Methadone and Hydromorphone For Spinal Surgery

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

Study Overview

• Status: Completed
• Conditions: Patient Satisfaction; Acute Postoperative Pain; Hydromorphone Use; Chronic Persistent Surgical Pain
• Intervention / Treatment: Drug: Methadone; Drug: Hydromorphone

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: methadone group; Patient will receive methadone 0.2 mg/kg at induction of anesthesia (single dose)	Drug: Methadone; Methadone 0.2 mg/kg administered at induction of anesthesia
Active Comparator: Hydromorphone group; Patients will receive hydromorphone 2 mg at the end of the surgical procedure	Drug: Hydromorphone; Hydromorphone 2 mg administered at the conclusion of anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hydromorphone Use at 24 Hours	Use of hydromorphone at 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hydromorphone Use Second 24 Hours		24-48 hours after surgery
Hydromorphone Use Third 24 Hours		48-72 hours after surgery
Pain Scores Postanesthesia Care Unit (PACU) Arrival	11-point verbal rating scale (0=no pain, 10=worst pain imaginable)	First 5 minutes after PACU arrival
Pain Scores 1 Hour After PACU Arrival	11-point verbal rating scale (0=no pain, 10=worst pain imaginable)	Pain scores at 60 minutes after PACU admission
Pain Scores 2 Hours After PACU Arrival	11-point verbal rating scale (0=no pain, 10=worst pain imaginable)	Pain scores at 120 minutes after PACU admission
Pain Scores on Postoperative Day One	11-point verbal rating scale (0=no pain, 10=worst pain imaginable)	Pain scores one day after PACU admission
Pain Scores on Postoperative Day 2	11-point verbal rating scale (0=no pain, 10=worst pain imaginable)	Pain scores 48 hours after PACU admission
Pain Scores Postoperative Day 3	11-point verbal rating scale (0=no pain, 10=worst pain imaginable)	Pain scores 72 hours after PACU admission
Patient Satisfaction Scores	Patient satisfaction with overall pain management will be determined using a 101-point verbal rating scale (0=highly dissatisfied (worst), 100=highly satisfied (best))	Postopertive day 1
Patient Satisfaction Scores	Patient satisfaction with overall pain management will be determined using a 101-point verbal rating scale (0=highly dissatisfied (worst), 100=highly satisfied (best))	postoperative day 2
Patient Satisfaction Scores	Patient satisfaction with overall pain management will be determined using a 101-point verbal rating scale (0=highly dissatisfied (worst), 100=highly satisfied (best))	Postoperative day 3
Chronic Persistent Surgical Pain-Weekly Frequency of Pain	0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant	One month after surgery
Chronic Persistent Surgical Pain-weekly Frequency of Pain	0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant	3 months after surgery
Chronic Persistent Surgical Pain-Weekly Frequency of Pain	0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant	6 months after surgery
Chronic Persistent Surgical Pain-Weekly Frequency of Pain	0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant	12 months after surgery

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: April 4, 2014
• First Submitted That Met QC Criteria: April 7, 2014
• First Posted (Estimate): April 8, 2014

Study Record Updates

• Last Update Posted (Actual): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: acute postoperative pain; methadone; hydromorphone; chronic persistent surgical pain
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Hydromorphone; Methadone
• Other Study ID Numbers: EH14-113

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No