A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects

In the context of a resurgence in interest in the perioperative use of methadone, the authors set about expanding an evidence base for multi-dose perioperative methadone use as compared with single dose intraoperative use in major paediatric surgery as part of enhanced recovery (ERAS).

They referred to their previous ‘before and after’ cohort study within a quality improvement programme (QIP) for posterior spinal fixation for idiopathic scoliosis, in which a multidose methadone regimen was compared with PCA opiate use, with a resultant reduction of average length of stay (LOS) from 3 to 2 days and a 23% reduction in average total morphine equivalent usage and a small reduction in average pain scores. In this more recent study, they aimed to provide a pharmacokinetic basis for this observation and to demonstrate an associated low rate of adverse events such as QTc prolongation and respiratory depression.

Of note in their first study, methadone was part of a newly implemented multi-faceted multimodal analgesia regimen with several other components, any or all of which may have contributed to the positive outcomes seen and may not represent a recommendation for methadone use specifically.

Two other studies were referenced: one in which methadone was again only one part of an ERAS protocol and another in which a single intraoperative dose seemed to produce a similar reduction in total morphine equivalent (24%) without any impact on LOS or pain scores. It appeared ERAS was not part of this latter study.

Overall, there appeared to be poor evidence that any of the pharmacokinetic trends determined either pain outcomes or adverse events (low R2 values). The sample size of 38 was small and composed of two different surgeries. Consequently, inferences about any outcomes, in particular less common adverse events like QTc prolongation, seemed difficult to make. A report on the total range of QTc values as opposed to an inter-quartile range would have been of more value. There was no indication of the severity of scoliosis and incidence of preoperative restrictive respiratory deficits.

Aside from a potential reduction in PCA usage with associated reduction in nursing burden and cost (up to 10-fold purported), there seemed little evidence of benefit to the patient for the specific use of methadone (whether single or multi-dose) as part of ERAS for major surgery. A randomised study comparing matched ERAS protocols with and without methadone would better answer this question.

Reviewed by Dr David Stoeter