Methadone in Spine Surgery
Primary Recommendation
For patients undergoing complex spine surgery, a single intraoperative dose of methadone (0.2 mg/kg) administered at the start of surgery should be strongly considered as part of a multimodal analgesic regimen, as it reduces postoperative opioid consumption by approximately 50% and significantly decreases pain scores for up to 72 hours postoperatively. 1, 2
Evidence Supporting Intraoperative Methadone Use
Acute Postoperative Benefits
Methadone 0.2 mg/kg given at surgical incision reduces postoperative opioid requirements by approximately 50% at 48 and 72 hours compared to traditional opioids (sufentanil or hydromorphone), with median morphine equivalents of 25 mg versus 63 mg at 48 hours (P = 0.023) 1
Pain scores are reduced by approximately 50% at 48 hours postoperatively in patients receiving methadone (mean 2.8 ± 2.0 versus 4.8 ± 2.4 on a 0-10 scale, P = 0.026) 1
Patient satisfaction with pain management is significantly higher in the methadone group through postoperative day 3 (all P = 0.001 to < 0.0001) 2
The analgesic benefits extend through postoperative days 1,2, and 3, with continued reductions in opioid consumption and pain scores 2
Longer-Term Outcomes
Methadone reduces the frequency of chronic pain at 3 months postoperatively (median score 0 [less than once weekly] versus 3 [daily] in the hydromorphone group, P = 0.004), though this benefit does not persist at 6 and 12 months 3
The greatest analgesic benefits occur during the first 3 months after surgery, when pain intensity and frequency are highest 3
Pediatric Population
In adolescents with idiopathic scoliosis undergoing posterior spinal fusion, methadone-based multimodal analgesia reduces length of hospital stay from a median of 3 days to 2 days (P < 0.001) 4
Total inpatient opioid consumption is significantly lower with methadone-based protocols (P < 0.001) 4
Time to first bowel movement is reduced (P < 0.001), and postdischarge pain-related phone calls decrease (P < 0.006) 4
Dosing and Administration
Standard Intraoperative Dosing
Administer methadone 0.2 mg/kg intravenously at the start of surgery (before surgical incision), not at closure 1, 2
This single dose provides analgesia lasting 48-72 hours due to methadone's long elimination half-life (approximately 30 hours) 5
Patients Already on Methadone Maintenance Therapy
Continue the patient's baseline methadone dose throughout the perioperative period to prevent withdrawal and reduce relapse risk 5, 6
For breakthrough pain, consider split-dosing the daily methadone (dividing into multiple doses) to improve analgesia, as methadone's analgesic duration (6-8 hours) is shorter than its elimination half-life 5
Administer additional short-acting opioids for acute postoperative pain, recognizing that higher doses will be required due to opioid tolerance 5, 7
Patients on methadone maintenance cannot be expected to derive analgesia from their baseline methadone dose for acute postoperative pain 7
Integration with Multimodal Analgesia
Core Multimodal Components
Methadone should be combined with the following evidence-based interventions for optimal pain control: 6
Pregabalin or gabapentin administered preoperatively and continued postoperatively 6
COX inhibitors (NSAIDs or COX-2 inhibitors like celecoxib), particularly safe for <2 weeks duration even after spinal fusion 6
Acetaminophen scheduled throughout the perioperative period 6
Local anesthetic wound infiltration with bupivacaine or liposomal bupivacaine for extended relief 6
Intravenous lidocaine or ketamine infusions as adjuncts 6
Opioid Stewardship
Limit postoperative opioid prescriptions to no more than 7 days to minimize risk of persistent opioid use 8
Opioid use within 7 days of surgery is associated with a 44% increased risk of use at 1 year, emphasizing the importance of multimodal strategies 6
Critical Safety Considerations
QT Prolongation Risk
Methadone can prolong the QT interval, requiring caution when combined with other QT-prolonging medications (class I/III antiarrhythmics, some neuroleptics, tricyclic antidepressants, calcium channel blockers) 7
Avoid drugs that induce electrolyte disturbances (hypomagnesemia, hypokalemia) such as diuretics and laxatives 7
Patients should be instructed to seek immediate medical attention for symptoms of arrhythmia (palpitations, dizziness, lightheadedness, syncope) 7
Drug Interactions
Methadone should only be administered by clinicians experienced in its use due to risk of accumulation 6
Avoid concurrent benzodiazepines whenever possible, as deaths have been reported with this combination 7
Exercise extreme caution with MAO inhibitors; if methadone is necessary, perform a sensitivity test with small incremental doses under careful observation 7
Special Populations
Methadone is preferred in renal insufficiency (GFR <30 mL/min/1.73 m²) as it has no active metabolites, unlike morphine, codeine, or meperidine 6
Reduce initial doses in elderly, debilitated patients, and those with hepatic impairment, hypothyroidism, or Addison's disease 7
Common Pitfalls and How to Avoid Them
Misconception About Addiction Risk
There is no evidence that using opioids for analgesia in patients on methadone maintenance increases relapse rates 5
Untreated pain is a more likely trigger for relapse than adequate analgesia 5
The theoretical risk of respiratory depression from combining methadone maintenance with perioperative opioids has never been demonstrated clinically 5
Timing of Administration
Methadone must be given at the START of surgery, not at closure, to maximize its long-acting analgesic benefits 1, 2
Giving methadone at closure (like traditional opioids) negates its primary advantage of providing extended postoperative analgesia 1
Inadequate Multimodal Approach
Methadone alone is insufficient; it must be part of a comprehensive multimodal regimen including gabapentinoids, NSAIDs, and acetaminophen 6
Overreliance on opioids (including methadone) without adjuncts leads to inadequate pain control and increased side effects 6
Patient Selection Errors
Identify patients with preoperative chronic pain, substance abuse history, or mental health comorbidities early, as they require tailored pain management strategies 6
Patients with preoperative opioid use will require higher postoperative doses due to tolerance 6
Current Evidence Quality
The strongest evidence comes from prospective randomized controlled trials demonstrating methadone's superiority over traditional opioids (hydromorphone, sufentanil, fentanyl) for complex spine surgery 1, 2
A 2025 scoping review confirms significant heterogeneity in dosing and timing, but consistently shows reduced pain scores and opioid consumption 9
Safety concerns from observational studies have not been confirmed by prospective randomized trials 9
Further research is needed on optimal dosing regimens and long-term antinociceptive benefits beyond 3 months 9