Effectiveness of Topical Administration of Opioids in Palliative Care: A Systematic Review [Authors' Abstract].
The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. This systematic review aimed to assess the quality of published literature and to examine whether topical opioids are effective in controlling pain in palliative care settings. After a systematic literature review, 19 studies (six randomized controlled trials [RCTs] and 13 case reports) met the inclusion criteria for the review. Eighteen studies favored topical opioids in pain relief, as evidenced by reductions in post-treatment pain scores, but time to onset and duration of analgesia varied widely. Because of the heterogeneity of the studies, meta-analysis was not possible. Despite clear clinical benefits described in small RCTs, there is a deficiency of higher-quality evidence on the role of topical opioids, and more robust primary studies are required to inform practice recommendations. N-of-1 trials should be encouraged for specific clinical circumstances.
LeBon, B., Zeppetella, G., & Higginson, I. J. (2009). Effectiveness of topical administration of opioids in palliative care: a systematic review. Journal of Pain & Symptom Management, 37, 913-7.
Commentary by Dana Rutledge
The clinical problem of painful skin and mucosal lesions is a challenge in all settings, but particularly in palliative care where systemic opioids may not be sufficient for pain relief or where patients may resist systemic opioids due to unfavorable side effects. This systematic review used the Centre for Evidence-Based Medicine methods, and was done appropriately, although the last search for primary studies was done in August 2006 and the publication date is May 2009 (a long window of time for newer studies to have been published).
Findings showed that topical opioids were used for both malignant and nonmalignant wounds as well as oropharyngeal mucositis. Applications for skin wounds were 1-6 times daily and every 2-3 hours for mouthwashes. Opioids were administered in a variety of carriers (e.g.., hydrogel). The primary finding was pain relief following use of topical opioids. Secondary findings indicated that 0.1% diamorphine (heroin) led to pain relief in one hour with duration between 24 and 48 hours, while topical morphine relieved pain immediately to 60 minutes after administration and lasted 2 to 45 hours in ulcers and one to four hours in mucositis.
Scarce reports were found related to adverse effects. Primarily reported were local effects such as itching, burning, and discomfort. Possible administration problems existed with exudates and possible tolerance with prolonged usage.
Due to the intrinsic difficulties with studies in palliative care patients (heterogeneity, low recruitment, high drop out rates), the authors recommended N of 1 trials. In N of 1 trials, a single subject receives a treatment or placebo in a randomly assigned order; data are collected on outcomes to determine effect in this one patient. For example, a palliative care patient with a wound might be set up to receive 6 days of treatment (3 days of a topical opioid/3 days of placebo; order determined in a random manner) with pain monitored carefully for severity, onset of pain relief, adverse effects etc.
