Clinical trial NCT01542645: The Effect of Choice of Intraoperative Opioid on Postoperative Pain
Official title: The Effect of Choice of Intraoperative Opioid on Postoperative Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Postoperative
Chronic Pain
Keywords: Fentanyl
Methadone
Thoracic Surgery
Lead sponsor: Endeavor Health
Sponsor class: OTHER
First posted: 2012-03-02
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Total Opioid Consumption in the Postoperative Period
timeFrame: First 3 days after surgery
Secondary outcomes:
measure: Postoperative Pain Scores
timeFrame: 2 hours after cardiac surgery
measure: Chronic Postoperative Pain Scores-Weekly Frequency of Pain
timeFrame: 1 months after surgery
measure: Marker of Myocardial Injury (Troponin I)
timeFrame: 12 hours after surgery
measure: 3 Months-Chronic Pain-weekly Frequency of Pain
timeFrame: 3 months
measure: 6 Months-Chronic Pain-weekly Frequency of Pain
timeFrame: 6 months
measure: 12 Months-Chronic Pain-weekly Frequency of Pain
timeFrame: 12 months
Other outcomes:
Locations:
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
Study officials:
affiliation: Endeavor Health
name: Glenn S. Murphy, MD
role: PRINCIPAL_INVESTIGATOR
References: