Perioperative pharmacokinetics of methadone in adolescents.
BACKGROUND
Methadone is frequently administered to adults experiencing anesthesia and receiving pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, however, no information on methadone pharmacokinetics in children of any age. The purpose of this investigation was to determine the pharmacokinetics of intravenous methadone in children undergoing surgery. Perioperative opioid-sparing effects were also assessed.


METHODS
Eligible subjects were children 5-18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3 days. Three groups of 10 to 11 patients each received intravenous methadone hydrochloride after anesthetic induction in ascending dose groups of 0.1, 0.2, and 0.3 mg/kg (up to 20 mg). Anesthetic care was not otherwise changed. Venous blood was obtained for 4 days, for stereoselective determination of methadone and metabolites. Pain assessments were made each morning. Daily and total opioid consumption was determined. Perioperative opioid consumption and pain was determined in a second cohort, which was matched to age, sex, race, ethnicity, surgical procedure, and length of stay, but not receiving methadone.


RESULTS
The final methadone study cohort was 31 adolescents (14 ± 2 yr, range 10-18) undergoing major spine surgery for a diagnosis of scoliosis. Methadone pharmacokinetics were linear over the dose range 0.1-0.3 mg/kg. Disposition was stereoselective. Methadone administration did not dose-dependently affect postoperative pain scores, and did not dose-dependently decrease daily or total postoperative opioid consumption in spinal fusion patients.


CONCLUSIONS
Methadone enantiomer disposition in adolescents undergoing surgery was similar to that in healthy adults.
Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri 63110, USA.
Anshuman
A
Sharma
Danielle
D
Tallchief
Jane
J
Blood
Thomas
T
Kim
Amy
A
London
Evan D
ED
Kharasch
D000293:Adolescent; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000768:Anesthesia, General; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008691:Methadone / Q000097:blood / Q000493:pharmacokinetics*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000097:blood / Q000188:drug therapy; D059035:Perioperative Period / Q000706:statistics & numerical data*; D012600:Scoliosis / Q000601:surgery
D000701:Analgesics, Opioid; D008691:Methadone