Clinical trial NCT02206685: A Trial Comparing Single Intra-op Dose of Methadone Versus Placebo in Patients Undergoing Spine Surgery
Official title: A Randomized Blinded Prospective Trial Comparing Single Intraoperative Dose of Methadone Versus Placebo in Pediatric Patients Undergoing Spine Surgery.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Thoracolumbar Scoliosis
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2014-08-01
Enrollment: 74
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which is a measurement used for evaluation of curves in scoliosis on an anterior-posterior radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40 degrees in the lumbar region) or when the curvature causes significant pain, or respiratory and cardiovascular restriction. Patient undergoing this surgical correction experience severe pain in the postoperative period and the management includes the use of opioid-based patient-controlled analgesia (PCA).

Detailed description: Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which is a measurement used for evaluation of curves in scoliosis on an anterior-posterior radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40 degrees in the lumbar region) or when the curvature causes significant pain, or respiratory and cardiovascular restriction. Patient undergoing this surgical correction experience severe pain in the postoperative period and the management includes the use of opioid-based patient-controlled analgesia (PCA).

Methadone is an opioid with one of the longest elimination half-life and has been used as an effective analgesic for acute, chronic, neuropathic, and cancer pain in adults, children, and even neonates1-5. Its long duration of action and antagonism to the N-methyl-d-aspartate receptor may decrease the need for PCA use in the postoperative period. Gourlay2 demonstrated the effectiveness and utility of perioperative methadone including the advantages of longer analgesia with no serious side effects of respiratory depression. A recent study by Gottschalk2 in adult patients demonstrated a 50% reduction of postoperative opioids at 48 hours and lower pain scores after a single bolus of methadone before surgical incision. However, a major weakness of the study is that patients did not receive equipotent intraoperative opioids. In addition, the adolescent patient population will undergo a much larger surgical incision with potential for greater postoperative pain. Despite this potential benefit, methadone is seldom used in the perioperative setting. A more recent pharmacokinetic study of methadone in adolescents undergoing spine surgery failed to show a reduction in opioid consumption as it was powered to determine pharmacokinetics and not a secondary endpoint of postoperative opioid consumption. An appropriately powered study is still required to determine the efficacy of methadone in reducing postoperative pain after spine surgery.

Eligibility criteria: Inclusion Criteria:

1. Patient age 10 - 17 years
2. Patients undergoing multilevel thoraco-lumbar spine surgery with instrumentation and fusion

Exclusion Criteria:

1. Preoperative methadone therapy
2. Inability to use the PCA
3. Allergy to methadone or morphine
4. Morbid obesity with a body mass index \>36.0 kg/m2
5. Patients with chronic renal failure defined by serum creatinine \>2.0 mg/dL
6. Liver failure defined as a history of cirrhosis or fulminant hepatic failure
7. Preoperative congenital heart disease or arrhythmias
8. Patient refusal to participate in study
9. Pregnancy (It is standard of care for all post menarche female patients to undergo a urine pregnancy test prior to surgery).

Primary outcomes:
measure: Opioid Usage
timeFrame: Admission to PACU to 72 hours post-operative
Secondary outcomes:
measure: Pain Scores
timeFrame: Admission to PACU to 72 hours post-operative
Other outcomes:
Locations:
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Kim Nguyen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nicholson AB. Methadone for cancer pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003971. doi: 10.1002/14651858.CD003971.pub3.
citation: Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available.
citation: 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.
citation: Sharma A, Tallchief D, Blood J, Kim T, London A, Kharasch ED. Perioperative pharmacokinetics of methadone in adolescents. Anesthesiology. 2011 Dec;115(6):1153-61. doi: 10.1097/ALN.0b013e318238fec5.
citation: Berde CB, Beyer JE, Bournaki MC, Levin CR, Sethna NF. Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children. J Pediatr. 1991 Jul;119(1 Pt 1):136-41. doi: 10.1016/s0022-3476(05)81054-6.