Topical Morphine for Analgesia in Patients With Skin Grafts
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Pain score in first 24 hours
研究概览
简要总结
The management of pain endured by patients after skin grafting is complex. Pain is the single most distressing symptom but as it is difficult to manage, it is often under-treated. These patients may experience pain from two types of wound: the original injury and from "skin-donor" sites, areas of healthy skin from which skin is surgically removed and used to cover the original injury. As the section of skin which is removed is standardized, the wound created at the donor site is uniform and so provides a model of an acute wound.
Opioids (such as morphine) are the backbone of treating the moderate to severe pain experienced by any patient. But due to their potentially severe side effects and that some patients do not experience sufficient relief from the treatment, optimal treatment schedules are still being sought after.
Topically applied morphine has provided effective and safe analgesia in several clinical models. We, therefore, wish to apply this treatment modality onto skin-graft donor wounds. If found to be effective this could be an appealing non-invasive method to treat the pain of this type of wound.
详细描述
Administration of morphine into the knee joint is the best-studied clinical procedure documenting the use of topically-applied opioids. When 1-5 mg morphine were injected into the knee joint, patients experienced pain relief for up to 24 hours, whereas similar doses given systemically (i.e. intravenously) were effective for 2-4 hours. Furthermore, the analgesic effect was reversed when the opioid antagonist naloxone was injected into the knee joint. Both these findings indicate that the effect is mediated by local opioid receptors in the knee joint.
Peripheral analgesic effects of opioids are not detectable in normal tissue but appear minutes to hours after initiation of inflammation. This suggests that opioid receptors are already present in the peripheral nerve terminals but under normal conditions they are not functional.
Research on application of opioids to skin wounds is very sparse and has primarily been performed in palliative care patients. These reports demonstrate that topical opioid gel (morphine or diamorphine) provided rapid and effective relief. In some patients pain subsided within 20 minutes after application with a long-lasting (7-8 hours) effect. Fundamental aspects regarding topical application of opioids onto skin wounds are still lacking. For example, issues such as optimal dose and dose-effect relationships have not been investigated. We hope to determine these in this study.
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
- Triple (Participant, Care Provider, 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
- •Patients undergoing skin-grafting
- •American Society of Anesthesiologists (ASA) classification I-II
- •Written consent
- •Either sex
- •Able to self-asses and report their pain level
排除标准
- •Alcohol abuse or addiction - current
- •Opioids and benzodiazepines abuse - life time
- •Known hypersensitivity to morphine
- •Major renal or hepatic dysfunction
- •Pregnancy or lactation
- •Sleep-apnoea-syndrome
- •Participation in other clinical studies
研究组 & 干预措施
Placebo
Gel with no active ingredient
干预措施: Placebo (Other)
Morphine .25 mg
Gel with 0.25 mg morphine per 100cm2 square of wound
干预措施: Morphine - .25 mg (Drug)
Morphine - .75 mg.
Gel with 0.75 mg morphine per 100cm2 square of wound.
干预措施: Morphine (Drug)
Morphine 1.25 mg.
Gel with 1.25 mg morphine per 100cm2 square of wound.
干预措施: Morphine (Drug)
结局指标
主要结局
Pain score in first 24 hours
时间窗: 24 hours after application of the medication
Sum of the differences in pain scores between the skin-donor site vs. original injury site taken over a 24 hour period after application of the medication.
次要结局
- Wound assessment(Average day 12 post-operative)
- Side effects(First 24 hours after surgery)
- Supplementary analgesic medications(First 24 hours after surgery)
- Analgesic medicine from 2nd post-operative day until dressings are removed.(Day 2 post-surgery through 12th post-op day on average)
- Pain Score(24 hours after surgery)
- Time course of analgesia for each drug concentration(First 24 hours after surgery)
- Pain score collection(Twice daily from day 2 post-op until day 8 post-op)
研究者
Yehuda Ullmann MD
Head, Plastic Surgery Department
Rambam Health Care Campus