Intraoperative Opioids and Postoperative Recovery After Hepatobiliary or Foregut Surgery

60 patients will be enrolled in this clinical trial. All patients presenting for elective
hepatobiliary or foregut surgery will be eligible for enrollment.

Patients will be randomized to receive either methadone or hydromorphone on the basis of a
computer generated random number table. Patients in each group will receive standard clinical
intraoperative doses of either methadone (0.3 mg/kg) or hydromorphone (0.03 mg kg). These
doses (0.3 mg/kg of methadone or 0.03 mg/kg of hydromorphone) represent dosages which appear
to be approximately equipotent. Study medications will be prepared by the pharmacy in 10 cc
syringes, and all clinicians will be blinded to group assignment Patients in the methadone
group will be administered two-thirds of the dose (6 cc or 0.2 mg/kg of methadone) on
induction of anesthesia as a bolus. The remainder of the dose (3 cc or 0.1 mg/kg of
methadone) will be administered at approximately 1.5-2 hours before the end of the procedure.
In the hydromorphone group, patients will receive two-thirds the dose (6 cc or 0.02 mg/kg) on
induction of anesthesia, and the remainder of the hydromorphone (3 cc or 0.01 mg/kg) will be
bolused 1.5-2 hours before surgery concludes. All other anesthestic management will be
standardized.

Data Collection The primary endpoint of the study is total dose of intravenous hydromorphone
used during the first 3 days after surgery. A blinded research assistant will record the
total doses of hydromorphone used in the PACU and with the PCA device during the first 24,
48, and 72 hour after surgery. Several secondary endpoints will be evaluated. Pain in the
postoperative period will be assessed at several time points; PACU arrival, 1, 2, 4, and 8
hours after surgery, and then approximately 8 AM and 4 PM on postoperative days 1-3. Pain
will be quantified by a blinded research assistant using an 11-point verbal rating scale
(0=no pain, 10=worst pain imaginable). Pain will be determined at rest and with coughing. The
presence or absence of nausea and vomiting will be determined. 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).

Inclusion Criteria:

- All patients presenting for elective hepatobiliary or foregut surgery will be eligible
for enrollment

Exclusion Criteria:

- Exclusion criteria include:

1. Preoperative renal failure (defined as a serum creatinine > 2.0 mg/dL.)

2. Morbid obesity

3. American Society of Anesthesiologists Physical Status IV or V

4. Age > 80 years

5. Pulmonary disease necessitating home oxygen therapy

6. Allergy to methadone or hydromorphone

7. Preoperative recent history of opioid or alcohol abuse