Methadone and Hydromorphone For Spinal Surgery
| Status: | Completed |
|---|---|
| Conditions: | Post-Surgical Pain |
| Therapuetic Areas: | Musculoskeletal |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 6/28/2018 |
| Start Date: | March 2014 |
| End Date: | September 2017 |
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
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
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.
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.
Inclusion Criteria:
- All patients presenting for elective posterior lumbar or thoracic spinal fusion
surgery will be eligible for enrollment.
Exclusion Criteria:
1. Preoperative renal failure (defined as a serum creatinine > 2.0 mg/dL.)
2. American Society of Anesthesiologists Physical Status IV or V
3. Pulmonary disease necessitating home oxygen therapy
4. Allergy to methadone or hydromorphone
5. Preoperative recent history of opioid or alcohol abuse
6. Inability to use a PCA device or speak the English language
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