Kyphosis, Scoliosis
Conditions
Keywords
Spinal Fusion, Opioid Analgesia
Brief summary
The overall objective is to develop a patient oriented research program to efficiently evaluate the effects of pharmacogenetic variants on the dose-response relationships and safety of opioids and non-opioid analgesics. If an opioid regimen can be created that produces excellent opioid analgesia with minimal toxicity related to supratherapeutic opioid concentrations (i.e., ventilatory depression), other non-opioid analgesics (i.e., gabapentin/pregabalin, ketamine, lidocaine, cyclooxygenase inhibitors, etc.) that may decrease preoperative opioid requirements can be more efficiently and safely evaluated. These interventions may limit the opioid related toxicities related to effect site concentrations that are below those required when opioids are the predominant analgesic, such as opioid related ileus. Methadone's slow elimination clearance and limited pharmacokinetic drug-drug interactions make it an attractive perioperative opioid. The first step towards personalized opioid analgesia is to determine the effect of common pharmacogenetic variants that affect either methadone metabolism (CYP2B6) or opioid elimination.
Detailed description
This study is being done to find the optimal dose of methadone (a long acting pain medication) that decreases the amount of pain that people have after spine surgery. Five different doses of methadone will be compared to each other, while keeping the remainder of the anesthetic routine for surgery. The investigators will determine the analgesic dose-response of methadone. The investigators will also determine the effect of methadone on the incidence of opioid related side effects, the quality of outcome of recovery, and the change in the 3-month opioid use.
Interventions
DRUGMethadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* ASA physical status I, II, and III * male and non-pregnant female * English-speaking * undergoing elective \< 3 vertebral level lumbar spine fusion (with and without interbody fusion)
Exclusion criteria
* Use of more than the equivalent of 20 mg of IV morphine/24 hr in the past 2 weeks * history of substance abuse at any time in the past * known QT prolongation * Non-elective operations (i.e., cancer or trauma) * severe hepatic impairment (serum albumin \<3.0 g/dL, history of liver disease) * pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time until initial request for postoperative analgesic. | 60 minutes after extubation, 24, 48, and 72 hours after methadone administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative pain at rest and with movement (numerical rating scale, NRS) | 60 minutes after extubation, 24, 48, and 72 hours after methadone administration | — |
| The number of occurrences of ventilatory depression during each evaluation interval | 60 minutes after extubation, 24, 48, and 72 hours after methadone administration | — |
| Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis | 60 minutes after extubation, 24, 48, and 72 hours after methadone administration | — |
| Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale) | 60 minutes after extubation, 24, 48, and 72 hours after methadone administration | — |
| Occurence of pruritis | 60 minutes after extubation, 24, 48, and 72 hours after methadone administration | — |
| Algometry to assess pain tolerance | Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration | — |
| The determination of minimum effective analgesic concentration of methadone. | 60 minutes after extubation, 24, 48, and 72 hours after methadone administration | — |
| Quality of Recovery: Quality of Recovery-40 score | 24, 48, and 72 hours after methadone administration | — |
| Patient analgesic satisfaction | 24, 48, and 72 hours after methadone administration | — |
| Assessment of back condition pre and post-operatively | Pre-operatively, 6 weeks and 3 months post-operatively | — |
| Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects | Preoperatively | CYP2B6 Polymorphism effect on 1. Time to first request for analgesia 2. Secondary outcomes |
| Pupillometry for assessment of sedation | Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration | — |
| Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS) | 24, 48, and 72 hours after methadone administration | — |
Countries
United States
Outcome results
None listed