Iatrogenic opioid abstinence syndrome (IOAS) has been reported in up to 57% of children receiving prolonged opioid therapy during their stay in the intensive care unit (ICU).1 To prevent withdrawal symptoms, opioids are usually tapered gradually. However, the gradual taper of a continuous infusion of an intravenous opioid may result in prolonged length of ICU stay. One method that has been evaluated for the treatment and prevention of IOAS is the initiation of a long acting opioid agent, such as oral methadone. However, there are no clear recommendations regarding the methadone dosing regimens for the management of IOAS and there were significant differences in the dosing regimens utilized in the various studies.
Recently, Johnson et al.2 reviewed the literature to describe the various initial methadone dosing strategies for prevention and treatment of IOAS in critically ill children and to provide practical considerations and recommendations when starting methadone. Eight reports, in English language, with a total of 183 patients were included in the review.3-10 There was a wide discrepancy in how IOAS was defined and how it was assessed in the studies. The initial methadone dose was determined using a weight-based approach or was derived from a formula, based on pharmacokinetic and equianalgesic conversions. Only one study provided a direct comparison between weight-based (low dose) and formula-based (high dose) dosing strategies.10 In two reports, intravenous methadone was used for the first 1-2 days7,8 before switching to enteral methadone, while another study started with intravenous morphine every 4 hours and, once stabilized, the patients were switched to enteral methadone.9 The initial dosing interval ranged from every 6 hours to every 12 hours. The duration of the methadone tapers ranged from 5 days to 6 weeks.
Withdrawal symptoms were reported in all studies evaluating methadone for the prevention of IOAS. Of the 183 patients included in the analysis, 55 (30%) of them experienced withdrawal symptoms. Only 3 studies reported the incidence of oversedation: a total of 7 patients had oversedation and required dose changes.5,9,10 The one study that compared the weight-based with the formula-based dosing approach found no significant difference in the development of withdrawal between the two groups (64.7% vs. 50%, p=0.5).10 However, sedation was reported more in the formula-based, compared to the weight-based dosing approach (2.9% vs. 15.4%, p=0.16).10
Based on the available literature, Johnson et al. recommended to start with the lowest dose of methadone and to titrate to the child's response to avoid oversedation.10 In this setting, the main goal is not pain control and therefore, the equipotent analgesic dose is not needed.10 Based on the authors' experience, a dose of 0.1 mg/kg/dose every 6 hours was recommended, though some patients may require doses up to 0.2 mg/kg/dose.10 It is also important to note that methadone is similar to verapamil and therefore patients may develop cardiac toxicities, such as bradycardia, hypotension, and cardiac arrhythmias. Bradycardia has been associated with ...