IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction

Condition(s) targeted: Scoliosis

Intervention: methadone (Drug)

Phase: Phase 3

Status: Enrolling by invitation

Sponsored by: University of Virginia

Official(s) and/or principal investigator(s):
Christopher Stemland, MD, Principal Investigator, Affiliation: UVA Anesthesiology

This is a pilot study to determine the pharmacokinetics of (R,S) methadone in adolescents. A total of approximately 15 patients will be required. The purpose is to determine the levels of R, S methadone at various time intervals after drug administration. Patients will receive methadone 0. 25 mg/kg IV at induction and a standardized anesthetic of remifentanil and propofol. At the conclusion of surgery (45 minutes prior to the completion), the patients will receive a loading dose of morphine based on respiratory rate. A morphine PCA will be utilized for postoperative analgesia. Pharmacokinetic data will be collected in addition to VAS scores, patient and parental satisfaction with analgesia, and a functional pain assessment.

Official title: IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Primary outcome: methadone levels

Detailed description: Study Procedures Following Surgery:

- VAS scores will be recorded at intervals of 1,2,3,4,5,6,8,12,16,20,24, 36, 48 , 72 hrs

(after extubation).

- Blood samples for PK will require 5ml per sample and may be obtained from an existing

IV or direct phlebotomy and will be obtained at 0min, 5min, 10 min, 15min, 20 min, 40 min, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10 hrs, 12hrs, 24hrs, 48 hrs, 72hrs, and 96hrs after study drug administration.

Minimum age: 12 Years. Maximum age: 19 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Pediatric scoliosis surgery secondary idiopathic scoliosis, congenital scoliosis,

- Age 12 - 19 inclusive

- ASA class I-II.

Exclusion Criteria:

- Preoperative opioid therapy in previous 2 weeks

- Known hepatic or renal impairment

- Inability to assess pain score due to neurological impairment, hearing impairment

- Allergy to methadone, morphine, fentanyl, propofol or remifentanil

- Pregnant or nursing

- Taking SSRI's, MAOI,anticonvulsants, gabapentin or lyrica

- ASA III or greater patients are excluded

- pre-existing chronic pain

University of Virginia Health System, Charlottesville, Virginia 22908, United States

Related publications:

Gourlay GK, Willis RJ, Wilson PR. Postoperative pain control with methadone: influence of supplementary methadone doses and blood concentration--response relationships. Anesthesiology. 1984 Jul;61(1):19-26.

Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67.

Claar RL, Walker LS. Functional assessment of pediatric pain patients: psychometric properties of the functional disability inventory. Pain. 2006 Mar;121(1-2):77-84. Epub 2006 Feb 9.

Walker LS, Greene JW. The functional disability inventory: measuring a neglected dimension of child health status. J Pediatr Psychol. 1991 Feb;16(1):39-58.

Vinik HR, Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg. 1998 Jun;86(6):1307-11.

Davis AM, Inturrisi CE. d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999 May;289(2):1048-53.

Holtman JR Jr, Wala EP. Characterization of the antinociceptive and pronociceptive effects of methadone in rats. Anesthesiology. 2007 Mar;106(3):563-71.

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.

Shir Y, Shenkman Z, Shavelson V, Davidson EM, Rosen G. Oral methadone for the treatment of severe pain in hospitalized children: a report of five cases. Clin J Pain. 1998 Dec;14(4):350-3.

Dale O, Hoffer C, Sheffels P, Kharasch ED. Disposition of nasal, intravenous, and oral methadone in healthy volunteers. Clin Pharmacol Ther. 2002 Nov;72(5):536-45.

Starting date: March 2009
Last updated: September 17, 2010