title: Safety and effectiveness of intravenous morphine for episodic (breakthrough) pain using a fixed ratio with the oral daily morphine dose.
abstract: Breakthrough pain is normally severe in intensity and has a rapid onset. The availability of supplemental doses of opioids (rescue medication) in addition to the continuous analgesic medication is the main treatment suggested to manage these pain flares. The intravenous (i.v.) route may provide analgesia fast enough, but has never been assessed in clinical studies. The aim of this open-label study was to verify the safety and effectiveness of an i.v. dose equal to one-fifth the calculated equianalgesic total daily dose in advanced cancer patients with episodic pain. A consecutive sample of 48 cancer patients treated with oral morphine, who reported an acceptable basal analgesia and reported episodic pains, were selected for the study. The intravenous dose of morphine was one-fifth of the oral daily dose, converted into an i.v. dose using an equianalgesic ratio of 1/3 (i.v./oral). Written orders were given and intravenous morphine (i.v.-M) was administered by nurses. For each episode, pain intensity and opioid-related symptoms were recorded at the start (T0), after achieving maximum pain relief (T1), and one hour after (T2). In five patients, blood samples were taken at the time intervals described for measuring plasma concentrations of morphine and related glucuronated metabolites. One hundred seventy-one breakthrough pains were recorded during admission. In 162 episodes, a reduction of pain intensity of more than 33% was obtained within a mean of 17.7 minutes, from a mean intensity of 7.9 (on a 0-10 numeric scale) to 3. One hundred thirty-six episodes had more than a 50% pain intensity decrease after the i.v.-M within a mean of 16.6 minutes, from a pain intensity of 7.9 to 2.6. No differences in age, sex, pain mechanism, and time of events were found. There was a trend but no statistically significant differences between the groups receiving different basal doses and time to reach the maximum effect. Twenty episodes in ten patients required an additional dose within 2 hours. Adverse effects were uncommon and were significantly related to the basal dose, and as a consequence, with the i.v.-M dose. Morphine concentration significantly increased at the time of pain intensity reduction, and then decreased. These observations suggest that i.v.-M at a dose equivalent to 20% of the basal oral dosage is safe and effective in the majority of patients experiencing pain exacerbation. This treatment is inexpensive and can be used at little risk to patients.
authors.affiliation: Anesthesia and Intensive Care Unit, Pain Relief and Palliative Care Unit, La Maddalena Cancer Center, Palermo, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Mercadante
authors.forename: Patrizia
authors.initials: P
authors.lastname: Villari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferrera
authors.forename: Mauro
authors.initials: M
authors.lastname: Bianchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Casuccio
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D010166:Palliative Care
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine