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Journal of Opioid Management
January/February 2010, Volume 6
, Number 1


Article
Letter to the editor. Awake fiberoptic intubation with target-controlled infusion of remifentanil in emergency surgery
Cyrus Motamed, MD; German Salazar, MD
January/February 2010; pages 11-11


Article
Letter to the editor. EREM versus IV PCA meta-analysis
Robert H. Blackshear, MD
January/February 2010; pages 12-14


Article
Pharmacokinetics of intranasal fentanyl spray in patients with cancer and breakthrough pain
Stein Kaasa, MD, PhD; Kristin Moksnes, MD; Thomas Nolte, MD; Daniele Lefebvre-Kuntz, MD; Lars Popper, MS, PhD; Hans Georg Kress, MD, PhD
January/February 2010; pages 17-26

Abstract
Objective: This study reports the pharmacokinetics, tolerability, and safety of an intranasal fentanyl spray (INFS) in patients with cancer and breakthrough pain (BTP). Design: A randomized, open-label, two-period, crossover trial. Patients: Nineteen adult patients (mean 57.8 years) with BTP, receiving opioid treatment for chronic background pain, from clinical departments in Austria, France, and Norway entered and completed the study. Intervention: Patients were randomly assigned to receive one of six INFS dose sequences: 50/100, 100/50, 50/200, 200/50, 100/200, and 200/100 µg. INFS was administered as a single dose in one nostril. Each dose was separated by a minimum of 48 hours. Main outcome measure: Plasma fentanyl concentrations were measured by high-performance liquid chromatography and tandem mass spectrometry from blood samples obtained at 0 (predose) and frequently up to 300 minutes after INFS administration. Blood pressure, peripheral oxygen saturation, and respiratory rate were assessed eight times during each of the two treatment periods. Results: Mean fentanyl plasma concentrations increased in a dose-dependent manner, peaking for all fentanyl doses 9-15 minutes after INFS administration. Median Tmax values were 15, 12, and 15 minutes for the 50, 100, and 200 µg doses of INFS, respectively. Mean (SD) values for Cmax were 351 (±226), 595 (±400), and 1195 (±700) pg/mL, respectively, indicating dose-proportionality. Six patients (31.6 percent) experienced adverse events during the treatment period, the majority being mild in severity. Conclusion: INFS at doses of 50, 100, and 200 µg showed a short Tmax and was well tolerated in patients with cancer. These results support INFS use in patients with cancer suffering from BTP. Keywords: intranasal administration, fentanyl, pharmacokinetics DOI 10.5055/jom.2010.0001


Article
Variability of transdermal fentanyl metabolism and excretion in pain patients
Joanna M. Cole, BA; Brookie M. Best, PharmD, MAS; Amadeo J. Pesce, PhD, DABCC
January/February 2010; pages 29-39

Abstract
Background: The rising popularity of the fentanyl transdermal patch and the striking number of deaths attributed to its prescribed use have brought attention to the large variability of fentanyl metabolism and the need for predictive models to prevent toxicity. Objective: The purpose of this study was to determine the amount of both intrasubject and intersubject variability in fentanyl metabolism and excretion, using urinary excretion data from patients with chronic pain prescribed the fentanyl transdermal patch. Methods: Liquid chromatography tandem mass spectrometry analytical technique was used to quantitate fentanyl and norfentanyl concentrations in spot urine specimens, after incubation with glucuronidase. Descriptive statistics and graphical analysis were conducted using Microsoft Excel 2007. Analysis was conducted on 206 subjects with = 2 visits listing transdermal fentanyl as current medication. Outliers and subjects with no detectable levels of drug were excluded, resulting in subject populations of 200 (all subjects analyzed) and 166 (subjects with drug concentrations above the instrument detection limit for all visits). Results: The geometric mean metabolic ratio (MR) of norfentanyl to fentanyl was 6.2 × ÷ 2.4. A wide distribution was observed in total fentanyl load (1,000-fold) and MR (200-fold). The intersubject geometric standard deviation in MR was 2.4 (95% confidence interval [CI] for MR: 1-37) and the intrasubject geometric standard deviation was 1.8 (95% CI for MR: 2-20). Conclusion: The level of intrasubject variability over time in the pharmacokinetics of the fentanyl patch is much greater than previously observed and may be due to variability in absorption, interference of metabolism by concomitant medications, and variable metabolism due to genetic polymorphisms. The variation in the MR between subjects and within subjects may explain the unpredictable adverse effects observed with use of transdermal fentanyl. Keywords: fentanyl patch, metabolism, excretion DOI: 10.5055/jom.2010.0002


Article
Oxycodone/acetaminophen at low dosage: An alternative pain treatment for patients with rheumatoid arthritis
William Raffaeli, MD; Claudia Pari, MD; Angelo Corvetta, MD; Donatella Sarti, PhD; Valentina Di Sabatino, MD; Giovanni Biasi, MD; Maurizio Galeazzi, MD
January/February 2010; pages 40-46

Abstract
Objectives: To assess efficacy and safety of the association oxycodone/acetaminophen (oxycodone/ acetaminophen) for pain treatment and disability improvement in patients with rheumatoid arthritis (RA). Methods: Patients with RA (n _ 29), suffering from moderate to severe pain for more than 3 months, were included in the study, except those under RA therapy with biological drugs. The treatment started with oxycodone/acetaminophen at the dosage of 5 mg/325 mg, and then the dosage was titrated until the attainment of good pain relief. Antiemetic and laxative therapy was used for the prophylaxis of known opioid-related adverse events. Results: Patients continued their RA therapy without changing the dosages, reported reduced pain intensity and disease activity, and improvement of disability. Forty-two percent of patients had a good clinical response to oxycodone/acetaminophen treatment, according to European League against Rheumatism (EULAR) assessment criteria, and 50 percent of patients reached the American College of Rheumatology 20 percent improvement criteria (ACR20). At the end of the study, the mean (_SD) daily effective oxycodone/acetaminophen dose was 13.8 (_6.8) mg/720.4 (_291.0) mg. No serious adverse event was observed. Nausea, vomiting, and stipsis of mild-moderate intensity were the most common adverse events. Conclusion: Oxycodone/acetaminophen at low dosages for the treatment of chronic pain in RA patients can be a good alternative to non-steroidal anti-inflammatory drugs (NSAIDs), allowing the reduction of their consumption, while keeping RA therapy stable. Keywords: opioids, pain control, rheumatoid arthritis, association oxicodone/acetaminophen DOI:10.5055/jom.2010.0003


Article
The effect of intravenous opioid patient-controlled analgesia with and without background infusion on respiratory depression: A meta-analysis
Jessica A. George, MD; Elaina E. Lin, MD; Marie N. Hanna, MD; Jamie D. Murphy, MD; Kanupriya Kumar, MD; Phebe S. Ko, BS; Christopher L. Wu, MD
January/February 2010; pages 47-54

Abstract
Background: Although the addition of a background infusion for intravenous patient-controlled analgesia (IV-PCA) has been identified as a risk factor for the development of respiratory depression, this has not clearly been examined in a systematic fashion. The authors undertook a systematic review and meta-analysis of available randomized controlled trials (RCTs) to examine whether the addition of a background or continuous infusion to an IV-PCA regimen would be associated with an increased risk of respiratory depression. Methods: Studies were identified by searching the National Library of Medicine’s PubMed database (1966 to November 30, 2008). Inclusion criteria were a clearly defined analgesic technique of demand-only IV-PCA versus IV-PCA utilizing both a demand dose and background infusion, opioid medication used, and randomized trials. Data were abstracted and analyzed with the RevMan 4.2.7 (The Cochrane Collaboration, 2004). Results: The search yielded 687 abstracts from which the original articles were obtained and data abstracted with a total of 14 articles analyzed. There were 402 subjects in the continuous IV-PCA with demand group versus the 394 subjects in the demand-only IV-PCA group. Addition of a background infusion to the demand dose for IV-PCA with opioids was associated with a significant increased risk for respiratory depression (odds ratio [OR] = 4.68, 95% confidence interval [CI]: 1.20-18.21). Subgroup analysis revealed that this increased risk was seen in adult but not in pediatric patients. Conclusions: Our meta-analysis indicates that the addition of a continuous or background infusion to the demand dose for IV-PCA is associated with a higher incidence of respiratory events than demand IV-PCA alone in adult but not in pediatric patients; however, our overall results should be interpreted with caution due to the relatively small sample size and the wide range of definitions for respiratory depression in studies examined. Keywords: background infusion, continuous infusion, patient-controlled analgesia, postoperative pain, meta-analysis DOI:10.5055/jom.2010.0004


Article
Weaning of opioids and benzodiazepines at home after critical illness in infants: A cost-effective approach
Erwin Ista, PhD, RN; Monique van Dijk, PhD; Saskia Gischler, MD, PhD; Mirjam de Leeuw, RN; Marten J. Poley, PhD; Dick Tibboel, MD, PhD
January/February 2010; pages 55-62

Abstract
Objective: To evaluate the feasibility of infants’ weaning of opioids and sedatives at home. Design: Retrospective observational study. Setting: Level 3 pediatric intensive care unit. Patients: Neonates treated for congenital diaphragmatic hernia (CDH) with extra corporeal membrane oxygenation (ECMO). Intervention: Eligible infants were discharged early and further weaned of analgesics and/or sedatives at home. Results: Of the 30 neonates treated for CDH with ECMO from 2003 to 2005, 15 survived. Five of these were weaned at home, on the guidance of telephone contact once a week. The mean infusion rates of morphine and midazolam for these children were significantly higher than those for other infants. Weaning at home took 11, 42, 107, 173, and 180 days, respectively, in the resultant mean savings on hospitalization costs per patient amounted to €150,000. Conclusions: The results indicate that home weaning reduced the length of hospital stay by a median of 107 days for the five infants in this study, and thereby considerably reduced healthcare costs. Parents need to be informed clearly about possible withdrawal symptoms and should consent in this strategy. The strategy of final weaning with the aid of weekly telephone consultations with a consultant pediatric intensivist was feasible for these parents. Keywords: opioids, benzodiazepines, withdrawal symptoms, drug weaning, children DOI:10.5055/jom.2010.0005


Article
Effect of preoperative rectal indomethacin on postoperative pain reduction after open appendectomy
Ali Jangjoo, MD; Mostafa Mehrabi Bahar, MD; Ehsan Soltani, MD
January/February 2010; pages 63-66

Abstract
Background: One of the major challenges faced by the treatment planning teams is how to manage postoperative pain. Previous studies agreed upon the effects of preoperative administration of nonsteroidal anti-inflammatory drugs on postoperative pain, but all have focused on patients with surgical noninflammatory diseases (ie, inguinal hernia or breast biopsy). The aim of this study was to evaluate the effects of rectal indomethacin on reducing postoperative pain in patients with acute appendicitis. Methods: It is a simple randomized, clinical trial including 200 patients with acute appendicitis who were divided into two groups (A1 and A2). The case group (A1) received 100 mg rectal indomethacin during 2 hours before the operation. Pain intensity was assessed in all patients using a visual analog scale (VAS). Similarly, total dosage of meperidine analgesic medication and postoperative time to use of rescue analgesia were evaluated. Results: Patients who received preoperative rectal indomethacin (A1) showed a significant reduction in the VAS score. Also, a reduction in total dose of meperidine and longer time to use of rescue analgesic medication were observed in A1 group. Conclusion: Preoperative administration of rectal indomethacin in acute appendicitis reduces postoperative pain. Keywords: postoperative pain, indomethacin, appendectomy DOI:10.5055/jom.2010.0006


Article
Case Study. Use of sublingual methadone for treating pain of chemotherapy-induced oral mucositis
Anita Gupta, DO, PharmD; Benjamin Duckles, MD; James Giordano, MPhil, PhD
January/February 2010; pages 67-69

Abstract
Chemotherapy-induced and radiation-induced mucositis is a debilitating and often painful condition resulting in an inability to swallow, and thus inability to maintain adequate quality of life and overall functioning. To date, attempts on palliation of mucositis-related pain have primarily used topical anesthetic solutions and intravenous opioids; these approaches have achieved only limited success, particularly in oncology patients. The authors present a novel case of mucositis-related pain that is effectively treated with sublingual methadone. Sublingual methadone is an alternative to standard treatment options for mucositis-related pain and has unique pharmacokinetic and pharmacodynamic properties that make methadone a suitable agent for this pathology. These properties are addressed and discussed, as is the need for additional study to better understand the potential benefits, burdens, and risks that may be associated with this formulation of methadone when treating chemotherapy-induced and/or radiation therapy-induced mucositis in patients with cancer. Keywords: mucositis, methodone, sublingual, esophageal, cancer DOI:10.5055/jom.2010.0007

Journal of Opioid Management
March/April 2010, Volume 6
, Number 2


Article
Letter to the editor Pain medication prescription and borderline personality disorder: A pilot study
Randy A. Sansone, MD; Michelle Mueller, MD; Amy Mercer, MD; Michael W. Wiederman, MD
March/April 2010; pages 83-84


Article
Correlation between myoclonus and the 3-glucuronide metabolites in patients treated with morphine or hydromorphone: A pilot study
Shawn McCann, MD; Tony L. Yaksh, PhD; Charles F. von Gunten, MD, PhD
March/April 2010; pages 87-94

Abstract
Background: The 3-glucuronide metabolites of morphine and hydromorphone have been implicated as a causative factor for patients exhibiting myoclonus. Objective: The primary goal of this study was to determine plasma levels of morphine-3-glucuronide (M3G) or hydromorphone-3-glucuronide (H3G) in patients demonstrating myoclonus and identify any trends or associations between the two. Setting: Patients were recruited from San Diego Hospice and the Institute for Palliative Medicine’s inpatient unit. Design: A prospective convenience sample comprised of 17 subjects, 12 with myoclonus and 5 without yoclonus. Analysis included demographic, metabolicand clinical variables. Plasma was assayed via high performance liquid chromatography for morphine, M3G, and morphine-6-glucuronide or hydromorphone and hydromorphone-3-glucuronide. Results: No trends or associations were identified between plasma levels of M3G or H3G and myoclonus. Ratio levels of 3-glucuronide metabolite to their corresponding parent opioid were dramatically lower than anticipated. Conclusion: In this small pilot study, it appears that the serum levels of metabolites M3G and H3G do not correlate with myoclonus. Keywords: morphine-3-glucuronide, hydromorphone-3-glucuronide, opioid neurotoxicity, myoclonus morphine, hydromorphone DOI:10.5055/jom.2010.0008


Article
Breakthrough pain in community-dwelling patients with cancer pain and noncancer pain, Part 1: Prevalence and characteristics
Russell K. Portenoy, MD; Daniel Bruns, PsyD; Bonnie Shoemaker, BSN; Steven A. Shoemaker, MD
March/April 2010; pages 97-108

Abstract
Background: Most breakthrough pain (BTP) studies assess patients with advanced cancer or those receiving inpatient care. Studies in noncancer populations are limited to surveys of pain clinics and patients with other advanced diseases. To better understand BTP, data are needed from less selected populations. Aim: The aim of this study was to evaluate BTP in opioid-treated ambulatory patients with chronic cancer or noncancer pain treated in community practices. Methods: Primary care physicians or community-based oncologists recruited a convenience sample for a cross-sectional study of BTP at 17 sites in the United States. Physicians could not be pain specialists. Patients were eligible if they had any type of pain for = 3 months and were receiving an opioid drug on a regular basis that controlled the pain. The patients responded to a structured interview comprising items that assessed the baseline pain and items that assessed BTP, if present. Results: In total, 355 patients were screened, 191 were eligible and 177 (93 percent) provided data for analysis. Seventy-eight patients had cancer pain and 99 had noncancer pain. Patients with cancer were older (mean ± SD age 61.3 ± 11.2 years vs 51.4 ± 13.6 years, p < 0.001), and patients without cancer had more neuropathic pain (21 vs 12 percent, p < 0.05) and a longer pain duration (median 3.5 vs 1 years, p < 0.001). BTP occurred in 33 percent with cancer and 48 percent with noncancer pain (p = 0.042). BTP did not vary by diagnosis, but neuropathic pain was more common in those with BTP (27 vs 10 percent, p < 0.001). In patients with and without cancer, the median daily number of episodes was 1, the median time to maximum pain was 1-2 minutes, and the median duration was 45-60 minutes. There were fewer BTP precipitants in the patients with cancer (46 vs 80 percent of pains, p < 0.05), and they had less predictable pain (p < 0.05). Conclusions: The prevalence of BTP among community-dwelling patients is lower than that found in prior studies of more selected populations. BTP is more prevalent among patients with noncancer pain than patients with cancer pain, and although there are many similarities, some differences may be relevant to treatment strategies. Keywords: breakthrough pain, chronic pain, survey DOI:10.5055/jom.2010.0009


Article
Breakthrough pain in community-dwelling patients with cancer pain and noncancer pain, Part 2: Impact on function, mood, and quality of life
Russell K. Portenoy, MD; Daniel Bruns, PsyD; Bonnie Shoemaker, BSN; Steven A. Shoemaker, MD
March/April 2010; pages 109-116

Abstract
Background: Prior studies of breakthrough pain (BTP) largely focus on patients with advanced cancer or those receiving inpatient care. Very few studies have evaluated BTP in populations with chronic noncancer pain. Data that illuminate the impact of BTP may not generalize to other, less selected patient populations. Aim: The aim of this study was to evaluate the impact of BTP in opioid-treated ambulatory patients with chronic cancer pain or noncancer pain treated in community practices. Methods: Eligible patients–those with any diagnosis who reported chronic pain for at least 3 months, who were receiving long-term opioid therapy, and who met criteria for controlled baseline pain–were recruited for a cross-sectional observational study by primary care physicians or community-based oncologists at 17 sites in the United States. The patients responded to a structured interview for breakthrough pain and also completed the Brief Pain Inventory-Modified Short Form (BPI-SF) and the Brief Battery for Health Improvement 2 (BBHI 2). Results: Of 355 patients screened, 191 were eligible and 177 (93 percent) provided data for analysis. Twenty-six of the 78 with cancer pain (33 percent) and 48 of the 99 with noncancer pain (48 percent) had BTP. Compared with those without BTP, both patients with cancer (p = 0.004) and patients without cancer (p = 0.019) with BTP had increased pain interference in function, as measured by the BPI-SF, and patients without cancer were more impaired than patients with cancer. On the BBHI 2, BTP was associated with increased somatic complaints (p = 0.036 cancer and p = 0.024 noncancer) and pain complaints (p = 0.037 cancer and p = 0.037 noncancer); among patients without cancer, BTP was also associated with increased difficulties with functioning (p = 0.023), depression (p = 0.039), and decreased quality of life (p = 0.003). Conclusions: These data extend published observations about the association between BTP and adverse effects on mood and function to populations undergoing routine treatment in the community setting and provide evidence that these associations are greater in those with noncancer pain. They suggest the need for additional studies to clarify causality and determine whether undertreatment of BTP is a factor contributing to adverse pain-related outcomes. Keywords: breakthrough pain, chronic pain, functional impairment, psychological distress DOI:10.5055/jom.2010.0010


Article
Utility of transdermal fentanyl for prevention of iatrogenic opioid abstinence syndrome in children
Peter N. Johnson, PharmD, BCPS; Donald Harrison, PhD; Christine Allen, MD
March/April 2010; pages 117-124

Abstract
Background: Iatrogenic opioid abstinence syndrome (IOAS) can occur in critically ill infants/children following abrupt discontinuation of opioids. There are no standard guidelines for the prevention of IOAS. Transdermal fentanyl (TF) has been infrequently used at our institution for the prevention of IOAS. Methods: This was a retrospective, descriptive study of children less than 18 years of age receiving TF for the prevention of IOAS. Baseline demographics, IV sedative/analgesic regimen, TF regimen, and IOAS symptoms were collected. The primary objective was to describe the TF regimen. The secondary objectives were to classify the number/type of withdrawal symptoms and to identify the number of intermittent opioids administered for withdrawal symptoms. Results: Fifteen patients were identified with a median age of 7 years (0.3-17); the median cumulative IV fentanyl dose prior to initiation of TF was 1,356 µg kg-1 (164.1-9595.8). The median initial dose of TF was 1.9 µg kg-1 h-1 (0.4-6.1) or 25 µg h-1 (12.5-500); TF was continued for a median duration of 16 days (5-27). To provide the desired dose, the TF patch was partially covered with Tegaderm™ in eight patients. Eighty-six intermittent opioid doses were administered during TF therapy with 51 (59 percent) administered within 5 days of TF initiation. Seven patients (46.7 percent) had IOAS. No significant differences in IOAS symptoms were observed between patients whose patch was partially covered versus not covered, 3 versus 4, respectively (p > 0.05). There was no correlation between the number of opioid doses administered and IOAS symptoms from days 1 to 5, correlation coefficient 0.347 (p _ 0.206). Conclusions: In this cohort, most patients required additional opioids for IOAS symptoms during the first 5 days of TF. TF therapy cannot be routinely recommended for the prevention of IOAS until further prospective studies can confirm these results. This pilot study highlights future directions to standardize documentation and to educate clinicians on IOAS symptoms. Keywords: children, transdermal fentanyl, opioid withdrawal DOI:10.5055/jom.2010.0011


Article
Teaching clinical opioid pharmacology with the Human Patient Simulator
Zaki Hassan, MD; Amy DiLorenzo, MA; Paul Sloan, MD
March/April 2010; pages 125-132

Abstract
Objective: Postoperative pain should be aggressively treated to decrease the development of chronic postsurgical pain. There has been an increase in the use of Human Patient Simulator (HPS) for teaching advanced courses in pharmacology to medical students, residents, and nurses. The aim of this educational investigation was to pilot the HPS for the training of medical students and surgical recovery room staff nurses in the pharmacology of opioids for the management of postoperative pain. Methods: The computerized HPS mannequin is fully monitored with appropriate displays and includes a voice speaker mounted in the head. Medical students and Postanesthesia care unit nurses, led by faculty in the Department of Anesthesiology in small groups of 4-6, participated in a 2- to 3-hour HPS course on the use of opioids for the management of acute postoperative pain. Trainees were asked to treat the acute and severe postoperative pain of a simulated patient. Opioid effects and side effects (such as respiratory depression) were presented on the mannequin in real time to the participants. Side effects of naloxone to reverse opioid depression were presented as a crisis in real time to the participants. Participants completed a 10-item course evaluation using a 5-point Likert scale (1 = strongly disagree; 5 = strongly agree). Results: Twenty-two nurses and nine medical students completed the HPS opioid pharmacology scenario. Almost all participants rated the HPS course very highly and rated every item as either agree or strongly agree. Most participants agreed that the simulator session improved their understanding of opioid pharmacology including opioid side effects and management of opioid complications. Course participants felt most strongly (median, interquartile range) that the simulator session improved their understanding of naloxone pharmacology (5, 0), simulators serve as a useful teaching tool (5, 0), and that they would be pleased to participate in any additional HPS teaching sessions (5, 0). Conclusions: The HPS provides a novel educational format to teach essential information regarding opioid pharmacology for the management of acute postoperative pain. The HPS provides a realistic format to teach the pharmacology of acute opioid side effects and the management of acute and life-threatening side effects of naloxone therapy. Keywords: patient simulation, resident education, opioid pharmacology, opioid pharmacodynamics, Human Patient Simulator, naloxone DOI:10.5055/jom.2010.0012


Article
Opioid use in young veterans
Phipson C. Wu, PharmD, BCPS; Courtney Lang, PharmD, BCPS; Noelle K. Hasson, PharmD; Steven H. Linder, MD; David J. Clark, MD
March/April 2010; pages 133-139

Abstract
Purpose: Data suggest an increase in prescription opioid abuse in recent years. Young veterans represent a group with major risk factors for prescription opioid abuse. The objectives of this study are: (A) to determine the prevalence of chronic opioid use in young veterans over time; (B) to describe the prescribing patterns and monitoring of chronic opioid therapy in young veterans; and (C) to assess opioid management within Veterans Affairs Palo Alto Health Care System (VAPAHCS) with an emphasis on effectiveness and safety. Methods: This is a Veterans Affairs Research and Development (R&D) Committee and IRB-approved retrospective, single-center study of young veterans aged 18-30 years on chronic opioid therapy during the study years January 1, 2003, to October 1, 2008. A subset of the study population who were receiving long-acting opioids for a minimum of 6 months was included in the effectiveness and safety analyses. Data were obtained from the Veterans Integrated Service Network (VISN 21) data warehouse, outpatient prescription records, and from electronic chart review. Results: The prevalence of chronic opioid use in young veterans has increased from 3 percent in 2003 to 4.5 percent in 2007. Patients on average were exposed to two different opioids and had three different opioid prescribers. Nearly 80 percent of the opioid prescriptions during the study were prescribed by primary care providers and less than 1 percent was from pain specialists. Only 31 percent of patients on chronic opioids had undergone urine drug testing and only 5 percent had signed opioid treatment agreements. No difference in median pain score was observed following initiation of long-acting opioid therapy, and 22 percent of patients (4 of 18) met the prespecified definition of being a responder to long-acting opioid therapy. Five patients (28 percent) on long-acting opioids experienced adverse drug reactions. Conclusion: The prevalence of chronic opioid use in young veterans has been on the rise in recent years. Young veterans receiving care at VAPAHCS have often had multiple opioid prescribers and have trialed multiple opioid analgesics. Many improvements in appropriate monitoring and management of these patients can be made, which may include providing more training to current staff, the development of an opioid refill clinic, and greater utilization of the pain management specialists. Further larger study is warranted to identify successful strategies for improving prescribing and monitoring of opioids as well as potential predictors of response to chronic long-acting opioid therapy. Keywords: opioids, veterans, pain, chronic, prevalence, monitoring, safety, efficacy DOI:10.5055/jom.2010.0013


Article
Comparison of the postoperative analgesic efficacy of intravenous patient-controlled analgesia with tramadol to intravenous patient-controlled analgesia with opioids
Jamie D. Murphy, MD; Dawn Yan, MD; Marie N. Hanna, MD; E. David Bravos, MD; Gillian R. Isaac, MD, PhD; Calvin A. Eng, MD; Christopher L. Wu, MD
March/April 2010; pages 141-147

Abstract
Background: Intravenous patient-controlled analgesia (IV PCA) with tramadol is an accepted method to deliver postoperative analgesia outside North America; however, the analgesic efficacy of this analgesic agent when compared with IV PCA with opioids is uncertain. As such, the authors undertook a systematic review to compare the analgesic efficacy of IV PCA tramadol with that of IV PCA with opioids. Methods: The authors used the National Library of Medicine’s Medline database to search for terms related to tramadol and patient-controlled analgesia. Inclusion criteria were randomized controlled trials (RCTs) comparing IV PCA tramadol with IV PCA opioid and RCTs published in the English language. Relevant data were abstracted from accepted studies. Meta-analysis was performed using RevMan 4.2.10 (The Cochrane Collaboration, 2004). A random effects model was used. Results: A total of 190 abstracts were obtained from the above search, and a total of 12 RCTs met the above inclusion criteria. There was no difference in weighted visual analog scale pain scores between IV PCA tramadol versus IV PCA opioid at 48 hours postoperatively or risk of sedation or fatigue. IV PCA tramadol was associated with a higher odds of postoperative nausea and vomiting [odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.07-2.14) but a lower odds of pruritus (OR = 0.43, 95% CI = 0.19-0.98). Discussion: IV PCA tramadol appears to produce similar pain scores when compared with that from IV PCA opioids; however, the side effect profile is different between the two groups. Because of the relatively small sample size, no determination of the relative “safety” (eg, respiratory depression) of one regimen over the other can be made, and larger RCTs would be needed for such a determination. Keywords: tramadol, patient-controlled analgesia, postoperative pain, meta-analysis DOI:10.5055/jom.2010.0014

Journal of Opioid Management
May/June 2010, Volume 6
, Number 3


Article
Letter to the editor. The abuse of prescription medications: A relationshup with borderline personality?
Randy A. Sansone, MD; Charlene Lam, BS; Michael W. Wiederman, PhD
May/June 2010; pages 159-160


Article
Letter to the editor. Intrathecal local anesthetics combined with high-dose intrathcal morphine for surgery
Annette Rebel, MD; Paul A. Sloan MD
May/June 2010; pages 161-161


Article
Letter to the editor. Thoracic epidural analgesics provide excellent cancer pain relief at the end of life
Paul A. Sloan, MD
May/June 2010; pages 166-167


Article
Evaluation of study discontinuations with tapentadol immediaterelease and oxycodone immediate release in patients with lowback or osteoarthritis pain
Gary Vorsanger, PhD, MD; Jim Xiang, PhD; Akiko Okamoto, ScD; David Upmalis, MD; Bruce Moskovitz, MD
May/June 2010; pages 169-179

Abstract
Objective: To examine discontinuations due to nausea and/or vomiting or constipation with tapentadol immediate release (IR) or oxycodone IR treatment. Design: Post hoc analyses of a 90-day, phase 3, randomized, double-blind, flexibledose study. Setting: United States, Canada, United Kingdom. Patients: Adults with moderate to severe low back or osteoarthritis (OA) pain for = 3 months. Interventions: Tapentadol IR 50 or 100 mg or oxycodone HCl IR 10 or 15 mg every 4-6 hours as needed. Main outcome measures: Adverse events and discontinuations were recorded. Results: Post hoc analyses included data from 679 patients receiving tapentadol IR and 170 receiving oxycodone IR (4:1 randomization). Tapentadol IR 50 or 100 mg and oxycodone HCl IR 10 or 15 mg provided similar levels of pain relief. Overall, 21.2 percent of patients receiving tapentadol IR discontinued treatment for adverse events versus 31.2 percent of patients receiving oxycodone IR. The percentage of patients who discontinued for nausea and/or vomiting was significantly lower with tapentadol IR (5.9 percent) than oxycodone IR (14.7 percent; p = 0.0003); patients treated with oxycodone IR discontinued because of nausea and/or vomiting significantly earlier than with tapentadol IR (p < 0.0001). The percentage of patients who discontinued because of constipation was significantly lower with tapentadol IR (1.5 percent) than with oxycodone IR (5.9 percent; p = 0.0023); patients treated with oxycodone IR discontinued because of constipation significantly earlier versus tapentadol IR (p = 0.0003). Conclusions: A lower percentage of patients discontinued because of nausea and/or vomiting or constipation with tapentadol IR versus oxycodone IR while receiving comparable pain relief, suggesting tapentadol may improve the management of low back and OA pain. Keywords: tapentadol, low back pain, osteoarthritis pain, study discontinuations, gastrointestinal tolerability, oxycodone DOI:10.5055/jom.2010.0015


Article
Long-term tolerability and effectiveness of oxymorphone extended release in patients with cancer
Neal E. Slatkin, MD; Michelle I. Rhiner, RN, MSN, NP; Errol M. Gould, PhD; Tina Ma, PhD; Harry Ahdieh, PhD
May/June 2010; pages 181-191

Abstract
Objective: To evaluate the long-term safety, tolerability, and effectiveness of oxymorphone extended release (ER) in patients with cancer-related pain. Design: Post hoc analysis of two = 1-year open-label extension studies. Setting: Multiple US cancer treatment facilities. Patients: Patients with cancer pain who had participated in two short-term crossover comparator trials of oxymorphone ER: one open-label and one doubleblind randomized. Interventions: Patients who had been taking oxymorphone ER continued the dose established in the previous study. Patients who had been taking a comparator opioid were switched to an equianalgesic dose of oxymorphone ER. All patients underwent individualized oxymorphone ER dose titration to optimize effectiveness and tolerability. Assessments: Current, average, worst, and least pain scores were normalized to a 100-point scale. Patients rated treatment on a five-point global assessment of study medication (Poor = 1 to Excellent = 5). All adverse events (AEs) were recorded. Results: Of the 80 patients who entered the extension trials, 26 completed 52 weeks, 7 discontinued owing to loss of effectiveness, and 20 discontinued owing to AEs, most of which were unrelated to study drug. No significant increase in mean (standard deviation [SD]) average pain intensity was observed from baseline (30.5 [19.6], 100-point scale) to final visit (35.9 [21.1], p = 0.37). The most common AEs were concomitant disease progression (28.8 percent, n = 23), nausea (22.5 percent, n = 18), dyspnea (16.3 percent, n = 13), fatigue (16.3 percent, n = 13), and edema of the lower limb (15 percent, n = 12). Conclusions: In these patients with pain related to cancer, oxymorphone ER was generally well tolerated and provided stable long-term pain control. Keywords: cancer, cancer pain, chronic pain, extension trial, opioid, oxymorphone DOI:10.5055/jom.2010.0016


Article
A randomized, placebo-controlled, double-blinded, parallel-group, 5-week study of buprenorphine transdermal system in adults with osteoarthritis
Catherine Munera, PhD; Margaret Drehobl, MD; Nelson E. Sessler, PharmD; Craig Landau, MD
May/June 2010; pages 193-202

Abstract
Background: This multicenter, parallel-group, 35-day study in adults with osteoarthritis (OA) pain evaluated the analgesic efficacy and safety of buprenorphine transdermal system (BTDS) designed for 7-day wear. Methods: Patients with OA pain inadequately controlled with nonsteroidal anti-inflammatory drugs or patients who had taken opioids for OA pain within the past year entered a 7-day run-in period during which they took ibuprofen only. Patients with pain = 7 on a 0-10 scale had their ibuprofen discontinued and were randomized into a 28-day double-blinded period to receive either BTDS at 1 of 3 dose levels (5, 10, or 20 µg/h) or placebo. Doses were titrated to effectiveness over a period of 21 days and maintained for 7 days. No rescue medication was allowed during the study. The primary efficacy measure was the proportion of patients who achieved treatment success, defined as a patient satisfaction score of good, very good, or excellent (on day 28 or at early discontinuation) for those who did not discontinue due to ineffective treatment. Results: More BTDS-treated patients experienced treatment success than placebo TDS-treated patients (44 percent and 32 percent; odds ratio = 1.66, p = 0.036). Fewer patients taking BTDS titrated to the highest dose compared with placebo (p < 0.05). There were two serious adverse events (both in the placebo group) and no deaths. The most common (= 5 percent) adverse events reported in BTDS treated patients were nausea, headache, dizziness, somnolence, application site pruritus, and vomiting. Conclusion: Compared with placebo, BTDS treatment was effective in treating patients with moderate to severe pain due to OA of the knee or hip. BTDS was well tolerated. Keywords: buprenorphine, transdermal, pain, analgesia, osteoarthritis, randomized controlled trials DOI:10.5055/jom.2010.0017


Article
Safety and tolerability of fentanyl iontophoretic transdermal system:Findings from a pooled data analysis of four clinical trials
Harold S. Minkowitz, MD; Joel Yarmush, MD; Malcolm T. Donnell, MD; Peter H. Tonner, MD; C.V. Damaraju, PhD; Roman J. Skowronski, MD, PhD
May/June 2010; pages 203-210

Abstract
Acute postoperative pain remains inadequately managed. Although patient controlled analgesia (PCA) represents a significant advance in postoperative pain management, drawbacks may include invasiveness and the potential for programming errors. The analysis presented here is based on pooled patient-level safety data from four multicenter, randomized, active-controlled trials that evaluated the safety and tolerability of the needle-free, preprogrammed fentanyl HCl iontophoretic transdermal system (ITS) versus morphine intravenous PCA for postoperative pain management; the results for patients who received fentanyl ITS are presented here. Adverse events (AEs), serious AEs, and clinically relevant respiratory depression were assessed across patient subpopulations categorized by age. A total of 1,288 patients, including 356 elderly (> 65 years of age) patients, received fentanyl ITS following surgery. The most commonly reported AEs included nausea, fever, vomiting, headache, anemia, pruritus, and hypotension. The incidence of AEs was generally lower for elderly patients than for patients 65 years or younger. Application-site reactions were reported for 18.6 percent of patients using fentanyl ITS and were generally mild to moderate in severity. No cases of clinically relevant respiratory depression were eported for patients who received fentanyl ITS. The results demonstrate that fentanyl ITS is safe and well tolerated for postoperative pain management for patients overall and for subpopulations divided according to age. Keywords: tolerability, pain management, postoperative, fentanyl ITS, patient-controlled analgesia DOI:10.5055/jom.2010.0018


Article
Psychosocial distress in patients treated for cancer pain: A prospective observational study
Sean O’Mahony, MB BCh, BAO; Joseph Lucien Goulet, PhD; Richard Payne, MD
May/June 2010; pages 211-222

Abstract
Introduction: Untreated emotional distress negatively impacts the management of cancer pain. Objectives: The authors evaluated 64 patients with cancer pain who completed baseline and follow-up measures to identify if (1) measures of psychosocial well being, pain intensity, and pain management were associated with survival time; (2) higher opioid doses were associated with less psychosocial distress; and (3) intrasubject correlations across time altered the relationship between pain, depression, social support, spirituality, and increased desire for hastened death (DHD). Methods: The main outcome measures included the Brief Pain Inventory (BPI), Daily Morphine Equivalent Dose (DMED), Beck Depression Inventory-II (BDI-II), DHD scale, Bottomley Social Support Scale, FACIT Spiritual Well-Being Scale (FACIT-Sp), Karnofsky Performance Rating Scale (KPRS), and State-Trait Anxiety Inventory (STAI). Results: There were significant differences between baseline and follow-up DHD (0.84 vs 1.38, p = 0.021) and BPI scores (6.36 vs 4.86, p < 0.001). Lower existential well being was associated with reduced survival (HR = 0.78, p = 0.019); improvement in pain was associated with longer survival (HR = 1.33, p = 0.034). Higher religious wellbeing was associated with higher probability of survival to 1 year (HR = 0.41, p = 0.014), as was higher KPRS (HR = 0.97, p = 0.001) but not DMED > 300 mg. Higher existential distress and lower Bottomley scores were associated with higher hazard ratios for death at 1 year (HR = 2.78, p = 0.02) and (HR = 14.94, p = 0.002). There were significant differences in average BDI-II for persons with BPI > 7 versus those with moderate or mild pain (12.12 vs 6.82, p < 0.0001) and in DHD (1.71 vs 0.64, p = 0.002). Depression decreased in persons with DMED > 300 mg between baseline and follow-up (-1.67 vs 2.72, p = 0.024). Mean DHD was lower for persons whose pain improved versus others (0.96 vs 2.0, p = 0.026). A generalized linear model was conducted with DHD as the dependent variable and the other above variables as predictors. Higher existential wellbeing and KPRS were associated with lower DHD (ß = -0.135, p = 0.049) and (ß = -0.79, p = 0.006), respectively. Conclusions: The major findings of this study are that in persons with cancer pain, lower social support and existential wellbeing, but not higher DMED, were associated with shorter survival time. Treatment of cancer pain was associated with lessening of emotional distress. Lower levels of existential wellbeing and physical performance status appear to be associated with greater DHD. Keywords: cancer pain, opioid medications, psychosocial wellbeing DOI:10.5055/jom.2010.0019


Article
Review article. Tapentadol: An initial analysis
Eric E. Prommer, MD
May/June 2010; pages 223-226

Abstract
Tapentadol hydrochloride (17(—)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol) is a newly released analgesic that works at two levels: by acting as a µ-opioid agonist and as a modulator of descending inhibitory pathways through its effects on neurotransmitters involved in these pathways. The theoretical advantage is the provision of synergistic analgesic activities, which may lessen the need for opioid escalation. The advantage is its potential as a possible new agent in neuropathic pain. Preclinical models confirm analgesic properties in acute pain and neuropathic pain models, but with less potency than morphine. Tapentadol has minimal CYP 450 interactions limiting potential for drug interactions. Human clinical trial data in nonmalignant pain suggest less potency than a step-3 opioid, and the drug remains to be tested in patients with cancer pain and neuropathic pain. Keywords: tapentadol, affinity, neuropathic DOI:10.5055/jom.2010.0020


Article
Case study. Outcome of acute heroin overdose requiring intensive care unit admission
Leonidas Grigorakos, MD, PhD; Katerina Sakagianni, MD; Evdoxia Tsigou, MD; George Apostolakos, MD;Giannis Nikolopoulos, MD; Dimitris Veldekis, MD
May/June 2010; pages 227-231

Abstract
Background: Heroin use carries a large burden of morbidity and mortality. Heroin overdose and in particular events that need intensive care unit (ICU) admission have not been widely examined. The aim of this study was to describe the causes of ICU admission and the outcome of patients with a heroin overdose. Methods: A retrospective chart review of all patients with a heroin overdose admitted to the ICU between 1987 and 2006 was conducted. Results: Forty-two records were available for review. The average age of the patients was 28 years. In the field, 19 persons were found in coma Glasgow Coma Scale (GCS < 8) and respiratory depression and were treated with naloxone. The reasons for ICU admission included hypoxemia in 37 (88 percent), 28 of whom had acute lung injury (ALI) and nine aspiration pneumonia, shock in three (7.2 percent) and persistent mental compromise in two patients (4.8 percent). Intubation and mechanical ventilation (MV) were instituted in 37 patients. In 19 of the 37 patients, weaning and extubation became possible within the first 24 hours. Sixteen patients suffered complications and received MV for 5 ± 2 days, with a mean length of ICU stay of 8 ± 1 days, while two patients succumbed because of anoxemic encephalopathy and brain death. The complications observed were acute respiratory distress syndrome in eight patients, severe sepsis in four, catheter-related bacteremia in one, iatrogenic pneumothorax in one, and rhabdomyolysis in two, while four among them died due to severe sepsis. Conclusions: In our study, ALI and aspiration pneumonia were the most frequently observed respiratory complications after acute heroin overdose requiring intubation and ICU admission. Mortality rate was 14.2 percent and was attributed to septic complications and irreversible brain damage. Keywords: heroin overdose, acute drug intoxication, ICU management DOI:10.5055/jom.2010.0021

Journal of Opioid Management
July/August 2010, Volume 6
, Number 4


Article
Characteristics of prescription opioid abusers in treatment: Prescription opioid use history, age, use patterns, and functional severity
Stephen F. Butler, PhD; Ryan A. Black, PhD; Jill M. Grimes Serrano, PhD; Mollie E. Wood, MPH; Simon H. Budman, PhD
July/August 2010; pages 239-252

Abstract
Research has raised the possibility that the length of time one engages in nonmedical use of prescription opioids may be associated with abuse of other drugs, more risky drug-related behavior, and more severe functional problems. This study drew on data from the Addiction Severity Index-Multimedia Version® Connect system. A total of 55,341 client assessments at substance abuse treatment centers were analyzed to help understand the impact of length of time one has abused opioids on the patterns of abuse and functional problems. From this larger sample, 5,686 individuals who had abused a prescription opioid within the past 30 days were studied. Multiple logistic regression analyses were run to examine the impact of length of time abusing any opioid, after adjusting for several demographic variables, on route of administration (injection or injection/snorting), other drugs abused, and functioning in the areas of medical status, employment, drug and alcohol use, legal status, family and social problems, and psychiatric status. Overall findings supported the hypothesis that length of opioid abuse is associated with higher risk of drug use patterns as well as functional problems. Keywords: prescription opioids, drug abuse, route of administration, ASI, age DOI:10.5055/jom.2010.0022


Article
Observations of medication compliance by measurement of urinary drug concentrations in a pain management population
Robert West, MS; Amadeo Pesce, PhD, DABCC; Cameron West, PhD; Bridgit Crews, PhD; Charles Mikel, PhD; Murray Rosenthal, DO, FAPA; Perla Almazan, CLS, MT (ASCP); Sergey Latyshev, MS
July/August 2010; pages 253-257

Abstract
Background: One of the major concerns of physicians treating pain patients with opioids is to determine whether the patients are compliant, and this is commonly determined by urine drug testing. There is limited information on which drugs these patients are most compliant with. There is also limited information as to how compliance is defined in terms of cutoffs. Objective: To compare reported patient medication use with the presence of the drug in the patients’ urine with defined cutoffs. Method: A retrospective study of the medications listed by the physicians’ offices and the confirmed drug test findings. A Millennium Laboratories database of 20,457 patient results was examined for the presence of the listed medications and was matched for the presence of the drugs above the analytical cutoffs. Results: For oxycodone and hydrocodone, the authors observed 23 and 24 percent noncompliance, respectively. For carisoprodol, they observed 33 percent noncompliance. For morphine, they observed 14 percent noncompliance. For methadone, they observed 9 percent noncompliance. Conclusions: Noncompliance is prevalent in this patient population and varies with the prescribed drug. Keywords: pain patients, medication compliance, opioids, carisoprodol DOI:10.5055/jom.2010.0023


Article
Rationales behind the choice of administration form with fentanyl: Delphi survey among Danish general practitioners
Ramune Jacobsen, PhD; Claus Møldrup, PhD; Lona Christrup, PhD
July/August 2010; pages 259-268

Abstract
Background and Aim: The aim of this study was to describe the rationale behind the choice of fentanyl administration forms among Danish general practitioners (GPs). Methods: Thirty-eight Danish GPs were contacted via an Internet survey system to perform a Delphi survey. In the brainstorming phase, the main reasons for prescribing and not prescribing fentanyl patches, oral transmucosal systems (OTFCs), and nasal sprays were identified. In the second phase, GPs were asked to rate the importance of each reason. Results and Discussion: Thirty-three GPs responded in the brainstorming phase, and 33 and 31 in two rating rounds, respectively. The most important reason to choose fentanyl patches was that patients’ clinical condition did not allow them to take analgesia orally. OTFCs were primarily seen as a self-administrative alternative to injections in case of breakthrough pain. The main reasons for not choosing OTFCs were intolerance to fentanyl and price. The most important possible rationale to choose fentanyl nasal spray was easy administration. The most important possible reasons to not choose fenanyl nasal spray were application side effects. Conclusions: The rationale behind the choice of administration form with fentanyl partly differed from those overviewed in the literature. Fentanyl nasal spray was seen as a better option for treatment of breakthrough pain among terminally ill patients if compared with OTFCs. Keywords: fentanyl, administration, rationale, general practitioners DOI:10.5055/jom.2010.0024


Article
Review article. Burden of opioid-associated gastrointestinal side effects from clinical and economic perspectives: A systematic literature review
Kim Boswell, MD; Winghan Jacqueline Kwong, PharmD, PhD; Shane Kavanagh, MSc
July/August 2010; pages 269-289

Abstract
Opioid analgesia is the mainstay of treatment for moderate to severe acute and chronic pain and is highly effective in relieving pain but can be limited by side effects, the most common of which affect the gastrointestinal (GI) and central nervous systems. A growing body of evidence demonstrates that opioid-associated GI side effects constitute an important health problem with significant humanistic and economic consequences that warrant consideration by healthcare professionals and administrators in optimizing patients’ pain management. This article documents the frequency of opioid-associated GI side effects and describes its clinical and economic burdens based on a systematic review of the medical literature between 1966 and 2008. Keywords: opioid, analgesic, side effect, burden, economic, quality of life, cost DOI:10.5055/jom.2010.0025


Article
Review article. Applying partially occluded fentanyl transdermal patches to manage pain in pediatric patients
Amy Mitchell, PharmD; Howard S. Smith, MD
July/August 2010; pages 290-294

Abstract
Fentanyl transdermal patches (FTPs) have been used for many years in the treatment armamentarium for chronic pain. By design, FTPs release drug into the skin at a constant rate and thereby provide drug in a fashion similar to continuous intravenous infusion without the disadvantages of a venous catheter and the constant presence of an analgesia pump. Pediatric patients may require doses of FTP other than the five commercially available strengths. Application of a partial FTP allows for more flexibility in dosing. Yet, very little information is provided in the literature to suggest a procedure for applying partial FTP. A technique of using a partially occluded FTP is presented in an effort to encourage further study of this and perhaps other techniques. Keywords: fentanyl transdermal patch, pain, partially occluded patch, gradual titration DOI:10.5055/jom.2010.0026


Article
Review article. Hydrocodone: Does it have a role in palliative care?
Eric Prommer, MD
July/August 2010; pages 295-299

Abstract
Hydrocodone is an epoxy-methoxy-methylmorphinan semisynthetic opioid (6-deoxy-3-O-methyl-6-oxomorphine hydrogen tartrate hemipentahydrate), which is structurally related to codeine, and is classified as a step 2 opioid on the World Health Organization’s stepladder for pain. Hydrocodone is typically found in fixed dose combination with acetaminophen and is often used for pain management. Hydrocodone is a heavily prescribed drug and it is important to understand the evidence base that is guiding this use. This article reviews the pharmacodynamics, pharmacology, and evidence base for the use of hydrocodone in palliative care. Keywords: opioids, hydrocodone, cytochrome oxidase, dyspnea, pain DOI:10.5055/jom.2010.0027


Article
Case study. Acute opioid withdrawal precipitated by ingestion of crushed Embeda (morphine extended release with sequestered naltrexone): Case report and the focused review of the literature
Xiulu Ruan, MD; Tao Chen, MD, PhD; Jeff Gudin, MD; John Patrick Couch, MD; Srinivas Chiravuri, MD
July/August 2010; pages 300-303

Abstract
Background: The introduction of newly formulated extended release (ER) morphine with sequestered naltrexone (Embeda) has provided another treatment option for moderate to severe persistent pain. Embeda was designed to be an abuse-deterrent opioid formulation. Naltrexone is a centrally acting opioid receptor antagonist that blocks the action of opioid. When taken as directed, insignificant amount of sequestered naltrexone would reach systemic circulation, but upon tampering, the released naltrexone may blunt the euphoria of opioids, and possibly precipitate opioid withdrawal in opioid-dependent patient. Objective: To describe a case report of a 50-year-old opioid-dependent male who developed acute opioid withdrawal after taking crushed Embeda. Case report: A 50-year-old male with severe, chronic low back pain due to degenerative disc disease was referred to our clinic for pain management. He was taking ER oxycodone 80 mg tid and Roxicodone 30 mg qid prn, with inadequate pain relief. A trial of ER oxymorphone was decided, at 40 mg 1-2 doses bid. The patient returned to the clinic 1 week early, out of his ER oxymorphone. At this time, the decision to switch him to Embeda was made, at 80 mg/3.2 mg, 1-2 doses bid. The patient and his family members were counseled about risk involved with tampering with Embeda. A few hours later, our clinic was informed that the patient was brought to emergency room by ambulance, in severe opioid withdrawal. He was treated with IV fluid, antiemetics, clonidine, and IV hydromorphone. His condition improved and he was discharged home the next morning. Later on, the patient admitted that he took two prescribed Embeda within half an hour, the 1st one whole and the 2nd one crushed. He further admitted that he did so against our medical advice. Conclusion: Taking tampered Embeda may precipitate opioid withdrawal in opioid-tolerant patient. To the best of our knowledge, this is the first report of induced opioid withdrawal following consumption of crushed Embeda. Keywords: morphine, naltrexone, opioid withdrawal, Embeda DOI:10.5055/jom.2010.0028

Journal of Opioid Management
September/October 2010, Volume 6
, Number 5


Article
Long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray for breakthrough cancer pain in opioid-tolerant patients
Russell K. Portenoy, MD; William Raffaeli, MD; Luis M. Torres, MD; Thomas Sitte; Akhil Chandra Deka, MD; Ileana Gonzalez Herrera, MD; Mark S. Wallace, MD
September/October 2010; pages 319-328

Abstract
Objective: To assess the long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray (FPNS) in patients with breakthrough cancer pain (BTCP). Design: A multicenter, open-label study. Patients: Patients with chronic cancer pain treated with = 60 mg/d oral morphine or equivalent experiencing 1-4 episodes per day of BTCP. Intervention: All patients entered into a 16-week treatment phase after undergoing a dose-titration phase with FPNS. Main outcome measures: Safety and tolerability were assessed by adverse events (AEs) and by nasal tolerability assessments. Consistency of effect was monitored through additional rescue medication use and FPNS dose change. Results: Four hundred three patients were included in the safety analyses. Of these, 356 patients entered the treatment phase and 110 patients completed the study. FPNS was self-administered for 42,227 episodes. During the treatment phase, 99 patients (24.6 percent) reported treatment-related AEs; most were mild or moderate and typical of opioids. Serious AEs were reported by 61 patients (15.1 percent), but only five were considered related to study drug. Of the 80 deaths that occurred during this study, one was assessed as possibly related to study drug. Nasal assessments revealed no significant local effects. No additional rescue medication was required after 94 percent of FPNS-treated episodes. More than 90 percent of patients required no increase in their initial dose of FPNS. Conclusions: FPNS use for BTCP was associated with AEs, typical of opioids, with no evidence of nasal toxicity. A large proportion of BTCP episodes were treated with a single dose, and doses remained stable over the 4-month period. Keywords: fentanyl, breakthrough cancer pain, intranasal DOI:10.5055/jom.2010.0029


Article
A double-blind, placebo-controlled study of dual-opioid treatment with the combination of morphine plus oxycodone in patients with acute postoperative pain
Lynn Webster, MD; Patricia Richards, MD, PhD; Warren Stern, PhD; Robin Kelen, RN, BA, CNN
September/October 2010; pages 329-340

Abstract
Objective: Animal and human studies suggest that coadministration of two opioids with different receptor binding properties may result in enhanced analgesia and fewer opioid-related adverse events (AEs). Q8003 (MoxDuo®), an oral dual-opioid formulation with a fixed ratio (3:2) of morphine and oxycodone, was evaluated for analgesic effects and safety in the management of acute moderate to severe pain. Design: Randomized, double-blind, placebo-controlled, ascending-dose cohort, dose-response study with flexible dosing. Setting: Private clinic. Patients: Adults undergoing unilateral bunionectomy surgery. Following surgery, patients were required to have moderate or severe intensity pain on a 4-point Likert scale and =4 on an 11-point Numerical Pain Rating Scale to continue in the study. Interventions: Q8003 was administered in four ascending-dose cohorts of 3/2, 6/4, 12/8, and 18/12 mg during the 48-hour period following surgery. Main Outcome Measures: Sum of the pain intensity differences from baseline over 48 hours (SPID48), percentage of responders, and use of ibuprofen. Results: Of 263 patients, 256 were randomly assigned to treatment. In patients treated with Q8003, 12 to 18 percent withdrew before study completion versus 30 percent on placebo. The mean dose of morphine/oxycodone per 6-hour period and the mean interdose interval (hours) was 6/4 mg (2.9), 9.8/6.5 mg (4.1), 11/7.5 mg (6.8), and 15/10 mg (6.6) for the 3/2-, 6/4-, 12/8-, and 18/12-mg groups, respectively. The mean SPID48 was significantly greater with each Q8003 dose when compared with placebo (p = 0.0017 for all doses versus placebo). The 12/8-mg group (11/7.5 mg/6 h) had the greatest percentage of patient responders (76 percent; p < 0.001 versus placebo) and required the fewest daily doses of ibuprofen. AEs were typical of those associated with opioid use, with the highest occurrence for nausea (38-65 percent) and low rates of somnolence (2-8 percent). Minimal or no changes in respiration and blood oxygenation were observed and euphoria was not reported. Conclusions: The 12/8 mg dose of Q8003, an immediate-release formulation, provided the optimal combination of analgesic efficacy and tolerability, with the 3/2 and the 6/4 mg doses being an effective alternative for treatment. Keywords: opioid, morphine, oxycodone, bunionectomy, postoperative pain, acute pain DOI:10.5055/jom.2010.0030


Article
Reference intervals: A novel approach to detect drug abuse in a pain patient population
Amadeo Pesce, PhD, DABCC; Cameron West, PhD; Robert West, MS; Bridgit Crews, PhD; Charles Mikel, PhD; Perla Almazan, CLS, MT (ASCP); Sergey Latyshev, MS; Murray Rosenthal, DO, FAPA; Paul Horn, PhD
September/October 2010; pages 341-350

Abstract
Background: Pain physicians have few objective ways of determining which of their patients are drug abusers. Traditionally, these include psychological tests, physical examination, patient history, and urine drug testing. The traditional urine drug testing information provided to pain physicians mainly identifies patient compliance or drug diversion with qualitative information, that is, the patient is positive or negative for the presence of the drug in excreted urine. Although this information is useful for establishing compliance and identifying diversion, it is incomplete because it does not identify drug abuse. Objective: The authors endeavored to determine whether quantitative urine drug testing and mathematical estimators of the upper limits of excretion could be used to identify possible drug abusers. Study Design: Analysis of quantitative urine drug tests and application of mathematical models for reference interval estimation of common analytes to determine whether they could be used to define upper 97.5 percentile limits of excretion in the pain patient population. Methods: The authors analyzed 8,971 consecutive urines from patients on chronic opioid therapy using nonparametric, parametric, robust, and transformed estimators to derive the upper 97.5 percentile concentration values of 31 drugs and their metabolites. Results: The authors showed that the mathematical models used to define reference intervals could be applied to urinary drug excretion. As an example, an upper limit of excretion of approximately 100,000 ng/mL was established for morphine. Limitations of the study included lack of information on medication history, time of last dose before urine collection, age, sex, and complete medical history. Better estimates of the upper limits of excretion can be obtained by physicians applying their knowledge of dosage and collection times. Conclusions: Application of a reference interval model allows identification of a patient population that excretes extremely high amounts of drug or its metabolite when compared with the rest of the population. Explanations for this high excretion include high dosage medication by prescription and drug abuse, determination of which can be done by the treating physician. The authors suggest that this patent-applied-for analytical model can become a potential tool to alert physicians to patients who may be abusing drugs. Keywords: reference interval, morphine, drug abuse, upper limits of excretion, pain patients, drug testing DOI:10.5055/jom.2010.0031


Article
Steady-state pharmacokinetics of extended-release hydromorphone (OROS® hydromorphone): A randomized study in healthy volunteers
Kenneth Todd Moore, MSc; Dominique St-Fleur, BSc; Nadia Cardillo Marricco, MSc; Jay Ariyawansa, MSc; Véronique Pagé, MSc; Jayalakshmi Natarajan, PhD; Gaetano Morelli, MD, FRCP; Ute Richarz, MD
September/October 2010; pages 351-358

Abstract
The steady-state pharmacokinetics of an extended-release formulation of hydromorphone, OROS® hydromorphone, was investigated in a randomized, openlabel, crossover study in healthy volunteers. Participants were randomly assigned to receive 16 mg of OROS hydromorphone once daily and 4 mg of immediaterelease hydromorphone four times daily for five consecutive days. The two treatments were separated by a washout period of 7-14 days. Naltrexone was given throughout both treatment periods to block the opioid effects of hydromorphone. Steady-state hydromorphone concentrations were statistically analyzed using Helmert contrasts to determine when steady state was reached. A total of 30 participants were enrolled, of whom 29 completed both treatment periods. The two treatments produced comparable steady-state plasma drug concentrations, but peakto- trough fluctuations were smaller with OROS hydromorphone (61 percent vs 172 percent) in comparison with immediate release hydromorphone. Overall systemic exposure to hydromorphone was similar between the two formulations. The ratio of the geometric means between the two formulations for the area under the concentration-time curves at steady state was 105.2 percent with a 90% confidence interval (CI) of 99.8-110.8 (geometric mean: 102.7 percent; 90% CI: 97.6-108.2 after correcting for measured drug content), which was within the bioequivalence range (80-125 percent). The analysis of Helmert contrasts showed that steady state conditions were attained by day 4. Both treatments were well tolerated. This study shows that OROS hydromorphone maintains steady-state plasma drug concentrations within the same range as immediate-release hydromorphone at the same total daily dose, with less fluctuation. Keywords: OROS hydromorphone, extended-release hydromorhphone, pharmacokinetics, opioids, osmotic pump DOI:10.5055/jom.2010.0032


Article
The Eastern North Carolina Opioid Prescribers Project: A model continuing medical education workshop
Mary K. Crozier, EdD; Sherrá McMillan, PhD Student; Suzanne Hudson, PhD; Stephanie Jones, MS
September/October 2010; pages 359-364

Abstract
The decision to prescribe opioid medications is complex. Physicians often struggle to balance the risks of medication diversion and abuse with the benefits of pain management. Nationally, more than 40 percent of primary care physicians report difficulty in discussing the possibility of prescription medication abuse with patients and more than 90 percent fail to detect symptoms of substance abuse. Continuing medical education workshops were developed in Eastern North Carolina to mitigate problems with opioid prescriptions. Attendance at these workshops suggests that prescribers are interested in improving opioid prescribing practices and reducing patient risk. Presurvey data indicate that prescribers are knowledgeable about screening tools and they consider patient risk factors for misuse. Keywords: opioids, prescription medication, substance abuse, substance misuse, drug-seeking patients, continuing medical education, risk reduction, opioid risk management DOI:10.5055/jom.2010.0033


Article
The impact of financial discharge from methadone maintenance therapy on incarceration
Nickolas D. Zaller, PhD; Jeannia J. Fu, BSc; Alexander R. Bazazi, BA; Josiah D. Rich, MD, MPH
September/October 2010; pages 365-370

Abstract
Objectives: The authors sought to analyze the relationship between financial discharge from methadone maintenance therapy (MMT) and subsequent involvement in the criminal justice system among individuals receiving state-subsidized MMT slots and individuals who were financially discharged from MMT. Methods: The authors examined state-level client treatment records from all individuals who were on a subsidized MMT slot and all individuals who were discharged due to their inability to pay (financial discharge) from one of the three MMT programs during an 18-month period. The authors cross-referenced these records, through a state-managed database, with records of the Department of Corrections. Results: Individuals in the control group had longer durations of stay in MMT and fewer other kinds of treatment admissions during the study period. An 81 percent of individuals in the financially discharged group received other treatment episodes versus 0.3 percent in the control group (p < 0.001). More than twice the number of individuals financially discharged from MMT were incarcerated during the study period when compared with the control group (67 percent vs 33 percent, p < 0.001). In logistic regression analysis, individuals in the control group had 0.26 times the odds of incarceration when compared with individuals financially discharged from MMT (95% CI: 0.09-0.73). Conclusions: MMT has been shown to reduce involvement in the criminal justice system, yet cost of MMT continues to inhibit its accessibility. Our data suggest that removal of cost as a barrier to access MMT may facilitate longer treatment duration and minimize involvement with the criminal justice system. Keywords: methadone maintenance therapy, financial discharge, incarceration DOI:10.5055/jom.2010.0034


Article
Case study. Patient selection and trialing techniques utilizing low-dose intrathecal morphine for chronic nonmalignant pain: A report of two cases
Jay S. Grider, DO, PhD; Michael E. Harned, MD; Paul A. Sloan, MD
September/October 2010; pages 371-376

Abstract
The administration of opioid analgesics via the intrathecal route is becoming more commonplace for a variety of chronic nonmalignant pathologic pain states. Despite this growing trend, there is very little information available to guide practitioners with regard to patient selection as well as intrathecal drug dosing paradigms. The authors describe the use of a protocol for patient selection, including pretrial preparation, as well as detailed very low-dose chronic intrathecal morphine dosing regimens to treat patients with refractory chronic nonmalignant pain. Keywords: intrathecal morphine, intrathecal drug delivery, low-dose opioid, chronic nonmalignant pain, intrathecal analgesics DOI:10.5055/jom.2010.0035

Journal of Opioid Management
November/December 2010, Volume 6
, Number 6


Article
Defining clinical issues around tolerance, hyperalgesia, and addiction: A quantitative and qualitative outcome study of long-term opioid dosing in a chronic pain practice
Jennifer P. Schneider, MD, PhD; Kenneth L. Kirsh, PhD
November/December 2010; pages 385-395

Abstract
Treatment with opioid medications has grown over the past decades, but has been surrounded by some ongoing controversy and debate to whether it is causing more harm than good for patients. To this end, the field of pain management has suffered from a lack of clarity about some basic definitions on concepts such as tolerance and hyperalgesia. Some characterize these issues as inevitable parts of opioid therapy while other schools of thought look at these issues as relatively rare occurrences. Unfortunately, most of the rhetoric around these topics has occurred with very little in the realm of real world data. To this end, the authors have reviewed the charts of 197 patients treated by a pain specialist for at least 1 year to better illustrate whether notions of tolerance and hyperalgesia are common occurrences and, more importantly, whether they occur within any type of specified timeframe. A total of 197 patient charts were reviewed. The sample had an average age of 49.39 years (range = 19-87 years; standard deviation [SD] = 12.48) and comprised 66 men (33.5 percent) and 131 women (66.5 percent). The patients were seen in the pain practice for an average of 56.52 months (range = 12-155 months; SD = 31.26). On average, the patients maintained an average daily dose of 180 mg morphine equivalents for a period of 35.1 months (range = 3-101 months; SD = 21.3). Looking at the pattern of medication usage change over time, 34.5 percent experienced dose stabilization after the initial titration, 13.2 percent had early dose stabilization within one dose change, and an additional 14.7 percent actually had dose decreases after surgeries or other interventional procedures. Only 6.6 percent of the sample had to be discharged or weaned from controlled substances over time in the clinic. Thus, it appears that tolerance and hyperalgesia are not foregone conclusions when considering placing a patient on long-term opioid therapy. Keywords: tolerance, dependence, opioids, hyperalgesia, long-term opioid therapy DOI:10.5055/jom.2010.0036


Article
Comparison of postoperative analgesia with epidural butorphanol/bupivacaine versus fentanyl/bupivacaine following pediatric urological procedures
Alexandra Szabova, MD; Senthilkumar Sadhasivam, MD, MPH; Yu Wang, MS; Todd G. Nick, PhD; Kenneth Goldschneider, MD
November/December 2010; pages 401-407

Abstract
Background: The aim of this retrospective study is to compare safety and efficacy of postoperative epidural butorphanol/bupivacaine with the gold-standard epidural analgesic infusion fentanyl/bupivacaine in children. Methods: With the Institutional Review Board’s approval, the authors searched their Pain Management Database and divided children who received epidural analgesia into two groups. Each butorphanol group subject was matched with two fentanyl group subjects. Demographic data, pain scores, epidural interventions, epidural side effects, use of rescue opioid analgesia and adjuvant analgesics, causes of epidural failure, time of first oral intake and ambulation, and length of stay were statistically compared. Results: A total of 191 patients were identified between 2000 and 2007; 58 in epidural butorphanol/bupivacaine and 133 in fentanyl/bupivacaine groups. Demographic data were comparable between the groups. The number of children with good pain control on postoperative days 1 and 2 in butorphanol (84 and 82 percent) and fentanyl (93 and 91 percent) groups were statistically similar (p = 0.06 and 0.13, respectively). Incidences of epidural side effects, especially pruritus, were significantly higher in the fentanyl group. Significantly more children in the butorphanol group required epidural rate changes when compared with those in the fentanyl group. Incidence of failed epidurals was significantly higher in the fentanyl group when compared with that in the butorphanol group. Clinically significant respiratory depression occurred in two children in the fentanyl group and in none of the children in the butorphanol group (p > 0.99). Conclusions: Epidural butorphanol provided similar analgesia to epidural fentanyl after urological procedures in children, but butorphanol caused less pruritus than fentanyl. Implication statement: Epidural analgesia with butorphanol/bupivacaine is effective in children undergoing urological procedures. When compared with epidural fentanyl, epidural butorphanol causes significantly less itching. Keywords: epidural, butorphanol, pediatric DOI:10.5055/jom.2010.0037


Article
Neonatal abstinence scores in opioid-exposed and nonexposed neonates: A blinded comparison
Hendrée E. Jones, PhD; Cheryl Harrow, RN-LRN, MS, FNP-BC, IBCLC; Kevin E. O’Grady, PhD; Michael Crocetti, MD; Lauren M. Jansson, MD; Karol Kaltenbach, PhD
November/December 2010; pages 409-413

Abstract
Twenty-nine opioid-exposed and 26 nonopioid-exposed neonates received neonatal abstinence syndrome (NAS) assessment by an examiner blinded to group status twice daily over the first two postnatal days. The opioid-exposed group had higher mean NAS scores than the nonopioid-exposed group. A 3-sign index, consisting of hyperactive moro reflex, mild tremors when undisturbed, and increased muscle tone, showed excellent discrimination between groups. The use of a 3-sign screening index in the days immediately after birth may provide a cost-effective mechanism for the identification of opioid-exposed infants, particularly in infants of women for whom identification of status as a substance user may not be immediately evident. Although a potentially useful screening tool, the 3-sign screening tool should not replace the full assessment of the opioid-exposed infant after birth. Keywords: neonate, methadone, substance abuse, pregnancy, women DOI:10.5055/jom.2010.0038


Article
Improved detection of ethyl glucuronide and ethyl sulfate in a pain management population using high-throughput LC-MS/MS
Bridgit Crews, PhD; Sergey Latyshev, MS; Charles Mikel, PhD; Perla Almazan, CLS, MT (ASCP); Robert West, MS; Amadeo Pesce, PhD, DABCC; Cameron West, PhD
November/December 2010; pages 415-421

Abstract
Background: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) have been proposed as markers for detecting alcohol use because they exhibit extended excretion lifetimes when compared with ethanol; however, their presence is not considered as absolute proof of alcohol use. Two methods are currently used for the detection and quantitation of EtG: immunoassay and mass spectrometry. The purpose of this study was to provide more patient data to better compare the two methods. Methods: A retrospective diagnostic accuracy study was performed to compare the methods. EtS was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as an additional comparative analyte. The investigators examined 4,287 sequential urines from pain patients to determine the incidence of alcohol use and the corresponding presence of EtG by immunoassay at a cutoff of 500 ng/mL. EtG and EtS were subsequently quantitated in all the urines using LC-MS/MS. Results: A total of 794 samples were found positive by immunoassay, and these results were compared at three distinct LC-MS/MS cutoffs of 100, 500, and 1,000 ng/mL. The incidence of ethanol use in this population was found to be at least 12 percent. Conclusions: Approximately 30 percent of the samples screened by immunoassay as positive were confirmed to be negative by LC-MS/MS. Keywords: ethyl glucuronide, ethyl sulfate, pain patients, alcohol abuse, immunoassay, LC-MS/MS DOI:10.5055/jom.2010.0039


Article
Cerebral measurements and their correlation with the onset age and the duration of opioid abuse
Reetta Kivisaari, MD, PhD; Pekka Rapeli, Psyc. Lic.; Koen Van Leemput, PhD; Seppo Kähkönen, MD, PhD; Varpu Puuskari, MD; Olga Jokela, MD; Taina Autti, MD, PhD
November/December 2010; pages 423-429

Abstract
Background: Opioid-dependent patients have been shown to have structural brain alterations. This study focuses on magnetic resonance imaging (MRI) measurements of brain and their correlation with the onset age and the duration of opioid abuse. Methods: Brain MRI was obtained from 17 opioid-dependent patients (mean age 34 years, SD 7 years) and 17 controls. Compulsive opioid use had begun between ages 15 and 31 (mean 20) and had continued from 5 to 26 years. All patients were tobacco smokers, six had also abused amphetamines and 11 benzodiazepines. Relative volumes of cerebral white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) spaces were measured. In addition, Sylvian fissure ratio (SFR), bifrontal ratio, and midsagittal cerebellar vermian area were correlated with the onset age and the duration of opioid abuse. Results: The total volume (GM + WM + CSF) of the cerebrum was significantly smaller in patients than in controls (Mann-Whitney U-test, p = 0.026) as well as the absolute volumes of GM and WM (p = 0.014 and p = 0.007, respectively). There was no significant difference in GM and WM volumes normalized with total cerebral volume. In contrast, the absolute volume of CSF did not significantly differ between the groups, but the relative volume of CSF was significantly higher in opioid dependents (p = 0.029). SFR and bifrontal ratio were larger in opioid dependents than in controls (p = 0.005 and p = 0.013). The SFR correlated negatively (p = 0.017, r = -0.569) and the area of vermis cerebelli correlated positively (p = 0.043, r = 0.496) with the onset age of opioid abuse. The length of opioid abuse and the area of vermis cerebellum had a negative correlation (p = 0.038, r = -0.523) even though the areas of cerebellar vermis did not significantly differ between opioid dependents and controls. The authors speculate that the onset of substance abuse in adolescence or early adulthood may have in part disturbed the late brain maturation process, as in normal development, the dorsolateral frontal cortex and superior parts of the temporal lobes are the last to maturate. Also, the cerebellar vermis may be affected by early onset substance abuse. It is possible that the brain is more vulnerable to substance abuse at a young age than later in life. Keywords: MRI, Sylvian fissure ratio, brain, opioid dependence, imaging, neuropsychological tests DOI:10.5055/jom.2010.0040


Article
A retrospective chart review of opioid-induced nausea and somnolence on commencement for cancer pain treatment
Yoshiaki Okamoto, BP; Satoru Tsuneto, MD, PhD; Mamiko Tsugane, PhD; Tatsuya Takagi, PhD; Etsuko Uejima, PhD
November/December 2010; pages 431-434

Abstract
Morphine, oxycodone, and fentanyl are major opioids available as controlledrelease morphine (CRM), controlled-release oxycodone (CRO), and transdermal fentanyl (TDF), respectively, in Japan. The authors conducted a retrospective chart review to examine (1) nausea and somnolence on commencement of CRM, CRO, and TDF for cancer pain treatment, (2) the antiemetic effectiveness of prochlorperazine to prevent opioid-induced nausea, and (3) the side effect of prochlorperazine on somnolence in patients with cancer pain. Four hundred thirteen patients with cancer were prescribed with CRM (N = 66), CRO (N = 196), and TDF (N = 151). The incidence of nausea on commencement of the TDF group (6.8 percent) was significantly lower than that of both the CRM group (22.6 percent) and the CRO group (35.4 percent; p < 0.001). There was no significant difference in the incidence of nausea on commencement of all groups combined with prochlorperazine at dosage of 15 mg/d. The incidence of somnolence on commencement of the TDF group (9.0 percent) was significantly lower than that of both the CRM group (31.3 percent) and the CRO group (41.5 percent; p < 0.001). The incidence of somnolence on commencement of the CRO group combined with prochlorperazine was significantly higher than that of the CRO combined without prochlorperazine (p < 0.05). In conclusion, the incidence of nausea and somnolence on commencement of TDF are significantly lower than that of both CRM and CRO for cancer pain treatment. Prochlorperazine at a dosage of 15 mg/d may not be effective in preventing opioid-induced nausea and may cause somnolence in patients with cancer pain. Keywords: opioid-induced nausea, opioid-induced somnolence, morphine, oxycodone, fentanyl, prochlorperazine, side effect, opioid DOI:10.5055/jom.2010.0041


Article
Current concepts in the management of opioid-induced constipation
John Brandon Walters, MD; Marcos Montagnini, MD, FACP
November/December 2010; pages 435-444

Abstract
Patients with chronic pain on daily opioid therapy are frequently burdened with symptoms of constipation. Opioid-induced constipation (OIC) contributes to an overall negative impact on the quality of life and may result in poor pain management outcomes. Laxative agents are crucial in opioid-related pain management. Following a careful assessment, a stepwise approach to OIC may provide comfort and relief to patients. This article reviews the pathophysiology, assessment, and pharmacological treatment of OIC. Novel approaches for OIC such as the peripheral opioid receptor antagonists and selective serotonin antagonists are also discussed. Keywords: constipation, laxatives, symptom management DOI:10.5055/jom.2010.0042


Article
The relationship between opioid and sugar intake: Review of evidence and clinical applications
David J. Mysels, MD, MBA; Maria A. Sullivan, MD, PhD
November/December 2010; pages 445-452

Abstract
Opioid dependence poses significant public health risks arising from associated morbidity and mortality caused by accidents, infectious diseases, and social ramifications of crime and unemployment, among other complications. Opioid use, acute and chronic, is also associated with weight gain, glycemic dysregulation, and dental pathology. The literature supporting the connection between opiate use and development of preference for sweet tastes is reviewed, and further association with dental pathology, weight gain, and loss of glycemic control are considered. Additionally, the impact of sweet tastes on the endogenous opioid system, as pertaining to analgesia, is also discussed. The authors discuss the clinical implications in relation to the aforementioned conditions while treating the opiate-dependent patient. Keywords: opioid, sugar, weight gain, diabetes, analgesia DOI:10.5055/jom.2010.0043