Measuring the Amount of Methadone or Morphine in the Blood of Neonates, Infants & Children After Cardiac Surgery.

Treatment:

Fentanyl will be administered for intraoperative analgesia by the treating anesthesiologist
in a dose range of 25 - 50 mcg/kg. No other intraoperative opioids will be given.

Subjects will receive intravenous methadone or morphine ("study drug") delivered by an
initial IV "bolus" injection followed by a nurse-administered patient controlled analgesia
(PCA) device for postoperative pain for a period of 24 hours. The initial dose of study drug
will be 0.2 mg/kg IV administered following admission to the ICU after surgery. The study
drug will then be given at a dose of 0.035 mg/kg IV as needed q30min via PCA. The study drug
may be increased or decreased in increments of 20-25% according to the discretion of the
investigator as needed to maintain a FLACC pain assessment tool < 4. Subjects will also
receive lorazepam 0.025 mg/kg IV q2hr as needed for agitation as indicated by specific
criteria. The study drug will be discontinued after 24 hours to facilitate "wash out"
sampling and determination of elimination half-life. Beginning at 24 hours, fentanyl will be
used for analgesia at an equianalgesic dose to be determined by the investigator based upon
the current PCA "study drug" dose.

Measurements and Monitoring:

- Blood samples will be obtained for measurement of concentrations of methadone
(methadone group) and morphine and its metabolites, morphine-3-glucuronide and
morphine-6-glucuronide (morphine group), prior to administration of initial bolus dose
(t = 0) and t = 5 min, 15 min, 30 min, 60 min, 2 hrs, 4 hrs and 6 hrs; thereafter,
blood samples will be obtained for measurement every 6 hrs for up to 90 hrs according
to availability of vascular access for phlebotomy.

- Continuous monitoring: temperature (rectal), electrocardiogram, heart rate, systemic
arterial blood pressure, central venous blood pressure, respiratory rate, oxygen
saturation (pulse oximetry)

- Intermittent recording (q1hr): urine output

- Lab Tests (at baseline[prior to study procedures] and 24 hours after initial dose of
study medication): arterial blood gas tensions, arterial lactate, Hb/Hct, BUN/Cr,
glucose, AST, ALT

- 12 lead ECG at hour 24 for determination of QTc.

- The Faces, Legs, Activity, Cry, Consolability (FLACC) Scale recoded every hour, and
preceding every study medication PCA dose for 24 hours.

- Subject follow up at 90 hours to record time of extubation, re-intubation if necessary,
and reason for re-intubation.

Primary Endpoints: Pharmacokinetics of methadone and morphine, including its metabolites
(morphine-3-glucuronide and morphine-6-glucuronide)

Secondary Endpoints:

- Pain scores (FLACC) during the 24 hours study period

- Amount of study drug administered during the 24-hour dosing period

- Changes in heart rate, systemic arterial blood pressure and laboratory test values