Open Access Open Access  Restricted Access Subscription or Fee Access

Characterization of early versus late opioid iatrogenic withdrawal syndrome in critically ill children transitioning from fentanyl infusions to methadone

Trager D. Hintze, PharmD, Jamie L. Miller, PharmD, BCPS, BCPPS, FPPA, Stephen B. Neely, MPH, Sin Yin Lim, PharmD, MS, Neha Gupta, MD, FAAP, Peter N. Johnson, PharmD, BCPS, BCPPS, FPPA, FCCM, FASHP

Abstract


Objective: Methadone is used to prevent opioid iatrogenic withdrawal syndrome (IWS) in children, but the optimal dose and overlap time with an opioid infusion have not been elucidated. The purpose was to compare clinical manifestations among patients who developed opioid IWS within 24 hours (early) versus 24 hours (late) of fentanyl discontinuation when enteral methadone was initiated.

Design: A retrospective, descriptive study.

Setting: Pediatric and cardiovascular intensive care units at a tertiary care health system.

Participants: Sixty-seven children received fentanyl infusions for 3 days and initiated on methadone prior to fentanyl discontinuation.

Main outcome measures: The primary objective was to compare clinical characteristics between those with early versus late opioid IWS. Opioid IWS was defined as a Withdrawal Assessment Tool-1 score 3 within 5 days of fentanyl discontinuation. Secondary objectives included a comparison of time to IWS, clinical characteristics, and risk factors among patients with and without IWS.

Results: Fifty children (74.6 percent) developed opioid IWS within a median time of 3.5 hours. No differences were noted for those with and without IWS. Thirty-seven patients (74.0 percent) with IWS developed early IWS. A higher percentage of males in the late versus early group developed IWS, 100 percent versus 51.4 percent, p = 0.002. The median overlap time with methadone and fentanyl was shorter in the early versus late IWS group without reaching statistical significance, 27.5 versus 64.0 hours, p = 0.127.

Conclusions: The majority developed opioid IWS, with most developing early IWS, despite methadone initiation. Future studies should evaluate the optimal methadone dosing and overlap time to prevent opioid IWS.


Keywords


withdrawal; methadone; fentanyl

Full Text:

PDF

References


Anand KJS, Wilson DF, Berger J, et al.: Tolerance and withdrawal from prolonged opioid use in critically ill children. Pediatrics. 2010; 125: E1208-E1225.

Katz R, Kelly HW, Hsi A: Prospective study of the occurrence of withdrawal in critically ill children who receive fentanyl by continuous infusion. Crit Care Med. 1994; 22: 763-767.

Curley MA, Wypij D, Watson RS, et al.: Protocolized sedation vs usual care in pediatric patients mechanically ventilated for acute respiratory failure: A randomized clinical trial. JAMA. 2015; 313: 379-389.

Best KM, Wypij D, Asaro LA, et al.: Patient, process, and system predictors of iatrogenic withdrawal syndrome in critically ill children. Crit Care Med. 2017; 45: 7-15.

Anand KJ, Clark AE, Willson DF, et al.: Opioid analgesia in mechanically ventilated children: Results from the multicenter measuring opioid tolerance induced by fentanyl study. Pediatr Crit Care Med. 2013; 14: 27-36.

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: 573-580.

Ista E, de Hoog M, Tibboel D, et al.: Psychometric evaluation of the Sophia Observation withdrawal symptoms scale in critically ill children. Pediatr Crit Care Med. 2013; 14: 761-769.

Johnson PN: Pain and sedation. In Eiland L, Todd T (eds.): Advanced Pediatric Therapeutics. 1st ed. Memphis, TN: Pediatric Pharmacy Advocacy Group, 2015: 433-459.

Johnson PN: Updates in the management of iatrogenic drug dependence in the pediatric ICU. In Mack EH, Goswami EAS (eds.): Current Concepts in Pediatric Critical Care. Mount Prospect, IL: Society of Critical Care Medicine, 2018: 1-14.

Galinkin J, Kohn JL: Committee on Drugs; Section on Anesthesiology and Pain Medicine; American Academy of Pediatrics: Recognition and management of iatrogenically induced opioid dependence and withdrawal in children. Pediatrics. 2014; 133: 152-155.

Tobias JD: Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit. Crit Care Med. 2000; 28: 2122-2132.

Tobias JD, Schleien CL, Haun SE: Methadone as treatment for iatrogenic narcotic dependency in pediatric intensive care unit patients. Crit Care Med. 1990; 18: 1292-1293.

Tobias JD, Deshpande JK, Gregory DF: Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit. Intensive Care Med. 1994; 20: 504-507.

Tobias JD: Outpatient therapy of iatrogenic opioid dependency following prolonged sedation in the pediatric intensive care unit. J Intensive Care Med. 1996; 11: 284-287.

Lugo RA, MacLaren R, Cash J, et al.: Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. Pharmacotherapy. 2001; 21: 1566-1573.

Robertson RC, Darsey E, Fortenberry JD, et al.: Evaluation of an opiate-weaning protocol using methadone in pediatric intensive care unit patients. Pediatr Crit Care Med. 2000; 1: 119-123.

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

Meyer MT, Berens RJ: Efficacy of an enteral 10-day methadone wean to prevent opioid withdrawal in fentanyl-tolerant pediatric intensive care unit patients. Pediatr Crit Care Med. 2001; 2: 329-333.

Bowens CD, Thompson JA, Thompson MT, et al.: A trial of methadone tapering schedules in pediatric intensive care unit patients exposed to prolonged sedative infusions. Pediatr Crit Care Med. 2011; 12: 504-511.

Jefferies SA, McGloin R, Pitfield AF, et al.: Use of methadone for prevention of opioid withdrawal in critically ill children. Can J Hosp Pharm. 2012; 65: 12-18.

Johnson PN, Miller J, Harrison D: Evaluation of initial methadone dosing for prevention of iatrogenic opioid abstinence syndrome in children. J Pediatr Intensive Care. 2012; 2: 105-113.

Giby K, Vaillancourt R, Varughese N, et al.: Use of methadone for opioid weaning in children: Prescribing practices and trends. Can J Hosp Pharm. 2014; 67: 149-156.

Steineck KJ, Skoglund AK, Carlson MK, et al.: Evaluation of a pharmacist-managed methadone taper. Pediatr Crit Care Med. 2014; 15: 206-210.

Srinivasan V, Pung D, O’Neill SP: Conversion from prolonged intravenous infusion to enteral methadone in critically ill children. World J Clin Pediatr. 2017; 6: 110-117.

Vipond JM, Heiberger AL, Thompson PA, et al.: Shortened taper duration after implementation of a standardized protocol for iatrogenic benzodiazepine and opioid withdrawal in pediatric patients: Results of a cohort study. Pediatr Qual Saf. 2018; 3(3): E079. DOI: 10.1097/pq9.0000000000000079.

Ibach BW, Miller JL, Woo S, et al.: Characterization of tolerance in children during fentanyl continuous infusions. J Pediatr Intensive Care. 2016; 6: 083-090.

Johnson PN, Skrepnek GH, Golding CL, et al.: Relationship between rate of fentanyl infusion and time to achieve sedation in nonobese and obese critically ill children. Am J Health-Syst Pharm. 2017; 74: 1174-1183.

WHO Multicentre Growth Reference Study Group: WHO Child Growth Standards: Length/Height-for-Age: Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index-for-Age: Methods and Development. Geneva, Switzerland: World Health Organization, 2006. Available at https://www.who.int/childgrowth/standards/technical_report/en/. Accessed December 9, 2020.

Centers for Disease Control and Prevention: Children's BMI tool for schools. 2011. Available at https://www.cdc.gov/healthyweight/bmi/calculator.html. Accessed December 9, 2020.

Ginsberg B, Howell S, Glass PS, et al.: Pharmacokinetic model driven infusion of fentanyl in children. Anesthesiology. 1996; 85: 1268-1275.

Best KM, Boullata JI, Curley MAQ: Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: A systematic review and conceptual model. Pediatr Crit Care Med. 2015; 16: 175-183.

Zuppa A, Corrado DJ, Zane NR, et al.: Midazolam dose optimization in critically ill pediatric patients with acute respiratory failure: A population pharmacokinetic-pharmacogenomic study. Crit Care Med. 2019; 47: E301-E309.

Gade C, Sverrisdottir E, Dalhoff K, et al.: Midazolam pharmacokinetics in obese and non-obese children and adolescents. Clin Pharmacokinet. 2020; 59: 643-654.

Fisher D, Grap MJ, Younger JB, et al.: Opioid withdrawal signs and symptoms in children: Frequency and determinants. Heart Lung. 2013; 42: 407-413.

Johnson PN, Boyles KA, Miller JL: Selection of the initial methadone regimen for the management of iatrogenic opioid abstinence syndrome in critically ill children. Pharmacotherapy. 2012; 32: 148-157.

Berde CB, Sethna NF, Holzman RS, et al.: Pharmacokinetics of methadone in children and adolescents in the perioperative period. Anesthesiology. 1987; 67: A519-A519.

Wachman EM, Hayes MJ, Brown MS, et al.: Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA. 2013; 309: 1821-1827.

Sarton E, Olofsen E, Romberg R, et al.: Sex differences in morphine analgesia: An experimental study in healthy volunteers. Anesthesiology. 2000; 93: 1245-1254.




DOI: https://doi.org/10.5055/jom.2023.0758

Refbacks

  • There are currently no refbacks.