Enteral Methadone to Expedite Fentanyl Discontinuation and Prevent Opioid Abstinence Syndrome in the PICU

Pharmacotherapy. 2001;21(12) 

In This Article

Abstract and Introduction

Study Objective. To determine if enterally administered methadone can facilitate fentanyl discontinuation and prevent withdrawal in children at high risk for opioid abstinence syndrome.
Design. Retrospective analysis.
Setting. Pediatric intensive care unit (PICU) in a tertiary care children's hospital.
Patients. Twenty-two children (aged 6.1 ± 5.4 yrs) who received continuous fentanyl infusion for 9 days or longer.
Intervention. Guidelines for initiating enteral methadone, rapidly tapering and discontinuing fentanyl infusions, and tapering methadone were implemented in the PICU. Development of opioid abstinence syndrome was evaluated during fentanyl and methadone dosage reductions and for 72 hours thereafter.
Measurements and Main Results. Children received fentanyl by continuous infusion for 17.8 ± 8.4 days. Peak fentanyl infusion rate was 5.9 ± 3.8 µg/kg/hour, and the median cumulative dose was 1302 µg/kg (range 354-7535 µg/kg). Methadone 0.50 ± 0.22 mg/kg/day was begun 1.6 ± 1.9 days before tapering fentanyl. The fentanyl infusion rate on starting the taper was 5.0 ± 3.6 µg/kg/hour. Fentanyl was tapered and discontinued in a median of 2.6 days (range 0-11.9 days). Twenty-one patients had no opioid abstinence syndrome during or after fentanyl taper. One patient experienced significant opioid withdrawal after fentanyl discontinuation, which resolved after reinstitution of fentanyl and increasing the dosage of methadone to 0.3 mg/kg every 6 hours. Overall, methadone was tapered and discontinued in 18.2 ± 11.9 days without precipitating opioid abstinence syndrome.
Conclusion. Enteral administration of methadone may expedite fentanyl discontinuation and reduce the risk of withdrawal in critically ill children at high risk for opioid abstinence syndrome.

Fentanyl is a synthetic opioid that is widely administered for sedation and analgesia in critically ill infants and children in the pediatric intensive care unit (PICU).[1] Its potency, short duration of action, lack of histamine release, and low potential for causing hemodynamic instability make it an excellent opioid in this patient population. In neonates fentanyl reduces the physiologic stress response associated with surgery and improves outcomes.[2] In the PICU, the drug is commonly administered by continuous infusion to provide uninterrupted analgesia and sedation. Unfortunately, continuous administration often produces rapid tolerance.[3,4,5] Consequently, patients who require long-term therapy often receive escalating doses of fentanyl, which frequently results in opioid dependence and abstinence syndrome when the agent is rapidly discontinued.[4,6,7,8] Signs and symptoms of opioid abstinence syndrome include neurologic manifestations, such as irritability, crying, myoclonus, increased muscle tone, tremors, and seizures; gastrointestinal dysfunction, such as poor feeding, vomiting, and diarrhea; and autonomic signs such as diaphoresis, fever, piloerection, dilated pupils, tachycardia, and hypertension.[8,9,10]

The risk of developing opioid abstinence syndrome on discontinuing fentanyl is greater than 50% in critically ill children who receive a continuous infusion for 5 days, and increases to 100% in those who require continuous infusion for 9 days or longer.[6] A slow taper may reduce the potential for precipitating withdrawal[11]; however, this may require days to weeks to complete. Enteral administration of methadone reportedly reverses signs and symptoms of opioid withdrawal in PICU patients.[12,13] In our experience, starting low-dosage enteral methadone before tapering fentanyl facilitates rapid discontinuation of fentanyl in high-risk patients without precipitating opioid abstinence syndrome. This permits patients to be discharged from the PICU while the dosage of methadone is slowly tapered. There are few data regarding the most appropriate dosage or time to start methadone, how rapidly fentanyl may be tapered, and how long methadone should be continued to prevent opioid withdrawal.


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