Pharmacokinetics in children

The average clearance and the steady state volume of distribution of remifentanil are high in younger children and decrease with increasing age to the values for healthy young adults in 17-year-olds. Linear maturation of remifentanil clearance may be explained by the fact that remifentanil is metabolized by unspecific tissue and plasma esterases. Maturation of their metabolic capacity, however, has not yet been studied. (Ziesenitz 2018).

The elimination half-life of remifentanil in neonates and infants (< 1 year) is comparable to  adults after correctection for lower bodyweight. Changes in the analgesic effect quickly follow changes in the infusion rate of remifentanil and are similar to those observed in healthy young adults (SmPC Ultiva). 

Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures:

The PK during postoperative sedation was described by a 2-compartment allometric model during postoperative sedation (Rigby Jones 2007)

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

In neonates: chest wall rigidity.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

The rapid administration of remifentanil provides insufficient sedation and is associated with a high risk of chest wall rigidity in preterm neonates (De Kort 2017). This can be managed by slow and continuous infusion and by using the minimum effective dose. (Maroni 2023)

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

References

1. Rademaker C.M.A. et al, Geneesmiddelen-formularium voor Kinderen, 2007
2. GlaxoSmithKline BV, SPC Ultiva (RVG 20601), www.cbg-meb.nl, Geraadpleegd 07 juli 2010, http://db.cbg-meb.nl/IB-teksten/h20601.pdf
3. Welzing L, 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(6), 1017-24
4. Zhong Y, et al., Evaluating efficacy and safety of sub-anesthetic dose esketamine as an adjuvant to propofol/remifentanil analgosedation <...>prospective, double-blinded, randomized, and placebo-controlled clinical trial., Front Pharmacol., 2023, 14, 1184663
5. Domagalska M, et al., Effectiveness of the Bilateral and Bilevel Erector Spinae Plane Block (ESPB) in Pediatric Idiopathic Scoliosis Surgery: A Randomized, Double-Blinded, Controlled Trial., J Pediatr Orthop., 2024, Aug 1;44(7), e634-e640
6. Szmuk P, et al., An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery: The T REX pilot study., Paediatr Anaesth., 2019, 29(1), 59-67
7. Standing JF, et al., Pharmacokinetic-pharmacodynamic modeling of the hypotensive effect of remifentanil in infants undergoing cranioplasty., Paediatr Anaesth., 2010, 20(1), 7-18
8. Seol TK, et al., Propofol-ketamine or propofol-remifentanil for deep sedation and analgesia in pediatric patients undergoing burn dressing changes: a randomized clinical trial., Paediatr Anaesth., 2015, 25(6), 560-6
9. Chambers N, et al., Remifentanil and the tunnelling phase of paediatric ventriculoperitoneal shunt insertion. A double-blind, randomised, prospective study., Anaesthesia, 2002, 57(2), 133-9
10. Han D, et al, Comparison of Analgesic Efficacy of Local Anesthetic Infiltration and Ultrasound-guided Abdominal Wall Nerve Block in Children Undergoing Ambulatory Inguinal Hernia Repair., J Perianesth Nurs, 2022, 37(5):, 699-705
11. Kaynar A, et al., Effects of different doses of remifentanil infusion on hemodynamics and recovery in children undergoing pediatric diagnostic cardiac catheterization., J Cardiothorac Vasc Anesth., 2011, 25(4), 660-4
12. Shen X, et al., Propofol-remifentanil intravenous anesthesia and spontaneous ventilation for airway foreign body removal in children with preoperative respiratory impairment., Paediatr Anaesth., 2012, 22(12), 1166-70
13. Giannantonio C, et al., Remifentanil analgosedation in preterm newborns during mechanical ventilation., Acta Paediatr., 2009, 98(7), 1111-5
14. Ross AK, et al., Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures., Anesth Analg., 2001, 93(6), 1393-401
15. Bellù R, et al., Opioids for newborn infants receiving mechanical ventilation, Cochrane Database Syst Rev, 2021, 3(3), Cd013732
16. Pereira e Silva YP, et al., Early awakening and extubation with remifentanil in ventilated premature neonates., Paediatr Anaesth., 2008, 18(2), 176-83
17. Xiang K, et al., Comparison of analgesic effects of remifentanil and fentanyl NCA after pediatric cardiac surgery., J Invest Surg, 2014, 27(4), 214-8
18. Demirel N, et al., Remifentanil analgesia during laser treatment for retinopathy of prematurity: a practical approach in neonatal intensive care unit., Am J Perinatol, 2014, 31(11), 983-6
19. Lago P, et al., Remifentanil for percutaneous intravenous central catheter placement in preterm infant: a randomized controlled trial., Paediatr Anaesth., 2008, 18(8), 736-44
20. Kinoshita M,et al., Opioids for procedural pain in neonates., Cochrane Database Syst Rev, 2023, 6(6), Cd015056
21. Li MY, et al., Application of propofol-remifentanil intravenous general anesthesia combined with regional block in pediatric ophthalmic surgery., BMC Anesthesiol., 2024, 24(1), 147
22. Maroni A, et al., Fetal, Preterm, and Term Neonate Exposure to Remifentanil: A Systematic Review of Efficacy and Safety., Paediatr Drugs, 2023, 25(5), 537-55
23. Lo C, et al., Association Between Intraoperative Remifentanil Dosage and Postoperative Opioid Consumption in Adolescent Idiopathic Spine Surgery: A Retrospective Cohort Study., Anesth Analg, 2021, 133(4), 984-90
24. Ziesenitz VC, et al., Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review., Clin Pharmacokinet., 2018, 57(2), 125-49
25. de Kort EH, et al., Insufficient Sedation and Severe Side Effects after Fast Administration of Remifentanil during INSURE in Preterm Newborns., Neonatology, 2017, 111(2), 172-6
26. Welzing L, et al., Remifentanil and propofol for weaning of mechanically ventilated pediatric intensive care patients., Eur J Pediatr., 2011, 170(4), 477-81
27. Malherbe S, et al., Total intravenous anesthesia and spontaneous respiration for airway endoscopy in children--a prospective evaluation., Paediatr Anaesth., 2010, 20(5), 434-8
28. Zhang JM, et al, [Effectiveness of bispectral index in intravenous anesthesia with remifentanil and propofol in children]., Zhonghua Yi Xue Za Zhi., 2008, 88(41), 2904-6
29. Pereira e Silva Y, et al., Morphine versus remifentanil for intubating preterm neonates., Arch Dis Child Fetal Neonatal Ed., 2007, 92(4), F293-4.
30. Rigby-Jones AE, et al., Remifentanil-midazolam sedation for paediatric patients receiving mechanical ventilation after cardiac surgery., Br J Anaesth., 2007, 99(2), 252-61
31. Shin SH, et al., 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), 451-5
32. Aspen Pharma Trading Limited, SmPC Ultiva (RVG 20601) 10-08-2018, www.geneesmiddelinformatiebank.nl

Changes