Methadone and Hydromorphone For Spinal Surgery
Condition: Hydromorphone Use; Acute Postoperative Pain; Patient Satisfaction; Chronic Persistent Surgical Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients undergoing major spinal surgery continue to experience moderate-to-severe pain
      during the first 2-3 days following the operative procedure. Pain complicates the recovery
      process, despite the routine practice of using potent opioid analgesics. The primary reason
      that pain is poorly controlled in patients undergoing major surgery is that most
      commonly-used opioids only produce analgesia for 2-4 hours. The intermittent use of these
      drugs results in periods of time when a patient will experience discomfort (at which time a
      nurse administers more drug or the button on a patient-controlled analgesic (PCA) system is
      pressed to deliver more medication). The use of a long-acting opioid may be advantageous in
      the perioperative setting. Methadone is an opioid that has a median duration of analgesia of
      24-36 hours. Therefore, a single dose administered in the operating room may reduce the need
      for pain medication and improve pain control for the first few postoperative days. The aim of
      this randomized clinical trial is to examine the effect of methadone (compared to
      hydromorphone) on postoperative pain management in patients undergoing major spine surgery
    

Detailed description: 
      Patients: 100 patients (ages 18-80) will be enrolled in this clinical trial. All patients
      presenting for elective posterior lumbar or thoracic spinal fusion 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 (0.2 mg/kg) or hydromorphone (2
      mg). An analysis of patients undergoing posterior lumbar fusion surgery at Evanston Hospital
      revealed that patients received, on average, approximately 2 mg of hydromorphone
      intraoperatively. The most commonly used doses of methadone administered in clinical studies
      have been either 0.2 mg/kg or a dose of 20 mg. Furthermore, these doses also represent
      dosages which appear to be approximately equipotent. Study medications will be prepared by
      the pharmacy, and all clinicians will be blinded to group assignment. Two syringes will be
      prepared for each patient, one which contains the study drug (either methadone 0.2 mg/kg or
      hydromorphone 2 mg), and the other containing the placebo (saline). If the patient is
      randomized to the methadone group, a 3 cc syringe containing 0.2 mg/kg of methadone and
      saline (total volume 3 cc) will be prepared, as well as a 10 cc syringe containing 10 cc of
      saline (placebo). If the patient is randomized to the hydromorphone group, a 3 cc syringe
      containing 3 cc of saline (placebo) will be prepared, as well as a 10 cc syringe containing 2
      mg of hydromorphone with 9 cc of saline (total volume 10 cc). At induction of anesthesia, the
      3 cc syringe containing either 0.2 mg/kg of methadone or placebo will be given over 5
      seconds. At the conclusion of surgery, the 10 cc syringe of either hydromorphone or placebo
      will be titrated slowly per clinician's preference. The administration of all other
      anesthetic agents will be standardized and reflect the usual practices of anesthesiologists
      at Evanston Hospital (spine protocol).

      Anesthesia will be standardized and include propofol for induction, a propofol and
      remifentanil infusion for maintenance (plus sevoflurane), and IV acetaminophen 1000 mg during
      the last 60 minutes of the case.

      On arrival to the postanesthesia care unit (PACU), patients will be assessed for pain by PACU
      nurses per standard protocols. Patients will be evaluated for pain on PACU arrival and then
      every 15 minutes. Patients will be administered hydromorphone 0.25-0.5 mg for pain, and doses
      will be repeated until the patient is comfortable (pain < 3 on a scale of 0-10; 0=no pain and
      10=worst pain imaginable). The patient will then be connected to a PCA device to deliver pain
      medication during the remainder of the postoperative period.

      All postoperative management will be per standard surgical protocols

      Sample Size: The primary end-point of the investigation is amount of hydromorphone used. In a
      clinical trial by Urban et al. of patients undergoing complex spine surgery using a standard
      anesthetic, average hydromorphone consumption in the first 24 hours was 27 mg (18). The
      investigators expect to see at least a 33% reduction in hydromorphone consumption in the
      methadone group. Group sample sizes of 39 and 39 achieve 91% power to detect a difference of
      9.0 between the null hypothesis that both group means are 27.0 and the alternative hypothesis
      that the mean of group 2 is 18.0 with estimated group standard deviations of 10.0 and 10.0
      and with a significance level (alpha) of 0.01000 using a two-sided two-sample t-test. The
      investigators plan to enroll a total of 100 patients to ensure complete collection of data.
    

Intervention name(s): Methadone; Hydromorphone
Intervention type(s): Drug; Drug
Intervention description(s): Methadone 0.2 mg/kg administered at induction of anesthesia; Hydromorphone 2 mg administered at the conclusion of anesthesia
Intervention MeSH terms: Methadone; Hydromorphone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: methadone; hydromorphone; acute postoperative pain; chronic persistent surgical pain