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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


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.


withdrawal; methadone; fentanyl

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