Abstract
Remifentanil is a relatively new synthetic opioid, which is not licensed worldwide for neonates and infants. Because of its unique pharmacokinetic properties with a short recovery profile, it could be the ideal opioid for neonates and infants, who are especially sensitive to respiratory depression by opioids. Therefore, we conducted a MEDLINE search on all articles dealing with the use of remifentanil in this important subgroup of patients. Most experience with remifentanil in neonates and infants is as maintenance anaesthesia during surgery. In approximately 300 neonates and infants, remifentanil proved to be an effective and safely used opioid for this indication. However, very limited data exist on remifentanil for analgesia and sedation of mechanically ventilated paediatric intensive care patients. Further research with remifentanil in neonates and infants should focus on this group of patients because remifentanil, with its very short context-sensitive half-life, could result in shorter extubation times compared with commonly used opioids such as morphine or fentanyl.
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References
Anand KJ, Scalzo FM. Can adverse neonatal experiences alter brain development and subsequent behavior? Biol Neonate 2000; 77(2): 69–82
Buskila D, Neumann L, Zmora E, et al. Pain sensitivity in prematurely born adolescents. Arch Pediatr Adolesc Med 2003; 157(11): 1079–82
Lidow MS. Long-term effects of neonatal pain on nociceptive systems. Pain 2002; 99(3): 377–83
Stevens B, McGrath P, Gibbins S, et al. Procedural pain in newborns at risk for neurologic impairment. Pain 2003; 105(1–2): 27–35
Banos JE, Barajas C, Martin ML, et al. A survey of postoperative pain treatment in children of 3–14 years. Eur J Pain 1999; 3(3): 275–82
Bremerich DH, Neidhart G, Roth B, et al. Postoperative pain therapy in pediatrics: results of a representative survey in Germany [in German]. Anaesthesist 2001; 50(2): 102–12
Johr M. Postoperative pain therapy in children [in German]. Schmerz 2000; 14(1): 45–55
Sittl R, Griessinger N, Koppert W, etal. Management of postoperative pain in children [in German]. Schmerz 2000; 14(5): 333–9
Egan TD, Lemmens HJ, Fiset P, et al. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology 1993; 79(5): 881–92
Glass PS, Hardman D, Kamiyama Y, et al. Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil (GI87084B). Anesth Analg 1993; 77(5): 1031–40
Dershwitz M, Hoke JF, Rosow CE, et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology 1996; 84(4): 812–20
Hoke JF, Shlugman D, Dershwitz M, et al. Pharmacokinetics and pharmacodynamics of remifentanil in persons with renal failure compared with healthy volunteers. Anesthesiology 1997; 87(3): 533–41
Scott LJ, Perry CM. Remifentanil: a review of its use during the induction and maintenance of general anaesthesia. Drugs 2005; 65(13): 1793–823
Katz R, Kelly HW. Pharmacokinetics of continuous infusions of fentanyl in critically ill children. Crit Care Med 1993; 21(7): 995–1000
Koehntop DE, Rodman JH, Brundage DM, et al. Pharmacokinetics of fentanyl in neonates. Anesth Analg 1986; 65(3): 227–32
Latasch L, Freye E. Pain and opioids in preterm and newborns [in German]. Anaesthesist 2002; 51(4): 272–84
Egan TD. Remifentanil pharmacokinetics and pharmacodynamics: a preliminary appraisal. Clin Pharmacokinet 1995; 29(2): 80–94
Wilhelm W, Wrobel M, Kreuer S, et al. Remifentanil: an update [in German]. Anaesthesist 2003; 52(6): 473–94
Davis PJ, Ross AK, Henson LG, et al. Remifentanil pharmacokinetics in neonates [abstract]. Anesthesiology 1997; 87(3A): A1064
Davis PJ, Wilson AS, Siewers RD, et al. The effects of cardiopulmonary bypass on remifentanil kinetics in children undergoing atrial septal defect repair. Anesth Analg 1999; 89(4): 904–8
Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology: drug disposition, action, and therapy in infants and children. N Engl J Med 2003; 349(12): 1157–67
Ross AK, Davis PJ, Dear Gd GL, et al. Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures. Anesth Analg 2001; 93(6): 1393–401
James MK, Feldman PL, Schuster SV, et al. Opioid receptor activity of GI 87084B, a novel ultra-short acting analgesic, in isolated tissues. J Pharmacol Exp Ther 1991; 259(2): 712–8
James MK, Vuong A, Grizzle MK, et al. Hemodynamic effects of GI 87084B, an ultra-short acting mu-opioid analgesic, in anesthetized dogs. J Pharmacol Exp Ther 1992; 263(1): 84–91
Patel SS, Spencer CM. Remifentanil. Drugs 1996; 52(3): 417–27
Glass PS, Gan TJ, Howell S. A review of the pharmacokinetics and pharmacodynamics of remifentanil. Anesth Analg 1999; 89 (4 Suppl.): S7–14
Davis PJ, Finkel JC, Orr RJ, et al. A randomized, double-blinded study of remifentanil versus fentanyl for tonsillectomy and adenoidectomy surgery in pediatric ambulatory surgical patients. Anesth Analg 2000; 90(4): 863–71
Ganidagli S, Cengiz M, Baysal Z. Remifentanil vs alfentanil in the total intravenous anaesthesia for paediatric abdominal surgery. Paediatr Anaesth 2003; 13(8): 695–700
Prys-Roberts C, Lerman J, Murat I, et al. Comparison of remifentanil versus regional anaesthesia in children anaesthetised with isoflurane/nitrous oxide. International Remifentanil Paediatric Anaesthesia Study group. Anaesthesia 2000; 55(9): 870–6
Weale NK, Rogers CA, Cooper R, et al. Effect of remifentanil infusion rate on stress response to the pre-bypass phase of paediatric cardiac surgery. Br J Anaesth 2004; 92(2): 187–94
Chanavaz C, Tirel O, Wodey E, et al. Haemodynamic effects of remifentanil in children with and without intravenous atropine: an echocardiographic study. Br J Anaesth 2005; 94(1): 74–9
Tirel O, Chanavaz C, Bansard JY, et al. Effect of remifentanil with and without atropine on heart rate variability and RR interval in children. Anaesthesia 2005; 60(10): 982–9
Amin HM, Sopchak AM, Esposito BF, et al. Naloxone-induced and spontaneous reversal of depressed ventilatory responses to hypoxia during and after continuous infusion of remifentanil or alfentanil. J Pharmacol Exp Ther 1995; 274(1): 34–9
Davis PJ, Galinkin J, McGowan FX, et al. A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy: I. Emergence and recovery profiles. Anesth Analg 2001; 93(6): 1380–6
Galinkin JL, Davis PJ, McGowan FX, et al. 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(6): 1387–92
Wee LH, Moriarty A, Cranston A, et al. Remifentanil infusion for major abdominal surgery in small infants. Paediatr Anaesth 1999; 9(5): 415–8
Schmidt J, Fechner J, Fritsch B, et al. Propofol-remifentanil versus sevoflurane-remifentanil for anesthesia for pediatric procedures in infants, children and adolescents [in German]. Anaesthesist 2001; 50(10): 757–66
Bell G, Dickson U, Arana A, et al. Remifentanil vs fentanyl/ morphine for pain and stress control during pediatric cardiac surgery. Paediatr Anaesth 2004; 14(10): 856–60
Akpek EA, Erkaya C, Donmez A, et al. Remifentanil use in children undergoing congenital heart surgery for left-to-right shunt lesions. J Cardiothorac Vasc Anesth 2005; 19(1): 60–6
Roulleau P, Gall O, Desjeux L, et al. Remifentanil infusion for cleft palate surgery in young infants. Paediatr Anaesth 2003; 13(8): 701–7
Pietrini D, Ciano F, Forte E, et al. Sevoflurane-remifentanil vs isoflurane-remifentanil for the surgical correction of craniosynostosis in infants. Paediatr Anaesth 2005; 15(8): 653–62
Chambers N, Lopez T, Thomas J, et al. Remifentanil and the tunnelling phase of paediatric ventriculoperitoneal shunt insertion: a double-blind, randomised, prospective study. Anaesthesia 2002; 57(2): 133–9
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(7): 596–602
Guruswamy V, Roberts S, Arnold P, et al. Anaesthetic management of a neonate with congenital cyst adenoid malformation. Br J Anaesth 2005; 95(2): 240–2
Koomen E, Poortmans G, Anderson BJ, et al. Jet ventilation for laryngotracheal surgery in an ex-premature infant. Paediatr Anaesth 2005; 15(9): 786–9
Sommer M, Riedel J, Fusch C, et al. Intravenous anaesthesia with remifentanil in a preterm infant. Paediatr Anaesth 2001; 11(2): 252–4
Tsiotou AG, Matsota P, Kouptsova E, et al. Use of remifentanil in an infant with surgically repaired Shone's syndrome. Paediatr Anaesth 2004; 14(3): 261–4
Kessler P, Ahrens P, Lischke V, et al. Einsatz von Remifentanil bei Neugeborenen und Sauglingen. Anaesthesiologie und Intensivmedizin 1999, 40, Abstractband DAK 99
Foubert L, Reyntjens K, De Wolf D, et al. Remifentanil infusion for cardiac catheterization in children with congenital heart disease. Acta Anaesthesiol Scand 2002; 46(4): 355–60
Reyntjens K, Foubert L, De Wolf D, et al. Glycopyrrolate during sevoflurane-remifentanil-based anaesthesia for cardiac catheterization of children with congenital heart disease. Br J Anaesth 2005; 95(5): 680–4
Ansermino JM, Brooks P, Rosen D, et al. Spontaneous ventilation with remifentanil in children. Paediatr Anaesth 2005; 15(2): 115–21
Antmen B, Sasmaz I, Birbicer H, et al. Safe and effective sedation and analgesia for bone marrow aspiration procedures in children with alfentanil, remifentanil and combinations with midazolam. Paediatr Anaesth 2005; 15(3): 214–9
Berkenbosch JW, Graff GR, Stark JM, et al. Use of a remifentanil-propofol mixture for pediatric flexible fiberoptic bronchoscopy sedation. Paediatr Anaesth 2004; 14(11): 941–6
Keidan I, Berkenstadt H, Sidi A, et al. Propofol/remifentanil versus propofol alone for bone marrow aspiration in paediatric haemato-oncological patients. Paediatr Anaesth 2001; 11(3): 297–301
Litman RS. Conscious sedation with remifentanil and midazolam during brief painful procedures in children. Arch Pediatr Adolesc Med 1999; 153(10): 1085–8
Litman RS. Conscious sedation with remifentanil during painful medical procedures. J Pain Symptom Manage 2000; 19(6): 468–71
Reyle-Hahn M, Niggemann B, Max M, et al. Remifentanil and propofol for sedation in children and young adolescents undergoing diagnostic flexible bronchoscopy. Paediatr Anaesth 2000; 10(1): 59–63
Glaisyer HR, Sury MR. Recovery after anesthesia for short pediatric oncology procedures: propofol and remifentanil compared with propofol, nitrous oxide, and sevoflurane. Anesth Analg 2005; 100(4): 959–63
Donmez A, Kizilkan A, Berksun H, et al. One center's experience with remifentanil infusions for pediatric cardiac catheterization. J Cardiothorac Vasc Anesth 2001; 15(6): 736–9
Tsui BC, Wagner A, Usher AG, et al. Combined propofol and remifentanil intravenous anesthesia for pediatric patients undergoing magnetic resonance imaging. Paediatr Anaesth 2005; 15(5): 397–401
Akinci SB, Kanbak M, Guler A, et al. Remifentanil versus fentanyl for short-term analgesia-based sedation in mechanically ventilated postoperative children. Paediatr Anaesth 2005; 15(10): 870–8
German JW, Aneja R, Heard C, et al. Continuous remifentanil for pediatric neurosurgery patients. Pediatr Neurosurg 2000; 33(5): 227–9
Stoppa F, Perrotta D, Tomasello C, et al. Low dose remifentanyl infusion for analgesia and sedation in ventilated newborns. Minerva Anestesiol 2004; 70(11): 753–61
Eck JB, Lynn AM. Use of remifentanil in infants. Paediatr Anaesth 1998; 8(5): 437–9
Pereirae Silva Y, Gomez RS, Barbosa RF, et al. Remifentanil for sedation and analgesia in a preterm neonate with respiratory distress syndrome. Paediatr Anaesth 2005; 15(11): 993–6
Crawford MW, Hayes J, Tan JM. Dose-response of remifentanil for tracheal intubation in infants. Anesth Analg 2005; 100(6): 1599–604
Cavaliere F, Antonelli M, Arcangeli A, et al. A low-dose remifentanil infusion is well tolerated for sedation in mechanically ventilated, critically-ill patients. Can J Anaesth 2002; 49(10): 1088–94
Adelmann CgM. Vergleich von Fentanyl und Sufentanil in der Analgo-Sedierung bei beatmeten reifen Neugeborenen mit Lungenversagen [Thesis/Dissertation]. Medizinische Fakultät der Universität zu Köln; 2004
Angst MS, Koppert W, Pahl I, et al. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain 2003; 106(1–2): 49–57
Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 2000; 93(2): 409–17
Vinik HR, Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg 1998; 86(6): 1307–11
Cortinez LI, Brandes V, Munoz HR, et al. No clinical evidence of acute opioid tolerance after remifentanil-based anaesthesia. Br J Anaesth 2001; 87(6): 866–9
Gustorff B, Nahlik G, Hoerauf KH, et al. The absence of acute tolerance during remifentanil infusion in volunteers. Anesth Analg 2002; 94(5): 1223–8
Lee LH, Irwin MG, Lui SK. Intraoperative remifentanil infusion does not increase postoperative opioid consumption compared with 70% nitrous oxide. Anesthesiology 2005; 102(2): 398–402
Minkowitz HS. Postoperative pain management in patients undergoing major surgery after remifentanil vs fentanyl anesthesia. Multicentre Investigator Group. Can J Anaesth 2000; 47(6): 522–8
Schraag S, Checketts MR, Kenny GN. Lack of rapid development of opioid tolerance during alfentanil and remifentanil infusions for postoperative pain. Anesth Analg 1999; 89(3): 753–7
Hahnenkamp K, Nollet J, Van Aken HK, et al. Remifentanil directly activates human N-methyl-D-aspartate receptors expressed in Xenopus laevis oocytes. Anesthesiology 2004; 100(6): 1531–7
Koppert W. Opioid-induced hyperalgesia. Pathophysiology and clinical relevance [in German]. Anaesthesist 2004; 53(5): 455–66
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Welzing, L., Roth, B. Experience with Remifentanil in Neonates and Infants. Drugs 66, 1339–1350 (2006). https://doi.org/10.2165/00003495-200666100-00003
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DOI: https://doi.org/10.2165/00003495-200666100-00003