bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-dose extended-release epidural morphine for pain after hip arthroplasty
Authors: Martin, MD Gavin , Hartmannsgruber, MD Maximilian , Riley, MD Edward , Manvelian, MD Garen
Published: February 2018

This randomized, double-blind study compared the safety and efficacy of a new single-dose extended-release epidural morphine (EREM) formulation for postoperative pain following hip arthroplasty. Patients were administered a single dose of EREM (10, 20, or 30 mg, n = 93) or a single epidural dose of placebo (n = 27) before surgery and general anesthesia. Following surgery, patients had access to fentanyl with the use of intravenous patient-controlled analgesia. Postoperative fentanyl use, time to first postoperative fentanyl use, pain intensity at rest and with activity, patient ratings of pain control, and adverse events were recorded. Compared with placebo-treated patients, single-dose EREM patients used less total supplemental fentanyl (p £ 0.049), had a longer time to first fentanyl use (p < 0.001), and were less likely to use any supplemental fentanyl (p £ 0.042). EREM-treated patients reported lower pain intensity for up to 48 hours postdose compared with placebo-treated patients. Single-dose EREM was effective for postoperative pain relief for up to 48 hours following hip arthroplasty, with a safety and tolerability profile consistent with that of other epidurally administered opioids.
Interpleural bupivacaine and intravenous oxycodone for pain treatment after thoracotomy in children
Authors: Kokki, MD, PhD Hannu , Laisalmi, MD Merja , Vanamo, MD, PhD Kari
Published: February 2018

Introduction: The results of studies exploring the efficacy of interpleural analgesia in children post-thoracotomy have frequently been inconclusive. In this pilot study, we have evaluated the efficacy and safety of interpleural bupivacaine and intravenous (IV) oxycodone in pain treatment after thoracotomy in 10 generally healthy children, aged 10 months to 12 years, with patent ductus arteriosus who underwent thoracotomy.Methods: After surgery, all 10 children were given ibuprofen 10 mg/kg rectally every six hours. The first dose of interpleural bupivacaine (2 mg/kg) was given with epinephrine at the end of surgery, and thereafter plain bupivacaine (1 mg/kg) was given every two hours if the pain score was 4 or higher on an 11-point numeric rating scale (0 = no pain, 10 = worst possible pain). For rescue analgesia, children were provided oxycodone 0.1 mg/kg IV if pain was not relieved sufficiently with ibuprofen and bupivacaine. Vital signs, pain scores, and all adverse effects were monitored continuously for 24 hours.Results: All 10 children needed both interpleural bupivacaine and IV oxycodone. The number of bupivacaine doses ranged between three and 10 (mean = 6.1, SD = 2.3), and the number of oxycodone doses ranged between one and 12 (mean = 6.0, SD = 3.6). No cases of low respiratory rate or low peripheral oxygen saturation or any serious adverse events were recorded.Conclusion: Scheduled nonopioid analgesic (ibuprofen) with interpleural bupivacaine did not provide sufficient analgesia for post-thoracotomy pain in young children. IV oxycodone was found to be an effective and safe opioid supplement to the pain regimen.
Ultra-low-dose opioid antagonists to enhance opioid analgesia
Authors: Sloan, MD Paul , Hamann, PhD, MD Scott
Published: February 2018

This article will review decades of science contributing to current interest in opioid excitatory pharmacology. A long history of clinical confusion provided the stimulus for recent, detailed in vivo and in vitro investigations of the neuropharmacologic mechanisms involved in analgesic and hyperalgesic actions of opioid agonists and antagonists. Following the discovery of central nervous system opioid excitatory-hyperalgesic processes in animals, detailed neuronal cell culture experiments established opioid receptor/G protein/adenylate cyclase neurobiochemical mechanisms for bimodal inhibitory versus excitatory actions of opioids. Once this novel model was available to explain the cellular mechanisms responsible for the duality of opioid actions, clinical translation of this technology began to emerge, with a primary focus on selective antagonism of opioid excitatory actions with concomitant low-dose opioid antagonists. Encouraging results from recent animal and clinical studies will be discussed as further evidence that therapeutic pain management may be improved through enhancement of opioid agonist analgesia by cotreatment with ultra-low-dose opioid antagonists that selectively attenuate opioid-mediated hyperalgesia.
Linkage to methadone treatment from acute opiate detoxification treatment
Authors: Zaller, PhD Nickolas D. , Thurmond, MPH Portia , Brett, PhD Jon , Carleton, MS James C. , Rich, MD, MPH Josiah D.
Published: February 2018

Methadone maintenance treatment (MMT) is a safe pharmacological treatment strategy for addiction to heroin and other opiates; however, linking individuals to MMT is often challenging. We present results from a pilot project (Project VISTA) funded by the Center for Substance Abuse Treatment that helps heroin-dependent injection drug users (IDUs) transition from acute heroin detoxification to MMT. Participants are referred to Project VISTA by the state detoxification center, and Project VISTA facilitates entry into an MMT program, providing full financial support for up to 24 weeks. In addition, Project VISTA provides case management and referral to ancillary services such as housing, other medical care, and mental health treatment. From May 2005 to May 2006, 60 individuals were enrolled in Project VISTA. A total of 41 participants (69.5 percent) remained in treatment for at least 24 weeks, with a mean number of weeks in treatment of 31. A Kaplan-Meier analysis was performed on all participants, and the incidence of individuals being discharged from treatment was 2 percent per week. Project VISTA, in cooperation with the state detoxification center and a Providence-based MMT program, has created a model that provides continuity of treatment services to high-risk, HIV-negative IDUs. Our model demonstrates that through facilitating the transition from an opiate detoxification program into an MMT program, individuals with chronic heroin addiction can successfully access and engage in treatment.
Safety and tolerability of high doses of intrathecal fentanyl for the treatment of chronic pain
Authors: Ouro, MD Sulane Do , Esteban, BS Santiago , Sibirceva, MD Una , Whittenberg, MD Beverly , Portenoy, MD Russell , Cruciani, MD, PhD Ricardo A.
Published: February 2018

Fentanyl is commonly used systemically or neuraxially for the management of chronic pain. It can be administered intrathecally via implanted pump, but it is generally considered only after trials of intrathecal (IT) morphine and hydromorphone have proven ineffective. Published experience with IT fentanyl is limited, and long-term therapy at relatively high doses has not been described previously. We describe four patients who were treated with IT fentanyl after other analgesic approaches had failed and who gradually underwent dose escalation to levels as high as 20 times those previously reported. Safety and tolerability were maintained during dose titration. Our experience highlights an expanding scope of practice in the use of IT opioids in general and fentanyl specifically and suggests that high-dose fentanyl can be used safely in highly selected patients.
Buprenorphine—A review of its role in neuropathic pain
Authors: Hans, MD Guy
Published: February 2018

Background: The use of opioids for the treatment of neuropathic pain remains somewhat controversial, since earlier studies indicate that neuropathic pain is generally less responsive to pure μ-opioid analgesia. A growing body of evidence now suggests that different opioids affect different pain pathways, and emerging data support the possibility of a role for buprenorphine in the management of neuropathic pain.Objective: This article reviews the preclinical and clinical data for the role of buprenorphine in the treatment of neuropathic pain.Research Design and Methods: Literature searches were carried out using PubMed (1988 to September 2006). Search terms included buprenorphine and neuropathic pain, as well as neuropathy, painful neuropathy, hyperalgesia, and allodynia. Clinical studies and case studies were included.Results: Several assays, including the formalin, cold tail flick, and diffuse noxious inhibitory control tests, have revealed buprenorphine’s potential efficacy in various pain types. These findings seem to support hypotheses regarding its unique analgesic mechanisms as compared with pure μ-opioids. The exact mechanism of this analgesic efficacy remains unknown. Preclinical assessments of buprenorphine demonstrate its sustained antihyperalgesic effect in several models of neuropathic pain. These findings are supported in clinical studies of oral, intrathecal, intravenous, and transdermal buprenorphine. Furthermore, these studies have demonstrated that, despite there being a ceiling effect for respiratory depression, no relevant analgesic ceiling effect is found with buprenorphine.Conclusions: Further studies are certainly warranted to identify the clinical neuropathic syndromes that are most sensitive to buprenorphine treatment, and to compare buprenorphine with other opioids in head-to-head trials of neuropathic pain.
Personality traits and sensitivity to pain in male chronic opioid addicts
Authors: Eisenberg, MD Elon , Cohen, MA Doron , Lawental, PhD Eli , Pud, PhD Dorit
Published: February 2018

Objective: Previous evidences concerning pain mechanisms, long-term opioids use, and personality traits evolve the possibility that pain perception and opioid abuse are two related phenomena and there is a need to take into account the specific personality traits as well, in examining the relationships among them. Opioid addicts (OAs) have been shown to exhibit different personality traits and pain perception as compared with healthy subjects. The aim of the present study was to examine the relations between personality traits and pain perception among in-treatment OAs in comparison with controls.Design: Participants (54 OAs, 59 controls), all males, were exposed to the cold pressor test and were evaluated for latency of pain onset (seconds); pain intensity (0-100 visual analogue scale [VAS)]); and pain tolerance (time for hand withdrawal). Personality traits were evaluated using Cloninger’s Tridimensional Personality Questionnaire, TPQ; harm avoidance, HA; reward dependence, RD; novelty seeking, NS.Results: In comparison with controls, OAs exhibited longer latencies, lower VAS scores, and shorter tolerance, and significantly higher NS, higher HA, and lower RD. Control group, but not OAs, showed a significant positive correlation between HA and VAS (r = 0.31, p = 0.02) and significant negative correlation between HA and tolerance (r = −0.29, p = 0.03).Conclusions: It is concluded that in contrast to healthy population, personality traits, as measured by the TPQ, do not predict pain perception in OAs.
Efficacy and safety of 12 weeks of osteoarthritic pain therapy with once-daily tramadol (Tramadol Contramid® OAD)
Authors: Fishman, MD Ritchard L. , Kistler, DO Charles James , Ellerbusch, MD Michael T. , Aparicio, MD Raul Tomas , Swami, MD Sharad S. , Shirley, DO Mark E. , Jain, MD Adesh K. , Fortier, MSc Louise , Robertson, BScN Sybil , Bouchard, MD, PhD Sylvie
Published: February 2018

This placebo-controlled study examined the analgesic efficacy, safety, and clinical benefit of Tramadol Contramid OAD, a once-daily formulation with both immediate- and extended-release components. Five hundred and fifty-two patients with moderate to severe pain due to osteoarthritis (OA) of the knee were randomized into this multicenter, double-blind, parallel arm study. After randomization to Tramadol Contramid OAD 100, 200, or 300 mg, or to placebo, patients’ dose was titrated to the fixed randomized dose and maintained for 12 weeks. Efficacy was evaluated with the Patients’ Global Rating of Pain Relief (median ratings at maintenance visits), and the Western Ontario and McMaster University (WOMAC) Pain and Physical Function subscales (percent difference, baseline to end of study) as coprimary endpoints. A responder analysis was conducted (percentage of patients who achieved a 30 percent improvement on their baseline WOMAC pain score). The difference from placebo on the median Patient Global Rating of Pain Relief at the four maintenance visits was statistically significant (200 and 300 mg: p ≤ 0.001). Treatment was rated effective or very effective by 75 percent and 80 percent of patients randomized to Tramadol Contramid OAD 200 mg and 300 mg, respectively. There was a 46 percent (300-mg dose; p = 0.016) and 43 percent (200-mg dose; p = 0.05) improvement on the WOMAC pain score (baseline to the end of the study) with Tramadol Contramid OAD compared with 32 percent for placebo. The responder analysis demonstrated a statistically significant difference in the percentage of patients who achieved a 30 percent improvement in their baseline WOMAC pain score for both Tramadol Contramid OAD 200 mg (65 percent; p = 0.0095) and 300 mg (65 percent; p = 0.0104) compared with placebo (50 percent). The type and incidence of adverse events were typical of tramadol (nausea, dizziness/vertigo, vomiting, somnolence, and constipation) and the intensity was mild to moderate in 87 percent of patients who experienced them regardless of dose. This study shows the efficacy and safety of Tramadol Contramid OAD 200 mg and 300 mg in patients with moderate or severe pain of the knee due to OA.
Prescribing opioids in renal failure
Authors: Droney, MB, BCh, MRCP(I) Joanne , Levy, PhD, FRCP Jeremy , Quigley, FRCP Columba
Published: February 2018

Opioids are commonly used in both cancer and noncancer pain. Many patients who require opioids have renal impairment. This can adversely influence the safety of opioids in these patients.Objectives: The objectives of this study were to (1) determine which opioids are most commonly prescribed in patients with renal impairment, (2) to identify differences in prescribing practices between two groups of physicians, and (3) to determine how renal impairment was recognized in this setting.Design and participants: A questionnaire postal survey was sent out to renal and palliative medicine consultants in UK and Ireland. One hundred and seventyeight (30.5 percent) questionnaires were completed.Results: A larger proportion of renal than palliative medicine physicians prescribed morphine in patients with renal impairment. A significant number of physicians did not adjust doses of morphine or codeine. Palliative medicine physicians were more likely to prescribe opioids other than morphine, with the exception of fentanyl which was widely used by both groups. Renal physicians were more likely to base their choice of opioid on glomerular filtration rate while palliative medicine physicians were more likely to be influenced by serum creatinine.Conclusions: Consensus guidelines drawing on expertise from both palliative and renal physicians are needed to promote safer use of opioids in this vulnerable patient group.
Family physicians’ proficiency in urine drug test interpretation
Authors: Reisfield, MD Gary M. , Webb, PhD Fern J. , Bertholf, PhD Roger L. , Sloan, MD Paul A. , Wilson, MD George R.
Published: February 2018

Objective: To determine the proficiency in urine drug test interpretation among family medicine physicians who order these tests 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 questions and one yes/no question was administered to 80 family medicine physicians attending a University of Kentucky Family Medicine Review Course. We calculated frequencies and performed χ2 analyses to examine bivariate associations between urine drug test utilization and interpretive knowledge.Results: The instrument was completed by 60/80 (75 percent) of eligible physicians (44 order urine drug testing; 16 do not). None of the physicians who order urine drug testing answered more than five of the seven questions correctly, and only 20 percent answered more than half correctly. Physicians who order urine drug testing performed better than physicians who do not order urine drug testing on only four of the seven questions, although there were no statistically significant differences between the groups on any question.Conclusions: Family medicine physicians who order urine drug testing to monitor their patients on chronic opioid therapy are not proficient in their interpretation. This study highlights the need for improved physician education in this area. It is imperative for physicians to work closely with certified laboratory professionals when ordering and interpreting urine drug tests.
Patterns of illicit drug use and retention in a methadone program: A longitudinal study
Authors: Davstad, MA Ingrid , Stenbacka, PhD Marlene , Leifman, MSE Anders , Beck, PhD Olof , Korkmaz, MD, PhD Seher , Romelsjo, MD, PhD Anders
Published: February 2018

Objective: This study aimed to analyze illicit drug use of participants in a methadone treatment program in relation to methadone dose, counseling, and retention.Methods: This was a longitudinal study of a cohort of 204 heroin-dependent subjects admitted for the first time to a methadone program in Stockholm. The patients were admitted between 1995 and mid-2000 and were followed until December 2000 or discharge. Up to June 11, 1998, individual psychosocial counseling was provided; after this date individual counseling was replaced with group counseling. Clinical data were collected from patient records and from a laboratory database. Rates of drugpositive urine analyses during different time periods were measured.Results: The mean observation time was 2.5 years for all patients. The one-year retention rate was 84 percent, and the two-year rate was 65 percent, with no major differences between the two counseling groups. Almost all patients relapsed to illicit drug use. Discharged patients had a significantly higher rate of positive urine samples (21 percent versus 9 percent) than patients who remained in treatment. Also, low methadone dose and younger age predicted discharge from treatment.Conclusion: The frequent urine monitoring showed that illicit drug use was rather common, even in a program with structured psychosocial interventions, although it was lower than in other studies. This testing policy can be used for early identification of patients at risk for drop-out or discharge who should be offered complementary interventions.
A randomized, open-label, multicenter trial comparing once-a-day AVINZA® (morphine sulfate extended-release capsules) versus twice-a-day OxyContin® (oxycodone hydrochloride controlled-release tablets) for the treatment of chronic, moderate to severe low back pain: Improved physical functioning in the ACTION trial
Authors: Rauck, MD Richard L. , Bookbinder, MD Stephen A. , Bunker, MD Timothy R. , Alftine, MD Christopher D. , Gershon, MD Steven , De Jong, MD Egbert , Negro-Vilar, MD, PhD Andres , Ghalie, MD Richard
Published: February 2018

This multicenter trial compared the efficacy, safety, and effect on quality of life and work limitation of once-daily extended-release morphine sulfate capsules (AVINZA9, A-MQD) and twice-daily controlled-release oxycodone HCl tablets (OxyContin9, O-ER) in subjects with chronic, moderate to severe low back pain. After randomization and a period of opioid dose titration, subjects (n = 266) underwent an eight-week evaluation phase and an optional four-month extension phase (n = 174 in extension phase). Subjects were assessed using the 12-item Short-Form Health Survey9 (SF-12) and the Work Limitations Questionnaire9 (WLQ). In both groups, significant improvements were observed in the SF-12 mean scores for physical functioning (p < 0.001), role physical (p < 0.0001), bodily pain (p < 0.0001), physical summary (p < 0.001), and mental component summary (p < 0.005). At the end of the titration period, greater relative improvements from baseline were seen in the SF-12 section on physical components in the A-MQD group versus the O-ER group, with significant differences observed for physical functioning (p = 0.0374), role physical (p = 0.0341), bodily pain (p = 0.0001), and physical summary (p = 0.0022). In both groups, SF-12 mean scores improved significantly for mental health (p < 0.01), role emotional (p < 0.01), social functioning (p < 0.0005), vitality (p < 0.005), and the mental component summary (p < 0.005), but no significant differences were noted between the two groups. Both groups reported improvement from baseline in WLQ physical demands scores, with no significant differences noted between the two groups. At the end of the evaluation phase, fewer subjects were unable to work due to illness or treatment in the A-MQD group than in the OER group (8.5percent versus 19.4percent, respectively; p = 0.0149). In conclusion, compared to twice-daily OxyContin, once-daily AVINZA resulted in significantly better and earlier improvement of physical function and ability to work.
Sleep improves when patients with chronic OA pain are managed with morning dosing of once a day extended-release morphine sulfate (AVINZA®): Findings from a pilot study
Authors: Rosenthal, DO Murray , Moore, PhD Polly , Groves, MD, PhD Eric , Iwan, BA Tad , Schlosser, MS Lisa Greenberg , Dziewanowska, MD, PhD Zofia , Negro-Vilar, MD, PhD Andres
Published: February 2018

Study objective: To investigate the effect of once-a-day extended release of morphine sulfate AVINZA® (A-MQD) on polysomnographic measures of sleep in a population of chronic osteoarthritic pain patients with sleep difficulties.Design: Single-center, single-blind, placebo-lead-in, 30 mg or 60 mg. Patients’ sleep and neurocognition were objectively measured at a sleep laboratory, and patients self-rated their pain, sleep, and other functions.Participants: Thirty-four participants (26 to 75 years old) complaining of sleep difficulties and chronic, stable pain secondary to hip or knee osteoarthritis.Interventions: Participants had a screening visit on current pain medication and then, following a singleblind placebo run-in period, received 30 mg/d of A-MQD for six days. At day 6, doses for participants with incomplete pain relief on the Brief-Pain-Inventory (BPI) pain scale were increased to 60 mg/d. Treatment continued for another eight days at the new dose level (14 days for a subgroup at 60 mg/d). Sleep was objectively measured by all-night polysomnography (PSG) at screening while on the participants’ current pain therapy, at baseline following a placebo run-in and at the end of treatment while on A-MQD.Outcome measures: PSG parameters evaluated included Total-Sleep-Time (TST), Wake-timeafter-Sleep-Onset (WASO), Sleep-Efficiency (SE), Latency-to-Persistent Sleep (LPS), Latency-to-REM-sleep, the Number-of-Awakenings (NAW), the time spent in each stage of sleep, and REM-sleep-latency. Subjective evaluations included participants’ estimations of sleep time and sleep quality, the Epworth-Sleepiness-Scale (ESS), the BPI, and participant acceptance of and relief due to current therapy. Assessments of neurocognitive function were also made.Results: Sleep initiation and maintenance tended to improve with A-MQD as demonstrated by the increases in TST and SE and decreases in WASO and NAW as compared with placebo-baseline values. Sleep architecture was preserved by the study drug and some increases in stage 2 and 3/4 sleep were seen compared with placebo baseline. Subjective ratings of sleep quality and sleep time were significantly improved with treatment, as were BPI scores and ratings of medication acceptance and pain relief. A-MQD was generally well tolerated.Conclusions: A-MQD was an effective treatment for pain, and this study treatment was associated with improvement of both objective and subjective sleep parameters in participants with chronic osteoarthritic pain.
Analgesic effects of lornoxicam after total abdominal hysterectomy
Authors: Sapolya, MD Ozgur , Karamanlhoglu, MD Beyhan , Memis, MD Dilek
Published: February 2018

The authors investigated, in a randomized, placebocontrolled, double-blinded study, the efficacy and safety of lornoxicam on pain after abdominal hysterectomy and on tramadol consumption in patients. Fifty patients were randomized to receive either oral placebo or lornoxicam 8 mg one hour before surgery. Anesthesia was induced with propofol and maintained with sevoflurane in 50 percent N2O/O2 with a fresh gas flow of 2 L/min (50percent N2O in O) and fentanyl (2 fig/kg). All patients received patient-controlled analgesia with tramadol with loading dose of 50 mg; incremental dose of 20 mg; lock out interval of 10 minute; and four-hour limit 300 mg. The incremental dose was increased to 30 mg if analgesia was inadequate after one hour. Patients were studied at one, two, four, eight, 12, and 24 hours for visual analogue (VAS) pain scores, heart rate, mean arterial pressure, periferic oxygen saturation, sedation, tramadol consumption, and length of hospitalization. VAS scores at one hour were significantly lower in the lornoxicam group (p < 0.001). The tramadol consumption at one, two, four, eight, and 12 hours was significantly lower in the lornoxicam group when compared with the placebo group (p < 0.001, p = 0.008, p = 0.029, p = 0.034, p = 0.042, respectively). Sedation scores were similar at all the measured times in the groups. Length of hospitalization was significantly shorter in lornoxicam group (4.8 ± 0.4 day) than placebo group (5.2 ± 0.5 day) (p = 0.005). There was difference in the incidence of nausea between the groups (p = 0.047). The number of patients and the doses ofantiemetics given during the first 24 hours after surgery in lornoxicam group were less than those in placebo group (p = 0.003, p = 0.034, respectively).In conclusion, a single oral dose of lornoxicam given preoperatively enhanced the analgesic effect of tramadol, decreasing tramadol consumption and side effects, and shortened the length of hospitalization.
Opioids applied topically to painful cutaneous malignant ulcers in a palliative care setting
Authors: Zeppetella, FRCP Giovambattista , Porzio, MD Giampiero , Aielli, MD Federica
Published: February 2018

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A pilot survey of attitudes and knowledge about opioid substitution therapy for HIV-infected prisoners
Authors: Springer, MD Sandra A. , Bruce, MD Robert D.
Published: February 2018

A majority of inmates in the state of Connecticut Department of Corrections use opioids or are opioid dependent before incarceration. None of the state’s prisons offer opioid substitution therapy other than for detoxification or maintenance therapy for women during pregnancy. On release to the community, most prisoners relapse to drug use and this has been associated with higher recidivism rates, and less adherence to antiretroviral medications for HIV-infected persons. Nationally and internationally, methadone (METH) and buprenorphine (BUP) have been found to decrease relapse to drug use, decrease recidivism rates, improve adherence to antiretroviral medications, decrease HIV-risk taking behaviors, and improve mortality. However, the general knowledge about opioid substitution therapy among correctional facility staff has been reported as substandard. This pilot study compiled results of answers to anonymous surveys from 27 individuals who work directly with inmates in a patient-care capacity for the Connecticut Department of Corrections (CT DOC) and CT DOC case-management referral program (Project TLC) in the year 2006. The surveys included questions regarding current attitudes and knowledge about opioid substitution therapy for prisoners. A minority of respondents refer released prisoners with a history of opioid dependency to METH or BUP treatment. The majority of correctional workers and case-management referral workers did not have knowledge about BUP or METH’s ability to improve health and decrease HIV risk taking behaviors. This study found that more education of individuals treating and caring for HIV-infected opioid dependent prisoners is needed.
Opioid-induced hyperalgesia: Pathophysiology and clinical implications
Authors: Mitra, MD, MAMS Sukanya
Published: February 2018

Background: Opioid-induced hyperalgesia (OIH) refers to a phenomenon whereby opioid administration results in a lowering of pain threshold, clinically manifest as apparent opioid tolerance, worsening pain despite accelerating opioid doses, and abnormal pain symptoms such as allodynia.Aim: The current review, while providing a clinically oriented updated overview on the pathophysiology of OIH, focuses predominantly on evidence-based clinical and management aspects of this important and often baffling phenomenon.Method: Online and manual search using key words such as opioid-induced hyperalgesia, opioid-induced abnormal pain sensitivity, opioid hyperalgesia, opioidinduced paradoxical pain, or opioid-induced abnormal pain, followed by full-text access and further crossreferencing.Results: The underlying pathophysiology of this phenomenon, although still unclear, appears to be related to an opioid-induced imbalance between the internal antinociceptive and pronociceptive systems. Clinical differentiation of an apparent opioid tolerance state includes OIH. Once diagnosed or provisionally considered, treatment strategies could include opioid dose reduction, opioid rotation, use of agents with NMDA receptor antagonism, and a properly timed coxib.Conclusion: Despite initial skepticism and reservations, the phenomenon of OIH in humans is now accepted a clinical reality and a challenge faced by anesthesiologists, intensivists, pain specialists, and other workers in a diverse range of settings from perioperative care to palliative care medicine.
Epidural haloperidol enhances epidural morphine analgesia: Three case reports
Authors: Colclough, MD George , McLarney, MD John T. , Sloan, MD Paul A. , McCoun, MD K. Todd , Rose, MD Gregory L. , Grider, MD J. S. , Steyn, MD P.
Published: February 2018

Epidural opioids provide significant postoperative analgesia; however, their use is often limited by side effects such as nausea and pruritus, or they require the addition of epidural local anesthetics with possible side effects of motor block and hypotension. Adjuncts to epidural opioid analgesia would benefit pain management. There is evidence that epidural butyrophenones may enhance opioid analgesics and reduce side effects. The authors present the first reported use of epidural haloperidol to enhance epidural morphine analgesia in three individuals. Pharmacodynamic interactions of haloperidol, which may explain its analgesic efficacy, are summarized.
Ketamine for acute and subacute pain in opioid-tolerant patients
Authors: Chazan, RN Shoshana , Ekstein, MD Margaret P. , Marouani, MD Nissim , Weinbroum, MD Avi A.
Published: February 2018

Prolonged acute pain, especially that of oncologic neurological origin, is at times difficult to control; it is seldom entirely alleviated by opioids. We report eight patients with severe pain, three of whom suffered from new onset oncologic metastatic bone pain, others had previous pain syndromes and presented with exacerbation of pain. Pain was associated with hyperalgesia and allodynia phenomena in two patients and with phantom pain in a third one. Tolerance to opioids had developed, and high IV doses of morphine, meperidine or fentanyl, and patient-controlled intravenous and epidural analgesia were insufficient. Several patients became dependent on opioids and could not be weaned from assisted ventilation.Pain was controlled with decreasing adjunct doses of ketamine. Within 5-10 days of ketamine and opioid protocols, pain was controlled and after an additional 5-7 days, ketamine could be stopped and pain controlled on oral regimens compatible with outpatient care.Ketamine is an efficient adjuvant analgesic for intractable severe pain, caused by metastasis, trauma, chronic ischemia, or central neuropathic pain. It is effective even when mega doses of IV, epidural, or oral opioids prove ineffective and when signs of tolerance have developed.
Subcutaneous dexmedetomidine infusions to treat or prevent drug withdrawal in infants and children
Authors: Tobias, MD Joseph D.
Published: February 2018

This retrospective study reports a cohort of pediatric patients in whom subcutaneous dexmedetomidine was used to treat or prevent drug withdrawal following prolonged sedation in the Pediatric Intensive Care Unit setting. There were seven patients ranging in age from 6 months to 3.75 years and in weight from 4.8 to 17.7 kg. The dexmedetomidine infusion before switching to subcutaneous administration varied from 0.8 to 1.4 μg/kg/h. Four of the patients had received dexmedetomidine in conjunction with an opioid as part of a sedation regimen during mechanical ventilation. In these four patients, the duration of the intravenous dexmedetomidine infusion varied from 4 to 10 days. In the three other patients, an intravenous dexmedetomidine infusion was used to treat withdrawal following the prolonged use of an opioid and/or a benzodiazepine. In these three patients, the duration of the intravenous dexmedetomidine varied from 3 to 5 days. Following the switch to subcutaneous dexmedetomidine, the infusion was gradually decreased by 0.1 μg/kg/h every 12 h. Subcutaneous access was maintained, and subcutaneous dexmedetomidine was administered for 4 to 7 days. No problems with the subcutaneous access were noted during treatment. No patient exhibited behavior suggestive of withdrawal during the use of subcutaneous dexmedetomidine. The maximum modified Finnegan score in the seven patients varied from 3 to 7. Our preliminary experience suggests that dexmedetomidine can be administered by subcutaneous infusion without difficulty or alteration of its efficacy. This approach allows the administration of dexmedetomidine when peripheral venous access becomes problematic and may facilitate the removal of central venous catheters in patients recovering from critical illnesses. It also offers the possibility of using dexmedetomidine in settings where peripheral venous access is not available such as home palliative care.
Edema caused by continuous epidural hydromorphone infusion: A case report and review of the literature
Authors: Ruan, MD Xiulu , Tadia, MD Riaz , Liu, MS Hainan , Couch, MD John Patrick , Lee, MD, PhD John Keun-Sang
Published: February 2018

Background: Intraspinal drug delivery (IDD) therapy has been increasingly employed in patients with intractable, nonmalignant pain. Before implantation of permanent intraspinal pump, an intraspinal opioid screening trial is conducted to demonstrate the efficacy. The patient-controlled continuous epidural opioid infusion trail, performed in an outpatient setting, is widely accepted by many interventional pain specialists.Objective: To report a case of severe edema observed during the continuous epidural hydromorphone infusion trial.Case Report: An otherwise healthy 68-year-old lady with a 5-year history of severe low back pain and bilateral leg pain because of failed back surgery syndrome was referred to our clinic for IDD therapy.A tunneled lumbar epidural catheter was placed at L2- L3 with catheter tip advanced to L1 under fluoroscopic guidance. Satisfactory catheter placement was confirmed by epidurogram. The catheter was then tunneled subcutaneously and connected to a Microject™ patient-controlled epidural analgesia (PCEA) pump (Codman, Raynham, MA). The pump was programmed to deliver hydromorphone (0.1 mg/ml) at basal rate of 0.3 ml/h. The bolus dose was 0.1 ml with a 60-minute lockout interval. The patient was instructed how to operate the infusion pump. During the following infusion trial, she reported satisfactory analgesia (>70 percent pain reduction) and was able to wean off her other systemic opioids. However, she developed diffuse edema and gained over 16 pounds during the 5-day infusion trial. Her edema finally resolved 3-4 days after termination of the epidural infusion.Conclusion: Edema may occur and persist during epidural hydromorphone infusion. This report represents the first case report, to the best of our knowledge, describing severe edema in a patient on continuous epidural hydromorphone administration during an outpatient epidural infusion trial.
Onset of analgesic effect and plasma levels of controlled-release tramadol (Tramadol Contramid once-a-day) 200-mg tablets in patients with acute low back pain
Authors: Sarbu, MD Adrian , Radulescu, MD Florin , Robertson, BScN Sybil , Bouchard, MD, PhD Sylvie
Published: February 2018

Background and Aims: Tramadol hydrochloride, a centrally acting, synthetic analgesic, has been available in Europe since 1977 in a variety of formulations and in the United States since 1995. Its clinical efficacy was established in a variety of painful conditions (cancer pain, neuropathic pain, and osteoarthritis). Nonetheless, little published data exist regarding the relationship between analgesic onset and minimum therapeutic plasma levels. Tramadol Contramid* once-a-day (OAD) demonstrates a pharmacokinetic profile with a sharp initial absorption slope similar to the pharmacokinetic profile of the immediate- release tramadol, suggesting that both the immediaterelease and the once-daily (Contramid) formulation may produce a similar onset of analgesia.Methods: This multicentre, open-label, single-dose study examined the pharmacokinetics/pharmacodynamics of Tramadol Contramid OAD in patients with acute low back pain. Patients who signed informed consent were screened and washed-out of prior analgesics. Patients received one dose of Tramadol Contramid OAD 200 mg. The patients indicated the time of onset of pain relief (stopwatch method). Ratings of pain intensity and pain relief and pharmacokinetic samples were taken prior to dosing, at the onset of pain relief, and 3 and 6 hours postdose. No rescue medication was permitted until the end of the study (6-hour postdose). Adverse events were monitored throughout the study.Results: Forty of the 47 patients enrolled completed the study. Onset of perceptible pain relief was achieved within 1 hour for the majority of patients and at plasma levels, suggesting a therapeutic threshold between 50 and 100 ng/mL. Two patients did not experience any pain relief.Conclusions: The results of this exploratory study suggest that similar to immediate-release tramadol, onset of analgesia for this controlled-release formulation of tramadol (Tramadol Contramid OAD) occurs within 1 hour at a mean therapeutic threshold concentration of 56 ± 38 ng/mL.
Prediction of withdrawal symptoms during opioid detoxification
Authors: Dijkstra, MSc Boukje A. G. , Krabbe, PhD Paul F. M. , De Jong, MD, PhD Cor A. J. , Van der Staak, PhD Cees P. F.
Published: February 2018

Objective: The severity of self-reported withdrawal symptoms varies during detoxification of opioid-dependent patients. The aim of this study is to identify subgroups of withdrawal symptoms within the detoxification trajectory and to predict the severity of withdrawal symptoms on the basis of drug-related and sociodemographic characteristics.Design and setting: A prospective study carried out in an in-patient setting in four addiction treatment centres in the Netherlands.Participants: Two hundred opioid-dependent patients who participated in a randomized controlled trial and completed more than 75 percent of the administrations of the subjective opioid withdrawal scales during rapid detoxification.Intervention and main outcome measure: Main outcome measure was the severity of opioid withdrawal as measured by the subjective opioid withdrawal scale during detoxification (18 measurements). Predictor baseline data were obtained on sociodemographic background, severity of addiction, psychopathology, personality disorder, and craving.Statistics: Those variables found to be statistically significant in univariate analyses were entered into multivariate regression models to predict the severity of subjective withdrawal.Results: No distinct subgroups could be identified despite substantial individual variability throughout the detoxification trajectory. The multiple regression results showed only four variables to predict the severity of withdrawal symptoms: baseline withdrawal symptoms, intravenous heroin use in the last 30 days, anxiety, and cluster C personality disorder. The variance explained by these sociodemographic variables was low while the largest amount of variance was explained by baseline withdrawal symptoms (27 percent).Conclusions: The results of the present study provide evidence that the severity of withdrawal symptoms during detoxification treatment is moderately predicted by the baseline severity of their withdrawal symptoms and not by drug- and patient-related characteristics.
Nebulized morphine for analgesia in an emergency setting
Authors: Bounes, MD Vincent , Ducassé, MD Jean Louis , Bona, MD Annie Momo , Battefort, MD Florent , Houze-Cerfon, MD Charles-Henri , Lauque, MD Dominique
Published: February 2018

Objective: To evaluate the efficacy and safety of inhaled morphine delivered in patients experiencing severe acute pain in an emergency setting.Patients and Methods: Patients were eligible for inclusion if they were aged 18 years or older, with a severe acute pain defined by a numerical rating scale (NRS) score of 60/100 or higher. The intervention involved administering a single dose of 0.2 mg/kg morphine nebulized using a Misty-Neb nebulizer system. NRSs were recorded and were repeated at 1, 3, 5, and 10 minute after the end of inhalation (T10). The protocol-defined primary outcome measure was pain relief (defined by an NRS score of 30/100 or lower) at T10. Secondary outcomes included differences between pain scores at baseline and at T10 and incidence of adverse events.Results: A total of 28 patients were included in this study. No patient experienced pain relief 10 minutes after the end of inhalation, and no adverse effects were recorded. Respective initial and final median NRS scores were 80 (70-90) and 70 (60-80), p < 0.0001. Despite achieving statistical significance, the value of this point estimate is less than the 14 NRS difference that was defined a priori as representing a minimum clinically significant difference in pain severity.Conclusion: 0.2 mg/kg nebulized morphine is not effective in managing acute pain in an emergency setting. In spite of the potential advantages of the pulmonary route of administration, opioids should be intravenous prescribed at short fixed intervals to control severe acute pain in an emergency setting.
The aging methadone maintenance patient: Treatment adjustment, long-term success, and quality of life
Authors: Rajaratnam, MD Ranjit , Sivesind, PhD David , Todman, PhD McWelling , Roane, MD David , Seewald, MD Randy
Published: February 2018

Objective: To evaluate the features and modes of adaptation to aging among Methadone Maintenance Treatment (MMT) enrollees.Setting: Beth Israel Medical Center in New York City.Participants: A sample of 156 MMT enrollees (103/66 percent males and 53/34 percent females) age 24-68 years. Twenty-nine percent of participants were aged 55 or older.Design: A cross-sectional, multivariate, correlational design.Outcome Measures: Participants were administered the MMSE, ASI, BSI, as well as measures of impulsiveness and quality of life (QOL).Results: Older adults were more likely to have had longer periods of treatment (p < 0.01), less likely to report current heroin use (p < 0.05) and overall drug use (p < 0.05), but were more likely to have a history of comorbid alcohol misuse (p < 0.01). Advanced age was also associated with less impulsiveness, hostility, paranoia, and interpersonal sensitivity (p < 0.01), more chronic medical problems (p < 0.05), greater use of medication for medical problems (p < 0.05), and more liberal take home medicine schedules (p < 0.01). However, no differences were found between older and younger participants with respect to their scores on the Overall Social Support scale (p > 0.05), the Personal Well-Being Index (p > 0.05) and the Satisfaction with Life Scale (p > 0.05), suggesting comparable levels of QOL. Furthermore, the rate of contact for older participants with medical professionals did not differ significantly from that of younger participants (p > 0.05). Only 7.1 percent of older participants reported regular contact with a primary care physician; a rate that is slightly lower than the rate in the overall population.Conclusions: The findings from the present study highlight at least two underappreciated challenges that clinicians are increasingly likely encounter in their work with the aging MMT population. These challenges are: (1) that despite numerous medical and psychiatric complaints, only a small proportion of MMT patients have regular contact with a primary care physician and the rate of contact does not appear to increase with age and (2) even with age-related declines in psychiatric comorbidity and illicit substance use, the suboptimal level of QOL that is characteristic of the MMT population as a whole does not improve with aging and length of tenure in MMT.
Buprenorphine: A review
Authors: Wakhlu, MD Sidarth
Published: February 2018

A significant breakthrough in the treatment of opioid addiction occurred with the passage of the Data Addiction Treatment Act of 2000 (DATA 2000),1 signed into law by President Clinton, which allowed physicians for the first time in more than eight decades to prescribe opioid medications for the treatment of opioid addiction in the normal course of their practice. Two years later, on October 8, 2002, Suboxone (Buprenorphine/Naloxone) and Subutex (Buprenorphine) received FDA approval for the treatment of opioid addiction. Prior to DATA 2000, opioid maintenance treatment was available through highly regulated methadone clinics. This article discusses opioid addiction in the United States today and the principles of buprenorphine therapy.
Pharmacological management of cancer pain
Authors: Montagnini, MD, FACP Marcos L. , Zaleon, PharmD Carolyn R.
Published: February 2018

Pain is one of the most common symptoms experienced by cancer patients during the course of their illness. It can negatively impact patients’ quality of life, functional status, and progress during rehabilitation. Despite the widespread availability of analgesic therapies, cancer pain remains undertreated. Developing knowledge and skills on cancer pain management is of extreme importance for healthcare providers dealing with cancer patients. The goal of this article is to review the principles of pharmacological therapy of cancer pain, to describe the basic pathophysiological mechanisms and etiologies of cancer pain, and to highlight the elements of a thorough pain assessment.