Topical opioids for wound palliation in select patients

Tampa, Fla—Patients with malignant wounds can suffer from significant pain, but the providers at Moffitt Cancer Center in Tampa found topical morphine can dampen the discomfort associated with these lesions.

“It's another possibility we can put in the toolbox,” said Rosalie El-Rady, ARNP, a nurse practitioner at the Moffitt Cancer Center, at the Oncology Nursing Society's Institutes of Learning.

Malignant wounds often are proliferative and fungating, can be ulcerating, and may have nodules and induration. They are associated with advanced and sometimes local cancers. Some of these wounds can become chronic and require care for years, while others represent progressive disease in the last weeks to months of life.

Patients most frequently complain about pain, but odor, pruruitus, bleeding, exudates, crusting, and psychosocial distress also present difficulties. Pain results from tumor compression of or invasion of the nerves or blood vessels, release of chemicals by the tumor cells, ischemia, inflammation, swelling, tissue debridement or trauma, infection, the exposure of the dermis, or a moisture imbalance.

“Our goal is to help that one patient at a time and make an improvement in that patient's life,” said Sloan Karver, MD, a palliative care physician at Moffitt Cancer Center (at right in photo; Rosalie El-Rady is on the left). “Patients [with a malignant wound] often have a horrible and obsessing problem. Plus, it's a constant reminder of their illness.”

The clinicians typically use topical morphine after more traditional modalities have been tried and failed. If the topical application provides sufficient relief, patients may be able to decrease the systemic dose.

 “On the other hand, if there are several types and areas of pain, as often occurs in advanced stages of cancer, systemic requirements may actually increase to cover the overall experience of pain,” Ms El-Rady reported

A compounding pharmacy must mix the topical opioid agent, adding morphine to either a hydrogel or silver sulfadiazine cream. The cream tends to adhere better on nodular and fungating wounds, Ms El-Rady said, adding that neither cream nor gel will stick if there is a significant degree of weeping. In ulcerated wounds, clinicians have used occlusive, transparent dressings to prevent the compounded gel from sliding out.

The pharmacy Moffitt providers use dispenses the drug in a container with a pump that metes out enough gel or cream for one application, hence preventing potential contamination of the contents. The medication is clean but not sterile. 

Although reports of topical morphine use date back to 1774 and 1885 and hospices have employed this treatment, little scientific evidence exists to support using opioids topically on open wounds. It remains an off-label use of morphine.

“It's something old that can be new to patients in a difficult situation,” Ms El-Rady said.

Three out of four small, short-term, randomized, control studies showed statistically significant pain relief with the therapy and no significant side effects in patients with ulcers. And several case reports indicate the topical treatment can relieve pain in a variety of wound types. Conducting a large-scale clinical trial would be difficult Dr Karver said, because relatively few patients experience malignant wounds.

Ms El-Rady described her patients reporting the treatment as “wonderful,” “a miracle,” and that it “takes the heat out.”

“Are topical opioids clinically relevant? Yes,” Ms El-Rady concluded. “In select patients, it may be useful.”

Researchers have proven the presence of opioid receptors in the nerve endings of human skin. They also have shown that the immune system plays a role in the endogenous opioid system. Endogenous opioids are released by a variety of leukocytes, including T cells, B cells, macrophages, monocytes, and granulocytes.

The treatment assists the body's own pain reduction mechanisms and appears to work best when inflammation is present, added Ms El-Rady, explaining that animal studies show that administering an opioid in the periphery activates opioid receptors, which increase during inflammation.

“When you have inflammation, membranes around the nerve loosen and allow substances to act on the nerve,” Ms El-Rady reported.

Ms El-Rady cautioned that providers must select appropriate patients. People who are opioid naive may experience systemic side effects. Wound size and the concentration of the medication also could affect systemic absorption. In the studies and case reports reviewed, the majority of patients had little to no systemic effects, and in both treatment and placebo groups, some itching and burning sensations were reported, indicating no increase in local effects with the addition of morphine, Ms El-Rady said.

Little is known if using a topical opioid contributes to delayed wound healing, but Ms El-Rady indicated that may be the case. One rat study showed an initial delay in wound healing with topical morphine, but, ultimately, wounds on the treated and untreated rodents closed within a similar time frame.

“There remain many questions about this therapy,” Ms El-Rady acknowledged. “But it makes me feel better knowing for those three or four patients per year, I can help their pain in a different way.”
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