The Effect of Choice of Intraoperative Opioid on Postoperative Pain
Condition: Pain, Postoperative; Chronic Pain
MeSH terms: Chronic Pain; Pain, Postoperative
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Methadone; Fentanyl
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): opioid; opioid
Intervention MeSH terms: Fentanyl; Analgesics, Opioid; Methadone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Fentanyl; Methadone; Thoracic Surgery