Intraoperative Methadone vs Morphine for Postoperative Pain Control in Patients Undergoing Surgery of the Tibia
| Status: | Terminated |
|---|---|
| Conditions: | Post-Surgical Pain |
| Therapuetic Areas: | Musculoskeletal |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 4/21/2016 |
| Start Date: | September 2011 |
| End Date: | July 2014 |
Intraoperative Methadone Versus Morphine for Postoperative Pain Control in Patients Undergoing Intramedullary Nailing or Open Reduction and Internal Fixation of the Tibia
The purpose of this study is to determine whether, for surgery of the tibia, one dose of
methadone provides better control of pain afterward as compared to morphine, which is the
usual drug given to control pain after surgery. Immediately after the beginning of general
anesthesia ("intraoperatively"), subjects will receive one dose of either methadone or
morphine, in the amount of 0.2 milligrams per kilogram of body weight, intravenously.
The primary hypothesis is that, subjects who receive one dose of methadone intraoperatively
will require less pain medicine than subjects who receive one dose of morphine
intraoperatively.
methadone provides better control of pain afterward as compared to morphine, which is the
usual drug given to control pain after surgery. Immediately after the beginning of general
anesthesia ("intraoperatively"), subjects will receive one dose of either methadone or
morphine, in the amount of 0.2 milligrams per kilogram of body weight, intravenously.
The primary hypothesis is that, subjects who receive one dose of methadone intraoperatively
will require less pain medicine than subjects who receive one dose of morphine
intraoperatively.
Satisfactory pain control can generally be achieved after major surgery of the tibia through
a combination of enteral and parenteral medications, neuraxial techniques (such as epidural
analgesia), and/or regional techniques (such as sciatic and femoral nerve block).
Intramedullary nailing (IMN) and open reduction/internal fixation (ORIF) of the tibia have
been important exceptions, and postoperative pain control can be difficult to achieve in
these cases.
Surgical repair of fractures of the tibial shaft and of the proximal tibia can be
complicated by compartment syndrome, with the possibility of substantial morbidity and loss
of function if not detected and treated promptly. It is not always possible to determine
preoperatively which tibial fractures are at high risk, and which are low risk for this
complication.
The hallmark of compartment syndrome, and often the earliest sign, is pain out of proportion
to the nature of the injury. This pain is poorly relieved by morphine or other strong
analgesics. In contrast, because peripheral nerve blocks, spinals, and epidurals can
completely block the neural transmission of nociceptive stimuli, they can obliterate this
important early warning sign. For this reason, orthopedic surgeons often request of
anesthesiologists that patients who are to undergo IMN or ORIF of at-risk tibial fractures
not receive neuraxial blocks or regional nerve blocks. As a result, patients who undergo
IMN/ORIF of the tibia often receive poor pain relief because they are denied these treatment
options, even though the vast majority do not go on to develop compartment syndrome.
A typical postoperative pain regimen for IMN/ORIF tibia patients usually begins with a
parenteral opioid such as morphine, along with an oral analgesic such as
acetaminophen/hydrocodone ("Vicodin"), acetaminophen/codeine ("Tylenol #3"), or tramadol.
The parenteral opioid is often given by patient-controlled analgesia pump (PCA), with
supplemental doses ordered for breakthrough pain. A major disadvantage of morphine is its
equilibration half-time of 2-4 hours. Thus there is considerable lag between the plasma
morphine concentration (which peaks immediately) and the morphine concentration at the
effector sites. This hysteresis results in the slow onset of analgesia, with peak analgesia
occurring some 80-90 minutes after IV administration. It can also result in excessive
somnolence, when several demand doses in a row finally take effect. Morphine has an
elimination half-time of 2-3 hours. These repeated bolus doses result in the classic
"see-saw" graph of plasma morphine concentration over time, with its peaks and troughs.
Methadone, in contrast, has a much lower equilibration half-time, on the order of 4-8
minutes. This results in quicker transfer of methadone from the plasma to its effector
sites, and hence quicker onset of action, with peak analgesia occurring in just 11.3
minutes. Methadone's elimination half-life after a single dose is approximately 24-36 hours,
resulting in prolonged analgesia, with less re-dosing necessary.
Most recently, for multilevel thoracolumbar spine surgery with instrumentation and fusion,
intraoperative intravenous methadone was shown to have substantial opioid-sparing effects
compared to intraoperative sufentanil bolus with sufentanil infusion, and similar rates of
side effects such as hypotension, respiratory depression, hypoxemia, arrhythmia, nausea, and
vomiting.
For these reasons, administering an intraoperative loading dose of 0.2 mg/kg methadone IV
should result in better analgesia for ORIF and IMN of the tibia, compared with an
intraoperative loading dose of 0.2 mg/kg morphine IV. This dose of methadone has previously
been shown to yield plasma concentrations above the Minimum Effective Concentration, without
excessive respiratory depression. This dose has been shown to provide long-lasting analgesia
after painful procedures, often to the point that subjects needed no supplemental analgesics
at all, or only non-narcotic analgesics.
a combination of enteral and parenteral medications, neuraxial techniques (such as epidural
analgesia), and/or regional techniques (such as sciatic and femoral nerve block).
Intramedullary nailing (IMN) and open reduction/internal fixation (ORIF) of the tibia have
been important exceptions, and postoperative pain control can be difficult to achieve in
these cases.
Surgical repair of fractures of the tibial shaft and of the proximal tibia can be
complicated by compartment syndrome, with the possibility of substantial morbidity and loss
of function if not detected and treated promptly. It is not always possible to determine
preoperatively which tibial fractures are at high risk, and which are low risk for this
complication.
The hallmark of compartment syndrome, and often the earliest sign, is pain out of proportion
to the nature of the injury. This pain is poorly relieved by morphine or other strong
analgesics. In contrast, because peripheral nerve blocks, spinals, and epidurals can
completely block the neural transmission of nociceptive stimuli, they can obliterate this
important early warning sign. For this reason, orthopedic surgeons often request of
anesthesiologists that patients who are to undergo IMN or ORIF of at-risk tibial fractures
not receive neuraxial blocks or regional nerve blocks. As a result, patients who undergo
IMN/ORIF of the tibia often receive poor pain relief because they are denied these treatment
options, even though the vast majority do not go on to develop compartment syndrome.
A typical postoperative pain regimen for IMN/ORIF tibia patients usually begins with a
parenteral opioid such as morphine, along with an oral analgesic such as
acetaminophen/hydrocodone ("Vicodin"), acetaminophen/codeine ("Tylenol #3"), or tramadol.
The parenteral opioid is often given by patient-controlled analgesia pump (PCA), with
supplemental doses ordered for breakthrough pain. A major disadvantage of morphine is its
equilibration half-time of 2-4 hours. Thus there is considerable lag between the plasma
morphine concentration (which peaks immediately) and the morphine concentration at the
effector sites. This hysteresis results in the slow onset of analgesia, with peak analgesia
occurring some 80-90 minutes after IV administration. It can also result in excessive
somnolence, when several demand doses in a row finally take effect. Morphine has an
elimination half-time of 2-3 hours. These repeated bolus doses result in the classic
"see-saw" graph of plasma morphine concentration over time, with its peaks and troughs.
Methadone, in contrast, has a much lower equilibration half-time, on the order of 4-8
minutes. This results in quicker transfer of methadone from the plasma to its effector
sites, and hence quicker onset of action, with peak analgesia occurring in just 11.3
minutes. Methadone's elimination half-life after a single dose is approximately 24-36 hours,
resulting in prolonged analgesia, with less re-dosing necessary.
Most recently, for multilevel thoracolumbar spine surgery with instrumentation and fusion,
intraoperative intravenous methadone was shown to have substantial opioid-sparing effects
compared to intraoperative sufentanil bolus with sufentanil infusion, and similar rates of
side effects such as hypotension, respiratory depression, hypoxemia, arrhythmia, nausea, and
vomiting.
For these reasons, administering an intraoperative loading dose of 0.2 mg/kg methadone IV
should result in better analgesia for ORIF and IMN of the tibia, compared with an
intraoperative loading dose of 0.2 mg/kg morphine IV. This dose of methadone has previously
been shown to yield plasma concentrations above the Minimum Effective Concentration, without
excessive respiratory depression. This dose has been shown to provide long-lasting analgesia
after painful procedures, often to the point that subjects needed no supplemental analgesics
at all, or only non-narcotic analgesics.
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
We found this trial at
1
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Ben Taub General Hospital Located in the heart of the Texas Medical Center, Ben Taub...
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