Single-dose Intraoperative Methadone for Early Ambulation and Sustained Pain Control in Spinal Fusion Surgery Patients

Methadone is a synthetic opioid analgesic with agonist properties at the µ-opioid receptor binding site that has long been used as an alternative to morphine and hydromorphone in patients with severe pain. It has a diffuse bioavailability and is highly efficacious through its oral form, yet its bioavailability is heavily dependent on variability in cytochrome P450 3A4 enzyme activity, and is quite variable amongst individuals. Methadone reaches peak plasma concentrations in 2.5 to 4 hours after oral administration, has a rapid onset, has a half-life is between 20-35 hours (range 5-130 hours), and analgesia may be reported for up to 108 hours after a single dose. Additionally, methadone's NMDA (N-methyl-D-aspartate) receptor site antagonism acts to inhibit enzymes such as adenyl cyclase and their downstream production of secondary signaling molecules like cyclic AMP (adenosine monophosphate). This activity may attenuate opioid tolerance and opioid abstinence syndrome as NMDA receptor agonism has been implicated in the development of hyperalgesia, acute and chronic tolerance, and chronic pain states.

IV dosing typically ranges from 2.5mg to 10mg every 8-12 hours, with PO forms dosed at 5-20mg every 6-8 hours.

In a study of surgical patients, 40% required no additional post-operative pain control after a single 20mg iv methadone dose intra-operatively, and the 35% that did require a single additional dose required it on average 18.4±6.6 hours post-operatively. The remainder received additional non-narcotic pain medications post-operatively which were sufficient to control pain to tolerable levels.

In a series of 29 patients undergoing multilevel thoracolumbar spine surgeries with instrumentation and fusion, patients were randomized to receive either methadone (0.2mg/kg) or sufentanil infusion of 0.25µg/kg/h after a load of 0.75 µg/kg.Post-operative pain control was delivered by patient-controlled analgesia and patients were assessed by visual analogue scale for pain, opioid dose, and side effected at 1, 2, and 3 days post-operatively. Patients reported less pain in the methadone group 48 hours post-operatively, as well as used less cumulative narcotic dose than the remifentanil control group. Side effects were not significantly different between the two groups. This study however, did not evaluate post-operative functional status, ambulation, and time to discharge.

The literature comparing methadone to more commonly used post-operative narcotics demonstrates that it manages pain better, decreases narcotic requirement, results in no additional adverse events, and is safe, even in children. Since the standard of care is narcotic usage to manage the significant pain of complex spinal surgery cases, it is understandable that methadone could be a desirable therapy to promote sustained pain control and early ambulation in these patients.