bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronically monitored single-use patient-controlled analgesia pumps in postoperative pain control
Authors: Zimmermann, MD Michael , Friedrich, MD Karin , Kirchner, MD Rolf
Published: February 2018

The present study was performed to establish whether analgesic consumption in the first four postoperative hours is a suitable basis for selecting the demand dose and predicting the likely analgesic requirement over the next 20 hours with single-use patient-controlled analgesia (PCA) pumps, and to establish whether this method provides effective pain control.Forty-two patients who had undergone a laparotic gynecological procedure (hysterectomy) were given an electronic PCA pump (Abbott Lifecare, Abbott Laboratories, Abbott Park, IL) for four hours (phase I) with a demand dose of 1 mg piritramide and a lockout period of five minutes for dose titration. Piritramide’s potency is comparable with that of morphine. The patients then received single-use PCA pumps (Baxter Infusor/Watch, Baxter, Deerfield, IL) for the next 20 hours (phase II) with a demand dose of 0.75 mg in Group A and 1.5 mg in Group B, depending on whether more or less than 10 mg pritramide had been consumed in phase I. A specially designed electronic recorder was used to measure the exact amount consumed and number of demands. Patients experiencing pain were free to receive additional piritramide at any time as rescue medication; however, these patients were withdrawn from the study.Ninety percent of the patients in group A said they were satisfied with or undecided as to the level of analgesia. The corresponding figure in group B was 95 percent. Piritramide consumption was significantly higher in group B than in group A. There were no significant differences between the groups regarding demographic data or duration of surgery, nor did either of these two parameters affect postoperative piritramide consumption. Significant alleviation of pain and improvement in visual analog scale scores from phase I [group A, 4.7 (range, 2.0 to 6.8); group B, 4.6 (range, 3.0 to 8.3)] to phase II [group A, 3.1 (range, 0.4 to 5.2); group B, 3.2 (range, 0.4 to 6.0)] was achieved in both groups. A significant difference in analgesic consumption up to 18 hours postoperatively was seen after dose titration. In the first four hours, the rate of successful demands was significantly higher in group A (80.9 percent) than in group B (40.9 percent). The number of successful demands was comparable in the two groups during phase II (A, 98.8 percent; B, 94.5 percent).In summary, total opioid consumption during the first four hours after operation showed two groups of patients with significantly different needs for piritramide (< 10 mg per 4 hours or > 10 mg per 4 hours). Two different dose regimes were applied using a high and a low bolus size in the following 20 hours. We concluded that effective pain control without respiratory depression was achieved with single-use PCA pumps. Opioid consumption varied significantly, whereas pain levels did not.
Opioids in the parturient with chronic nonmalignant pain: A retrospective review
Authors: Hadi, MD, FRCPC Ibrahim , Da Silva, MD, FRCPC Orlando , Natale, MD, FRCSC Renato , Boyd, MD, FRCPC David , Morley-Forster, MD, FRCPC Patricia K.
Published: February 2018

The purpose of this research was to determine the neonatal outcomes of women who had been taking medically prescribed opioids throughout their pregnancy. A retrospective case study was done of 15 pregnancies associated with maternal opiate use between January 1, 1999, and September 30, 2002. Two cases were excluded due to coaddiction. Neonatal data were collected including gestational age, head circumference, length, birth weight, Apgar score at one and five minutes, details of resuscitation required, and Neonatal Abstinence Score. There were 13 pregnancies, which resulted in 13 live births; opioids prescribed included oxycodone, codeine, meperidine, fentanyl, dilaudid, morphine, and methadone. There were four babies with one-minute Apgar score = 5, and two babies with five-minute Apgar score = 5. It was concluded that neonatal growth markers in this population were within normal limits as plotted on the standard growth and development record of Gairdner-Pearson. Five out of 13 (38.5 percent) neonates were diagnosed with opioid discontinuation syndrome.
Barriers and facilitators to methadone maintenance therapy use among illicit opiate injection drug users in Vancouver
Authors: Callon, BSc Cody , Wood, PhD Evan , Marsh, MD David , Li, PhD Kathy , Montaner, MD Julio , Kerr, PhD Thomas
Published: February 2018

Methadone maintenance therapy (MMT) has been increasingly implemented as the treatment of choice for opiate-addicted individuals and has been associated with reduced harm related to opiate addiction. Barriers to MMT uptake still exist, however, and many opiate-addicted individuals do not access this form of treatment.We examined barriers to and facilitators of MMT access among opiate users enrolled in a prospective cohort study of injection drug users (IDUs). We identified individuals who had initiated MMT during follow-up interviews and used generalized estimating equations to identify sociodemographic and drug-related variables associated with MMT access.Of the 1,587 participants recruited into the Vancouver Injection Drug User Study, 1,463 individuals were eligible for the present analysis. Factors negatively associated with MMT use included male gender (odds ratio [OR] = 0.41; 95 percent confidence interval [CI], 0.32 to 0.52), Aboriginal ethnicity (OR = 0.37; 95 percent CI, 0.29 to 0.48), recent incarceration (OR = 0.82; 95 percent CI, 0.72 to 0.93), Downtown Eastside residence (OR = 0.86; 95 percent CI, 0.75 to 0.97), sex-trade involvement (OR = 0.80; 95 percent CI, 0.67 to 0.95), syringe lending (OR = 0.76; 95 percent CI, 0.66 to 0.89), denied addiction treatment (OR = 0.81; 95 percent CI, 0.68 to 0.96), heroin injection (OR = 0.51; 95 percent CI, 0.44 to 0.59), nonfatal overdose (OR = 0.59; 95 percent CI, 0.51 to 0.68), and injecting in public (OR = 0.75; 95 percent CI, 0.63 to 0.89). Older age (OR = 1.03; 95 percent CI, 1.01 to 1.04), human immunodeficiency virus (HIV) positivity (OR = 1.89; 95 percent CI, 1.52 to 2.23), and crack cocaine smoking (OR = 1.41; 95 percent CI, 1.22 to 1.62) were positively associated with MMT use.Our study identified a large number of barriers to and facilitators of MMT use among IDUs. While some populations such as HIV-positive individuals are frequently accessing MMT, identified barriers among men and Aboriginal IDUs are of great concern. These findings indicate the need for additional interventions aimed at maximizing coverage of MMT and other treatments for opiateaddicted individuals.
High-dose methadone and QTc prolongation: Strategies to optimize safety
Authors: Schmittner, MD John , Krantz, MD Mori J.
Published: February 2018

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Modafinil: Is it ready for prime time?
Authors: Prommer, MD Eric
Published: February 2018

Psychostimulants have been used to treat many symptoms associated with advanced cancer. The primary role of psychostimulants in such cases is the treatment of symptoms such as cancer-related fatigue, opioid-induced sedation, depression, and cognitive dysfunction associated with malignancies. These uses for psychostimulants came after approval for treatment of disorders such as attention deficit disorder. Modafinil, a new psychostimulant, is following a similar path after its approval for use in attention deficit disorder in 1998. Modafinil has been used to treat fatigue associated with neurodegenerative disorders such as multiple sclerosis and amyotrophic lateral sclerosis. It is now being increasingly used for cancerrelated symptoms targeted by psychostimulants. Preliminary evidence from literature review suggests that modafinil is efficacious in improving opioid-induced sedation, cancer-related fatigue, and depression. There is no evidence to support its use in the treatment of cognitive dysfunction related to cancer or to support its having analgesic properties. Well-designed, randomized, controlled clinical trials are still needed to further elucidate the precise role of this drug in the care of patients with cancer. Specifically, large placebo-controlled trials with modafinil must be conducted in patients with cancer, with specific attention paid to pain control, depression, cognitive function, and adverse effects.
The influence of chief complaint on opioid use in the emergency department
Authors: Puntillo, RN, DNSc, FAAN Kathleen , Neighbor, MD Martha , Chan, APRN, BC, PhD Garrett K. , Garbez, RN, MS, ACNP Roxanne
Published: February 2018

The aim of this study was to explore factors influencing emergency department (ED) clinicians’ use of opioids in treating selected patients. Patients who either received or did not receive opioids in the ED, as well as their nurses and physicians, were interviewed before patient discharge. We found that the decrease in patients’ mean (SD) pain intensity from the time of admission to the ED (7.3 ± 2.4 on a 0 to 10 numeric rating scale) to discharge (5.0 ± 2.9) was statistically significant (t93 = 8.4, p < 0.001, 95 percent CI = 1.7, 2.8) for all groups except those with trauma-related pain. The factor that most frequently led physicians of patients with abdominal pain and nurses in general to administer no opioids was that the patient was “not in that much pain.” However, the patients in question had self-reported pain scores that indicated moderate pain. Our findings lead us to conclude that clinicians inaccurately infer severity of patient pain. This in turn can influence the prescription of opioids and the patient’s decrease in pain.
Determinants of variation in analgesic and opioid prescribing practice in an emergency department
Authors: Heins, MD Alan , Grammas, BS Marianthe , Heins, RN, MSN, CRNP Janet Kaye , Costello, MD Melissa W. , Huang, MS Kun , Mishra, PhD Satya
Published: February 2018

Objective: Adequate treatment of patients’ pain is a top priority for the World Health Organization (WHO), American Medical Association (AMA), and American College of Emergency Physicians (ACEP), but “adequate” is not clearly defined. Most previous studies of emergency department (ED) pain treatments have centered on musculoskeletal pain in terms of rates of analgesia and disparities in treatment based on race and age. This study will examine complaints of pain other than musculoskeletal and will focus on treatment disparities that may result from differences in patient and physician characteristics.Methods: This retrospective study is of ED patients 18 years and older with nonmusculoskeletal pain who were seen by ED faculty over a period of eight weeks. Logistic regression and c2 tests were performed to quantify effects of doctor, patient, and clinical characteristics on rates of ED analgesia, ED opioids, and analgesic prescriptions at discharge.Results: A total of 1,360 patients were included. There was wide variation in the type and frequency of ED analgesia depending on the attending doctor. For example, patients seen by one specific ED doctor were less than half as likely to receive any analgesia and seven times less likely to receive an opioid than those seen by another doctor. Age, race, doctor’s training and experience, and whether the patient had chronic pain were important predictors of ED analgesia. There were similar findings for ED opioids and discharge analgesics.Conclusion: Pain practices in EDs are highly variable and seem inadequate when measured against the goals of WHO, AMA, and ACEP. Patient age, race, and type of pain and the physician’s identity, training, and experience all contribute to practice variation. Further research is needed to identify the causes of these variations, and there is a need to develop interventions to standardize and improve pain assessment and treatment.
Breakthrough pain in opioid-treated patients with neuropathic pain
Authors: Simon, MD, RPh Steve , Bennett, MD Daniel S. , Rauck, MD Richard , Taylor, MD Donald , Shoemaker, MD Steven
Published: February 2018

Objective: This report aims to describe the prevalence and characteristics of breakthrough pain in patients with neuropathic pain.Methods: The study represents data from a subset of patients from a larger survey of 228 patients with chronic noncancer pain. Patients were identified from nine pain programs and were administered a telephone questionnaire. The study population comprised 45 chronic noncancer pain patients with primary neuropathic pain diagnoses who were being treated with opioids.Results: Pain had been present for a median of six years. Medications used for pain in addition to opioids included nonsteroidal anti-inflammatory agents (29 percent), antidepressants (60 percent), and anticonvulsants (53 percent). Thirty-five of the patients (78 percent) described a total of 42 distinct types of breakthrough pain. The median number of episodes per day was two; the median time to maximum intensity was 10 minutes, and the median duration of pain was 60 minutes. Patients could identify a precipitant for 62 percent of the pains, and 88 percent of the precipitants were activity related. The onset of breakthrough pain could not be predicted for 48 percent of the pains and could only sometimes be predicted for 29 percent of the pains.Conclusion: Breakthrough pain is common in opioidtreated patients with chronic neuropathic pain. Such pain often has a rapid onset and a relatively short duration, and it is frequently difficult to predict, similar to breakthrough pain in cancer patients.
Can we continue to do business as usual?
Authors: Eliot Cole, MD, MPA B.
Published: February 2018

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Medicolegal rounds: Medicolegal issues and alleged breaches of standards of medical care in a patient motor vehicle accident allegedly related to chronic opioid analgesic therapy
Authors: Fishbain, MD, FAPA David A. , Lewis, PhD John E. , Cole, PsyD Brandly , Rosomoff, BSN, MBA Renné Steele , Rosomoff, MD, DMedSc, FAAPM Hubert L.
Published: February 2018

The objective of this medicolegal case report is to present the details of the case of a chronic pain patient (CPP) who was placed on chronic opioid analgesic therapy (COAT) and was involved in a motor vehicle accident, alleged in litigation to be related to COAT. COAT standards are in a process of evolution, and this process is influenced by recent literature developments. We aim to present both the plaintiff's and defendant's expert witnesses' opinions on whether the defendant physician fell below the "standard" in allowing the CPP to drive. Both the methadone and the driving literature are utilized to explain the defendant's and plaintiff's experts' opinions and the differences between them. Based on these opinions, we have attempted to develop some recommendations on how pain physicians should approach the problem of deciding whether patients should be allowed to drive when on COAT.
Buprenorphine: A unique opioid with broad clinical applications
Authors: Vadivelu, MD Nalini , Hines, MD Roberta L.
Published: February 2018

The analgesic potential of buprenorphine, a high-affinity partial m agonist, has been a subject of study for several decades. The drug is now widely recognized as being extremely effective in relieving perioperative pain, with little of the addictive potential or risk associated with pure m agonists. Studies have suggested that buprenorphine produces adequate analgesia via almost any route of administration, including transdermal and subcutaneous. It has also been used, with positive results, in the treatment of opioid addiction, and potential remains for research into other roles, e.g., as an anti-inflammatory agent or an antihyperalgesic medication.
King of Pain: What Elvis’s death tells us about media coverage of celebrities and the pain/addiction interface
Authors: Passik, PhD Steven D. , Kirsh, PhD Kenneth L.
Published: February 2018

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A comparison of oral midazolam, oral tramadol, and intranasal sufentanil premedication in pediatric patients
Authors: Bayrak, MD Fatma , Gunday, MD Isil , Memis, MD Dilek , Turan, MD Alparslan
Published: February 2018

Background: This study was designed to evaluate the efficacy and safety of oral midazolam, tramadol drops, and intranasal sufentanil for premedication of pediatric patients.Methods: Sixty children, three to 10 years of age, who were designated as American Society of Anesthesiologists physical status I and who were undergoing adenotonsil- lectomy as inpatients were randomized to receive a dosage of 0.5 mg/kg (total of 4 mL) midazolam in cherry juice (n = 20, Group M), 3 mg/kg tramadol drops (n = 20, Group T), or 2 mg/kg intranasal sufentanil (n = 20, Group S). Clinical responses (sedation, anxiolysis, cooperation) and adverse effects (respiratory, hemodynamic, etc.) were recorded. Safety was assessed by continuous oxygen saturation monitoring and observation. Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate) were recorded before drug administration (baseline) and then every 10 minutes until the induction of anesthesia.Results: Mean blood pressure decreased significantly afterfive minutes of intranasal sufentanil administration relative to GroupsM (p < 0.01) and T (p < 0.05), whereas heart rate remained unchanged. Oxygen saturation and respiratory rate decreased significantly after 20 and 30 minutes of intranasal sufentanil administration relative to Groups Mand T(p < 0.05). Anxiety scores showed rates of 45percent in Group M, 5percent in Group T, and 40 percent in Group S. Anxiety scores in Groups M and S were better than those of Group T (p < 0.01). Cooperation scores for face-mask acceptance showed rates of 85 percent in Group M, 45percent in Group T, and 85percent in Group S (p < 0.01).Conclusion: Intranasal sufentanil and oral midazolam are more appropriate premedication options than tramadol drops in children.
Increasing prevalence of prescription opiate misuse over time among rural probationers
Authors: Havens, PhD, MPH Jennifer R. , Oser, PhD Carrie B. , Leukefeld, DSW Carl G.
Published: February 2018

Prescription opiate misuse is a major public health issue, especially in rural areas. The purpose of this analysis was to examine trends in prescription opiate misuse over time in a cohort of community-based rural proba-tioners. Participants (N = 800), recruited over a four-year period, were divided into cohorts according to the year in which they were interviewed. Prescription opiate misuse increased significantly between 2001 and2004 (p < 0.001). After adjustment for changes in demographic characteristics of the cohorts, misuse of prescription opiates was still significantly greater in 2004 compared with 2001. These data suggest changes in drug use patterns among community-based rural probationers from street to prescription drugs. Implications of the findings are discussed.
The addition of haloperidol, propofol, or midazolam to sufentanil for intravenous sedation in the intensive care unit using bispectral index
Authors: Tukenmez, MD Baris , Memis, MD Dilek , Pamukcu, MD Zafer
Published: February 2018

Aim: Inadequate sedative techniques may adversely affect morbidity and mortality in the intensive care unit (ICU), and the search for the ideal sedative agent continues. Combinations of hypnotics and opiates have are commonly used for sedation. In this study, the authors aimed to assess whether or not the addition of a haloperidol, propofol, or midazolam infusion decreased the sufentanil requirements by using bispectral index (BIS).Material and Methods: The study involved 60 patients in the ICU. All patients received 0.5 μg/kg sufentanil IV bolus. Immediately after, group S received 0.25 μg/kg sufentanil infusion, group SH received sufentanil infusion + haloperidol 3 mg/h infusion, group SP received sufentanil infusion + propofol 25 μg/kg/min infusion, and group SM received sufentanil infusion + midazolam 0.04 mg/kg/h infusion, for 6 hours. Average BIS values 61-80 and Ramsay Sedation Score 2-5 were kept at a range of by decreasing or increasing sufentanil levels in all groups and hourly sufentanil consumption was determined. Hemodynamic and biochemical parameters and arterial blood gases were determined at baseline and were repeated in study hours. Results: There was no significant difference in hemodynamic and biochemical parameters and arterial blood gases among the groups. Propofol, midazolam, haloperidol infusion, when added to sufentanil infusion, decreased the consumption of sufentanil in all the measured times (p < 0.001).Conclusions: The authors aimed to determine the effects of haloperidol, propofol, or midazolam infusion when added to sufentanil infusion in a short period of time. The authors found that propofol, midazolam, and haloperidol infusion decreased the sufentanil requirements in ICU patients.
OxyContin® use and misuse in three populations: Substance abuse patients, pain patients, and criminal justice participants
Authors: Wunsch, MD Martha J. , Cropsey, PsyD Karen L. , Campbell, MS Eleanor D. , Knisely, PhD Janet S.
Published: February 2018

Objective: This study was designed to describe and compare individuals in rural Appalachia prescribed, abusing or diverting OxyContin® a region with high rates of prescription medication abuse and misuse.Setting and Participants: Fifty subjects treated for OxyContin®abuse, 34 subjects prescribed OxyContin®for pain and 50 subjects incarcerated due to OxyContin®-related charges from rural Appalachia.Interventions: The Addiction Severity Index, DSM-IV Checklist, and an investigator developed questionnaire were administered to all three groups.Results: All three groups included individuals prescribed OxyContin® for pain and demographic variables and psychiatric/medical histories failed to discriminate between the pain and substance abuse (SA) subjects. SA and criminal justice subjects were significantly more likely to have a current DSM-IV diagnosis of psychoactive abuse/dependence and more likely to be younger and unmarried.Conclusion: This study found that these groups are not distinct and in depth evaluations, including a detailed SA history, are needed to identify the pain patient at risk for abuse and/or diversion of prescribed opioids.
Association of transdermal fentanyl and oral transmucosal fentanyl citrate in the treatment of opioid naïve patients with severe chronic noncancer pain
Authors: Collado, MD, PhD Francisco , Torres, MD, PhD Luis M.
Published: February 2018

Background: Chronic noncancer pain is often undertreated.Aims: To assess the efficacy of fentanyl transdermal therapeutic system (TTS) associated with oral transmucosal fentanyl citrate (OTFC) for breakthrough pain in patients with chronic noncancer pain.Methods: A total of 215 patients with chronic (≥6 months), severe (VAS ≥ 8) noncancer pain participated in a 6-month prospective study. The starting dose of 12 μg/h fentanyl TTS was titrated in 25 μg/h increments to a visual analog scale (VAS) score ≤ 4. OTFC was administered as single-unit doses of 400 μg.Results: The mean (SD) VAS score decreased from 9.86 (0.35) at baseline to 2.05 (0.96) at 6 months. The percentage of patients with poor quality of sleep decreased from 99 percent at baseline to 2.8 percent at the end of the study. The percentage of patients with inadequate pain control decreased from 16.2 percent at month 1 to 2.3 percent at month 6. Pain control was achieved with the 50 μg/h dose in 48 percent of patients, the 75 μg/h dose in 18 percent, and the 100 μg/h dose in 5 percent (only two patients required >100 μg/h). The daily use of single-unit doses of OTFC decreased from 4.64 at month 1 to 2.62 at month 6. Headache, nausea/vomiting, constipation, and somnolence of mild or moderate intensity were the most common side effects. Treatment was discontinued because of nausea/vomiting in seven patients, somnolence in three, and dermatitis in two.Conclusions: Fentanyl TTS associated with OTFC for breakthrough pain is a feasible and effective strategy in opioid naïve patients with severe chronic nonmalignant pain.
Epidemiology of opioid pharmacy claims in the United States
Authors: Williams, PhD, MS Rachel E. , Sampson, BS Timothy J. , Kalilani, MBBS, PhD Linda , Wurzelmann, MD, MPH John I. , Janning, PharmD Stephen W.
Published: February 2018

Objective: To describe opioid pharmacy claims patterns in the United States among an insured population.Design: Information was obtained from the US insurance claims database, IMS Lifelink™, between 1997 and 2002. Descriptive statistics of opioid claims patterns were described with stratification by gender, age, and year of use.Results: The prevalence of insured people with opioid claims increased from 17.1 percent in 1997 to 18.4 percent in 2002. Among people with an opioid claim, 24 percent had ≥30 days and 10 percent had ≥90 days of days supplied based on the insurance claims. Prevalence varied by type of opioid; 56 percent of people with a claim received propoxyphene, 43 percent received codeine, 23 percent received oxycodone, and 17 percent received hydrocodone. Sustained-release opioids were found among 6 percent of those with a claim. With respect to the dose of opioids in the pharmacy claims (expressed as morphine equivalent total daily dose), 71 percent had claims for <50 mg, 55 percent had claims for 50-99 mg, and 24 percent had claims for ≥100 mg. Women, individuals with cancer, and older patients had significantly more pharmacy claims as well as claims for higher doses of opioids (p < 0.05). Internal medicine and family practice specialists were responsible for 22.4 percent and 20.9 percent of all opioid claims.Conclusions: Opioid pharmacy claims increased slightly over time. Older patients, women and patients with a cancer diagnosis had significantly more opioid claims and claims for higher doses than the younger patients, men, and those without cancer.
The opioid-exposed newborn: Assessment and pharmacologic management
Authors: Jansson, MD Lauren M. , Velez, MD Martha , Harrow, RNC-LRN, MS, FNP-BC, IBCLC, RLC Cheryl
Published: February 2018

The infant exposed to opioids in utero frequently presents a challenge to the neonatal care provider in the assessment and treatment of symptoms of Neonatal Abstinence Syndrome (NAS) after birth. This review is intended to provide the healthcare professional with a brief review of current evidence and practical guidelines for optimal evaluation and pharmacologic management of the opioid-exposed newborn.
Two milligrams IV hydromorphone is efficacious for treating pain but is associated with oxygen desaturation
Authors: Chang, MD, MS Andrew K. , Bijur, PhD Polly E. , Napolitano, MD Antonio , Lupow, MD Jason , Gallagher, MD E. John
Published: February 2018

Objective: To evaluate the safety and efficacy of a single dose of 2 mg IV hydromorphone administered to emergency department patients in acute severe pain.Design: Prospective interventional.Setting: Urban academic emergency department.Patient, participants: Nonelderly adults (21-64 years old) with acute severe pain and baseline oxygen saturation (SO2)≥95 percent.Interventions: Two milligrams IV hydromorphone administered over 2-3 minutes.Main outcome measures: The primary outcome was use of naloxone as a reversal agent. Secondary outcomes included degree of pain relief as measured on a numerical rating scale, frequency of oxygen desaturation (SO2 < 95 percent), and side effects.Results: Of the 269 patients, none received IV naloxone. Median pain scores fell from 10 (worst pain possible) at baseline to 1 within 5 minutes and to 0 (no pain) at 30 minutes. SO2 was ≥95 percent at all time points in 68 percent of patients (95 percent CI 62-73 percent), while 26 percent (95 percent CI 21-32 percent) had one or more SO2 levels between 90-94 percent, and 6 percent (95 percent CI 4-10 percent) had SO2 values below 90 percent at one or more time points. The lowest SO2 was 82 percent. The incidence of nausea and vomiting were 16 percent and 7 percent, respectively.Conclusions: Two milligrams IV hydromorphone provides efficacious and rapid pain relief in nonelderly adults presenting to the ED with acute severe pain. However, oxygen desaturation below 95 percent occurred in about one third of patients. Although no noticeable clinical signs of hypoxemia occurred, a conservative interpretation of this finding suggests that 2 mg IV hydromorphone is too much opioid to be given routinely to patients in pain as a single initial dose.
ADDICTION VERSUS DEPENDENCE: CARRYING THE DEBATE FORWARD
Authors: Pal Singh Balhara, MD, DNB Yatan , Mathur, MA, CHt, PhD Scholar Shachi
Published: February 2018

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EREM VERSUS IV PCA META-ANALYSIS
Authors: Blackshear, MD Robert H. , Sumida, MD Shawn M. , Murphy, MD Jamie D. , Wu, MD Christopher L.
Published: February 2018

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Select practice behaviors of clinicians on the use of opioids for adolescents with subacute and chronic nonmalignant pain
Authors: Saroyan, MD John M. , Cheng, MPH Wendy Y. , Taylor, BA Damani C. , Afzal, MD Amna , Sonty, MPhil, PhD Nomita , Sullivan, MD, PhD Maria A.
Published: February 2018

Objectives: To characterize the opioid prescribing and monitoring practices of providers for chronic nonmalignant pain (CNP) and subacute postoperative pain (SAPOP) in adolescents.Design: Web-based cross-sectional self-report survey.Setting: Free-standing pediatric tertiary academic center.Participants: A total of 183 physicians and nurse practitioners were eligible. Of 115 (62.8 percent) participants who responded, 108 (93.9 percent) completed the survey.Main outcome measures: Self-reported frequency of opioid prescription for SAPOP and CNP conditions and frequency of associated monitoring practices.Results: For 10 of the 13 pain conditions included, some participants endorsed “monthly or more opioid prescriptions” while others endorsed “opioids do not represent appropriate management.” Opioid prescribing is present for almost all pain conditions but is substantially more common for nonacute vaso-occlusive-related sickle cell disease, scoliosis correction, and video-assisted pectus excavatumrelated pains. When compared with the reference group, CNP with no identifiable pathology, the odds ratio (OR) of an opioid being prescribed for CNP states with identifiable pathology was not significantly higher. The OR for SAPOP was significantly higher (p < 0.0001). None of the opioid prescribers reported collecting urine toxicology before or during opioid therapy.Conclusions: This survey identifies a diversity of self-reported clinician opioid prescribing practices for adolescents with CNP and SAPOP. Urine collection for drug toxicology screening is not utilized by opioid prescribers. Surveys of similar clinician practice behaviors at other institutions are warranted to replicate this finding and to establish common clinical practice for usage and monitoring of opioids in conditions where guidelines do not yet exist.
A comparison of methods of administering the Opioid Risk Tool
Authors: Jones, PhD Ted , Passik, PhD Steven D.
Published: February 2018

Risk assessment and stratification have become important aspects for the prescription of opioids to patients with chronic pain. Recent research has shown that the Opioid Risk Tool (ORT), a widely used risk assessment tool, has poor predictive abilities when compared with other risk assessment methods. This study compares two different methods of administration of the ORT to further study this issue. Patients at a pain practice were given an ORT to complete per the usual method of administration. In addition, a separate blinded ORT was completed by a psychologist after conducting a clinical interview with the patient. The results of the patient-completed ORT (PC-ORT) and the clinician-completed ORT (CC-ORT) were compared. There were significant differences found between the two, with the psychologist usually rating the patient higher in risk. The CC-ORT demonstrated better prediction of aberrant drug-taking behavior than the PC-ORT. The items that were discrepant between the two suggest that the differences were primarily due to comprehension issues. A strategy to help maximize the usefulness of the ORT derived from this finding and clinical experience is discussed.
Switching from high doses of pure µ-opioid agonists to transdermal buprenorphine in patients with cancer: A feasibility study
Authors: Lundorff, MD Lena , Sjøgren, DmSci, MD Per , Hansen, MD Ole Bo , Jonsson, MD Torsten , Nielsen Per Rotbøll , Christrup, PhD, MSc(Pharm) Lona
Published: February 2018

Background: Several myths on buprenorphine’s pharmacology exist: possible analgesic ceiling effect, feasibility of combination with other opioid agonists, and the reversibility of side effects. Aim to evaluate: 1) if cancer patients receiving high doses of pure agonists could obtain adequate pain relief after switching to transdermal (TD) buprenorphine and 2) whether the numbers of breakthrough pain episodes after switching increased and whether they could be treated with the same doses of pure agonist as before switching.Design: The prospective open multicenter study included outpatients with moderate-to-severe cancer pain satisfactorily controlled.Setting: Patients were switched from the usual pure agonist to TD buprenorphine and were titrated to a stable dose. The assessments were: 1) daily self-assessment of pain intensity, numbers of rescue medications, and pain interference with sleep; 2) brief pain inventory; 3) pain relief and pain intensity; 4) quality of life; and 5) adverse events and symptoms.Results: Eighteen patients receiving 150-516 mg of morphine/day were included. The buprenorphine dose at the end of the study varied between 52.5 and 140 mg/h. No difference in pain before and after switching was shown. The level of rescue doses was maintained. The patches were well tolerated. A significant decrease in fatigue and an increase in global health status were seen after the switch.Conclusion: It is feasible to switch cancer patients from high doses of pure µ- opioid agonists to TD buprenorphine without eliciting any antagonist effects, but the dose conversion factor is individual and the switching process should be tailored for the individual patient.
Methadone conversion in infants and children: Retrospective cohort study of 199 pediatric inpatients
Authors: Fife, PharmD Alexandra , Postier, MPH Andrea , Flood, PhD Andrew , Friedrichsdorf, MD, FAAP Stefan J.
Published: February 2018

Objective: Methadone administration has increased in pediatric clinical settings. This review is an attempt to ascertain an equianalgesic dose ratio for methadone in the pediatric population using standard adult dose conversion guidelines. Setting: US tertiary children's hospital.Patients: Hospitalized pediatric patients, 0-18 years of age.Main outcome measures: A retrospective chart review was conducted for patients who were converted from their initial opioid therapy regimen (morphine, hydromorphone, and/or fentanyl) to methadone. The primary endpoint was whether or not a dose correction was needed for methadone in the 6 days following conversion using standard dose conversion charts for adults. Documented clinical signs of withdrawal, unrelieved pain, or oversedation were examined.Results: The majority (53.7 percent) of the 199 children were converted to methadone on intensive care units prior extubation or postextubation. The mean conversion ratio was 23.7 mg of oral morphine to 1 mg of oral methadone (median, 18.8 mg:1 mg, SD = 25.7). Most patients experienced an adequate conversion (n = 115, 57.8 percent), while 83 (41.7 percent) appeared undermedicated, and one child was oversedated. There were no associations found with conversion ratios for initial morphine dose, days to conversion, or effect of withdrawal of concomitant agents with potential for withdrawal.Conclusions: Opioid conversion to methadone is commonly practiced at our institution; however, dosing was significantly lower compared to adult conversion ratios, and more than 40 percent of children were undermedicated. The majority of children in this study received opioids for sedation while intubated and ventilated; therefore, safe and efficacious pediatric methadone conversion rates remain unclear. Prospective studies are needed.
Methadone prolongs cardiac conduction in young patients with cancer-related pain
Authors: Anghelescu, MD Doralina L. , Patel, MD Rakesh M. , Mahoney, MD Daniel P. , Trujillo, MD Luis , Faughnan, BSN Lane G. , Steen, MSN Brenda D. , Baker, MD Justin N. , Pei, MS Deqing
Published: February 2018

Objective: Methadone prolongs cardiac conduction, from mild corrected QT (QTc) prolongation to torsades de pointes and ventricular fibrillation, in adults. However, methadone use for pain and its effects on cardiac conduction have not been investigated in pediatric populations.Methods: A retrospective review of QTc intervals in patients receiving methadone analgesia was conducted. Medical records from a 4-year period (September 2006 to October 2010) at a pediatric oncology institution were reviewed, and correlations were tested between cardiac conduction and methadone dosage and duration of therapy, electrolyte levels, renal and hepatic dysfunction, and concurrent medications.Results: Of the 61 patients who received methadone, 37 met our inclusion criteria and underwent 137 electrocardiograms (ECGs). During methadone treatment, the mean QTc was longer than that at baseline (446.5 vs 437.55 ms). The mean methadone dose was 27.0 ± 24.3 mg/d (range, 5-125 mg/d; median, 20 mg/d) or 0.47 ± 0.45 mg/kg per day (range, 0.05-2.25 mg/kg per day; median, 0.37 mg/kg per day), and the mean duration of therapy was 49 days. The authors identified a correlation between automated and manual ECG readings by two cardiologists (Pearson r = 0.649; p < 0.0001), but the authors found no correlations between methadone dose or duration and concurrent QTc-prolonging medications, sex, age, electrolyte abnormalities, or renal or hepatic dysfunction.Conclusion: At a clinically effective analgesic dose, methadone dosage and duration were not correlated with QTc prolongation, even in the presence of other risk factors, suggesting that methadone use may be safe in pediatric populations. The correlation between automated and manual ECG readings suggests that automated ECG readings are reliable for monitoring cardiac conductivity during the reported methadone-dosage regimens.
Abuse deterrence testing: A dose ratio escalation study examining naloxone coadministered with intravenous hydromorphone in non-treatment-seeking, opioid-dependent drug users
Authors: Levy-Cooperman, PhD Naama , Schoedel, PhD Kerri A. , Reiz, BSc Joseph L. , Thompson, PhD David , Chakaraborty, MStat Bijan , Geoffroy, MD Pierre , Michalko, PharmD, MBA Kenneth J.
Published: February 2018

Objective: To assess the reduction in intravenous (IV) abuse potential of hydromorphone from different dose ratio combinations with naloxone in opioid-dependent drug users.Design: Randomized, blinded, dose ratio escalation study.Setting: Single center.Participants: Following conversion to a stable IV dose of hydromorphone, 12 non-treatment-seeking, opioid-dependent subjects were randomly assigned and received at least one dose of study drug; seven subjects received all five study treatments. Five subjects withdrew early from the treatment phase: adverse events (2) and participant decision (3).Interventions: Participants underwent a dose-selection phase to stabilize on an individualized hydromorphone dose. Stable subjects were dosed intravenously on 5 consecutive days. The dose received was one of five hydromorphone/naloxone dose ratios that included the combination of hydromorphone and placebo naloxone. Hydromorphone/naloxone treatment always involved increasing dose ratios of naloxone (8:1, 6:1, 4:1, and 2:1) with the hydromorphone-placebo naloxone treatment randomly assigned within the sequence of dose ratios.Main outcome measures: Drug Liking visual analog scale (VAS), Objective Opioid Withdrawal Scale (OOWS) and Subjective Opioid Withdrawal Scale (SOWS). Results: Hydromorphone/naloxone placebo produced subjective effects typical of opioid administration, while hydromorphone/naloxone dose ratios were associated with significant increases in SOWS and OOWS scores (p < 0.05). Compared with hydromoprophone/naloxone placebo, naloxone reduced the effects of hydromorphone on most measures, including Drug Liking VAS, the antagonism was greatest for the 4:1 and 2:1 ratios.Conclusions: This study was an ethical investigation of the abuse deterrence potential of four hydromorphone/naloxone dose ratios. The IV coadministration of commercially available IV solutions of hydromorphone and naloxone in 4:1 and 2:1 ratios had statistically greater reductions of abuse-related opioid effects and triggers of withdrawal symptoms and there was a convergence of subjective and objective pharmacodynamics results and safety findings. An oral modified-release product, developed with a 2:1 hydromorphone/naloxone ratio, may have important public health benefits by reducing high-risk, IV abuse of prescription opioids, while providing pain relief when ingested orally and used in accordance with the Product Monograph.
Fentanyl in a pectin gel treating breakthrough pain
Authors: Bujedo, MD Borja Mugabure , Karlsson, PhD Brynjar
Published: February 2018

Breakthrough pain (BTP) currently represents a challenge for health professionals dedicated to the treatment of pain. In this descriptive 1-year follow-up study on three patients with BTP from vertebral crush, in the context of multiple myeloma, the authors have observed the great either efficacy or tolerability profile of fentanyl pectin nasal spray. The most relevant findings in this study were better adherence to treatment compared to previously opioids and also great personal satisfaction. Because of common pathophysiological mechanism for noncancerous pain of bone origin, these good results could open the door to investigation of the use of this drug in this patient´s group.
International Conference on Opioids, June 5-7, 2016
Authors: DeVito, Jr. Richard A.
Published: February 2018

The 2016 International Conference on Opioids (ICOO2016) was held in Boston, June 5-7, 2016, at the Joseph B. Martin Conference Center at Harvard Medical School. Attendees from around the world participated in this two plus day conference that featured renowned speakers from many countries presenting the latest research, ethics, legal and clinical application of opioids. Posters Presented June 5-7, 2016
What's in a number? Recommending practicality in the DATA 2000 patient limits
Authors: Barthwell, MD, DFASAM Andrea G. , Young, JD, PhD Jonathan M. , Barnes, JD Michael C. , Kulkarni, JD Shruti R.
Published: February 2018

According to the Substance Abuse and Mental Health Services Administration, 2.4 million individuals have an opioid use disorder (OUD). Yet, nearly 80 percent of them—more than 1.9 million people—do not receive treatment. Medication-assisted treatment (MAT), specifically with buprenorphine, has proven to be effective in treating patients with OUDs while also reducing costs to the healthcare system, criminal justice system, and workforce. Despite its effectiveness, barriers to MAT continue to exist. Consequently, many individuals must wait months, if not years, to receive treatment. This article analyzes the US Department of Health and Human Services’ final rule (Final Rule) on MAT, common barriers to treatment, and the cost-benefit of treatment in light of the current opioid abuse epidemic. The article finds that while the Final Rule was a step in the right direction, it does not go far enough to adequately address the epidemic. Finally, the article proposes practical recommendations for increasing patient access to treatment for OUDs, including increasing the patient limit for highly qualified addiction treatment providers so that they can practice addiction medicine on a full-time basis and exempting buprenorphine products labeled by the US Food and Drug Administration for direct administration from the practitioner's patient limit.
Prevalence and correlates of coprescribing anxiolytic medications with extensive prescription opioid use in Veterans Health Administration patients with metastatic cancer
Authors: Barry, PhD Declan T. , Sofuoglu, MD Mehmet , Kerns, PhD Robert D. , Wiechers, MD Ilse R. , Rosenheck, MD Robert A.
Published: February 2018

Objective: To examine the prevalence and correlates of concomitant anxiolytic prescription fills in Veterans Health Administration (VHA) patients with metastatic cancer who have extensive prescription opioid use.Design, Setting, and Participants: National VHA data for fiscal year 2012 were used to identify veterans diagnosed with metastatic cancer (ICD-9 codes 196-199) who also had extensive prescription opioid use (at least 10 opioid prescriptions during the year, comprising the highest 29 percent of opioid users). Bivariate and multivariate analyses were used to examine correlates of receiving anxiolytic medication among veterans with metastatic cancer and extensive prescription opioid use.Results: Of the 5,950 veterans with metastatic cancer and extensive prescription opioid use, 51 percent also received anxiolytic medication, of whom 64 percent had a medical indication and 85 percent had a psychiatric or medical indication for psychotropics. Of those with extensive prescription opioid use who filled an anxiolytic, 64 percent also received antidepressants and 38 percent received three or more classes of psychotropic medication (ie, polypharmacy). In multivariate analyses, factors associated with receipt of an anxiolytic included any anxiety disorder, insomnia, the prescription of antidepressants or antipsychotics, bipolar disorder, younger age, more emergency department visits, and greater number of opioid prescriptions.Conclusions: VHA patients with metastatic cancer and extensive prescription opioid use who are prescribed anxiolytics are likely to have a Food and Drug Administration-approved indication for psychotropics, and anxiolytics in particular, but represent a clinically vulnerable group which merits careful monitoring.
Clinically relevant concentrations of opioids for in vitro studies
Authors: Boland, FRCP, PhD Jason W. , Pockley, PhD A. Graham
Published: February 2018

Objectives: Numerous in vitro studies have evaluated the influence of opioids on many biological and immunological processes. The concentrations that have been used in these studies span a large range and often do not reflect levels that are present in the relevant patient groups. This article reviews the literature concerning the concentrations of opioids that are detected in patients so that the concentrations of opioids that are used for in vitro studies can better reflect those that are present clinically. This will enable scientists and clinicians to more effectively model and interpret potentially relevant clinical effects from in vitro studies.Methods: Data on the concentrations of six commonly used opioids from clinical studies in adults were collected by searching PubMed (Medline).Results: A total of 42 relevant studies were included in the review. Concentrations of the opioids from previous clinical studies were mostly between 1 and 10 ng/mL for buprenorphine, 1 and 10 ng/mL for fentanyl, 50 and 500 ng/mL for methadone, 25 and 250 ng/mL for morphine, 10 and 100 ng/mL for oxycodone, and 100 and 1,000 ng/mL for Tramadol and were dependent on the patient group and indication under investigation.Conclusions: Concentrations of opioids used in vitro should include those that are present in the relevant clinical setting if the effects of opioids detected in vitro are to be of potential relevance to the clinical setting. Therefore, it is essential that these concentrations in the relevant clinical context(s) are known.