Methadone Versus Morphine for Orthopedic Surgery Patients
Condition: Fracture; Pain, Postoperative
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      The investigators propose to compare analgesia by methadone and ketamine with a combination
      of morphine and ketamine in orthopedic surgery patients with moderate to severe pain. The
      investigators hypothesize that when given with ketamine before surgical incision, methadone
      is more effective than morphine in reducing postoperative morphine consumption and reducing
      pain during movement.
    

Detailed description: 
      Patients will receive 1-4 mg midazolam before being transferred to the operating room. All
      patients will receive standard ASA monitoring. In the operating room, the anesthesiologist
      will open a randomization envelope to determine patient group assignment (see below).
      Patients will be anesthetized with 0.2 mg/kg ketamine, 2 µg/kg fentanyl and propofol or
      etomidate IV. Muscle relaxant of the anesthesiologist's choice will be given and the patient
      will be intubated. After intubation, the computer-generated randomization codes stored in
      opaque envelopes will be opened. The patients will be randomized to one of two groups:

        1. Methadone group: Patients will receive 0.2 mg/kg of methadone IV immediately after
           intubation

        2. Control group: Patients will receive 0.2 mg/kg of morphine IV immediately after
           intubation

      The unblinded investigator will draw the drug and dilute to a total volume of 10 cc. This
      syringe will be handed to the anesthesia provider, who will administer the medication after
      induction. They will be maintained with oxygen, air and an inhalational agent of
      anesthesiologist's choice, targeted at BIS between 40 and 60. Additional analgesia will be
      provided with fentanyl in 50 µg increments as required throughout surgery. At the end of
      surgery the neuromuscular block will be reversed and patients will breathe spontaneously.
      Fentanyl will be titrated to maintain a respiratory rate of 12-15 breaths per minute to
      obtain an O2 saturation > 95% and the other extubation criteria are met before tracheal
      extubation . The intraoperative use of narcotics, sedatives and anesthetic drugs will be
      noted. The type of surgery, the duration of surgery and use of additional analgesics and
      antiemetics will be noted.

      An investigator blinded to randomization will track the patients in the PACU. If rescue
      medication is necessary, morphine IV will be given in 2-4 mg increments up to a total of 20
      mg. If the patients continue to report pain (VAS > 4), IV hydromorphone will be given in 0.5
      mg dose every 10-15 minutes until the patient has adequate analgesia (VAS < 4), as decided by
      the PACU nurse.

      Patients will receive morphine patient-controlled analgesia (PCA) for pain relief as the
      primary analgesic. Percocet (Acetaminophen/Oxycodone 325 mg/5 mg) or Lortab
      (Acetaminophen/Hydrocodone 325/5 mg) will be prescribed as needed to maintain VRS < 4.

      In the PACU, vital signs including respiratory rate, heart rate, non-invasive blood pressure,
      sedation score and oxygen saturation will be recorded every 15 minutes. VAS scores for pain
      will be obtained from the patient every 15 minutes until the patient is discharged to the
      floor. VAS (visual analog scale) is a 100-mm scale where 0 = no pain and 100 = worst pain
      imaginable. The investigator will record sedation scores every 15 minutes using the following
      scale until patient is discharged to the floor:

      0-Patient is fully alert

        1. Patient has intermittent sedation

        2. Patient sedated but responsive to verbal stimuli

        3. Patient unresponsive to verbal stimuli

      Patients will be seen at 8 am and 4 pm on the following day and will be contacted at home or
      in the hospital on POD 2 and 3 for information regarding pain scores and analgesic
      requirement. The initial dose of rescue analgesic and time it is given will be recorded. VAS
      at rest and on movement will be recorded, when the patients are seen or VRS will be recorded
      via phone contact. Morphine or other analgesics required during the first 24 and 48 hours
      after surgery, and times to first ambulation, first fluid, solid and flatus will be recorded,
      as will incidence and severity of postoperative nausea and vomiting be recorded.

      Our primary outcome will be opioid consumption during the 48 hours after surgery. All
      analgesics consumed will be converted to morphine equivalent.

      The secondary outcomes will be

        1. Overall rescue analgesic, converted into equipotent doses compared between the two
           groups

        2. Side effects with special attention paid to respiratory rate and possible respiratory
           depression, and PONV

        3. Visual pain score at 48 h post-op.
    

Intervention name(s): Methadone; Morphine
Intervention type(s): Drug; Drug
Intervention description(s): Patients will receive 0.2 mg/kg of methadone IV immediately after intubation; Patients will receive 0.2 mg/kg of morphine IV immediately after intubation
Other intervention name(s): Symoron; Dolophine; Amidone; Methadose; Physeptone; Heptadon; 6-(Dimethylamino)-4,4-diphenylheptan-3-one (IUPAC name); Opiate; (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol
Intervention MeSH terms: Morphine; Methadone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Surgery, Orthopedic; Pain, Postoperative