부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jpainsymman.2007.12.016 Byline: Ola Dale (a)(b)(d), Maria Piribauer (a), Stein Kaasa (a)(c)(e), Kristin Moksnes (a)(b), Heidi Knobel (a)(e), PA[yen]l Klepstad (a)(b)(d) Abstract: The European Association for Palliative Care guidelines for treatment of cancer pain recommend a double dose (DD) of immediate-release morphine at bedtime instead of single doses (SD) repeated every four hours throughout the night. A previous open controlled study reported more side effects after DD than after SD. The present study was a randomized, double-blind, crossover study comparison of DD and SD of immediate-release morphine during the night, followed by an open pharmacokinetic study. The primary outcome was average pain intensity during the night, as measured on an 11-point numerical rating scale. Secondary outcomes were morning pain, number of rescue medications, adverse effects (nausea, xerostomia, tiredness, sleep quality, and number of awaking episodes) and patient preference. Morphine and metabolites were quantified by a validated liquid chromatography-tandem mass spectrometry method. Nineteen patients completed the clinical study; 13 participated in the pharmacokinetic follow up. Average pain during the night for DD vs. SD was close to statistical significance (mean 0.8 and 1.4, respectively, P =0.058; mean [95% confidence interval] for the difference was 0.50 [0.02, 1.0]). A similar trend was observed for strongest night pain (P =0.069) and sleep quality (P =0.077). Only two patients required rescue morphine. Four patients had no treatment preference; nine and six favored DD and SD, respectively. DD patients displayed higher area under the curve for morphine and morphine-6-glucuronide during the first part of the night. Although DD tended to perform slightly better than SD, a difference in average pain during the night of 0.50 has little clinical significance, and the two procedures are, therefore, clinically equivalent. It is speculated whether the initial higher exposure to morphine-6-glucuronide may have clinical significance. Author Affiliation: (a) Pain and Palliation Research Group, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway (b) Departments of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway (c) Departments of Molecular Biology and Cancer Research, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway (d) Department of Anaesthesiology and Emergency Medicine, St. Olav's University Hospital, Trondheim, Norway (e) Department of Palliative Medicine Unit, Department of Oncology, St. Olav's University Hospital, Trondheim, Norway Article History: Accepted 28 December 2007 Article Note: (footnote) The authors have no conflicts of interest.