The Influence of Pharmacogenetics on Methadone Dose, Safety, and Outcomes After Spine Fusion
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Time until initial request for postoperative analgesic.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Methadone 0.5 mg/kg
Methadone 0.5 mg/kg
干预措施: Methadone (Drug)
Methadone 0.4 mg/kg
Methadone 0.4 mg/kg
干预措施: Methadone (Drug)
Methadone 0.3 mg/kg
Methadone 0.3 mg/kg
干预措施: Methadone (Drug)
Methadone 0.2 mg/kg
Methadone 0.2 mg/kg
干预措施: Methadone (Drug)
Methadone 0.15 mg/kg
Methadone 0.15 mg/kg
干预措施: Methadone (Drug)
结局指标
主要结局
Time until initial request for postoperative analgesic.
时间窗: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
次要结局
- Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects(Preoperatively)
- Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis(60 minutes after extubation, 24, 48, and 72 hours after methadone administration)
- Patient analgesic satisfaction(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)
- Occurence of pruritis(60 minutes after extubation, 24, 48, and 72 hours after methadone administration)
- Postoperative pain at rest and with movement (numerical rating scale, NRS)(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)
- Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS)(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)
- The determination of minimum effective analgesic concentration of methadone.(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)
- Quality of Recovery: Quality of Recovery-40 score(24, 48, and 72 hours after methadone administration)
- Pupillometry for assessment of sedation(Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration)
研究者
Dhanesh Gupta
Associate Professor of Anesthesiology & Neurological Surgery
Northwestern University