bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensibility and readability of patient self-administered Opioid Assessment Screening Tools
Authors: Wallace, PhD Lorraine S. , Keenum, PharmD, DO Amy J. , Roskos, MD Steven E.
Published: February 2018

Objective: The aims of this study were to evaluate the cognitive complexity and reading demands of patient self-administered Opioid Assessment Screening Tools (OASTs) for use in adults with nonmalignant pain.Methods: Using comprehensive search strategies, we identified english-language OASTs with established validity and reliability for inclusion in our study. Cognitive complexity of individual OAST statements or questions were assessed using three techniques (number of items, number of words, and linguistic problems), whereas readability was measured using the Flesch- Kinkaid formula.Results: Four (n = 4) were identified and included in our review: Current Opioid Misuse Measure (COMM), Pain Medication Questionnaire (PMQ), Screener and Opioid Assessment for Patient with Pain, and Screening Tool for Addiction Risk (STAR). Number of total OAST statements or questions ranged from a low of 14 (STAR) to a high of 26 (PMQ), whereas number of words (length) per statement or question averaged from a low of 10.2 ± 1.1 (STAR) to a high of 15.9 ± 3.8 (PMQ). The STAR (1.3 ± 1.1) had the fewest number of linguistic problems per statement or question, whereas the PMQ (3.0 ± 1.4) had the most linguistic problems per statement or question. Although, readability of OASTs ranged from approximately sixth (STAR) to eighth (COMM, PMQ) grade, there was notable variation in readability across individual statements or questions.Conclusions: Our study demonstrates that formatting characteristics, including linguistic problems, and high readability of several OAST statements or questions may hinder many patients’ ability to accurately complete and comprehend OASTs independently.
Morphine prescription in end-of-life care and euthanasia: French home nurses’ opinions
Authors: Bendiane, PhDc Marc Karim , Bouhnik, PhDc Anne-Deborah , Favre, PhD Roger , Galinier, MD Anne , Obadia, MD Yolande , Moatti, PhD Jean-Paul , Peretti-Watel, PhD Patrick
Published: February 2018

Objective: This study aimed to investigate factors that might lead French homecare nurses to consider the pre-scription of high-dose morphine to terminally ill patients to be euthanasia.Methods: The researchers conducted an anonymous telephone survey among a random sample of602 French homecare nurses (response rate = 75percent) in 2005.Results: Overall, 27percent of responding home nurses considered prescribing high-dose morphine to terminally ill patients to be euthanasia. Such an opinion was more frequently held by older nurses, those who had not followed terminally ill patients during the previous three years, and those with less knowledge about pain management involving opioid analgesics.Conclusion: There is an urgent need to strengthen pain management education among French homecare nurses—especially regarding the use of morphine—in order to both improve their technical skills and correct some misconceptions about opioid analgesics.
Fentanyl: Are we paying too high a price?
Authors: Fodale, MD Vincenzo , Romeo, MD Manuela , Mafrica, MD Federica
Published: February 2018

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Are we still scratching the surface? A case of intractable pruritus following systemic opioid analgesia
Authors: Tarcatu, MD Dana , Tamasdan, MD Cristina , Moryl, MD Natalie , Obbens, MD, PhD Eugenie
Published: February 2018

This article describes a case of severe opioid-induced pruritus following systemic morphine administration. Symptoms did not resolve after administration of antihistamines or rotation to fentanyl or hydromorphone, but oral oxycodone and small-dose intravenous naloxone did alleviate the patient’s itching. The pathogenesis of opioidinduced pruritus and the rationale for opioid rotation are briefly discussed. Current and possible future therapeutic options are mentioned.
Relationship between fentanyl dosage and immune function in the postoperative period
Authors: Yardeni, MD Israel Z. , Beilin, MD Benzion , Mayburd, MD Eduard , Alcalay, MSc Yifat , Bessler, PhD Hanna
Published: February 2018

Background: Anesthesia and surgery are associated with impairment of the immune system expressed as an excessive proinflammatory immune response and suppression of cell mediated immunity. Opioids, an integral part of anesthetic technique, possess an inhibitory effect on both humoral and cellular immune responses. It was the aim of the present study to examine the effect of various doses of fentanyl on cytokine production during the perioperative period.Intervention: The effect of large (LDFA, 70-100 μg/kg), intermediate (IDFA, 23-30 μg/kg) and small (SDFA, 2-4 μg/kg) doses of fentanyl on the immune function in the postoperative period was investigated.Participants: Sixty patients, randomly assigned to one of the three groups according to the dose of fentanyl were included in the study.Methods: The ex vivo secretion of IL-1β, IL-2, IL-6, and IL-10 and NK cell cytotoxicity (NKCC) of peripheral blood mononuclear cells (PBMC) was tested before, and at 24, 48, and 72 hours following surgery.Results: The pattern of postoperative secretion of the proinflammatory cytokines IL-1β and IL-6 and that of the anti-inflammatory cytokine IL-10 differed significantly between patients receiving SDFA and those receiving IDFA and LDFA, but was similar between the last two groups. A similar suppression of NKCC and IL-2 secretion was observed in the three groups.Conclusions: The diminished proinflammatory cytokine response observed in patients treated by LDFA and IDFA suggests that although more stable immune function can be achieved by those methods in comparison with SDFA, it is recommendable to apply IDFA to avoid the side effects that might be observed using LDFA method.
Pharmacokinetics of oral tramadol in patients with liver cancer
Authors: Ibraheem Mohamed Kotb, MD Hassan , Ahmed Fouad, PhD Ihab , Mohamed Fares, MD Khaled , Galal Mostafa, MD Mostafa , Abd El-Rahman, MSc Ahmad M.
Published: February 2018

Background: There are no studies reported on pharmacokinetics of opioids in patients with hepatocellular carcinoma, the fifth most common cancer in the world.Methods: The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls. Plasma tramadol concentrations were measured in venous samples at intervals up to 12 hours by high-pressure liquid chromatography. All pharmacokinetic variables were evaluated using one-compartment model.Results: Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively). The area under the serum concentration-time curve increased significantly in patients with primary and metastatic cancer of liver than in control [1,933 μg/h/L (SD = 41), 1,327 μg/h/L (SD = 51), 1,138.5 μg/h/L (SD = 31), respectively]. Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control. Reduced clearance and impaired elimination was significantly observed in patients with liver carcinoma than control. Clearance was reduced to 50 percent of control, and elimination halflife increased up to three folds in patients with primary liver carcinoma than that of control. Satisfactory pain relief with minimal side effects was observed all over study period.Conclusion: It is recommended to lengthen the dose interval of oral tramadol, if it is to be used in patients with liver cancer for analgesic purposes, to 50 mg every 12 hours as it is proved to be effective and safe.
Oxymorphone and oxymorphone extended release: A pharmacotherapeutic review
Authors: Sloan, MD Paul Alexander , Barkin, PharmD, MBA Robert L.
Published: February 2018

The treatment of chronic pain remains an enormous challenge in the United States. Opioid analgesics are an important component of pharmacotherapy for chronic pain and have proven efficacy in the management of cancer and noncancer chronic pain. The newest addition to oral opioid pharmacotherapy is oral oxymorphone, a semisynthetic opioid agonist that is now available in oral immediate-release (IR) and extended-release (ER) formulations. This review discusses the pharmacology, pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and clinical use of oral oxymorphone IR and ER formulations for the management of moderate to severe pain for different types of patients in a variety of settings. Two published studies evaluated the efficacy and safety of oxymorphone IR in patients with moderate to severe postoperative pain and demonstrated that it provides rapid and effective analgesia and is generally well tolerated. Six published randomized controlled trials and three published open-label studies evaluated the efficacy and safety of oxymorphone ER for chronic cancer or noncancer pain. These trials found analgesic efficacy and tolerability comparable to that provided by morphine controlled release (CR) or oxycodone CR; treatment effects with oxymorphone ER were durable for treatment periods of 12 weeks at the same dose or up to 1 year with little dose escalation. Titrated doses of oxymorphone ER were effective and generally well tolerated in both opioid-experienced and opioid-naïve patients. Aspects of oxymorphone metabolism and limited protein binding may simplify treatment in certain populations.
Prevalence of opioid dispensings and concurrent gastrointestinal medications in an elderly population from Ontario, Canada
Authors: Williams, PhD, MS Rachel , Bosnic, BA Nevzeta , Duncan, PhD, MS Ashlee W. , Brogan, BA Michael , Cook, PhD Suzanne F.
Published: February 2018

Background: Although opioid analgesics are effective therapeutic agents, gastrointestinal (GI) side effects represent a challenging consequence of treatment. In an elderly population, age-related physiological changes, such as decreased GI functioning and dehydration, may compound the adverse effects of opioids; therefore, appropriate prophylactic treatment, utilizing laxatives and/or acid suppressants, is particularly important in an elderly population.Aim: This study describes the prevalence of outpatient opioid dispensings and the concomitant dispensing of opioids and GI medications in a population 65 years or older enrolled in the Ontario Drug Benefit Program in 2005.Methods: Using a retrospective cohort design, dispensings of opioids, laxatives, and acid suppressants were identified using claims reimbursement data. Concurrent dispensings were defined as having at least one “GI medication-dispensed day” overlapping an “opioid-dispensed day.”Results: More than 18 percent of the elderly, drug plan population was dispensed an opioid in 2005. Women had more opioid dispensings and were dispensed opioids for extended periods of time as compared with men. Approximately half of patients with an opioid dispensing were concomitantly dispensed a GI medication; these medications were dispensed nearly twice as frequently among people with chronic opioid dispensings when compared with people with nonchronic opioid dispensings.Conclusions: Although laxatives are commonly recommended in patients taking opioids, only half of the older adults in Ontario who were dispensed an opioid also received a concomitant GI medication dispensing. As the elderly are more likely to develop opioid-induced constipation, the prophylactic use of laxatives and/or acid suppressant medications is often necessary to mitigate the side effects associated with their pain management.
A PARADOXICAL, NOVEL APPROACH: COMBINING MINUTE NALOXONE WITH MORPHINE INTRATHECAL INFUSION
Authors: Ruan, MD Xiulu
Published: February 2018

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Increasing deaths from opioid analgesics in the United States: An evaluation in an interventional pain management practice
Authors: Manchikanti, BA Kavita n. , Manchikanti, MD Laxmaiah , Damron, RN Kimberly S. , Pampati, MSc Vidyasagar , Fellows, MA Bert
Published: February 2018

Objective: To assess the prevalence of opioid-related deaths in patients in an interventional pain management tertiary referral center.Methods: Patient deaths from March 2003 to February 2007 were evaluated.Results: From March 2003 to February 2007, 2,179 patients were receiving opioids in 2003, 2,445 in 2004, 2,804 in 2005, and 2,965 in 2006, respectively. Overall, 86 percent of the patients were referred by a physician and 90 percent of patients received interventional techniques. There were a total of 91 deaths, of which 60 were categorized as natural deaths, 25 were characterized as accidental deaths, and 6 were characterized as suicidal. Of the 18 drug poisoning deaths, 5 deaths were positively related to prescription drugs, 7 deaths were probably related to prescription drugs, and 6 deaths had no relation to the prescription drugs provided. Total opioidrelated deaths were 12 over this 4-year period with 0.46 in 2003, 2.04 in 2004, 2.85 in 2005, and 1.35 in 2006 per 1,000 population. In contrast, deaths definitely related to prescription opioids were 5 (0.92 per 1,000) over a period of 4 years. In the suicidal group, there were a significantly higher proportion of patients with generalized anxiety disorder.Conclusions: In an interventional pain management practice (a tertiary referral center), the total prevalence of opioid-related deaths varied from 0.46 to 1.78 per 1,000 from 2003 to 2006 with a total of 12 deaths over a period of 4 years. The deaths definitely related to opioid prescriptions were 5 with a rate of 0 to 1.43 per 1,000 over a period of 4 years.
Hospital morbidity associated with the natural history of heroin use
Authors: Tait, PhD, BSc (Hons) Robert J. , Hulse, PhD, BBSc (Hons) Gary K.
Published: February 2018

Objective: To assess changes in hospital morbidity associated with heroin use from pre-initiation, recreational to dependent use, and changes following treatment.Design: Analysis of hospital admission data assessed over six, 6-month periods (before and after heroin initiation; two dependent heroin use periods; and post-oral and post-sustained release naltrexone treatment).Participants: A sequential cohort of 139 patients for whom date of initial heroin use, regular heroin use, and two periods of heroin dependence (prior to treatment with oral and implant naltrexone) were known.Outcome Measures: The West Australian Data Linkage System was used to assemble hospital admission data. Admissions were analyzed as follows: “all cause” admissions and then subgrouped as “mental health (MH) other,” “MH opioid related,” “MH non-opioid drug related,” and “opioid overdoses.”Results: The database identified 130 (94 percent) of the participants with 76 (59 percent) being male. The mean length of follow-up from first heroin use was 9.4 (SD 4.9) years. Significant increases in morbidity were not found in the periods pre-first and post-first heroin use, but were found from pre-heroin use to dependent use for “all cause,” “MH opioid related,” and “opioid overdose” admissions. A significant decline in these measures was observed from the first dependent period to the post-implant period. “MH opioid related” admissions declined from the first to the second period of dependent heroin use.Conclusions: Findings suggest that the movement to dependent heroin use increases hospital morbidity; that morbidity in the presence of treatment does not necessarily increase; and the treatment with a sustained release preparation may be more effective than oral naltrexone in arresting morbidity.
Pain management in chronic kidney disease: The pharmacokinetics and pharmacodynamics of hydromorphone and hydromorphone-3-glucuronide in hemodialysis patients
Authors: Davison, MD, MHSc (bioethics), FRCP(C) Sara N. , Mayo, PhD, SFO Patrick R.
Published: February 2018

Objective: To describe the pharmacokinetics of hydromorphone (HM) and its primary metabolite hydromorphone- 3-glucuronide (H3G) both on and off dialysis in relation to the pharmacodynamic measurements of pain.Design: Prospective, open-label, observational study.Setting: Canadian, university-based renal program.Participants: Twelve anuric hemodialysis patients with chronic pain, established on immediate-release HM.Main Outcome Measures: HM and H3G plasma concentrations were measured during and between hemodialysis treatments using a reverse-phase highperformance liquid chromatography assay with liquid chromatography/mass spectrometer/mass spectrometer detection. The McGill Pain Questionnaire (MPQ) and a Visual Analogue Scale (VAS) were used to measure pain. Noncompartmental analyses were conducted. Adverse effects were recorded.Results: HM did not substantially accumulate (accumulation factor R = 2.7 (1.6)), most likely due to the rapid conversion to H3G. Conversely, H3G accumulated between dialysis treatments (R = 12.5 (12.1)) but appeared to be effectively removed during hemodialysis (1.8 (0.7), p = 0.03). HM resulted in >65 percent reduction in pain over dosing intervals. Mean MPQ pain scores decreased from 39.8 (18.2) to 12.3 (16.2) on dialysis and from 35.0 (18.5) to 15.5 (13.6) between dialysis treatments. Mean VAS pain scores decreased from 7.5 (2.5) to 3.0 (1.5) on dialysis and from 5.9 (3.2) to 4.4 (1.6) between dialysis treatments. No clinically significant opioid toxicity was observed. The accumulation of H3G between hemodialysis treatments was associated with greater sensory-type pain (r = 0.76, p < 0.0001) and reduced duration of analgesia.Conclusions: HM may be a safe and effective opioid for use in selected hemodialysis patients.
Integration of viral hepatitis services into opioid treatment programs
Authors: Kresina, PhD Thomas F. , Bruce, MD, MA, MSc R. Douglas , Lubran, MS Robert , Clark, MD, JD, FASAM H. Westley
Published: February 2018

Opioid treatment programs (OTPs) dispense methadone and buprenorphine under specific federal regulations to individuals diagnosed with opioid dependence. OTPs can provide a comprehensive therapeutic milieu, often including primary medical care, psychosocial counseling, vocational rehabilitation, ongoing performance monitoring, and other vital services. Because of the high prevalence of infectious diseases, particularly hepatitis C virus infection, model OTPs are developing comprehensive care and treatment programs that integrate general medical and infectious disease-related medical care with substance abuse and mental health services. Integrating hepatitis care services in the substance abuse treatment settings fosters access to care for patients with multiple comorbidities, many who otherwise would not receive needed care. Improving health related outcomes for this patient population with complex medical problems requires an advanced integrated model of care for OTPs that can be exemplified through establishing resources needed to prevent hepatitis infection as standard of care. Outcomes management becomes possible through enhancing current capability of existing dispensing programs. This may serve as a national model for highly cost-efficient healthcare that has a measurable outcome of improved health.
Clinical rationale for administering fentanyl to cancer pain patients: Two Delphi surveys of pain management experts in Denmark
Authors: Jacobsen, MS, MPH Ramune , Møldrup, PhD Claus , Christrup, PhD Lona
Published: February 2018

Objective: To describe the rationale behind the choice of fentanyl administration forms as reported by Danish nurses and physicians specializing in pain management.Methods: Sixty nurses and 60 physicians specializing in pain management in Denmark were contacted via an Internet survey system to perform two Delphi surveys. In the brainstorming phase, the main reasons for administering and not administering fentanyl patches and oral transmucosal fentanyl citrate (OTFC) were identified. In the second phase, the nursing and medical experts rated the importance of these reasons on an 11-point Numerical Rating Scale.Results: Responses from 10 pain nurses and 14 pain doctors were used for the final analysis. Impossible or difficult oral intake of analgesia was the most important reason to administer fenantyl patches, whereas patients’ dermatological problems and neuropathic pain origin were the most important reasons for not administering fenantyl patches in both panels. OTFC was presented as an alternative or second choice administration form for breakthrough cancer pain by both nurses and doctors. A damaged mouth, the high cost, and energy required for administration of this medication were reported as the main reasons why OTFC was only rarely prescribed to cancer pain patients in Denmark.Conclusions: The reasons for administering fentanyl in different administration forms reported by Danish pain nurses and pain specialists partly differed from those derived from the literature. Studies of pain management traditions could improve the understanding of the reasons for analgesic administration.
FDA approvals of generic drugs: Impact on the diversion of opioid analgesics with a potential for abuse
Authors: Inciardi, PhD James A. , Surratt, PhD Hilary L. , Stivers, BA Yamilka , Cicero, PhD Theodore J.
Published: February 2018

Generic drugs account for half of all prescription drug purchases in the United States. Although they are bioequivalent to their branded counterparts, they are typically sold at substantial discounts from the branded price. Given this, the purpose of this analysis is to examine the impact of the introduction of generic forms of selected opioids on their diversion to the illicit marketplace. The analgesics in this analysis include oxycodone ER (extended release), and the fentanyl transdermal patch. The data were collected through a postmarketing surveillance initiative supported by the Researched Abuse Diversion and Addiction-Related Surveillance (RADARS®) System risk management program, gathered on a quarterly basis from a national sample of police and regulatory agencies. The results indicate that with oxycodone ER and the fentanyl transdermal patch, the diversion of their generic formulations occurs less often than that of the branded products, and that the introduction of the generic formulations did not significantly increase the overall levels of diversion during the period covered by this analysis. Although diversion did not increase in the short-term, the need for longer term monitoring appears warranted.
Methadone as an analgesic for patients with chronic pain in methadone maintenance treatment programs (MMTPs)
Authors: Blinderman, MD, MA Craig D. , Sekine, MD Ryuichi , Zhang, MS Baohui , Nillson, MS Matthew , Shaiova, MD Lauren
Published: February 2018

Background: Limited case reports have suggested a role for methadone as an analgesic for chronic pain in patients maintained on methadone for treatment of opiate addiction. Patients with HIV are disproportionately represented in this population and often have severe, debilitating chronic pain syndromes of multiple etiologies, including cancer-related pain syndromes.Objective: This study evaluated the safety and efficacy of initiating and maintaining additional methadone for chronic pain in HIV-positive patients with ongoing treatment for opiate addiction in methadone maintenance treatment programs (MMTPs).Methods: We performed a retrospective chart review of 53 HIV/AIDS patients (36 male, 17 female; 24 with cancer) with diverse chronic pain syndromes who were followed in an HIV Pain Clinic and were currently enrolled in an MMTP. The outcome measure was pain, assessed using a numeric rating scale (0-10). Incidence of heroin use was also measured.Results: The mean methadone dose initially prescribed for analgesia was approximately equal to 67 percent of the methadone dose used in the MMTP for addiction. Over the 12-month retrospective observation period, methadone was titrated to approximately 200 percent of the methadone maintenance dose. The mean pain score at initial visit to the Pain Clinic was 9.4 + 1.03. After methadone for analgesia has been administered for 1 month, the mean pain score decreased to 5.35 ± 1.7 (p < 0.001), at 3 months, 4.8 ± 1.3 (p < 0.001), at 6 months, 4.2 ± 1.7 (p < 0.001), and at 12 months, 4.2 ± 1.4 (p < 0.001). No serious adverse events or side effects were observed with methadone therapy for analgesia.Conclusion: HIV/AIDS patients with chronic pain enrolled in MMTPs achieved improved analgesia with no serious side effects when additional methadone was administered for pain relief. Further controlled studies are needed to confirm our findings and to establish the safety and efficacy of methadone therapy for chronic pain in this population.
Physicians’ pain management confidence versus competence
Authors: Douglass, PharmD Mark A. , Sanchez, PharmD, BCPS Gail M. , Alford, MD, MPH Daniel P. , Wilkes, RNC, MS, AOCN Gail , Greenwald, MD Jeffrey L.
Published: February 2018

Objective: To assess awareness of existing pain management guidelines and compare physicians’ confidence versus competence in selected pain management skills.Design: Prospective survey study.Setting: A large urban tertiary medical center.Patients, participants: All Department of Medicine interns, senior residents, and attending physicians were sent a questionnaire; the overall response rate was 30 percent (91/304).Interventions: The questionnaire assessed physicians’ awareness of the institution’s pain management guidelines, their self-reported comfort level (confidence) with, and a knowledge assessment (competence) of three pain management skills (managing chronic-continuous pain, equianalgesic dose conversion, and managing breakthrough pain) using validated, standardized case vignettes.Main outcome measures: A comparison of physicians’ confidence with their competence in these pain management skills.Results: A total of 23 percent (21/91) of the respondents reported an awareness of the institution’s pain management guidelines. Interns were significantly less confident than senior residents in all three pain management skills (p < 0.001, 0.006, 0.02) but nonsignificantly more competent in two of three skills (chronic-continuous pain, dose conversion). Attendings were generally more confident and nonsignificantly more competent than senior residents in all three pain management skills.Conclusions: The underutilization of the pain management guidelines illustrates that the mere existence of these resources as a means of ensuring optimal pain management is insufficient. Creative pain management educational initiatives are needed to address the disparity between physician confidence and competence.
Midazolam as an antiemetic in patients receiving epidural morphine for postoperative pain relief
Authors: Elhakim, MD Mokhtar , Elfattah, MD Hany Abd , El-Din, MD Dalia Nasr , El-Kabarity, MD Reem , Atef, MD Azia , El-Fakey, MD Atef
Published: February 2018

Purpose: Epidural morphine has been associated with a significant incidence of postoperative nausea and vomiting (PONV). The authors have evaluated the prophylactic effects of midazolam in preventing nausea and vomiting following epidural morphine for postoperative pain control.Methods: The authors studied 80 women (n = 40 in each group) undergoing total abdominal hysterectomy under epidural anesthesia, in a randomized, double-blind, placebo-controlled study. At the end of the surgery, all patients received epidural morphine 3 mg for postoperative pain. Before morphine injection, the midazolam group received lowdose midazolam infusion (1 mg bolus followed by 1 mg h-1), while the placebo group received IV saline.Results: Patients in the midazolam group reported a lower incidence of total PONV, and a lower frequency of rescue antiemetic request than those in the placebo group (p < 0.05). In addition, midazolam was associated with a reduced incidence of pruritus following epidural morphine (p < 0.05).Conclusion: The authors conclude that low-dose midazolam infusion is effective in the prevention of nausea, vomiting, and pruritus following epidural morphine for postoperative pain control.
Safety and effectiveness of coadministration of intrathecal sufentanil and morphine in hyperbaric bupivacaine-based spinal anesthesia for cesarean section
Authors: Draisci, MD Gaetano , Frassanito, MD Luciano , Pinto, MD Raffaella , Zanfini, MD Bruno , Ferrandina, MD Gabriella , Valente, MD Alessio
Published: February 2018

Subarachnoid block is a widely used technique for cesarean section. Opioids adding to the local anesthetics can improve its quality. In this prospective, randomized, double blind, controlled trial, we compared the effects of coadministration of intrathecal sufentanil and morphine with intrathecal sufentanil and a single administration of subcutaneous morphine. Sixty-four pregnant women scheduled for elective cesarean section under spinal anesthesia were assigned to two groups according to the way of administration of morphine: intrathecal sufentanil (5 μg) plus intrathecal morphine (150 μg) (ITM group), and intrathecal sufentanil (5 μg) plus single administration of 10 mg subcutaneous morphine (SCM group). In both groups, the local anesthetic used was hyperbaric bupivacaine 0.5 percent (10 mg). Both groups received 1 g acetaminophen every 6 hours. In the postoperative period, pain was recorded on a 0-100 visual analog scale (VAS) and intravenous tramadol (100 mg) was administered if VAS score was >40 mm. Collateral effects, such us nausea, itching, respiratory depression, and sedation were assessed. VAS scores at rest and on coughing were significantly higher in the SCM group than in the ITM group between 3 and 24 hours. The mean titrated dose of tramadol consumed was also significantly greater in the SCM group than in the ITM group (p < 0.05). The time to first administration of tramadol was lower in the SCM group versus the ITM group (p < 0.05). The incidence of nausea was significantly lower in the SCM group than in the ITM group (p < 0.05). There was no significant group difference in the incidence of pruritus (p > 0.05). In conclusion, coadministration of sufentanil and morphine into the subarachnoid space was effective and provided longer pain relief than intrathecal sufentanil plus a single injection of subcutaneous morphine, despite a higher incidence of side effects such as nausea and vomiting.
Methylnaltrexone reduced body weight gain in ob/ob mice
Authors: Yuan, MD, PhD Chun-Su , Wang, PhD Chong-Zhi , Attele, MD Anoja , Zhang, PhD Liu
Published: February 2018

Objective: Opioids may function to regulate food intake and body weight, an activity that could be predominantly centrally mediated. In this study, the authors evaluated the effects of a peripherally acting opioid receptor antagonist, methylnaltrexone, on weight changes in adult obese ob/ob mice.Results: After a 12-day treatment with naloxone 0.3 mg/kg, weight was reduced from 63.7 ± 1.1 g in the control group to 59.2 ± 0.9 g in the naloxone group (p < 0.05). After a 12-day treatment with methylnaltrexone 3.0 mg/kg, weight increase completely ceased. The body weight was 63.9 ± 1.0 g in the control group when compared with 55.9 ± 1.2 g in the drug group (p < 0.01). The effect of methylnaltrexone (1.0 mg to 3.0 mg/kg) on weight changes was dose-dependent (p < 0.01). Methylnaltrexone significantly reduced daily food intake (p < 0.05), but did not affect body temperature and energy expenditure. Using HPLC analysis, no detectable naltrexone levels were found in association with methylnaltrexone administration. Whether the observed methylnaltrexone effects are primarily related to the antagonism of endorphinergic system remains to be investigated.Conclusions: Our results suggest that the peripheral opioid mechanism contributes to modulating food ingestion and methylnaltrexone may have clinical importance in obesity management.
Comparison of the effect of adding remifentanil to patient-controlled tramadol or morphine for postoperative analgesia after major abdominal surgery
Authors: Unlugenc, MD Hakki , Tetiker, MD Sibel , Büyükkurt, MD Selim , Guler, MD Tayfun , Isik, MD Geylan
Published: February 2018

Objective: In this study, the authors investigated the effect of the addition of remifentanil to tramadol or morphine for patient-controlled analgesia (PCA).Design: Prospective, randomized, double-blind, controlled study.Setting: University Hospital.Patients, participants: The authors randomly allocated 133 patients undergoing major abdominal surgery to receive IV PCA with tramadol alone, tramadol plus remifentanil, morphine alone or morphine plus remifentanil.Interventions: Bolus doses of tramadol (0.2 mg/kg), tramadol (0.2 mg/kg) plus remifentanil (0.2 μg/kg), morphine (0.02 mg/kg), or morphine (0.02 mg/kg) plus remifentanil (0.2 μg/kg) were available every 10 minutes without time limit or background infusion.Main outcome measure(s): Discomfort, sedation, pain scores, side effects, and total and bolus tramadol and morphine consumption were recorded for up to 24 hours after the start of PCA.Results: Pain scores at rest and movement were greater with tramadol alone than in the other groups at 1, 2, and 6 hours (p < 0.0125). The addition of remifentanil reduced cumulative tramadol consumption at 6, 12, and 24 hours, but not morphine consumption. More patients required supplementary rescue analgesia with meperidine, and with greater dosage, with tramadol alone (p < 0.001), and the incidence of nausea was greater with tramadol alone. The addition of remifentanil not only significantly improved discomfort scores in remifentanil groups, but also increased the degree of sedation in morphine-remifentanil group.Conclusions: After major abdominal surgery, adding remifentanil to PCA tramadol resulted in better pain scores, lower analgesic consumption, and fewer side effects when compared with tramadol alone. However, analgesic outcome with remifentanil was not prominent in MR group as much as in TR group.
The use of opioids in a pregnant woman with lumbar disc herniation: A case report
Authors: Matsumoto, MD Emi , Yoshimura, MD Kazuaki , Nakamura, MD Eiichiro , Hachisuga, MD Toru , Kashimura, MD Masamichi
Published: February 2018

It is not easy to diagnose lumbar disc herniation during pregnancy due to the limitation of the examinations and it is also difficult to control the severe pain during this time. A pregnant woman with lumbar disc herniation was transferred to our hospital at the 23rd week of gestation. The pain was successfully controlled with opioids and epidural anesthesia. At the 35th week of gestation, she delivered a girl weighing 2316 g smoothly with an Apgar score of 8/9 without neonatal abstinence syndrome from morphine. In this case, opioid administration was found to be useful for perinatal care with lumbar disc herniation.
Interventional treatment of back pain in a patient with cancer
Authors: Sloan, MD Paul Alexander , Grider, DO, PhD J. S.
Published: February 2018

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Improvement of pain physicians’ practices of opioid management: Population-based urinary excretion data
Authors: Pesce, PhD, DABCC Amadeo , Crews, PhD Bridgit , Latyshev, MS Sergey , Mikel, PhD Charles , Almazan, CLS, MT (ASCP) Perla , West, MS Robert , Rosenthal, DO, FAPA Murray , West, PhD Cameron
Published: February 2018

Background: Physicians treating patients for chronic pain have limited means of determining whether a person is taking their medications as prescribed and are not taking extra medication. Complicating patient treatment regimens is the fact that pain physicians’ prescribing practices may come under scrutiny by the Drug Enforcement Agency and other licensing agencies. If questioned, doctors can be hard-pressed to substantiate that their particular practices meet the established standard of care. It would be helpful to establish that their patients adhere to medications when compared with other practices. Previous studies show that urinary excretion data transformed by mathematical models can produce a reliable range of expected values for pain medications and may be useful to help resolve the aforementioned issues.Purpose of the study: To provide comparative urinary excretion information data on three commonly prescribed opioid medications (morphine, hydrocodone, and oxycodone).Methods: This retrospective study involved quantitative analysis of 300,000 urine specimens for three test drugs using previously described methods. The results were analyzed as percent frequency distributions and logarithmic functions.Results: The authors established a creatinine-normalized range of urinary concentration values for each drug. Results for two practices were compared with the meta-findings, providing quantitative evidence of overall standard of care prescription practice by that physician.Conclusions: Expected urinary drug excretion values for morphine, hydrocodone, and oxycodone can potentially benefit pain physicians by showing that they are within the expected standard of care, helping to establish patient compliance, and identifying patients whose metabolism of these drugs may put them at risk.
THE ABUSE OF PRESCRIPTION MEDICATIONS: A RELATIONSHIP WITH BORDERLINE PERSONALITY?
Authors: Sansone, MD Randy A. , Lam, BS Charlene , Wiederman, PhD Michael W.
Published: February 2018

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THORACIC EPIDURAL ANALGESICS PROVIDE EXCELLENT CANCER PAIN RELIEF AT THE END OF LIFE
Authors: Sloan, MD Paul A.
Published: February 2018

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Role of codeine in palliative care
Authors: Prommer, MD Eric
Published: February 2018

Codeine is designated as one of the essential medicines of palliative care for symptoms such as pain and diarrhea. Essential drugs for palliative care are drugs that are effective for the treatment of common symptoms in palliative medicine, easily available, and are affordable. Codeine is recommended for the management of mild to moderate pain and is available as a combination product or as a stand-alone opioid. It is a prodrug and exhibits an affinity to μ-opioid receptors 200 times lower than morphine. Codeine is metabolized in the liver to inactive metabolites, which account for 90 percent of the transformed product, and morphine, which accounts for 10 percent of the transformed product and provides the main analgesic effect. The production of morphine is dependent on cytochrome oxidase 2D6 enzyme activity, which may not be fully active in some populations. The purpose of this review is to examine the efficacy of codeine for common symptoms encountered in palliative medicine, which has led to its designation as an essential medicine for palliative care.
Primary care survey of the value and effectiveness of the Washington State Opioid Dosing Guideline
Authors: Morse, MPH Josiah S. , Stockbridge, MD, MPH Hal , Egan, MPH Kathleen B. , Mai, PharmD Jaymie , Wickizer, PhD Thomas , Franklin, MD, MPH Gary M.
Published: February 2018

Purpose: To evaluate the acceptability and usefulness of the Washington State Opioid Dosing Guideline (Guideline) developed for primary care providers for the treatment of chronic noncancer pain. The Guideline contains innovative tools, such as an online dosing calculator, and recommendations to assist providers, including a “yellow flag” threshold of 120 mg/d morphine equivalent dose (MED) at which specialty consultation is recommended.Methods: Using a convenience sample, an anonymous web-based survey was conducted among primary care providers in Washington (WA) state. Physician/administrative leaders in four regional and two statewide healthcare systems and associations distributed the electronic links to primary care providers in their organizations.Results: Six hundred fifty-five (n) providers completed the survey representing 20 percent of the total number contacted. The majority (89 percent) of providers in this sample treat chronic pain patients, and more than half (54 percent) have frequent concerns about addiction, tolerance, and diversion. Forty-five percent had read and applied the Guideline in their practice. The majority of these providers found the Guideline to be helpful and 86 percent find the threshold of 120 mg/d MED dose reasonable or too high. Some key best practices such as tracking pain and function using structured instruments and use of urine drug testing are infrequently used.Conclusions: Results from this survey suggest that the recommendations and tools given in the Guideline, including the threshold of 120 mg/day MED dose, are acceptable and useful to a large majority of primary care providers in WA state. Substantial additions to the Guideline based on needs identified in this survey were added in June 2010 and wider dissemination is planned.
Plasma cyclic guanosine 3′,5′-monophosphate levels: A marker of glutamate-nitric oxide-guanyl cyclase activity?
Authors: Engelhardt, MD, PhD, FRCA Thomas , Zaarour, MD Christian , Crawford, MBBS, FRCPC Mark W.
Published: February 2018

Objectives: Remifentanil-based anesthesia can lead to acute opioid tolerance and/or hyperalgesia. A low-dose intraoperative infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine did not result in reduced postoperative morphine consumption after remifentanil-based anesthesia in adolescents. This study investigates the potential role of the glutamate-nitric oxide-cyclic guanosine 3′,5′-monophosphate (cyclic GMP) pathway in the failure of low-dose ketamine to prevent remifentanil-induced acute opioid tolerance and/or hyperalgesia.Design and setting: Prospective, double-blind, placebo-controlled randomized clinical trial at a university teaching hospital.Patients, participants, and interventions: Thirty-four adolescents receiving remifentanil-based anesthesia for surgical correction of idiopathic scoliosis were randomly assigned to receive either intraoperative ketamine administered as a bolus dose of 0.5 mg/kg in 10 mL of normal saline and a continuous intravenous infusion of 4.0 μg/kg/min or an equal volume of saline.Main outcome measures: Blood samples were collected before and after the administration of ketamine for analyzing the concentrations of cyclic GMP, ketamine, and norketamine. Blood samples were analyzed using high-performance liquid chromatography and an enzyme immunoassay.Results: The median (interquartile range) value of the concentration of plasma cyclic GMP decreased from 23.7 (17.4-26.7) to 14.8 (14.0-17.3) nmol/L after ketamine infusion (p < 0.005) and from 23.9 (16.3-29.2) to 16.3 (14.5-18.6) nmol/L after saline infusion (p < 0.005). The median value of the concentration of plasma cyclic GMP at the end of ketamine infusion did not differ significantly when compared with that after saline infusion (p = 0.07). The concentration of plasma cyclic GMP was inversely correlated with the concentration of plasma ketamine (r = −0.61).Conclusions: This study suggests that the low dose of intraoperative ketamine infused was insufficient to suppress the NMDA receptor pathway. The concentrations of plasma cyclic GMP may serve as an indirect biological marker of ketamine-induced NMDA receptor antagonism.
Prolonged QT interval by methadone: Relevance for daily practice? A prospective study in patients with cancer and noncancer pain
Authors: Van den Beuken-van Everdingen, MD, PhD Marieke H. J. , Geurts, MSc José W. , Patijn, MD, PhD Jacob
Published: February 2018

Introduction: Increased methadone use in patients with pain has raised concerns that the effect of methadone on the QT interval duration and the potential risk of torsades de pointes (TdP) has been underestimated. Most studies on prolonged QT intervals by methadone are performed in maintenance patients; however, doses of methadone in pain treatment are much lower. Hardly any studies have prospectively addressed QT interval prolongation by methadone in patients with pain, and this study aims to address this literature gap. Methods: In a period of 3 years, while 130 patients used methadone as pain treatment at a stable dose for at least 1 week, 12-lead electrocardiograms (ECGs) were performed. Corrected QT times, demographic features, methadone dose, duration of therapy, and relevant comedication were documented.Results: The findings included 50 percent of 130 patients, with a mean methadone dose of 18.2 mg/d, were potentially at risk for TdP. Beyond this, 5 percent were at definite risk for TdP. No correlations were found between QTc and gender, age, serum potassium or magnesium levels, methadone dose, underlying disease, or comedication.Conclusion: The study found that in our patients with pain, with relatively low doses of methadone, 5 percent had QTc times ≥500 ms and were thus at serious at risk for TdP. ECGs have to be made in all patients with methadone therapy 1 week after introducing methadone (or after dosage increases).
Effect of intraoral and subcutaneous morphine on dyspnea at rest in terminal patients with primary lung cancer or lung metastases
Authors: Gamborg, RN Helle , Riis, RN Jette , Christrup, MSc (Pharm), PhD Lona , Krantz, MD Torben
Published: February 2018

Background: Dyspnea is considered as one of the most frequent and distressing symptoms in patients with advanced cancer, and systemic administration of morphine has been reported to have beneficial effect on this complaint. Aim and design: The effect of red morphine drops (RMD) given orally and kept in the mouth as long as possible before swallowing to alleviate dyspnea was compared to the effect of morphine given subcutaneously (SCM) in a double-blind, double-dummy trial.Participants: Twenty consecutive terminally ill patients with primary lung cancer or lung metastases admitted to Sankt Lukas Hospice were included in the study. All patients had dyspnea at rest, and they received either 1/12 of their 24-hour morphine dose as RMD or 60 percent of this dose as SCM. Perceived breathlessness was evaluated on a Visual Analogue Scale (VAS) during a 60 minutes observation time, and pulse rate, respiratory rate and oxygen saturation were assessed as well.Results: Compared to baseline both RMD and SCM showed a small, but statistical significant effect on VAS (mean decrease of 1.1 [RMD] and 1.7 [SCM]) and pulse rate (mean decrease of 4 per minute [RMD] and 6 per minute [SCM]), the effect being significantly larger after SCM.Conclusions: The study confirms the beneficial effect of morphine on dyspnea in terminally ill patients, and we conclude that RMD is an attractive alternative to injected morphine, when self-administration is preferable.
Educational gaps among healthcare providers: An institution needs assessment to improve pain management for postsurgical patients
Authors: González-Fernández, MD, PhD Marlís , Aboumatar, MD, MPH Hanan , Conti, RN, MS Deena , Patel, MD Amit M. , Purvin, MD Michael A. , Hanna, MD Marie
Published: February 2018

Objective: Nurses should be educated in pain management because they are more likely than other healthcare professionals to educate patients about their pain. The authors sought to identify the knowledge gaps in postoperative pain management among postsurgical nursing staff and the existence of institutional policies and educational programs to support them in delivering optimal pain management services.Setting: Academic hospital.Participants: Two hundred seventy-seven registered nurses, nurse practitioners, nurse managers, physician assistants, and other health professionals.Interventions: Nurses participated in an online, anonymous survey that consisted of 43 questions in two broad categories: (1) knowledge and attitudes about pain management and (2) institutional pain management and assessment.Main Outcome Measure: Knowledge base of surgical nursing staff regarding postoperative pain management.Results: The overall mean knowledge score was 44.84 percent, with the highest percent of correct answers in the cancer pain category (54.03 percent). Recognition of signs and symptoms of pain had the lowest correct response rate (40.91 percent). Forty-nine percent of respondents reported that pain management protocols tailored to the specific population treated were available, 42 percent reported that patient pain education was always performed, 29 percent reported that they received regular training about pain management, and 17 percent had access to national pain management guidelines.Conclusion: The survey results demonstrate general gaps in pain management knowledge among nurses, particularly in recognizing signs and symptoms of pain. This work may guide the development of programs that improve postoperative pain management by increasing the frequency of nurses' pain education and improving the availability of pain-related policies and protocols.