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

Pharmacotherapy. 2001;21(12) 

In This Article

Methods

Guidelines for beginning methadone and rapidly discontinuing fentanyl were implemented in 1994 for the PICU. The aim is to expedite fentanyl discontinuation while minimizing development of opioid abstinence syndrome. According to the guidelines, children are identified as being at high risk for the syndrome if they receive a continuous intravenous fentanyl infusion for 9 days or longer.[4,6] In these patients, enterally administered methadone is started 1-2 days before beginning a rapid fentanyl taper. The initial dosage of methadone -- 0.1 mg/kg every 6 hours -- was based on published reports and our own clinical experience in treating opioid abstinence syndrome.[9,12,13] According to the guidelines, clinicians are permitted to prescribe higher dosages of methadone at their discretion, particularly if intravenous fentanyl is given for a prolonged period (weeks) or if there is concern about underlying pain. After methadone is begun, the dosage of fentanyl is reduced 10-15% of the original dose every 8 hours until the infusion is discontinued in 2-3 days. Physicians are permitted to taper the fentanyl dosage more rapidly or slowly as required by the clinical situation. If signs or symptoms of withdrawal occur during the taper, the taper is suspended, an extra dose of fentanyl or methadone is administered, the maintenance dosage of methadone is increased by 50%, and the fentanyl taper is resumed 24 hours later. Two days after fentanyl is discontinued, the dosage of methadone is tapered by increasing the interval to every 8 hours for 2 days, then every 12 hours for 2 days, followed by 25% reductions of the original dose every 2-3 days until methadone is discontinued.

Guidelines for tapering and discontinuing benzodiazepines after long-term administration were instituted at the same time as the fentanyl-methadone guidelines. Accordingly, sedation is maintained with an oral benzodiazepine as soon as an enteral feeding tube is placed.[14] The dosage of benzodiazepine is reduced by 25-50% at the time of extubation. Beginning 2-3 days later, the dosage interval is extended to every 8 hours for 2-3 days, followed by a 25% reduction of the original dosage every 2-3 days. The entire taper requires approximately 14 days.

The institutional review board waived the requirement for informed consent, and approval for the retrospective study was obtained from the medical records committee. Medical records were identified by searching the PICU database over a 3-year period (after implementation of the guidelines) for patients who received continuous fentanyl infusion for 9 days or longer and who also received scheduled methadone. Patients were excluded from the analysis if they had received a previous course of fentanyl and/or another opioid analgesic.

The following data were obtained from medical records: patient demographics (age, weight, race, primary diagnosis, and length of PICU stay and hospitalization); laboratory values (hepatic transaminases, albumin, blood urea nitrogen, serum creatinine); fentanyl regimen (cumulative dose, peak infusion rate, total duration of infusion, time to discontinuation measured from the time that the taper began); methadone regimen; concomitant sedatives (e.g., midazolam, lorazepam, diazepam, and pentobarbital), and other concomitant drugs.

Commencement of the fentanyl taper was defined as a dosage reduction of 25% or more that followed a stable dose for 48 hours or longer. Opioid abstinence syndrome was defined as the presence of documented signs of the syndrome that interfered with the comfort or care of the patient: agitation or irritability, crying or inconsolability, tremors, tachycardia, hyper-tension, tachypnea, increased muscle tone, choreoathetoid movements, myoclonus, seizures, regurgitation or emesis, loose or watery stools, increased frequency of stools, diaphoresis, piloerection, or dilated pupils.[7,10,15] To be classified as having opioid abstinence syndrome, these signs must have arisen within 72 hours of the last dosage reduction of fentanyl or methadone, were determined by the medical team to require treatment, and were attenuated or reversed with additional or increased dosages of opioids. A diagnosis of opioid withdrawal was not made if a more likely diagnosis was apparent from review of the record. All information was obtained from physicians' and nurses' progress notes, nursing flow sheets, and drug administration records.

Data are presented as either mean ± SD or median (for skewed data) and analyzed by Student's t test or Mann-Whitney U test when appropriate. Reduction in the rate of fentanyl administration over time was analyzed by Friedman's repeated-measures analysis of variance on ranks using Dunn's post hoc comparison. Correlations were determined using Pearson product moment correlation. Stepwise multiple linear regression was used to determine variables associated with time to fentanyl discontinuation. Statistical significance was set a priori at a p value of 0.05 or lower. Statistical analysis was performed with SigmaStat software version 2.03 (SPSS, Inc., Chicago, IL).

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