Intervention: Morphine
Trial phase: Not Applicable
ATC code: A07DA52 | N02AA01 | N02AA51 | N02AG01
SMILES: [H][C@@]12C=C[C@H](O)[C@]3([H])Oc4c(O)ccc5c4[C@]13CCN(C)[C@]2([H])C5
Sex: All
Age groups: Adult
Healthy volunteers: No
Participants at risk: 8
Group description: 0.2 mg/kg morphine by actual body weight, administered over ten minutes, initiated after induction of anesthesia and endotracheal intubation complete.

Morphine: 0.2 mg*kg-1 by actual body weight, administered over 10 minutes, once induction of anesthesia and endotracheal intubation are complete.
Eligibility criteria:
Inclusion Criteria:

Subjects scheduled for elective, non-emergent intramedullary nailing (IMN) or open reduction/internal fixation (ORIF) of the tibia at Ben Taub General Hospital
Able to give consent (not cognitively impaired or intoxicated)
Subjects must be 18-50 years of age
American Society of Anesthesiologists (ASA) physical status I-III
Scheduled for primary intramedullary nailing or open reduction/internal fixation of fractures of the tibial shaft or proximal tibia. This must be the first operation for this injured extremity.
Associated fractures of the fibula will be allowed.
Minor lacerations or other associated injuries like "road rash" or open wounds requiring skin graft are permitted

Exclusion Criteria:

Subjects who have taken preoperative opioids for more than 7 days before surgery (i.e., tolerant)
Regular use of opioids (whether recreational/illicit or prescribed) within the six months before injury
Subjects who are recommended to receive a regional nerve block or a neuraxial technique (spinal or epidural) by the attending orthopedic surgeon
Subjects who refuse general anesthesia
Subjects deemed to be moderately or severely hypovolemic
External fixator already in place on the injured extremity
Presence of other moderate-to-severe or distracting injuries, such as orthopedic, cervical spine, neurological, intra-abdominal, or intra-thoracic injuries. Minor abrasions/lacerations such as "road rash" or open wounds are acceptable. Associated fibular injuries are acceptable. Small peripheral injuries such as a finger or toe requiring percutaneous pinning are acceptable. Small skin grafts (no more than 100 cm^2) are permitted
Pregnancy or breastfeeding (verify urine pregnancy test)
Associated or pre-existing head injury or Traumatic Brain Injury
Difficulty or inability to understand the study or the protocol
Severe obesity (BMI > 36.0 kg/m^2)
Known respiratory or cardiovascular problems, such as obstructive sleep apnea, or oxygen saturation of less than 96% on room air
Acute bronchial asthma
Chronic renal failure (serum creatinine > 2.0 mg/dL)
Liver failure (defined as history of cirrhosis or fulminant hepatic failure)
History of myocardial infarction or heart failure
History of prolonged QT syndrome (QTc 450ms or more for men and 460ms or more for women)
Known contraindications to methadone including hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture
History of allergic reaction to morphine, methadone, acetaminophen, or hydrocodone
Taking medications known to induce or inhibit the cytochrome p450 enzyme systems, such as azole antifungals, macrolide antibiotics, and selective serotonin reuptake inhibitors
Taking antiretroviral medications (any)
Consumption of grapefruit or grapefruit juice within past 5 days