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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Northwestern Memorial Hospital
Chicago, Illinois, United States
Time until initial request for postoperative analgesic.
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
The determination of minimum effective analgesic concentration of methadone.
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Postoperative pain at rest and with movement (numerical rating scale, NRS)
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
The number of occurrences of ventilatory depression during each evaluation interval
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis
Time frame: 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)
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Occurence of pruritis
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Algometry to assess pain tolerance
Time frame: 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)
Time frame: 24, 48, and 72 hours after methadone administration
Quality of Recovery: Quality of Recovery-40 score
Time frame: 24, 48, and 72 hours after methadone administration
Patient analgesic satisfaction
Time frame: 24, 48, and 72 hours after methadone administration
Assessment of back condition pre and post-operatively
Time frame: 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
CYP2B6 Polymorphism effect on 1. Time to first request for analgesia 2. Secondary outcomes
Time frame: Preoperatively
Pupillometry for assessment of sedation
Time frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
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