Methadone conversion in infants and children: Retrospective cohort study of 199 pediatric inpatients

Alexandra Fife, PharmD; Andrea Postier, MPH; Andrew Flood, PhD; Stefan J. Friedrichsdorf, MD, FAAP

doi:10.5055/jom.2016.0324

Authors

Alexandra Fife, PharmD
Andrea Postier, MPH
Andrew Flood, PhD
Stefan J. Friedrichsdorf, MD, FAAP

DOI:

https://doi.org/10.5055/jom.2016.0324

Keywords:

methadone, opioid conversion, pediatric, withdrawal, oversedation

Abstract

Objective: Methadone administration has increased in pediatric clinical settings. This review is an attempt to ascertain an equianalgesic dose ratio for methadone in the pediatric population using standard adult dose conversion guidelines.

Setting: US tertiary children's hospital.

Patients: Hospitalized pediatric patients, 0-18 years of age.

Main outcome measures: A retrospective chart review was conducted for patients who were converted from their initial opioid therapy regimen (morphine, hydromorphone, and/or fentanyl) to methadone. The primary endpoint was whether or not a dose correction was needed for methadone in the 6 days following conversion using standard dose conversion charts for adults. Documented clinical signs of withdrawal, unrelieved pain, or oversedation were examined.

Results: The majority (53.7 percent) of the 199 children were converted to methadone on intensive care units prior extubation or postextubation. The mean conversion ratio was 23.7 mg of oral morphine to 1 mg of oral methadone (median, 18.8 mg:1 mg, SD = 25.7). Most patients experienced an adequate conversion (n = 115, 57.8 percent), while 83 (41.7 percent) appeared undermedicated, and one child was oversedated. There were no associations found with conversion ratios for initial morphine dose, days to conversion, or effect of withdrawal of concomitant agents with potential for withdrawal.

Conclusions: Opioid conversion to methadone is commonly practiced at our institution; however, dosing was significantly lower compared to adult conversion ratios, and more than 40 percent of children were undermedicated. The majority of children in this study received opioids for sedation while intubated and ventilated; therefore, safe and efficacious pediatric methadone conversion rates remain unclear. Prospective studies are needed.

Author Biographies

Alexandra Fife, PharmD

Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota

Andrea Postier, MPH

Scientific Investigator, Department of Pain Medicine, Palliative Care and Integrative Medicine, Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota

Andrew Flood, PhD

Career Scientist, Head of Design and Analytics Core, Research and Sponsored Programs, Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota

Stefan J. Friedrichsdorf, MD, FAAP

Medical Director, Department of Pain Medicine, Palliative Care and Integrative Medicine, Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota; Associate Professor, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota. E-mail: Stefan.Friedrichsdorf@childrensmn.org.

References

Berde C, Sethna N, Holzman R: Pharmacokinetics of methadone in children and adolescents in the peri-operative period. Anesthesiology. 1987; 67: A519.

Chana SK, Anand KJS, Rutter N: Can we use methadone for analgesia in neonates? Arch Dis Child Fetal Neonatal Ed. 2001; 85(2): 79F-81F.

Davies D, DeVlaming D, Haines C: Methadone analgesia for children with advanced cancer. Pediatr Blood Cancer. 2008; 51(3): 393-397.

McCarthy JJ, Leamon MH, Willits NH, et al.: The effect of methadone dose regimen on neonatal abstinence syndrome. J Addict Med. 2015; 9(2): 105-110.

Brown MS, Hayes MJ, Thornton LM: Methadone versus morphine for treatment of neonatal abstinence syndrome: A prospective randomized clinical trial. J Perinatol. 2015; 35(4): 278-283.

Johnson PN, Miller JL, Hagemann TM, et al.: External validation of the medication taper complexity score for methadone tapers in children with opioid abstinence syndrome. Ann Pharmacother. 2014; 48(2): 187-195.

Jones GM, Porter K, Coffey R, et al.: Impact of early methadone initiation in critically injured burn patients: a pilot study. J Burn Care Res. 2013; 34(3): 342-348.

Fernandez-Carrion F, Gaboli M, Gonzalez-Celador R, et al.: Withdrawal syndrome in the pediatric intensive care unit. Incidence and risk factors. Med Intensiva. 2013; 37(2): 67-74.

Anghelescu DL, Faughnan LG, Hankins GM, et al.: Methadone use in children and young adults at a cancer center: A retrospective study. J Opioid Manag. 2011; 7(5): 353-361.

Siddappa R, Fletcher JE, Heard AM, et al.: Methadone dosage for prevention of opioid withdrawal in children. Paediatr Anaesth. 2003; 13(9): 805-810.

Williams PI, Sarginson RE, Ratcliffe JM: Use of methadone in the morphine-tolerant burned paediatric patient. Br J Anaesth. 1998; 80(1): 92-95.

Drake R, Longworth J, Collins JJ: Opioid rotation in children with cancer. J Palliat Med. 2004; 7(3): 419-422.

Fine PG, Portenoy RK: Establishing “best practices” for opioid rotation: Conclusions of an expert panel. J Pain Symptom Manage. 2009; 38(3): 418-425.

Lawlor P: Dose ratios among different opioids. In Bruera E, Portenoy RK (eds.): Topics in Palliative Care. New York, NY: Oxford University Press, 2001: 247-276.

Gourlay GK, Cherry DA, Cousins MJ: A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Pain. 1986; 25(3): 297-312.

Friedrichsdorf SJ: From Coke to Pepsi to Mountain Dew? Rotating opioids in advanced pediatric palliative care. AAHPM Winter Q Clin Pearls. 2014; 15(4): 8-9.

Gudin JA: The changing landscape of opioid prescribing: long-acting and extended-release opioid class-wide Risk Evaluation and Mitigation Strategy. Ther Clin Risk Manag. 2012; 8: 209-217.

Mercadante S, Caraceni A: Conversion ratios for opioid switching in the treatment of cancer pain: A systematic review. Palliat Med. 2011; 25(5): 504-515.

Pereira J, Lawlor P, Vigano A, et al.: Equianalgesic dose ratios for opioids. A critical review and proposals for long-term dosing. J Pain Symptom Manage. 2001; 22: 672-687.

Toombs JD, Kral LA: Methadone treatment for pain states. Am Fam Physician. 2005; 71(7): 1353-1358.

von Gunten C: Methadone: Starting dosing information No. 86. J Palliat Med. 2004; 7(2): 304-305.

Jacox A, Carr D, Payne R: New clinical-practice guidelines for the management of pain in patients with cancer. N Engl J Med. 1994; 330(9): 651-655.

Patanwala AE, Duby J, Waters D, et al.: Opioid conversions in acute care. Ann Pharmacother. 2007; 41(2): 255-266.

Moryl N, Santiago-Palma J, Kornick C, et al.: Pitfalls of opioid rotation: Substituting another opioid for methadone in patients with cancer pain. Pain. 2002; 96(3): 325-328.

Johnson P, Boyles K, Miller J: Selection of the initial methadone regimen for the management of iatrogenic opioid abstinence syndrome in critically ill children. Pharmacotherapy. 2012; 32(2): 148-157.

Walker P, Palla S, Pei B-L, et al.: Switching from methadone to a different opioid: What is the equianalgesic dose ratio? J Palliat Med. 2008; 11(8): 1103-1108.

Weschules DJ, Bain KT: A systematic review of opioid conversion ratios used with methadone for the treatment of pain. Pain Med. 2008; 9(5): 595-612.

Gazelle G, Fine PG: Methadone for the treatment of pain #75. J Palliat Med. 2003; 6(4): 620-621.

Dolophine® Hydrochloride CII (Methadone Hydrochloride Tablets, USP) [package insert]. Columbus, OH: ROXANE Laboratories Inc, 2006.

Schechter N, Berde C, Yaster M: Pain in infants, children, and adolescents—An overview. In Schechter N, Berde C, Yaster M (eds.): Pain in Infants, Children, and Adolescents. Philadelphia, PA: Lippincott Williams & Wilkinsl, 2003: 3-18.

Merkel SI, Voepel-Lewis T, Shayevitz JR, et al.: The FLACC: A behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997; 23(3): 293-297.

Krechel SW, Bildner J: CRIES: A new neonatal postoperative pain measurement score. Initial testing of validity and reliability. Pediatr Anesth. 1995; 5(1): 53-61.

Franck LS, Scoppettuolo LA, Wypij D, et al.: Validity and generalizability of the Withdrawal Assessment Tool-1 (WAT- 1) for monitoring iatrogenic withdrawal syndrome in pediatric patients. Pain. 2012; 153(1): 142-148.

Franck LS, Harris SK, Soetenga DJ, et al.: The Withdrawal Assessment Tool-1 (WAT-1): An assessment instrument for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients. Pediatr Crit Care Med. 2008; 9(6): 573-580.

Finnegan LP, Kron RE, Connaughton JF, et al.: A scoring system for evaluation and treatment of the neonatal abstinence syndrome: A new clinical and research tool. In Moriselli PL, Garattini S, Sereni F (eds.): Basic and Therapeutic Aspects of Perinatal Pharmacology. New York, NY: Raven Press, 1975: 139-155.

Curley MA, Harris SK, Fraser KA, et al.: State Behavioral Scale: A sedation assessment instrument for infants and young children supported on mechanical ventilation. Pediatr Crit Care Med. 2006; 7(2): 107-114.

Argoff CE: Clinical implications of opioid pharmacogenetics. Clin J Pain. 2010; 26(suppl 10): S16-S20.

Brennan MJ: The clinical implications of cytochrome p450 interactions with opioids and strategies for pain management. J Pain Symptom Manage. 2012; 44(6 suppl): S15-S22.