bluuebunny/crossref_metadata_2025 huggingface dataset:
Arrested on heroin: A national opportunity
Authors: Boutwell, MD, MPP Amy E. , Nijhawan, MD Ank , Zaller, PhD Nickolas , Rich, MD, MPH Josiah D.
Published: February 2018

Objectives: Heroin addiction in the United States exacts significant social, economic, medical, and public health costs, estimated at almost $22 billion in 1996. The national drug control strategy of arrest and mandatory sentencing of drug offenders over the past two decades has resulted in ever greater numbers of drug users who encounter the criminal justice system each year. No estimate of heroin use among the US incarcerated population exists. The authors attempted to estimate the proportion of heroin-using individuals who pass through the corrections system annually to determine the potential impact of interventions designed to link heroin-using individuals to addiction treatment.Methods: The authors constructed an estimate by employing the following elements: arrestee drug-testing data, total number of arrests, an estimate of the mean annual number of arrests in a drug-using population, estimates of arrestees incarcerated, and estimates of heroin use and addiction in the US population. The authors present each component of the estimate and how it was derived, and conclude by discussing the degree of uncertainty in the estimates and the implications of our results for policy makers.Results: Using a conservative estimate, the authors found that 24 percent to 36 percent of all heroin addicts pass through the corrections system each year, representing more than 200,000 individuals.Conclusions: Viewed as a public health opportunity, effective linkage to addiction treatment could ultimately reduce the costs associated with poor health, disease transmission, criminality, and recidivism that heroin use exacts on individuals and communities.
Opioid administration for acute abdominal pain in the pediatric emergency department
Authors: Klein-Kremer, MD Adi , Goldman, MD Ran D.
Published: February 2018

The use of opioid analgesia for acute abdominal pain of unclear etiology has traditionally been thought to mask symptoms, alter physical exam findings, delay diagnosis, and increase morbidity and mortality. However, studies in children and adults have demonstrated that administering intravenous opioids to patients with acute abdominal pain induces analgesia but does not delay diagnosis or adversely affect diagnostic accuracy. This review discusses the effects of opioid administration on pain relief and diagnostic accuracy in children with moderate to severe acute abdominal pain who have been evaluated in the emergency department. We hold that current evidence supports the administration of opioids to children with acute abdominal pain, and future trials will help determine safe and effective timing and dosing related to opioid administration.
Developmental pharmacokinetics of opioids in neonates
Authors: Allegaert, MD, PhD Karel , Simons, MD, PhD Sinno H. , Vanhole, MD, PhD Christine , Tibboel, MD, PhD Dick
Published: February 2018

Recognition and treatment of pain are now important indicators of the quality of care being delivered to neonates. However, population-specific characteristics have to be considered, necessitating an integrated, population-specific approach. Such an approach starts with a systematic evaluation of pain, using a validated pain-assessment instrument, and should be followed by effec-tive interventions, mainly based on appropriate, i.e, safe and effective, administration of analgesics. We will illustrate the impact of age on the pharmacokinetics and metabolism of opioids using recently collected and reported observations of tramadol disposition in early neonatal life. Although distribution volume and clearance display age-dependent maturation, it is important to recognize that important, unexplained interindividual variability in drug metabolism is still observed. Research questions in the field of developmental pharmacokinetics of opioids should focus on covariables of relevance in the interindividual variability of both pharmacokinetics and pharmacodynamics of opioids in neonates and on long-term outcomes in preterm and term neonates to whom opioids were administered, with regard to behavioral consequences and effects on pain thresholds.
Urine drug test interpretation: What do physicians know?
Authors: Reisfield, MD Gary M. , Bertholf PhD Roger , Barkin, MBA, PharmD Robert L. , Webb, PhD Fern , Wilson, MD George
Published: February 2018

Objective: To determine the level of urine drug test (UDT) interpretive knowledge of physicians who use these instruments to monitor adherence in their patients on chronic opioid therapy.Methods: A seven-question instrument consisting of six five-option, single-best-answer multiple choice ques¬tions and one yes/no question was completed by 114 physicians (77 who employ UDT and 37 who do not) attending one of three regional opioid education confer¬ences. We calculated frequencies and performed %2 analyses to examine bivariate associations between UDT utilization and interpretive knowledge.Results: The instrument was completed by 80percent of eligible respondents. None of the physicians who employ UDT answered all seven questions correctly, and only 30 percent answered more than half correctly. Physicians who employ UDTperformed no better on any of the ques¬tions than physicians who do not employ UDT.Conclusions: Physicians who employ UDT to monitor patients receiving chronic opioid therapy are not profi¬cient in test interpretation. This study highlights the need for improved physician education; it is imperative for physicians to work closely with certified laboratoryprofes- sionals when ordering and interpreting these tests.
Using methadone to treat opioid-induced hyperalgesia and refractory pain
Authors: Axelrod, MD, JD David J. , Reville, MS, CRNP Barbara
Published: February 2018

A patient was treated for several years with high doses of opioids for malignant pain. During a recent hospitalization, the patient’s pain remained uncontrolled despite escalating doses of various opioids. We suspected that this patient suffered from the clinical phenomenon of opioid-induced hyperalgesia (OIH). The patient was then rotated from her other opioids to methadone, and her pain was adequately controlled within several days. Methadone, because of its NMDA antagonist properties, offers an effective treatment for OIH. The use of methadone for analgesia is complex and should be undertaken only by practitioners who have appropriate experience.
Prevalence of opioid dependence in spine surgery patients and correlation with length of stay
Authors: Walid, MD, PhD Mohammad Sami , Hyer, PhD Leon , Ajjan, MD Mohammed , Barth Aaron C. M. , Robinson, Jr, MD Joe Sam
Published: February 2018

Objective: We addressed the prevalence of opioid dependence (OD) in spine surgery patients and its correlation with length of stay (LOS) as the most important determinant of hospital cost.Methods: The study took place at Georgia Neurosurgical Institute and the Medical Center of Central Georgia between March 2006 and January 2007. A prospective convenience sample of 150 spine surgery patients (48 lumbar diskectomy, 60 cervical decompression and fusion, and 42 lumbar decompression and fusion [LDF]) was assembled. Patients were interviewed before surgery using a questionnaire designed in accordance with the World Health Organization and DSM-IV-TR criteria for the diagnosis of OD. The prevalence of OD was calculated based on questionnaire results. Pain intensity was quantified during admission using a 0-to-10 pain scale. We used pain intensity multiplied by duration of pain in months (WR index) as a new parameter. Lengths of stay were collected following patients’ discharge from hospital. Pearson correlation and regression analysis were performed using SPSS software.Results: Thirty (20.00 percent) patients were opioid dependent. The prevalence was highest among LDF patients (23.81 percent), females (22.78 percent), and, to a lesser degree, Caucasians (20.87percent). There was no correlation between OD and age (r = 0.08, p > 0.1) or between OD and LOS (r = 0.09, p > 0.1). This study proved a very significant positive correlation between OD and pain intensity (r = 0.24, p < 0.01) and between OD and the WR index (r = 0.30, p < 01). On the other hand, there was a significant positive correlation between LOS and age(r= 0.42, p < 0.01), between LOS and the number of previous spine surgeries (r = 0.28, p < 01), and between LOS and duration of pain (r = 0.18, p < 0.05). Regression analysis showed that age, ethnicity, and type of surgery were the main determinants of LOS.Conclusions: Chronic pain and prolonged use of opioids raise the prevalence of OD in spine surgery patients to 20 percent. The lack of effect of OD on LOS after surgical intervention means that efforts to decrease LOS by trying to satisfy patients’ craving for opioids will not be fruitful. Older, African-American LDF patients with a lengthy history of pain and multiple spine surgeries in the past are the most likely to stay longer in hospital.
Do pain specialists meet the needs of the referring physician? A survey of primary care providers
Authors: Wilkens, MD Jane R. , Belgrade, MD Miles J.
Published: February 2018

Objective: To study the factors that influence the use of opioids in the management of chronic noncancer pain (CNCP) by primary care providers (PCPs) for patients returning from a pain specialist.Design: A survey of PCPs.Setting: Two physician groups in the Minneapolis-St. Paul metropolitan area.Participants: Two seventy-six PCPs surveyed and 80 surveys returned. Main outcome measures: Participants rated the importance of specific concerns regarding the role of pain specialists and the use of opioids in the management of CNCP. Past experience with pain specialists, comfort using opioids, and opinions regarding a trilateral opioid agreement were also examined.Results: The top concerns for PCPs were as follows: the use of opioids in patients with chemical dependency or psychological issues, the escalation of opioid dosing, and the use of opioids in pain states without objective findings. They also ranked highly the importance of coordinating the return of patients from a pain specialist with explicit opioid instructions and the availability of consultation by phone or a timely follow-up visit. PCPs were supportive of the concept of a trilateral opioid agreement.Conclusions: PCPs have significant concerns regarding the prescribing of opioids in CNCP. They desire closer collaboration with pain specialists, including more explicit plans of care when patients are transferred back to them. The trilateral agreement may provide one framework for better collaboration.
Patients with chronic pain on opioid therapy taking dronabinol: Incidence of false negatives using radioimmunoassay
Authors: Narang, MD Sanjeet , Wasan, MD, MSc Ajay D. , Ross, MD Edgar L. , Michna, MD Edward , Chen, MD Jui-Yuan , Jamison, PhD Robert N.
Published: February 2018

Background: Serum blood toxicology screens are believed to be important to monitor compliance and to identify levels of illicit substances in patients taking opioids for their chronic pain.Methods: In this study, the authors examine the incidence of tetrahydrocannabinol (THC) in consecutive blood samples of patients given dronabinol. We assessed the incidence of THC in 27 patients who participated in a single-dose, double-blind crossover trial of dronabinol (Marinol® capsules), a synthetic Δ9-THC, as part of a larger study, to determine the reliability of the toxicology screening. Subjects were randomly administered 10 mg or 20 mg of dronabinol or placebo over the course of three 8-hour visits for a combined 228 serum blood samples. Levels of THC were quantified using radioimmunoassay.Results: The majority of the samples (57.4 percent) showed presence of study drug as expected. However, 43 samples (42.6 percent) showed no detectable evidence of THC 4 and 8 hours after administration of dronabinol. Five subjects showed lower serum levels on the higher dose (20 mg) than on the lower dose (10 mg) after 4 hours, and two subjects showed lower levels with the higher dose after 8 hours. One subject had no detectable THC on any dose of dronabinol.Conclusions: These toxicology reports point to higher than anticipated false-negative results with radioimmunoassay blood serum screening. Results could be explained by the lower sensitivity of this screening technique and also in how oral cannabinoids are metabolized. Further investigations are needed on the accuracy of the detection of THC among patients known to have used dronabinol.
Effect of buprenorphine on psychomotor functions in patients on buprenorphine maintenance
Authors: Singhal, MBBS, MD, MRCPsych Ankush , Tripathi, MBBS, MD, MRCPsych B.M. , Raj Pal, MBBS, MD Hem , Jena, PhD Renuka , Jain, MSc, PhD, Cchem, FRSC Raka
Published: February 2018

Objective: Patients on buprenorphine maintenance for opioid dependence often abuse its additional doses over and above the maintenance dose. Being a psychoactive agent, it may affect psychomotor performance with all its consequences, for example, effect on quality of life. This study was conducted to assess the effects of its additional doses on psychomotor performance in patients who are maintained on it.Design and Setting: This was an interventional study, carried out in an in-patient setting in a tertiary care national drug dependence treatment center.Participants: It included 19 subjects maintained on buprenorphine, 4 mg/d (s/L) for at least a month.Intervention: Maintenance dose was followed by three administrations of buprenorphine, 2 mg, at two hourly intervals (cumulative dose design).Main Outcome Measures: Subjects were assessed on digit symbol substitution test, trail making, digit span, and delayed recall, after each administration and the next morning. Results: Performance of subjects on Digit Symbol Substitution Test (χ2 = 52.98, p < 0.000) and Trail Making Test-A (χ2 = 26.29, p < 0.000) and B (χ2 = 42.08, p < 0.000) improved significantly with each assessment while other tests were unaffected.Conclusions: Improvement in psychomotor performance (which could be true effect of drug itself or a result of other factors, eg, inadequate maintenance dose or practice effect) though contrasting with some of the earlier findings, does have significant clinical implications regarding the long-term use of buprenorphine. It would be worthwhile repeating this type of study in a placebo controlled design to further verify the results.
Very-low-dose ketamine for the management of pain and sedation in the ICU
Authors: De Pinto, MD Mario , Jelacic, MD Jill , Edwards, PhD, MD William T.
Published: February 2018

Management of pain in critically ill patients can be very difficult. In the attempt to provide comfort with adequate levels of opioids and sedatives, respiratory depression and cardiovascular instability may become difficult to control in patients with labile hemodynamics and poor cardiopulmonary reserve. The use of medications like ketamine, an anesthetic agent that in subanesthetic doses has been reported to be effective in preventing opioidinduced tolerance and to have analgesic properties, may be of help, especially in patients who develop tolerance, leading to rapidly escalating doses of opioids and sedatives. The case report presented here shows how a very low dose of ketamine can be helpful for the management of pain and sedation in critically ill patients, especially when they are ready to be weaned from mechanical ventilation, and very high doses of opiods and sedatives do not permit it.
Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain
Authors: Vorsanger, PhD, MD Gary J. , Xiang, PhD Jim , Gana, MD, PhD Theophilus J. , Pascual, MD, MPH Maria Luz G. , Fleming, MS R. Rosanna B.
Published: February 2018

Background: This study evaluated the safety and efficacy of tramadol ER 300 mg and 200 mg versus placebo once daily in the treatment of chronic low back pain, using an open-label run-in followed by, without washout, a randomized controlled study design.Methods: Adults with scores ≥40 on a pain intensity visual analog scale (VAS; 0 = no pain; 100 = extreme pain) received open-label tramadol ER, initiated at 100 mg once daily and titrated to 300 mg once daily during a three-week open-label run-in. Patients completing run-in were randomized to receive tramadol ER 300 mg, 200 mg, or placebo once daily for 12 weeks.Results: Of 619 patients enrolled, 233 (38 percent) withdrew from the run-in, primarily because of adverse event (n = 128) or lack of efficacy (n = 41). A total of 386 patients were then randomized to receive either 300 mg (n = 128), 200 mg (n = 129), or placebo (n = 129). Following randomization, mean scores for pain intensity VAS since the previous visit, averaged over the 12-week study period, increased more in the placebo group (12.2 mm) than in the tramadol ER 300-mg (5.2 mm, p = 0.009) and 200-mg (7.8 mm, p = 0.052) groups. Secondary efficacy scores for current pain intensity VAS, patient global assessment, Roland Disability Index, and overall sleep quality improved significantly (p ≤ 0.029 each) in the tramadol ER groups compared with placebo. The most common adverse events during the double-blind period were nausea, constipation, headache, dizziness, insomnia, and diarrhea.Conclusions: In patients who tolerated and obtained pain relief from tramadol ER, continuation of tramadol ER treatment for 12 weeks maintained pain relief more effectively than placebo. Adverse events were similar to those previously reported for tramadol ER.
Role of patient-based health status outcome measurements in opioid management for low back pain
Authors: Podichetty, MD, MS Vinod K. , Varley, DO Eric S. , Secic, MS Michelle
Published: February 2018

Objective: The aim of the study was to identify patient factors that correlate with a strong response to opioid pain medications in low back pain patients.Design: Prospective analysis.Setting: Tertiary Institutional Spine Care Center.Patients, Participants: All patients visiting a tertiary referral spine center with primary diagnosis of low back pain (n = 486) and minimum duration of 6 months.Interventions: Opioid medication.Main Outcome Measures: Analysis factors included visual analog pain scale (VAS), symptom relief scores, and results on 36-item Short Form Health Survey (SF-36). A longitudinal descriptive analysis and a multivariable logistic regression were performed on the results of the VAS and SF-36 scores.Results: The average age of opioid and nonopioid treated patients was 62 years versus 64 years, (p = 0.13) and gender distributions at 53 percent versus 50 percent female (p = 0.43). SF-36 scores were statistically significant and associated with the opioid categorization. For every unit increase in symptom relief score, the likelihood of opioid use is doubled (OR = 2.1, 95 percent CI = 1.5-2.8, p < 0.001); and increased by 25 percent with each 10-point decrease in the social functioning quality of life score (OR = 0.98, 95 percent CI = 0.96-0.99, p = 0.006).Conclusions: Social quality of life and symptom relief measurements comprise the optimal set of independent factors that correlate most strongly with a response to opioid use in low back pain patients.
Tapering chronic opioid therapy in neuropathic facial pain: An interdisciplinary approach
Authors: Chandwani, BDS, FOP Brijesh P. , Kulich, PhD Ronald J. , Andrew, PhD Lainie , Scrivani, DDS, DMedSc Steven
Published: February 2018

This case report presents a patient with chronic orofacial pain who was considered to be an appropriate candidate for chronic opioid therapy, a treatment uncommonly considered at most facial pain centers. Her opioid treatment proved ineffectual, and conservative approaches were addressed. She was successfully tapered off the use of a long-acting opioid within a relatively short time, using an interdisciplinary approach involving an aggressive biobehavioral approach.
Management of chronic nonmalignant pain: A needs assessment in an Internal Medicine Resident Continuity Clinic
Authors: Yanni, MD Leanne M. , Weaver, MD Michael F. , Johnson, MD, PhD Betty A. , Morgan, PharmD Laura A. , Harrington, MD Sarah E. , Ketchum, PhD Jessica M.
Published: February 2018

Introduction: The authors hypothesized that Internal Medicine (IM) residents experience a lack of preparation, confidence, and reward when managing patients with chronic nonmalignant pain (CNMP) in their continuity clinic and that they exhibit deficiencies in CNMP management practices, particularly when opioids are prescribed.Methods: As part of a quality improvement project in the IM resident continuity clinic, the authors performed a needs assessment through a self-administered resident questionnaire and a retrospective chart review.Results: Fifty-seven percent of respondents rated their CNMP preparation as “fair” or “poor,” 89 percent reported that their experience was “much less” or “somewhat less” rewarding than managing patients with other chronic conditions, and 58 percent reported that CNMP management “negatively” or “very negatively” affected their view of primary care as a career. Twenty-eight charts of patients receiving opioids during a 1-year study period were reviewed. Although residents were likely to document pain diagnoses (93 percent) and pain scores (82 percent) as well as utilize medication agreements (82 percent), they were less likely to document illicit substance use (39 percent), document legal history (32 percent), or obtain prior medical records (39 percent). Few urine drug screens were ordered (18 percent) and 25 percent of patients had fewer than four face-to-face visits during the year.Discussion: The questionnaire indicated that IM residents lack preparation in managing CNMP, which results in lack of confidence and reward. The chart review revealed management practice deficiencies in risk assessment and prescription drug misuse monitoring. As a result, the authors have implemented curricular interventions, integrated a pain clinic within the continuity clinic, optimized residency program clinic scheduling, and developed tools for consistency in management practices.
Opioid rotation in patients with cancer: A review of the current literature
Authors: Vadalouca, MD, PhD, FIPP Athina , Moka, MD Eleni , Argyra, MD, PhD Erifilli , Sikioti, MD Panayiota , Siafaka, MD, PhD Ioanna
Published: February 2018

Cancer is a public health problem worldwide and a major cause of death or disability. Pain is one of the most common and feared symptoms in patients with cancer with marked impact on quality of life. According to the WHO analgesic ladder, opioids are the mainstay of cancer pain management, if well-accepted guidelines are systematically applied. Oral morphine has been widely used in treating cancer pain of moderate to severe intensity and remains the preferred first choice to many clinicians for its familiarity/availability/costs. However, a significant proportion of patients under oral morphine do not have successful outcomes, often switched to alternative strong opioids. Opioid rotation is a therapeutic maneuver aiming in improving analgesic response and/or reducing adverse effects, including change to different medication using the same administration route, maintaining the current medication but altering administration route, or both. In this review, a detailed presentation of the available literature, regarding opioid rotation strategy, up to now is performed. Indications, principles, opioid doseconversion recommendations, and guidelines in oncology patients are presented. An outline of the evidence supporting the use of this therapeutic modality on clinical benefit/outcome is attempted. Mechanisms contributing to patients’ variable opioid response are underlined. Since 1/3 of population will die from cancer (80 percent with severe pain in their final year of life), effective pain control remains an ongoing challenge. Opioid rotation may be useful in opening the therapeutic window and establishing a more advantageous analgesia/toxicity relationship. However, too much work is to be done to further individualize analgesic therapy for patients with cancer.
Intrathecal drug delivery for management of cancer and noncancer pain
Authors: Simpson, FRCA Karen H. , Jones, FRCA Iain
Published: February 2018

Intrathecal drug delivery (ITDD) has been an option for the management of persistent pain since the 1980s. The discovery of opioid receptors in the central nervous system was the impetus for early attempts to deliver opioids intraspinally. Approximately, 10-20 percent patients with cancer pain get inadequate analgesia from conventional medical management; this group particularly may benefit from ITDD. However, there is also some evidence for the use of ITDD in those with noncancer pain. This review presents options for ITDD, available drugs, evidence for efficacy, principles of patient selection, and problems with the intrathecal route.
Balanced anesthesia with remifentanil and desflurane: Clinical considerations for dose adjustment in adults
Authors: Nöst, MD Ralph , Thiel-Ritter, MD Antje , Scholz, MD Stefan , Hempelmann, MD Gunter , Müller, MD Matthias
Published: February 2018

Background: The intraoperative combination of volatile anesthetics with opioids is a well-accepted technique because of its hemodynamic stability and side effects. This study in adults was designed to determine the pharmacodynamic interactions between different dosages of remifentanil and desflurane in response to skin incision.Methods: A total of 60 patients were enrolled in this study. Patients were prospectively randomized to receive 0, 0.1, 0.15, or 0.25 μg/kg/min remifentanil. Anesthesia was induced with remifentanil, propofol, and succinylcholine. Thereafter, a group-specific desflurane concentration was administered using Dixon’s up-and-down technique. After a “wash out” and equilibration period, patients were observed for defense movements up to 1 minute after skin incision. Mean arterial pressure and heart rate were recorded before induction of anesthesia (baseline), at surgical incision, as well as 2 and 4 minutes thereafter. Time until extubation was assessed after stopping desflurane and remifentanil at the end of the surgery.Results: Remifentanil at 0.1, 0.15, or 0.25 μg/kg/min reduced desflurane requirements by 74, 83, and 90 percent, respectively. The time course of mean arterial pressure did not differ between the study groups. However, compared with the group without remifentanil, heart rate was significantly lower in patients receiving 0.15 or 0.25 μg/kg/min remifentanil. No difference between the groups was observed with regard to extubation time.Conclusion: Remifentanil reduces in a dose-dependent manner the desflurane requirements for skin incision without increasing recovery time. An infusion rate higher than 0.1 μg/kg/min results in a significantly decreased heart rate.
Effects of perineural tramadol on sensory and motor conduction of ulnar nerve
Authors: Öztürk, MD Ertan , Zinnuroğlu, MD Murat , Ali Sezer, MD Özer , Gökyar, MD İsmail , Beyazova, MD Mehmet , Kaya, MD Kadir
Published: February 2018

Study objective: We aimed to study the effects of perineural tramadol on both sensory and motor conduction of ulnar nerve by electroneurography (ENG).Design: Prospective.Setting: Physical Medicine and Rehabilitation Electrophysiology Laboratory.Patients: Eight healthy volunteers.Intervention: Either 3-mL of saline or 50 mg of tramadol in 3-mL saline was initially administered perineurally to ulnar nerve of nondominant extremity. After two weeks, volunteers who received tramadol were given saline, whereas the ones who received saline were given tramadol.Measurements: Baseline sensory and motor responses of ulnar nerve were recorded by ENG prior to injection of study solutions. Perineural injections were realized by means of a teflon-coated needle and a nerve stimulator. Following injections, sensory and motor responses were monitored every five minutes in the first hour and then every 10 minutes until the sensory and motor amplitudes reached at least 80 percent of the baseline value.Main Results: Perineural tramadol administration showed a significant decrease from baseline measurement in the sensory response amplitude with respect to saline administration (65.9 percent vs 12.7 percent, p < 0.05). Decrease in the motor response amplitudes from baseline versus saline was insignificant (32.9 percent vs 15.2 percent). Sensory block was observed in all of the subjects after tramadol injection when compared with saline administration and lasted 25 minutes (p < 0.05). The duration of motor block lasted 12.5 minutes, and motor block developed in four out of eight subjects when compared with saline administration (p < 0.05). Time to reach maximum sensory and motor block were 15 and 10 minutes, respectively, after tramadol injection.Conclusions: Tramadol has a brief local anesthetic-like action when administered to ulnar nerve perineurally.
Influence of prior opioid exposure on diagnostic facet joint nerve blocks
Authors: Manchikanti, MD Laxmaiah , Boswell, MD, PhD Mark V. , Manchukonda, BDS Rajeev , Cash, RT Kimberly A. , Giordano, PhD James
Published: February 2018

Objective: To determine the influence of prior opioid use on the diagnostic validity of controlled comparative local anesthetic blocks in the diagnosis of facet joint involvement in chronic spinal pain.Methods: Data were evaluated from 438 patients with chronic spinal pain who underwent diagnostic facet joint nerve blocks. Patient data were divided into four groups based on the level of opioid use: group I (no opioid use), group II (low opioid use), group III (moderate opioid use), and group IV (high opioid use). Facet joint involvement was diagnosed utilizing controlled comparative local anesthetic blocks with 1 percent preservative- free lidocaine and 0.25 percent preservative-free bupivacaine.Results: Prior and current opioid use did not show relationship to the diagnostic validity of controlled comparative local anesthetic blocks. Among patients not using opioids (group I), the prevalence of facet joint pain was shown to be 33 percent in the cervical spine, 40 percent in the thoracic spine, and 18 percent in the lumbar spine, with false-positive results with a single lidocaine block of 53 percent, 33 percent, and 54 percent, respectively. Facet joint involvement in patients with opioid use ranged from 37 percent to 53 percent in the cervical spine, 13 percent to 67 percent in the thoracic spine, and 28 percent to 33 percent in the lumbar spine.Conclusions: Overall, this evaluation demonstrated that current or prior opioid use is not associated with interference of the validity of controlled comparative local anesthetic blocks in diagnosing spinal facet jointrelated pain.
Cancer pain management at a tertiary care cancer center in India—A retrospective analysis of 3,238 patients
Authors: Bhatnagar, MD Sushma , Mishra, MD Seema , Srikanti, MD Madhurima , Gupta, MD Deepak
Published: February 2018

Effective pain control is essential for the management of patients with cancer. About 70-80 percent of patients with cancer present in an advanced stage of disease. Patients with advanced cancer frequently experience intractable pain, with diverse symptoms that can make daily living impossible and affect the quality of life. This article reports the management of 3,238 patients with cancer pain over a period of five years. Nearly 89.6 percent patients had good pain relief, with Visual Analogue Scale score less than 3. These promising results were achieved by careful patient assessment, close liaison with clinicians from other specialties, and using a variety of analgesic regimen including oral analgesics, anesthetic procedures, psychological interventions, and supportive care. However, the main stay of treatment was oral analgesics, following the principles of World Health Organization ladder, with continuing follow-up.
Intensity and treatment of symptoms in 3,030 palliative care patients: A cross-sectional survey of the EAPC Research Network
Authors: Laugsand, PhD-student Eivor Alette , Kaasa, MD Stein , De Conno, MD Franco , Hanks, MD Geoffrey , Klepstad, MD Pål
Published: February 2018

Objective: This study aimed to describe intensity and treatment of symptoms other than pain in European palliative care units.Patients: A total of 3,030 patients, including 2,064 that used an opioid, were included from 143 palliative care centers, in 21 European countries.Results: Pain was treated with analgesics corresponding to the WHO pain ladder step I (n = 374), II (n = 497), and III (n = 1,567). Frequencies of symptoms observed as moderate or severe were for generalized weakness (50 percent), fatigue (48 percent), anxiety (28 percent), anorexia (26 percent), constipation (18 percent), focal weakness (18 percent), depression (18 percent), and dyspnoea (15 percent). When comparing WHO-groups, cancer diagnoses, metastasis sites, countries, and genders, we found that some of the symptom intensities and treatments differed significantly between subgroups. A majority of patients used drugs for symptom management. Still, more than one-third of patients assessed to have moderate or severe constipation did not receive any treatment. The corresponding numbers for depression, confusion, nausea, vomiting, or anxiety were approaching 40 percent and for poor sleep about 50 percent. Prescription practice of antiemetics, laxatives, and psychotropic drugs varied widely between countries both in terms of preparation and percent of patients receiving a specific treatment.Conclusions: This survey shows that clinically relevant symptoms are frequent and that one-third to half of the patients with a symptom observed as moderate or severe do not receive any treatment aimed to reduce the symptom intensity. Several symptoms and treatments differed between WHO-groups, cancer diagnoses, metastasis locations, countries, and genders. Prescription practice varied between countries both in terms of medication administered and percent of patients receiving specific treatment.
Factors affecting dosing regimens of morphine sulfate extended-release (KADIAN) capsules
Authors: Weil, MD Arnold J. , Nicholson, MD Bruce , Sasaki, MD John
Published: February 2018

Although most extended-release morphine formulations are indicated for use once-daily (q24h) or twicedaily (q12h), KADIAN® (morphine sulfate extendedrelease) capsules, which contain polymer-coated, extended-release morphine sulfate pellets, are indicated for q24h and q12h dosing. This analysis identified factors that might impact decisions to choose q24h or q12h regimens for patients with chronic, nonmalignant pain. Data were obtained from a supplemental analysis of the KRONUS-MSP trial, a community-based, open-label, 4-week study in which patients with chronic, nonmalignant pain (N = 1,428) were randomized to KADIAN q24h dosed either AM or PM. At week 2, investigators could switch to q12h dosing if indicated. For this analysis, demographics, baseline pain features, efficacy outcomes (changes in pain intensity, sleep interference, quality of life [SF-36v2 Health Survey], and Patient and Clinician Global Assessments of Therapy) were compared between patients who remained on q24h regimens and those who switched to q12h. By week 4 (n = 1,042), 56.8 percent of patients reporting were on q24h dosing, and 43.2 percent were dosing q12h. Older patients remained on q24h regimens more frequently than did younger patients. There were no differences in dosing regimen based on sex or race. Mean daily KADIAN doses and baseline pain scores were lower in patients who remained on q24h compared with those who switched to q12h. Patients who switched to q12h had higher pain scores at baseline and week 2 compared with patients who remained on q24h dosing. They demonstrated a smaller degree of change on the other efficacy outcomes than those who remained on q24h dosing at the week 2 visit. However, once switched to q12h, improvements in efficacy measures at week 4 were comparable between the two schedules; Patient and Clinician Global Assessments of Therapy scores also increased compared with previous therapy. Results were significant versus baseline for all outcomes. Adverse event rates were similar for the two groups; the most common adverse events were constipation and nausea. Results demonstrate that KADIAN was effective in relieving pain and improving sleep and quality-of-life scores, regardless of whether patients dosed q24h or q12h, and that dosing decisions can be made, based on individual factors, within the first few weeks of therapy.
Prescription drug fatalities among women in rural Virginia: A study of medical examiner cases
Authors: Wunsch, MD Martha J. , Nakamoto, PhD Kent , Nuzzo, MA Paul A. , Behonick, PhD George , Massello, MD William , Walsh, PhD Sharon L.
Published: February 2018

Objective: To evaluate female drug overdose deaths from the Office of the Chief Medical Examiner, Western Virginia (1997-2003) for demographics, medical history, toxicology results, and prescribed medications.Design: Autopsy reports, death investigations, and hospital/physician notes were reviewed for 330 fatal drug poisonings among women. Data were evaluated with both qualitative and quantitative methods.Results: Most decedents were Caucasian (95 percent), their average age was 42.8 years, and the predominant manner and cause of death was accidental and polydrug toxicity, respectively. Drugs were identified on toxicology or assigned as a cause of death in all 330 cases. The three most common drug classes detected on toxicology were opioids (n = 239; 72.4 percent), antidepressants (n = 201; 60.9 percent), and sedative/anxiolytic/muscle relaxant (SAMR) (n = 161; 48.8 percent) with all three drug classes detected in 89 (27 percent) cases. Illicit drugs identified included cocaine (n = 33; 10 percent) and heroin (n = 3; 0.9 percent). Prescriptions for opioids, SAMR, and antidepressants were found in decedent name in 48 percent, 67.1 percent, and 58 percent of cases, respectively, and 46.1 percent of cases were prescribed at least one medication from each of those three drug classes.Conclusion: Although many decedents held prescriptions, and often for multiple drugs, toxicological findings indicate the frequent presence of other therapeutic drugs in the absence of a prescription. Moreover, many of these cases held simultaneous prescriptions for which there are known drug interactions. It is likely that misuse, fatal medication errors, abuse, and addiction were factors in the increased numbers of these deaths. Interventions to prevent prescription overdose deaths must involve education of both physicians and patients.
A pilot study about the feasibility and cost-effectiveness of electronic compliance monitoring in substitution treatment with buprenorphine—naloxone combination
Authors: Tacke, MD, PhD Ulrich , Uosukainen, MSci (Pharm) Hanna , Kananen, BSci (Pharm) Marjo , Kontra, Pharm Lic Kirsi , Pentikäinen, MD Hannu
Published: February 2018

Objectives: The purpose of the study was to investigate whether or not compliance monitoring by microchip could offer a feasible method for reducing abuse and/or diversion of medication from unsupervised substitution treatment for opioid addiction.Design: Naturalistic, 4-week pilot study in out patients.Patients and interventions: All our patients (N = 12) on buprenorphine—naloxone combination (Suboxone®) received their medication for 6 days in a compliance-monitoring device (PharmaDDSi®, StoraEnso), which registers date and time of tablet removal. Patients were instructed to take all tablets as one dose. Time cues were displayed and discussed with the patients during their weekly visits for supervised drug administration and counseling.Main outcome measures: Regularity of registered time cues, treatment costs in comparison with routine treatment, patients’ answers from a questionnaire on acceptability, and effect on drug diversion.Results: Six patients showed good compliance, in two patients irregularities were minor, but in two others lack of adherence to treatment instructions was detected. Patients with several comorbid psychiatric diagnoses showed on an average the longest intervals between removal of first and last tablet of the daily dose. One-fourth of the patients reported that compliance monitoring had helped to avoid diversion. Total cost savings during the 4-week period was a reduction of 39 percent, which was mainly due to fewer visits to the clinic.Conclusions: Compliance monitoring by PharmaDDSI® with weekly feedback was well accepted and subjectively increased compliance with substitution treatment. Future studies will show whether a technical solution for compliance monitoring in real time can help to reduce drug abuse and noncompliance in substitution treatment and other opioid treatments.
Postoperative analgesia after radical prostatectomy with high-dose intrathecal morphine and intravenous naloxone: A retrospective review
Authors: Rebel, MD Annette , Sloan, MD Paul , Andrykowski, PhD Michael
Published: February 2018

Background and methods: Intrathecal opioids (ITOs) have been used for decades to control postoperative pain. Intrathecal opioid dosing is limited, however, by opioid-related side effects, most importantly respiratory depression. To overcome these limitations, we combined intrathecal morphine with a continuous intravenous (IV) postoperative naloxone infusion to control opioid-related side effects. The purpose of this study is to document the efficacy and safety of high-dose intrathecal morphine combined with postoperative naloxone infusion to provide postoperative analgesia after major surgery. After IRB approval, a retrospective chart analysis was performed on 35 patients who had a radical prostatectomy from 2004 to 2006. All patients received a single injection of ITOs before anesthesia, a typical general anesthestic, followed by naloxone infusion at 5 μg/kg/h started 1 hour post-ITOs and continued for 22 hours postoperatively. The following information was collected: patient age, height, weight, anesthesia technique/time, and dose of ITOs given. Postoperative pain relief was assessed for 48 hours using the Visual Analog Score (VAS) for pain (0, no pain; 10, worst pain), perioperative opioid use, NSAID consumption, and ability of patient to ambulate. The safety of this novel treatment was assessed with opioid-related side effects and vital signs. All data are reported as mean (SD).Results: Mean ITOs given were morphine 1.3 (0.3) mg combined with fentanyl 56 (9) μg. The intrathecal morphine dose ranged from 0.8 to 1.7 mg. The mean worst pain VAS in the first 12 hours postoperatively was only 1.0 (1.7). The first NSAID dose was given 6.6 (3.1) hours post-ITOs. The first opioid on the floor was given an average of 22.6 (14.5) hours post-ITOs. A mean of only 5.7 (12.3) morphine equivalents were required on postoperative day 1 (POD 1). On POD 2, the mean worst pain VAS was only 2.6 (2.2) with only 5.7 (6.2) morphine equivalents needed to provide pain relief. On POD 1, 25 patients required no additional opioids for their entire hospital stay. Overall, 11 of 35 patients did not require any additional postoperative opioids. Thirtyfour patients (97 percent) were able to ambulate in the first 12 hours postoperatively. No opioid-induced respiratory depression was observed. Opioid-related side effects (pruritus, nausea) were infrequent and minor.Conclusions: High-dose ITOs combined with postoperative IV naloxone infusion provided excellent analgesia for radical prostate surgery. IV naloxone infusion appeared to control opioid side effects without diminishing the analgesia. No serious adverse effects were noted.
Effect of prior treatment with ultra-low-dose morphine on opioid- and nerve injury-induced hyperalgesia in rats
Authors: Wala, PhD Elzbieta P. , Sloan, MD Paul A. , Holtman Jr, MD, PhD Joseph R.
Published: February 2018

Background: In addition to producing analgesia, opioids can increase sensitivity to pain (opioid-induced hyperalgesia [OIH]) in humans and rodents. Tolerance/OIH is likely mediated by similar mechanisms that lead to development of hyperalgesia after nerve injury (neuropathic pain). OIH may be a reason for loss of opioid efficacy and/or a worsening of pain. Ultra-low-dose (ULD) opioid evokes hyperalgesia independently of analgesia. Tolerance to ULD-OIH develops with repeated dosing in rats.Objective: The effects of ULD opioids were characterized in two distinct situations where hyperalgesia is expected to occur: following acute opioid treatment and after nerve injury.Design: First, ULD morphine was repeatedly administered (2× day for 5 days) by intrathecal (i.t., 0.01 μg) or intraperitoneal (i.p., 20 μg/kg) routes in rats. Second, morphine (0.01 μg i.t.; 20 μg/kg i.p.) was administered (2× day for 5 days) prior to acute morphine (30 μg i.t.; 10 mg/kg i.p). Third, ULD morphine (20 μg/kg/2× day, i.p.) was given either immediately after nerve injury (days 1-28) or when hyperalgesia was manifested (days 7-14). The tail-flick and paw-pressure tests were used in noninjured and nerve-injured rats, respectively.Results: Tolerance was developed to OIH with repeated ULD morphine by the i.p. route but not the i.t. route. Prior exposure to ULD morphine (i.p.) caused prolongation of morphine analgesia in intact rats and inhibition of the development (but not reversal) of hyperalgesia in nerve-injured rats. Abolishment of OIH (pain desensitization) may diminish activation of pain facilitatory systems due to nerve injury and opioid treatment.Conclusions: Although the translational aspect of this preclinical study has limitations, the present data may suggest a new strategy for the pre-emptive use of ULD opioids to prevent the development of neuropathic pain with certain procedures or disease states.
AWAKE FIBEROPTIC INTUBATION WITH TARGET-CONTROLLED INFUSION OF REMIFENTANIL IN EMERGENCY SURGERY
Authors: Motamed, MD Cyrus , Salazar, MD German
Published: February 2018

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PAIN MEDICATION PRESCRIPTION AND BORDERLINE PERSONALITY DISORDER: A PILOT STUDY
Authors: Sansone, MD Randy A. , Mueller, MD Michelle , Mercer, MD Amy , Wiederman, MD Michael W.
Published: February 2018

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Morphine and cancer progression: Hydrogen peroxide points to need for more research
Authors: Bosshart, MD Herbert
Published: February 2018

Background: Morphine is widely used in the management of intractable cancer pain. However, conflicting views exist on two suspected nonanalgesic properties of morphine: suppression of immune function and inhibition of cancer progression.Methods: In vitro measurement of the tumor growth-inhibiting signaling molecule, hydrogen peroxide (H2O2), released from the cultured acute monocytic leukemia cell line, THP-1, in the presence or absence of morphine.Results: Morphine at concentrations of 10−8 M significantly reduced H2O2 release from THP-1 cells.Conclusions: These results provide a proof of concept for morphine’s ability to inhibit H2O2 production and release in a leukemia cell system and point to a possible and as yet unrecognized tumor-promoting effect of morphine. More research is needed to systematically examine this suspected morphine-associated tumor-promoting effect.