Topically applied opioids for the management of painful cutaneous ulcers in a palliative care setting.

Abstract

Painful cutaneous ulcers are a clinical challenge as the pain can be difficult to control, frequently requiring a combination of pharmacological and non-pharmacological measures. There is evidence suggesting topical opioid application might be efficacious in the management of painful cutaneous ulcers, however this is largely based on case reports. Methods A series of clinical and laboratory studies were undertaken to determine the utility of opioids applied topically to painful cutaneous ulcers, these included surveys of hospice admissions to determine the prevalence of painful ulcers and the effective dose of topical opioid; a randomised, double-blind, placebo-controlled crossover trial design to assess the utility of morphine/IntraSite gel mixture, HPLC analysis to determine the mixture’s bioavailability and physical stability, and microbiological studies to determine its microbiological stability. Results A survey of 323 hospice admissions over a two-year period identified 125 patients with 221 ulcers, mostly caused by either pressure (183 ulcers) or trauma (25); 147 (67%) of all ulcers were painful. Compared to placebo, morphine/IntraSite mixture was more efficacious; it was safe and well tolerated in this population. Morphine applied topically appears to have an analgesic effect even at low doses of morphine irrespective of background analgesic medication. HPLC analyses suggested morphine and its metabolites might be detectable in the plasma of patients with large ulcers, but only at low concentrations. In addition morphine/IntraSite gel mixture was physically and, under certain storage conditions, microbiologically stable for 28 days allowing the mixture to be prepared and stored before use. Conclusions The studies confirmed that painful cutaneous ulcers are a significant clinical problem in hospice patients and that morphine/IntraSite mixture can be used safely and effectively in this patient group. Bioavailability studies support the possibility that the opioid analgesic effect is local rather than systemic, and stability studies show the morphine/IntraSite combination, once mixed, can be stored for up to 28 days, allowing the mixture to be prepared and stored before use. Given that ulcers can vary in aetiology, size, severity and temporal characteristics of pain, an individualised titration protocol is recommended. Further research is required to confirm and extend these findings to other ulcers and clinical settings