Managing Cancer Pain and Symptoms of Outpatients by Rotation to Sustained-release Hydromorphone A Prospective Clinical Trial Stefan Wirz, MD, Hans Christian Wartenberg, MD, Christian Elsen, Maria Wittmann, MD, Marta Diederichs, and Joachim Nadstawek, MD Purpose: In this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromor- phone for controlling pain and symptoms in outpatients with cancer pain. Methods: Before and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical Rating Scales (NRS)], or as categorical parameters, and analyzed by descriptive and confirmatory statistics (ANOVA, Wilcoxon, w 2 ). Results: Rotation was successful in 64% of patients experiencing pain (60%), and gastrointestinal (32%) and central (26%) symptoms under oral morphine (38%), transdermal fentanyl (22%), tramadol (20%), oxycodone (12%), or sublingual buprenorphine (8%). NRS of pain (4.1 to 3.2; P = 0.015), gastrointestinal symptoms, especially defecation rates (P = 0.04), and incidence of insomnia improved after an increase in morphine-equivalent doses from 108.9 to 137.6mg/d without modifying concomitant analgesics or coanalgesics. Conclusions: Switching the opioid to oral hydromorphone may be a helpful technique to alleviate pain and several symptoms, but it is still not clear to what extent the underlying mechanisms, such as the technique of rotation itself, better dose adjustment, or using a different opioid have an impact. Key Words: hydromorphone, opioid, rotation, symptom, cancer pain, outpatient, constipation (Clin J Pain 2006;22:770–775) P ain and symptoms have a negative impact on the quality of life of patients with cancer pain. Despite the publication of guidelines, many patients still suffer from inadequate analgesia and experience side-effects from their opioid medication, forcing them to discontinue opioid therapy. 1–4 Various schemes for the management of opioid- related symptoms comprise the use of several substances, for example, laxatives, antiemetics, and psychotropic drugs. However, improvements in the incidence and severity of symptoms have also been attributed to the technique of rotating opioids. Few prospective investiga- tions have been published on pain and side-effects after rotation of cancer patients to oral sustained-release hydromorphone, especially on hydromorphone. 5,6 There- fore, we evaluated the technique of opioid rotation for the management of pain and symptoms by administering oral sustained-release hydromorphone to outpatients with outpatient cancer pain. METHODS Study Design, Assessment This investigation was a controlled, prospective, observational cohort study. Data were collected over a period of 5 consecutive days before and after rotation to hydromorphone, interrupted by an adaptation period of 14 days. Demographic and general medical data, for example, age, sex, cancer diagnosis, concurrent diseases or disorders, were obtained by examining and interviewing the out- patients directly. Patients assessed their own general condition on a 100 mm scale at the beginning of the investigation (0 = worst condition, 100 = no impairment, best condition). Pain at rest was assessed via Numerical Rating Scales (NRS, 0-10, 0 = no pain, 10 = worst pain imagin- able), at 4 time points over 5 consecutive days (7.00 AM, 1.00 PM, 7.00 PM, and 10.00 PM). The investigators filled in a standardized questionnaire form listing central, gastrointestinal, and other symptoms. Patients rated the symptoms sedation, dizziness, nausea, ‘‘the subjective sensation of being constipated,’’ dry mouth, and itching by 11 step NRS Scales (NRS, 0-10, 0 = no symptom, 10 = worst symptom imaginable) (numerical parameters). Incidences of myoclonic jerks, insomnia, emesis, and defecation rate that could not be rated by NRS were counted (categorical parameters). Copyright r 2006 by Lippincott Williams & Wilkins Received for publication July 26, 2005; accepted June 15, 2006. From the Clinic for Anesthesiology and Intensive Care Medicine, Pain Clinic Department, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany. The authors wish to state that no grants or other financial support have influenced the course or results of the study. Reprints: Stefan Wirz, MD, Clinic for Anesthesiology and Intensive Care Medicine, Pain Clinic, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany (Schmerzambulanz, Klinik und Poliklinik fu¨r Ana¨ sthesiologie und Operative Intensivmedizin, Rheinische Friedrich-Wilhelms-Universita¨ t, Sigmund-Freud-Str. 25, D-53105 Bonn, Deutschland) (e-mails: s.wirz@web.de; postoperativ@web.de). ORIGINAL ARTICLE 770 Clin J Pain  Volume 22, Number 9, November/December 2006