The Use of Topical Opioids for Systemic Pain Management
Article Outline
To the Editor:
Topical opioids have been used for peripheral pain management in wound care, including painful decubitus ulcers1, 2, 3, 4, 5, 6 or burns.7 Topical nonsteroidal anti-inflammatory drugs have been used for musculoskeletal pain8, 9 and 5% lidocaine patches have been used for neuropathic pain such as postherpetic neuralgia.10 In general, all of these applications are employed for localized pain relief. The following case represents a unique application of a topical analgesic to relieve systemic pain.
Case
Mr. X was a 90-year-old male Holocaust survivor. His diagnoses included a head and neck cancer diagnosed six months previously, controlled congestive heart failure, and mild dementia. He was experiencing uncontrolled pain in his mouth secondary to his cancer. Initially, his pain had been controlled with regular oral (liquid) hydromorphone. Over several months, his pain increased and the hydromorphone was titrated to match his needs. Eventually, his analgesic was changed to a 25 mcg fentanyl patch to reduce his need to swallow pills. The liquid oral hydromorphone was kept for breakthrough (BT) doses.
Over a period of several weeks, his overall condition deteriorated. His ability to swallow decreased, pain increased, and the dose of fentanyl was titrated upwards. Within a few months, his fentanyl dose was increased to 100 mcg every 72
hours. His ability to swallow was extremely poor and he began refusing oral medications. In an attempt to ensure management of his BT pain, his hydromorphone was changed to the subcutaneous route, with the appropriate dosage conversion. However, due to his experiences during the war as a Holocaust survivor, he refused any injections. Neither would he agree to suppositories. Swallowing was now a painful process and oral meds were being rejected. The choices for BT medication routes became virtually nonexistent.
In consultation with a pharmacist, the hospice team discussed possible options, with a particular focus on the possibility of adapting hydromorphone for a topical application. The pharmacist suggested a Lipoderm cream base, similar to a pluronic/lecithin organogel, to help drive the drug through the skin into the bloodstream. A challenge was a lack of information about accurate conversion from oral hydromorphone to topical hydromorphone for systemic application.
The topical option was discussed with the family physician. Based on prior experience with topical opioids for wound management and the low dosage for the BT (2mg), the decision was to use the equivalent oral dose topically and then monitor the patient closely for pain control and possible side effects. The patient was started on a topical dose of 0.2mL every hour as needed. The hydromorphone cream (2mg/0.2mL) was dispensed from the pharmacy in a syringe. The instructions were to apply 0.2mL on the patient's skin and then gently rub it into the skin. The nurses were instructed to use the cream on healthy tissue only, not on the cancer site, and to wear gloves when applying the hydromorphone formulation.
The cream was used twice the following day for BT doses. Within 15minutes of application, good effect was indicated by reduced restlessness. No adverse effects, such as confusion, hallucinations, or oversedation, were observed, then or in the following months. Four weeks after commencing the topical hydromorphone, the patient's pain was such that the fentanyl patch was increased to 125 mcg every 72hours. The BT dose was increased to 4mg using a 4mg/0.2mL concentration of hydromorphone cream. Pain control was again temporarily achieved with these changes.
During the following weeks, the topical hydromorphone was used on a regular basis to determine whether, and to what degree, this would improve overall pain control. In addition to a 125 mcg fentanyl patch applied every 72hours, a maximum dose of 32mg of topical hydromorphone cream was applied every 4hours, with BT doses of the topical hydromorphone 16mg every hour as needed. Using this combination, the patient's restlessness decreased, resistance to repositioning reduced, and he experienced what appeared to be good pain control, as confirmed by his personal attendant, family and the nursing staff. Ultimately, Mr. X became unconscious and died peacefully.
Comment
The use of a topical route to deliver peripheral analgesia is by no means a new health care practice, as evidenced in the literature.1, 2, 3, 4, 6 Vaile and Davis9 reviewed the literature regarding topical nonsteroidal anti-inflammatory drug use and reported that for a topical medication to be successful, it must reach the target site and have efficacy at that site. This may involve both systemic involvement and direct penetration. The skin layers the medication must penetrate include the stratum corneum (top layer of dead epidermal cells), the epidermis (viable cells but no blood vessels), the basement membrane, and the dermis (containing blood vessels). Only after the medication has moved into the dermis layer can absorption into the systemic circulation occur. There is a direct relationship between the medication's molecular size and skin penetration. The hydromorphone molecule is small enough to penetrate the skin.
There have been no prior reports of a similar use of topical hydromorphone. However, in a related report, Twillman et al.6 reviewed a group of nine case studies. With a single exception, all were palliative patients who had skin ulcers that were either open or inflamed. In all but the one case, the topical opioid (morphine infused into IntraSite gel at a 0.1% weight-to-weight solution) was effective for pain relief. The exception was an individual who had no inflammation or open skin. Similarly, Long et al.7 carried out a double-blind, placebo-controlled pilot study to assess the side effects and efficacy of morphine-infused silver sulfadiazine cream for burn wound pain. The treatment group reported improved pain control and for a longer duration than the placebo group; there were trends toward reduced use of anxiolytics, unwanted systemic side effects, and the need for oral or parental analgesics.
There is evidence to suggest that analgesia in the above-mentioned cases achieved pain control through binding to opioid receptors in peripheral tissues, such as immune cells, peripheral nerves, inflamed tissues, and cardiac muscle.4 Although the study of Long et al.7 suggested that there may have been some systemic absorption, there were no blood or morphine metabolite levels taken to determine this and the participants in the study of Twillman et al.6 were taking systemic opioids as well to control their pain.
In conclusion, in an attempt to provide comfort to a patient for whom the conventional routes of analgesic administration were not an option, topical opioids were used for systemic pain control. The vehicle to facilitate absorption of the opioid to the vascular system was a Lipoderm cream. To further the use of topical opioids for systemic pain management, clinical research is required.
References
- . The use of topical opioids to relieve pressure ulcer pain. Nurs Stand. 2005;19(45):90–92
- . Analgesic effect of topical opioids on painful skin ulcers. J Pain Symptom Manage. 1995;10(7):493
- . Treatment of painful sickle cell leg ulcers with topical opioids. Blood. 2002;99(3):1096
- . Potential uses of topical opioids in palliative care—report of 6 cases. Pain. 1999;80:121–125
- . Topical and peripherally acting analgesics. Pharmacol Rev. 2003;55(1):1–20
- . Treatment of painful skin ulcers with topical opioids. J Pain Symptom Manage. 1999;17(4):288–292
- Morphine-infused silver sulfadiazine (MISS) cream for burn analgesia: a pilot study. J Burn Care Rehabil. 2001;22(2):118–123
- . Oral versus topical NSAIDs in rheumatic disease—a comparison. Drugs. 2000;60(3):555–574
- . Topical NSAIDS for musculoskeletal conditions—a review of the literature. Drugs. 1998;56(5):783–799
- . Recent advances in pharmacotherapy for cancer pain management. Cancer Pract. 2002;10(Suppl. 1):S14–S20
PII: S0885-3924(08)00214-5
doi:10.1016/j.jpainsymman.2008.02.004
© 2008 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
