UNCORRECTED PROOF 2 Opioid-induced or pain relief-reduced symptoms in advanced 3 cancer patients? 4 Sebastiano Mercadante a,b, * , Patrizia Villari a , Patrizia Ferrera a , Alessandra Casuccio c 5 a Anesthesia & Intensive Care Unit and Pain Relief & Palliative Care Unit La Maddalena Cancer Center, Via San Lorenzo Colli 312, 6 90146 Palermo, Italy 7 b Intensive Care and Emergency, Universita ` di Palermo, Italy 8 c Universita ` di Palermo, Italy Received 30 June 2004; accepted 17 February 2005 11 Abstract 12 Background: While opioids in increasing doses may produce adverse eﬀects, the same adverse eﬀects may be associated with poor 13 pain control. Moreover, in the clinical setting symptomatic treatment and illness may balance the outcome of opioid titration. Some 14 adverse eﬀects may tend to disappear continuing the treatment in a long-term period. 15 Aims: The aim of this study was to monitor the eﬀects of a rapid opioid titration combined with symptomatic treatment in 16 patients with poor relief and to monitor these changes in the following period of 20 days. 17 Methods: A consecutive sample of 35 patients admitted to an acute Pain Relief and Palliative Care Unit were titrated with opi- 18 oids, according to a department policy, allowing administration of parenteral opioids to assist opioid titration with oral or trans- 19 dermal opioids. 20 Results: Thirty-three patients were followed up for the period of the study. Pain was adequately controlled and doses were opioid 21 doses were stable after a mean of 40 h. Opioid escalation index (OEI) was extremely high initially, and then progressively declined at 22 the following study intervals. Weakness and nausea and vomiting did not change, as well as confusion and appetite. Drowsiness, 23 constipation and dry mouth signiﬁcantly increased and then did not change, although a signiﬁcant decrease in drowsiness was sub- 24 sequently observed. Well-being improved some weeks after opioid stabilization. In multivariate analysis, drowsiness and dry mouth 25 were correlated to opioid doses. 26 Conclusion: The eﬀects reported were often due to multiple causes. A rapid decrease in pain intensity induced by rapid opioid 27 titration does not produce changes in weakness, nausea and vomiting, appetite. While constipation appears the most relevant prob- 28 lem, resistant to common symptomatic treatment, drowsiness initially produced by acute opioid dose increase and the achievement 29 of pain relief, tends to spontaneously decrease, probably as the result of late tolerance. Improved well-being may be the late positive 30 eﬀect of pain relief, also inﬂuenced by the setting of home care. 31 Ó 2002 Published by Elsevier Ltd on behalf of European Federation of Chapters of the International Association for the study of 32 Pain. 33 Keywords: Opioids; Cancer pain; Adverse eﬀects; Prospective longitudinal study; Advanced cancer patients 34 35 1. Introduction 36 Pain is one of the most feared consequences of can- 37 cer. Opioids are the mainstay of cancer pain manage- 38 ment, but successful pain management with opioids 1090-3801/$30 Ó 2002 Published by Elsevier Ltd on behalf of European Federation of Chapters of the International Association for the study of Pain. doi:10.1016/j.ejpain.2005.02.006 * Corresponding author. Present address: Anesthesia & Intensive Care Unit and Pain Relief & Palliative Care Unit La Maddalena Cancer Center, Via San Lorenzo Colli 312, 90146 Palermo, Italy. Tel.: +39 091 6806521/6806111; fax: +39 091 680 6906. E-mail address: terapiadeldolore@la-maddalena.it (S. Merca- dante). www.EuropeanJournalPain.com European Journal of Pain xxx (2005) xxx–xxx YEUJP 617 No. of Pages 7, DTD = 5.0.1 28 February 2005 Disk Used ARTICLE IN PRESS