The Effect of Choice of Intraoperative Opioid on Postoperative Pain

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Glenn S. Murphy, MD, NorthShore University HealthSystem Research Institute
ClinicalTrials.gov Identifier:
NCT01542645
First received: February 26, 2012
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

The primary aim of this randomized, double-blind study is to examine the effect of a single intraoperative dose of methadone on postoperative pain and analgesic requirements in patients undergoing cardiac surgery with cardiopulmonary bypass. These patients will be compared to subjects receiving a standard dose of the "traditional" intraoperative opioid (fentanyl). Secondary outcome measures to be assessed will include standard recovery variables (such as length of postoperative intubation, ICU length of stay, incidence of nausea or vomiting, level of sedation). In addition, patients will be assessed for the development of chronic postoperative pain.


Condition Intervention Phase
Pain, Postoperative
Chronic Pain
Drug: Methadone
Drug: Fentanyl
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by NorthShore University HealthSystem Research Institute:

Primary Outcome Measures:
  • Total Opioid Consumption in the Postoperative Period [ Time Frame: First 3 days after surgery ] [ Designated as safety issue: No ]
    Total intravenous morphine used first three days (72 hours after ICU admission)


Secondary Outcome Measures:
  • Postoperative Pain Scores [ Time Frame: 2 hours after cardiac surgery ] [ Designated as safety issue: No ]
    Pain was assessed on a 11-point verbal analogue scale with 0=no pain, 10=worst pain imaginable

  • Chronic Postoperative Pain Scores [ Time Frame: 1,3,6, and 12 months after surgery ] [ Designated as safety issue: No ]
  • Marker of Myocardial Injury (Troponin I) [ Time Frame: 12 hours after surgery ] [ Designated as safety issue: Yes ]
    In a cohort of patients undergoing only coronary artery bypass graft surgery (n=75), serum troponins will be measured postoperatively to determine whether methadone has a potential cardioprotective effect.


Enrollment: 164
Study Start Date: September 2010
Estimated Study Completion Date: September 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methadone Drug: Methadone
Methadone (0.3 mg/kg) will be administered intraoperatively, with half of the dose given at induction of anesthesia (over 5 minutes) and the remainder administered as an infusion over the next 2 hours.
Active Comparator: Fentanyl Drug: Fentanyl
Fentanyl (12 mcg/kg) will be administered intraoperatively, with half of the dose given at induction of anesthesia (over 5 minutes) and the remainder administered as an infusion over the next 2 hours.

Detailed Description:

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. In a cohort of patients undergoing only coronary artery bypass graft surgery (n=75), serum troponins will be measured postoperatively to determine whether methadone has a potential cardioprotective effect.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01542645

Locations
United States, Illinois
NorthShore University HealthSystem
Evanston, Illinois, United States, 60201
Sponsors and Collaborators
NorthShore University HealthSystem Research Institute
Investigators
Principal Investigator: Glenn S. Murphy, MD NorthShore University HealthSystem
  More Information

No publications provided

Responsible Party: Glenn S. Murphy, MD, Director, Cardiac Anesthesia and clinical Research, NorthShore University HealthSystem Research Institute
ClinicalTrials.gov Identifier: NCT01542645     History of Changes
Other Study ID Numbers: ENH10-256
Study First Received: February 26, 2012
Results First Received: March 26, 2014
Last Updated: April 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by NorthShore University HealthSystem Research Institute:
Fentanyl
Methadone
Thoracic Surgery

Additional relevant MeSH terms:
Pain, Postoperative
Chronic Pain
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Neurologic Manifestations
Nervous System Diseases
Fentanyl
Methadone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Antitussive Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on August 01, 2014