Methadone vs. Fentanyl Administration on Postoperative Pain Control in Pediatric Patients Undergoing Cardiac Surgery

NCT02747875 | Terminated Results

• 1 other identifier: 7364
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if methadone improves postoperative pain control in pediatric patient's undergoing cardiac surgery.

Conditions

Opioid Use, Unspecified

Keywords

pediatric; cardiac bypass surgery; methadone; fentanyl; morphine

Outcome Measures

Primary Outcomes (1)

• Total Opioid Dose, in Morphine Equivalents, in the First 24 Hours After Pediatric Cardiac Bypass Surgery.

  The distribution of the total opioid dose in the first 24 hours will be evaluated by randomization group (methadone vs. fentanyl) and differences between groups will be tested. It is hypothesized that compared to fentanyl, methadone administered intraoperative will result in a significantly lower total opioid dose (morphine or oxycodone) during the first 24 hour postoperative period. Assuming no difference between the two treatment strategies in the population, a total sample size of 52 in each group will provide 80% power to detect an effect size of 0.1. Significance will be measured as a 30% reduction in postoperative pain requirement.

  24 hours

Secondary Outcomes (1)

• Opioid-related Adverse Events Including: Respiratory Failure, Cardiovascular Instability, and Postoperative Nausea and Vomiting

  24 hours

Study Arms (2)

Control - Fentanyl

ACTIVE COMPARATOR

Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment.

Drug: Fentanyl

Treatment - Methadone

ACTIVE COMPARATOR

Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment.

Drug: Methadone

Interventions

Methadone DRUG

The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.

Treatment - Methadone

Fentanyl DRUG

The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.

Also known as: Sublimaze

Control - Fentanyl

Eligibility Criteria

• Age: 2 Years - 7 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age greater than or equal to 2 years and less than 8 years at the time of randomization.
• Weight greater than 6 kg.
• American Society of Anesthesiologists (ASA) physical status of ASA I, II, or III (Appendix I).
• Informed consent to participate from the parent or legally authorized guardian.
• Scheduled for congenital cardiac bypass surgery.

You may not qualify if:

• History or a family (parent or sibling) history of malignant hyperthermia.
• Known significant hepatic disorders determined by medical history, medical record documentation, physical examination, or laboratory tests obtained during the routine preoperative cardiac surgery evaluation or cardiology visit (International Normalized Ratio (INR)\>1.5).
• Emergency Cardiac Surgery.
• History of chronic nausea and/or vomiting.
• Currently receiving inotropic agents or using a pacemaker.
• Prexisting long QTc interval of greater than 460ms determined by medical history, medical record documentation, or electrocardiogram obtained during the routine preoperative cardiac surgery evaluation.
• History of documented pulmonary hypertension, respiratory dysfunction, or requirement of supplemental oxygen therapy.
• History of opioid abuse, addiction, or tolerance.
• Obesity defined as a body weight greater than 130% of the ideal weight.
• Participation in another clinical trial or any study that may interfere with participation in this trial.
• History of allergic reaction to methadone or fentanyl.

Sponsors & Collaborators

• Andrew Waberski: lead

Study Sites (1)

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (24)

• Barletta JF. Clinical and economic burden of opioid use for postsurgical pain: focus on ventilatory impairment and ileus. Pharmacotherapy. 2012 Sep;32(9 Suppl):12S-8S. doi: 10.1002/j.1875-9114.2012.01178.x.

  PMID: 22956490 RESULT

• Oderda G. Challenges in the management of acute postsurgical pain. Pharmacotherapy. 2012 Sep;32(9 Suppl):6S-11S. doi: 10.1002/j.1875-9114.2012.01177.x.

  PMID: 22956493 RESULT

• Lee LA, Caplan RA, Stephens LS, Posner KL, Terman GW, Voepel-Lewis T, Domino KB. Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology. 2015 Mar;122(3):659-65. doi: 10.1097/ALN.0000000000000564.

  PMID: 25536092 RESULT

• Chia YY, Liu K, Wang JJ, Kuo MC, Ho ST. Intraoperative high dose fentanyl induces postoperative fentanyl tolerance. Can J Anaesth. 1999 Sep;46(9):872-7. doi: 10.1007/BF03012978.

  PMID: 10490157 RESULT

• Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003 Aug;97(2):534-540. doi: 10.1213/01.ANE.0000068822.10113.9E.

  PMID: 12873949 RESULT

• Katz J, Jackson M, Kavanagh BP, Sandler AN. Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin J Pain. 1996 Mar;12(1):50-5. doi: 10.1097/00002508-199603000-00009.

  PMID: 8722735 RESULT

• Naguib AN, Tobias JD, Hall MW, Cismowski MJ, Miao Y, Barry N, Preston T, Galantowicz M, Hoffman TM. The role of different anesthetic techniques in altering the stress response during cardiac surgery in children: a prospective, double-blinded, and randomized study. Pediatr Crit Care Med. 2013 Jun;14(5):481-90. doi: 10.1097/PCC.0b013e31828a742c.

  PMID: 23644384 RESULT

• Bowdle TA, Even A, Shen DD, Swardstrom M. Methadone for the induction of anesthesia: plasma histamine concentration, arterial blood pressure, and heart rate. Anesth Analg. 2004 Jun;98(6):1692-1697. doi: 10.1213/01.ANE.0000114085.20751.20.

  PMID: 15155330 RESULT

• Ward RM, Drover DR, Hammer GB, Stemland CJ, Kern S, Tristani-Firouzi M, Lugo RA, Satterfield K, Anderson BJ. The pharmacokinetics of methadone and its metabolites in neonates, infants, and children. Paediatr Anaesth. 2014 Jun;24(6):591-601. doi: 10.1111/pan.12385. Epub 2014 Mar 26.

  PMID: 24666686 RESULT

• Udelsmann A, Maciel FG, Servian DC, Reis E, de Azevedo TM, Melo Mde S. Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting. Rev Bras Anestesiol. 2011 Nov-Dec;61(6):695-701. doi: 10.1016/S0034-7094(11)70078-2. English, Multiple languages.

  PMID: 22063370 RESULT

• Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011 Mar-Apr;14(2):145-61.

  PMID: 21412369 RESULT

• 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.

  PMID: 10215686 RESULT

• Liu JG, Liao XP, Gong ZH, Qin BY. The difference between methadone and morphine in regulation of delta-opioid receptors underlies the antagonistic effect of methadone on morphine-mediated cellular actions. Eur J Pharmacol. 1999 Jun 4;373(2-3):233-9. doi: 10.1016/s0014-2999(99)00270-8.

  PMID: 10414444 RESULT

• Bastero P, DiNardo JA, Pratap JN, Schwartz JM, Sivarajan VB. Early Perioperative Management After Pediatric Cardiac Surgery: Review at PCICS 2014. World J Pediatr Congenit Heart Surg. 2015 Oct;6(4):565-74. doi: 10.1177/2150135115601830.

  PMID: 26467871 RESULT

• Lotsch J. Pharmacokinetic-pharmacodynamic modeling of opioids. J Pain Symptom Manage. 2005 May;29(5 Suppl):S90-103. doi: 10.1016/j.jpainsymman.2005.01.012.

  PMID: 15907650 RESULT

• Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633.

  PMID: 25837528 RESULT

• 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 RESULT

• Gourlay GK, Willis RJ, Lamberty J. A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control. Anesthesiology. 1986 Mar;64(3):322-7. doi: 10.1097/00000542-198603000-00004.

  PMID: 3954126 RESULT

• 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.

  PMID: 6742480 RESULT

• 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.

  PMID: 2066846 RESULT

• Stemland CJ, Witte J, Colquhoun DA, Durieux ME, Langman LJ, Balireddy R, Thammishetti S, Abel MF, Anderson BJ. The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion. Paediatr Anaesth. 2013 Jan;23(1):51-7. doi: 10.1111/pan.12021. Epub 2012 Sep 14.

  PMID: 22978825 RESULT

• Voepel-Lewis T, Zanotti J, Dammeyer JA, Merkel S. Reliability and validity of the face, legs, activity, cry, consolability behavioral tool in assessing acute pain in critically ill patients. Am J Crit Care. 2010 Jan;19(1):55-61; quiz 62. doi: 10.4037/ajcc2010624.

  PMID: 20045849 RESULT

• Moss AJ. Measurement of the QT interval and the risk associated with QTc interval prolongation: a review. Am J Cardiol. 1993 Aug 26;72(6):23B-25B. doi: 10.1016/0002-9149(93)90036-c.

  PMID: 8256751 RESULT

• Price LC, Wobeter B, Delate T, Kurz D, Shanahan R. Methadone for pain and the risk of adverse cardiac outcomes. J Pain Symptom Manage. 2014 Sep;48(3):333-42.e1. doi: 10.1016/j.jpainsymman.2013.09.021. Epub 2014 Jan 28.

  PMID: 24480532 RESULT

MeSH Terms

Interventions

Methadone; Fentanyl

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Andrew Waberski, Assistant Professor
• Organization: Children's National Hospital

awabersk@childrensnational.org

2024762025

Study Officials

• Andrew T Waberski, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 13, 2016
• First Posted: April 22, 2016
• Study Start: September 1, 2016
• Primary Completion: February 7, 2019
• Study Completion: February 7, 2019
• Last Updated: June 1, 2021
• Results First Posted: June 1, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)