The Effect of Choice of Intraoperative Opioid on Postoperative Pain

Patients will be randomized to receive either methadone or fentanyl on the basis of a
computer generated random number table. Patients in each group will receive standard
intraoperative doses of either methadone or fentanyl that will allow for early tracheal
extubation (within 4-8 hours of the conclusion of the surgical procedure). Study infusions
will be prepared by the pharmacy, and all clinicians will be blinded to group assignment
(methadone group-0.3 mg/kg-100 mL normal saline; fentanyl group-12 μg/kg-100 mL normal
saline).

Pain will be assessed by blinded observers using a 11-point verbal analogue scale (0=no
pain, 10=worst pain imaginable). Assessment for pain will be performed 15 minutes
post-extubation and then 2, 4, 8, 12, 24, 48, and 72 hours after tracheal extubation. Pain
will be determined at rest, with coughing, and during movement. At the same time pain data
is collected, several other clinical assessments will be completed. The presence or absence
of nausea and vomiting will be determined, and severity quantified using a 4-point ordinal
scale (0=none, 3=severe). Level of sedation will be measured by observers using a 4-point
sedation scale (0=fully awake, 1=mildly sedated (seldom drowsy and easy to awake),
2=moderately sedated (often drowsy and easy to awake), 3=severely sedated (somnolent,
difficult to awake). Pruritis will also be measured using a 4-point scale (0=none,
3=severe). Any episodes of hypoventilation (respiratory rate < 8 breaths/min) or hypoxemia
(oxygen saturation < 90%) during the study period will be recorded. Patient satisfaction
with overall pain management will be determined using a 100-point verbal rating scale
(1=highly dissatisfied (worst), 100=highly satisfied (best)). Respiratory rate, oxygen
saturation (in ICU), and mean arterial blood pressure at the time of evaluation will be
noted.

Postoperative pain will be managed according to standard institutional protocols. In the
ICU, intravenous morphine will be administered for initial pain management (1 mg for
mild-moderate pain, 2 mg for moderate-severe pain). Patients will be transitioned to oral
pain medication when oral intake is tolerated (Norco tablets). The amount of pain
medication administered during each study interval (listed above) will be recorded.

Other standard recovery variables will be recorded. These include time of initiation of
ventilator weaning, time of tracheal extubation, arterial blood gas following extubation,
time of ICU discharge, and time of hospital discharge. Time of first flatus and bowel
movement will be recorded. Any complications during the hospitalization will be recorded.

Patients will be provided with a survey and self-addressed envelope following discharge from
the hospital to determine the presence or absence of chronic persistent surgical pain.
These data will be mailed by each patient 1, 3, 6, and 12 months postoperatively. The
survey will assess the nature and severity of pain related to the surgical procedure.

Inclusion Criteria:

- All patients presenting for elective cardiac surgery with CPB will be eligible for
enrollment.

Exclusion Criteria:

1. Preoperative renal failure requiring dialysis

2. Significant hepatic dysfunction (liver function tests > 2 times upper normal limit)

3. Preoperative ejection fraction < 30%

4. Pulmonary disease necessitating home oxygen therapy

5. Preoperative requirement for inotropic agents or intraaortic balloon pump to maintain
hemodynamic stability

6. Allergy to methadone or fentanyl

7. Preoperative pain, use of preoperative opioids, or recent history of opioid abuse