Intraoperative Methadone for Postoperative Pain Management in Spinal Fusion Surgery: a Prospective, Double-blind, Randomised Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Opioid consumption (mean cumulative MME)
研究概览
简要总结
A prospective double-blind, randomized controlled trial investigating the effect of a single-dose of intraoperative methadone in patients undergoing spinal fusion.
详细描述
During early recovery after surgery, intravenous opioids are typically administered to control the pain, either as intermittent bolus administration by nursing staff or by a patient-controlled analgesia device. Unfortunately, repeated doses or boluses of shorter-acting opioids, such as morphine, oxycodone and fentanyl, result in fluctuating blood concentrations, with the inherent risk of only relatively brief periods of adequate pain relief. Moreover, the use of shorter-acting opioids increases the risk of opioid-associated side effects, such as sedation, nausea and vomiting. An alternative approach to the postoperative use of shorter-acting opioids is therefore called for.
In this respect, methadone is an opioid with unique pharmacological properties that may be advantageous when applied intraoperatively. A single-dose of this long acting opioid could provide a stable analgesia and potentially reduce the need for shorter-acting opioids
Method:
150 patients will be included in an investigator-initiated, prospective, randomised, double-blind, controlled trial with three arms: intervention arm 1 (methadone administered at induction 0.15-0.2 mg/kg ideal body weight), Intervention arm 2 (methadone administered in the end of surgery 0.15-0.2 mg/kg ideal body weight), Control arm (morphine administered in the end of surgery 0.15-0.2 mg/kg ideal body weight).
The study will be GCP-monitored, and is approved by the Danish Health and Medicines Authority (2020103115) and the Central Denmark Region Committees on Health Research Ethics (1-10-72-278-20).
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)
盲法说明
Randomisation and study medication will be handled by the hospital pharmacy. All research team members, caregiving clinicians and enrolled patients will be blinded to the study allocation arms and the randomisation list will be concealed until all statistical analyses are made.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients (≥18 years ≤85) scheduled for elective spinal fusion surgery are screened for inclusion.
排除标准
- •Allergy to study drugs
- •American Society of Anaesthesiologists (ASA) physical status IV or V
- •Prolonged QTc-interval assessed by electrocardiogram(> 440 milliseconds)
- •Inability to provide informed consent
- •Severe respiratory insufficiency(Oxygen treatment at home)
- •Known or clinical signs of heart failure (Ejection Fraction <30%)
- •Acute alcohol intoxication/delirium tremens
- •Known or clinical signs of increased intracranial pressure
- •Acute liver disease
- •Acute abdominal pain
- •Known or clinical signs of severe liver dysfunction (cirrhosis, inflammation/hepatitis or liver malignancies)
- •Known or clinical signs of severe kidney insufficiency(eGFR<30)
- •Pregnancy: women of childbearing potential will be tested with serum-HCG prior to surgery, unless the woman is using a birth control method that may be considered as highly effective (based on CTFG 'recommendations related to contraception and pregnancy testing in clinical trials'). Women of childbearing potential is defined as women between menarche and post-menopausal, unless permanently steril. Post-menopausal is defined as no menses for 12 months without alternative medical cause.
- •Breastfeeding mothers
- •Existing treatment with a high risk of QTc-interval prolongation
- •Existing treatment with opioids (at least the last 7days) exceeding 60 mg morphine equivalents daily
- •Planned postoperative treatment with epidural analgesics and/or ketamine infusion
- •Treatment with rifampicin
- •Spinal fusion surgery over >4vertebral levels
- •Spinal fusion surgery due to malignant disease
研究组 & 干预措施
Methadone, induction
Patients receive methadone 0.15-0.2 mg/kg ideal bodyweight 10 minutes prior to surgery start (Syringe A).
45 minutes before expected extubation patients will receive saline (syringe B).
干预措施: Methadone (Drug)
Methadone, end of surgery
Patients receive saline 10 minutes prior to surgery start (Syringe A). 45 minutes before expected extubation patients will receive methadone 0.15-0.2 mg/kg ideal bodyweight (syringe B).
干预措施: Methadone (Drug)
Morphine
Patients receive saline 10 minutes prior to surgery start (Syringe A). 45 minutes before expected extubation patients will receive morphine 0.15-0.2 mg/kg ideal bodyweight (syringe B).
干预措施: Morphine (Drug)
结局指标
主要结局
Opioid consumption (mean cumulative MME)
时间窗: 24 hours
Opioid consumption within the first 24 hours after extubation
次要结局
- Readiness to discharge(2-24 hours)
- Level of sedation(1 hour)
- 3 months follow-up(3 months)
- Nausea and/or vomiting (PONV)(6 - 24 hours)
- Adverse events(1-24 hours)
- Patient satisfaction with pain management(24 hours)
- Given treatment according to patient and investigator(24 hours)
- Pain intensity (NRS, 0-10) at rest and coughing(1-72 hours)