Topical Morphine for Analgesia in Patients With Skin Grafts
Information source: Rambam Health Care Campus
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Skin Transplantation; Pain
Intervention: Placebo (Other); Morphine - .25 mg (Drug); Morphine (Drug); Morphine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Rambam Health Care Campus Official(s) and/or principal investigator(s): Yehuda Ullman, M.D., Principal Investigator, Affiliation: Rambam Health Care Campus
Summary
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.
Clinical Details
Official title: Topical Morphine for Analgesia in Patients With Skin Grafts
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Pain score in first 24 hours
Secondary outcome: Pain ScoreTime course of analgesia for each drug concentration Side effects Supplementary analgesic medications Analgesic medicine from 2nd post-operative day until dressings are removed. Pain score collection Wound assessment
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Diabetes
- Participation in other clinical studies
Locations and Contacts
Department of Plastic Surgery, Rambam Medical Center, Haifa 31096, Israel
Additional Information
Related publications: Krajnik M, Zylicz Z, Finlay I, Luczak J, van Sorge AA. Potential uses of topical opioids in palliative care--report of 6 cases. Pain. 1999 Mar;80(1-2):121-5. Stein C, Comisel K, Haimerl E, Yassouridis A, Lehrberger K, Herz A, Peter K. Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med. 1991 Oct 17;325(16):1123-6. Porzio G, Aielli F, Verna L, Cannita K, Marchetti P, Ficorella C. Topical morphine in the treatment of painful ulcers. J Pain Symptom Manage. 2005 Oct;30(4):304-5. Ribeiro MD, Joel SP, Zeppetella G. The bioavailability of morphine applied topically to cutaneous ulcers. J Pain Symptom Manage. 2004 May;27(5):434-9. Stein A, Yassouridis A, Szopko C, Helmke K, Stein C. Intraarticular morphine versus dexamethasone in chronic arthritis. Pain. 1999 Dec;83(3):525-32. Zeppetella G, Ribeiro MD. Morphine in intrasite gel applied topically to painful ulcers. J Pain Symptom Manage. 2005 Feb;29(2):118-9. Stein C, Schäfer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med. 2003 Aug;9(8):1003-8. Review.
Starting date: December 2006
Last updated: October 27, 2011
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