Dosing of Methadone for Spine Surgery

Patients with spine surgery experience a significant amount of pain that can interfere with healing, rehabilitation and contribute to morbidity in the post-operative period. This study will compare post-operative opioid requirement at 24 and 48 hours to determine if methadone given in small aliquots until respiratory depression can act as a self-control to determine the correct dose required.

• Standard dosing of methadone (Drug): Subject will receive 0.2 mg/kg based on ideal body weight of methadone after the intubation and before positioning.
• Aliquots of methadone titrated to apnea (Drug): Subjects will receive incremental aliquots of methadone up to 0.5 mg/Kg based on ideal body weight titrated to apnea. Each subject will receive a 5-10 mg loading dose then aliquots of 5mg each, given at 3 to 5 minute time intervals.

Primary outcomes

• Change in Opioid Requirement for Complex Spine Surgery Patients 24, 48, and 72 Hours Postop [Postop 24 hours, Postop 48 hours, Postop 72 hours]: The milligram morphine equivalence (MME) dose was computed for each patient in each 24 hour period using IV (intravenous) administration and by mouth (PO). The outcome measure is defined as the difference between 24 hour periods in the cumulative morphine milligram equivalence dose across both IV (intravenous) administration and by mouth (PO). The difference was calculated by subtracting the MME dose value at the later time point minus the MME value at the earlier time point (e.g., value at 24 hours postop minus value at baseline).

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Patients must consent to participate and sign the IRB-approved informed consent prior to beginning any study specific procedures.
2. At or between the ages 18 to 75 years.
3. Undergoing multilevel thoracic, thoracolumbar and/or lumbar spine surgery with instrumentation and fusion.

Exclusion Criteria:

1. Methadone or buprenorphine use.
2. Morbid obesity with BMI>40 Kg/m2.
3. Chronic renal failure with creatinine>2.0 mg/dL.
4. Liver failure as determined by cirrhosis or history of fulminant hepatic failure.
5. Current or historical alcohol abuse.
6. Current or historical drug abuse.
7. Patients with history of prolonged QTc, as defined as a QTc value >450 ms in males and >460 ms in females.
8. Patients with ASA status IV or V.
9. Surgical diagnosis including spine tumor, infection, or trauma.
10. In the Principal Investigator's opinion is not a candidate for the study.
11. Unwilling to sign the informed consent form.

Participant flow

Outcome results

• Change in Opioid Requirement for Complex Spine Surgery Patients 24, 48, and 72 Hours Postop (Primary), Mean, milligram morphine equivalence: Standard Dosing of Methadone 37.3 +/- 28.1; Aliquots of Methadone Titrated to Apnea 68.1 +/- 47.3 (p 0.1449)

Adverse events

Time frame: 3 days

• Results publication: Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24. PMID 20418538

• Study Protocol and Statistical Analysis Plan (PDF, 2024-05-21)

• Christoph Seubert, MD, Principal investigator, University of Florida