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

The proposed study will be conducted at Children's National Health System (CNHS). Pediatric
subjects undergoing cardiac surgery requiring cardiopulmonary bypass will be recruited.
Eligible and consenting participants will be assigned a unique identification number and will
be randomly assigned to receive either methadone or fentanyl using a computer-generated
randomization scheme. A total of 52 participants will be enrolled to each arm of the study,
providing 80% power to detect a 30% difference between groups.

Once informed consent is obtained the inpatient pharmacist at CNHS will randomly assign
eligible participants to receive methadone or fentanyl. The pharmacist will prepare 0.3
mcg/kg of methadone and 20 mcg/kg of fentanyl for loading dose administration, diluted to 10
mL.

The IDS pharmacy will store and maintain all medications per Department of Pharmacy standard
operating procedures for waste of a controlled substance (C-II) drug.

The treatment phase will begin at the induction of general anesthesia and finish at the end
of the surgical procedure. Standard anesthetic practice for monitoring, induction, and
maintenance of general anesthesia will be preserved throughout.

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

As per standard anesthetic practice, the subject will continue to be evaluated for
hemodynamic stability, postoperative risk of bleeding, and respiratory effort. Morphine at
0.05 mg/kg per dose will be administered intravenously as needed for pain control. Surgical
procedures and times will be recorded in the operative report via the electronic medical
record.

Postoperative ICU Phase The postoperative cardiac intensive care unit phase will begin at
admission to the Cardiac Intensive Care Unit (CICU) and will end on the third day of hospital
admission. Postoperative care including hemodynamic stability, resuscitation, and respiratory
support will be at the discretion of the CICU team.

As per CICU protocol, the nurse will monitor and record vital signs and pain scale (FLACC)
scores beginning at handoff from the anesthesia team to the intensive care team. The nurse
will continue to document vital signs including: blood pressure, heart rate, respiratory
rate, oxygen saturation, temperature, minute ventilation when mechanically ventilated, and
oxygen supplementation when appropriate, in the electronic medical record every hour. As per
nursing protocol, FLACC scores will be recorded in the electronic medical record every 4
hours or when the nursing staff witnesses pain during the entirety of the subject's CICU
stay.

All subjects will receive analgesics and sedation medication based on CICU postoperative pain
control and agitation protocol

Data Collection The investigator or designee, blinded to group assignment, will collect all
of the relevant data from the electronic medical record within six months of the cardiac
surgery and enter it into the Medical Center's proprietary web-based data-entry and
data-management system, REDcap (Research Electronic Data Capture). The source of information
will be medical records at the Children's National Health System "Anesthesiology" and "Bear
Tracks" information systems provided by Cerner Corporation.

Data will be obtained specifically for research purposes. Subject identifiers (e.g. name,
date of birth, address) will not be entered into the REDcap system. The previously assigned
unique identification numbers will be used.

Statistical Considerations Significance will be measured as a 30% reduction in postoperative
pain requirement. Statistical analysis will be used to evaluate any differences between the
randomization groups in opioid-related adverse events during the first 24-hour postoperative
period.

Inclusion Criteria:

1. Age greater than or equal to 2 years and less than 8 years at the time of
randomization.

2. Weight greater than 6 kg.

3. American Society of Anesthesiologists (ASA) physical status of ASA I, II, or III
(Appendix I).

4. Informed consent to participate from the parent or legally authorized guardian.

5. Scheduled for congenital cardiac bypass surgery.

Exclusion Criteria

Subjects will not be eligible to participate in the study if any of the following exclusion
criteria apply:

1. History or a family (parent or sibling) history of malignant hyperthermia.

2. 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).

3. Emergency Cardiac Surgery.

4. History of chronic nausea and/or vomiting.

5. Currently receiving inotropic agents or using a pacemaker.

6. 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.

7. History of documented pulmonary hypertension, respiratory dysfunction, or requirement
of supplemental oxygen therapy.

8. History of opioid abuse, addiction, or tolerance.

9. Obesity defined as a body weight greater than 130% of the ideal weight.

10. Participation in another clinical trial or any study that may interfere with
participation in this trial.

11. History of allergic reaction to methadone or fentanyl.