Intraoperative Opioids and Postoperative Recovery After Hepatobiliary or Foregut Surgery

The primary aim of this randomized, double-blind study is to examine the effect of a single intraoperative dose of methadone on analgesic requirements during the first three days after hepatobiliary or foregut surgery. These patients will be compared to subjects receiving a standard dose of the "traditional" intraoperative opioid (hydromorphone). Secondary outcome measures to be assessed will include postoperative pain scores and standard recovery variables such as hospital length of stay.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Methadone; Drug: Hydromorphone

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Methadone; Patients in the methadone group will be administered 0.3 mg/kg of methadone intraoperatively: 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.	Drug: Methadone; Patients in the methadone group will be administered 0.3 mg/kg of methadone intraoperatively: 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.
ACTIVE_COMPARATOR: Hydromorphone; Patients in the hydromorphone group will receive 0.03 mg/kg of hydromorphone; 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.	Drug: Hydromorphone; Patients in the hydromorphone group will receive 0.03 mg/kg of hydromorphone; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain medication used (hydromorphone)	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.	First 72 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain scores	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.	First 72 hours after sugery
The presence or absence of nausea and vomiting	The presence or absence of nausea and vomiting will be determined by a blinded research assistant	First 72 hours after surgery
Level of sedation	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).	First 72 hours after surgery

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2011
• Primary Completion (ACTUAL): June 1, 2018
• Study Completion (ACTUAL): June 1, 2018

Study Registration Dates

• First Submitted: March 3, 2012
• First Submitted That Met QC Criteria: March 3, 2012
• First Posted (ESTIMATE): March 7, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 6, 2021
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Methadone; Postoperative pain; Hydromorphone; Hepatobiliary surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Hydromorphone; Methadone
• Other Study ID Numbers: EH11-232