesth. 2011;21:1274–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Sammartino M, Garra R, Sbaraglia F, De Riso M, Continolo N, Papacci P. Experience of remifentanil in extremely low-birth-weight babies undergoing laparotomy. Pediatr Neonatol. 2011;52:176–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Kim BR, Kim JH, Kim KW, Choe WJ, Park JS. Anesthetic management of a preterm neonate intracranial aneurysm clipping. Korean J Anesth. 2014;67:S85–6.CrossRefGoogle Scholar
  33. 33.
    Sammartino M, Bocci MG, Ferro G, Mercurio G, Papacci P, Conti G, Lepore D, Molle F. 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.CrossRefPubMedGoogle Scholar
  34. 34.
    Demirel N, Bas AY, Kavurt S, Celik IH, Yucel H, Turkbay D, Hekimoğlu E, Koc O. Remifentanil analgesia during laser treatment for retinopathy of prematurity: a practical approach in neonatal intensive care unit. Am J Perinatol. 2014;31:983–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Shah V, Ohlesson A. The effectiveness of premedication for endotracheal intubation in mechanically ventilated neonates: a systematic review. Clin Perinatol. 2002;29:535–54.CrossRefPubMedGoogle Scholar
  36. 36.
    Aranda JV, Carlo W, Hummel P, Thomas R, Lehr VT, Anand KJ. Analgesia and sedation during mechanical ventilation in neonates. Clin Ther. 2005;27:877–99.CrossRefPubMedGoogle Scholar
  37. 37.
    Cook-Sather SD, Tulloch HV, Cnaan A, Nicolson SC, Cubina ML, Gallagher PR, Schreiner MS. A comparison of awake versus paralyzed tracheal intubation for infants with pyloric stenosis. Anesth Analg. 1998;86:945–51.PubMedGoogle Scholar
  38. 38.
    Badiee Z, Vakiliamini M, Mohammadizadeh M. Remifentanil for endotracheal intubation in premature infants: A randomized controlled trial. J Res Pharm Pract. 2013;2:75–82.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Dewhirst E, Naguib A, Tobias JD. Chest wall rigidity in two infants after low-dose fentanyl administration. Pediatr Emerg Care. 2012;28:465–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Crawford MW, Hayes J, Tan JM. Dose-response of remifentanil for tracheal intubation in infants. Anesth Analg. 2005;100:1599–604.CrossRefPubMedGoogle Scholar
  41. 41.
    Pereira e Silva Y, Gomez RS, Marcatto Jde O, Maximo TA, Barbosa RF, Simões e Silva AC. Morphine versus remifentanil for intubating preterm neonates. Arch Dis Child Fetal Neonatal Ed 2007;92:F293-4.Google Scholar
  42. 42.
    Avino D, Zhang WH, De Villé A, Johansson AB. Remifentanil versus morphine-midazolam premedication on the quality of endotracheal intubation in neonates: a noninferiority randomized trial. J Pediatr. 2014;164:1032–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Choong K, Al Faleh K, Doucette J, Gray S, Rich B, Verhey L, Paes B. Remifentanil for endotracheal intubation in neonates: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2010;95:F80–4.Google Scholar
  44. 44.
    Penido MG, Oliveira Silva DF, Tavares EC, Silva YP. Propofol versus midazolam for intubating preterm neonates: a randomized controlled trial. J Perinatol. 2011;31:356–60.CrossRefPubMedGoogle Scholar
  45. 45.
    Norman E, Wikström S, Hellström-Westas L, Turpeinen U, Hämäläinen E, Fellman V. Rapid sequence induction is superior to morphine for intubation of preterm infants: a randomized controlled trial. J Pediatr. 2011;159:893–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Norman E, Wikström S, Rosén I, Fellman V, Hellström-Westas L. Premedication for intubation with morphine causes prolonged depression of electrocortical background activity in preterm infants. Pediatr Res. 2013;73:87–94.CrossRefPubMedGoogle Scholar
  47. 47.
    Welzing L, Kribs A, Huenseler C, Eifinger F, Mehler K, Roth B. Remifentanil for INSURE in preterm infants: a pilot study for evaluation of efficacy and safety aspects. Acta Paediatr. 2009;98:1416–20.CrossRefPubMedGoogle Scholar
  48. 48.
    Lago P, Tiozzo C, Boccuzzo G, Allegro A, Zacchello F. Remifentanil for percutaneous intravenous central catheter placement in preterm infant: a randomized controlled trial. Paediatr Anaesth. 2008;18:736–44.CrossRefPubMedGoogle Scholar
  49. 49.
    Shin SH, Kim HS, Lee J, Choi KY, Lee JH, Kim EK, Park MS, Choi JH. A comparative study of two remifentanil doses for procedural pain in ventilated preterm infants: a randomized, controlled study. Pediatr Crit Care Med 2014;15-5.Google Scholar
  50. 50.
    Joshi G, Tobias JD. Remifentanil to facilitate high-resolution computed tomography imaging of the chest or magnetic resonance imaging in infants. South Med J. 2009;102:1121.CrossRefPubMedGoogle Scholar
  51. 51.
    Berkenbosch JW, Graff GR, Stark JM, Ner Z, Tobias JD. Use of a remifentanil-propofol mixture for pediatric flexible fiberoptic bronchoscopy sedation. Paediatr Anaesth. 2004;14:941–6.CrossRefPubMedGoogle Scholar
  52. 52.
    Pereira e Silva Y, Gomez RS, Barbosa RF, Simões e Silva AC. Remifentanil for sedation and analgesia in a preterm neonate with respiratory distress syndrome. Paediatr Anaesth 2005;15:993–6.Google Scholar
  53. 53.
    Tobias JD. Remifentanil: Applications in the Pediatric ICU population. Amer J Pain Manage. 1998;8:114–7.Google Scholar
  54. 54.
    Pereirae Silva YP, Gomez RS, Marcatto J de O, Maximo TA, Barbosa RF, eSilva AC. Early awakening and extubation with remifentanil in ventilated premature neonates. Paediatr Anaesth 2008;18:176–83.Google Scholar
  55. 55.
    Stoppa F, Perrotta D, Tomasello C, Cecchetti C, Marano M, Pasotti E, Barbieri MA, Conti G, Pirozzi N. Low dose remifentanyl infusion for analgesia and sedation in ventilated newborns. Minerva Anestesiol. 2004;70:753–61.PubMedGoogle Scholar
  56. 56.
    Giannantonio C, Sammartino M, Valente E, Cota F, Fioretti M, Papacci P. Remifentanil analgosedation in preterm newborns during mechanical ventilation. Acta Paediatr. 2009;98:1111–5.CrossRefPubMedGoogle Scholar
  57. 57.
    Welzing L, Oberthuer A, Junghaenel S, Harnischmacher U, Stützer H, Roth B. 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.CrossRefPubMedGoogle Scholar
  58. 58.
    Howard RF, Lloyd-Thomas A, Thomas M, Williams DG, Saul R, Bruce E, Peters J. Nurse-controlled analgesia (NCA) following major surgery in 10,000 patients in a children’s hospital. Paediatr Anaesth. 2010;20:126–34.CrossRefPubMedGoogle Scholar
  59. 59.
    Morton NS, Errera A. APA national audit of pediatric opioid infusions. Paediatr Anaesth. 2010;20:119–25.CrossRefPubMedGoogle Scholar
  60. 60.
    Ansermino JM, Brooks P, Rosen D, Vandebeek CA, Reichert C. Spontaneous ventilation with remifentanil in children. Paediatr Anaesth. 2005;15:115–21.CrossRefPubMedGoogle Scholar
  61. 61.
    Barker N, Lim J, Amari E, Malherbe S, Ansermino JM. Relationship between age and spontaneous ventilation during intravenous anesthesia in children. Paediatr Anaesth. 2007;17:948–55.CrossRefPubMedGoogle Scholar
  62. 62.
    Weale NK, Rogers CA, Cooper R, Nolan J, Wolf AR. Effect of remifentanil infusion rate on stress response to the pre-bypass phase of paediatric cardiac surgery. Br J Anaesth 200;92:187–94.Google Scholar
  63. 63.
    Komatsu R, Turan AM, Orhan-Sungur M, McGuire J, Radke OC, Apfel CC. Remifentanil for general anaesthesia: a systematic review. Anaesthesia. 2007;62:1266–80.CrossRefPubMedGoogle Scholar
  64. 64.
    Ellenbroek B, Schwarz M, Sontag KH, Jaspers R, Cools A. Muscular rigidity and delineation of a dopamine-specific neostriatal subregion: tonic EMG activity in rats. Brain Res. 1985;345:132–40.CrossRefPubMedGoogle Scholar
  65. 65.
    Lui PW, Lee TY, Chan SH. The possible mechanism of fentanyl-induced muscle rigidity. Ma Zui Xue Za Zhi. 1991;29:542–7.PubMedGoogle Scholar
  66. 66.
    Anand KJ, Willson DF, Berger J, Harrison R, Meert KL, Zimmerman J, Carcillo J, Newth CJ, Prodhan P, Dean JM, Nicholson C. Tolerance and withdrawal from prolonged opioid use in critically ill children. Pediatrics. 2010;125:e1208–25.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Guignard B, Bossard AE, Coste C, Sessler DI, Lebrault C, Alfonsi P, Fletcher D, Chauvin M. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology. 2000;93:409–17.CrossRefPubMedGoogle Scholar
  68. 68.
    Vinik HR, Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg. 1998;86:1307–11.PubMedGoogle Scholar
  69. 69.
    Crawford MW, Hickey C, Zaarour C, Howard A, Naser B. Development of acute opioid tolerance during infusion of remifentanil for pediatric scoliosis surgery. Anesth Analg. 2006;102:1662–7.CrossRefPubMedGoogle Scholar
  70. 70.
    Welzing L, Link F, Junghaenel S, Oberthuer A, Harnischmacher U, Stuetzer H, Roth B. Remifentanil-induced tolerance, withdrawal or hyperalgesia in infants: a randomized controlled trial. RAPIP trial: remifentanil-based analgesia and sedation of paediatric intensive care patients. Neonatology. 2013;104:34–41.CrossRefPubMedGoogle Scholar
  71. 71.
    Loop T, Priebe HJ. Prospective, randomized cost analysis of anesthesia with remifentanil combined with propofol, desflurane or sevoflurane for otorhinolaryngeal surgery. Acta Anaesthesiol Scand. 2002;46:1251–60.CrossRefPubMedGoogle Scholar
  72. 72.
    Beers RA, Calimlim JR, Uddoh E, Esposito BF, Camporesi EM. A comparison of the cost-effectiveness of remifentanil versus fentanyl as an adjuvant to general anesthesia for outpatient gynecologic surgery. Anesth Analg. 2000;91:1420–5.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Anesthesiologists 2016

Authors and Affiliations

  1. 1.Department of Anesthesiology and Pain MedicineNationwide Children’s HospitalColumbusUSA
  2. 2.Department of Anesthesiology and Pain MedicineThe Ohio State University College of MedicineColumbusUSA
  3. 3.Department of PediatricsThe Ohio State University College of MedicineColumbusUSA

Personalised recommendations