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Publications American Journal of Disaster Medicine Opioid Management
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January/February 2008; pages 8-10
January/February 2008; pages 11-12
January/February 2008; pages 13-17 Abstract 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. Key words: opioids, primary care, chronic noncancer pain, trilateral agreement
January/February 2008; pages 21-26 Abstract 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 ?9-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. Keywords: chronic pain, marinol, dronabinol, cannabinoids, serum blood screening, radioimmunoassay, marijuana, opioids
January/February 2008; pages 27-33 Abstract Background: Anesthesia and surgery are associated with impairment of the immune system expressed as an excessive proinflammatory immune response and suppression of cell mediated immunity. Opioids, an integral part of anesthetic technique, possess an inhibitory effect on both humoral and cellular immune responses. It was the aim of the present study to examine the effect of various doses of fentanyl on cytokine production during the perioperative period. Intervention: The effect of large (LDFA, 70-100 ?g/kg), intermediate (IDFA, 23-30 ?g/kg) and small (SDFA, 2-4 ?g/kg) doses of fentanyl on the immune function in the postoperative period was investigated. Participants: Sixty patients, randomly assigned to one of the three groups according to the dose of fentanyl were included in the study. Methods: The ex vivo secretion of IL-1?, IL-2, IL-6, and IL-10 and NK cell cytotoxicity (NKCC) of peripheral blood mononuclear cells (PBMC) was tested before, and at 24, 48, and 72 hours following surgery. Results: The pattern of postoperative secretion of the proinflammatory cytokines IL-1? and IL-6 and that of the anti-inflammatory cytokine IL-10 differed significantly between patients receiving SDFA and those receiving IDFA and LDFA, but was similar between the last two groups. A similar suppression of NKCC and IL-2 secretion was observed in the three groups. Conclusions: The diminished proinflammatory cytokine response observed in patients treated by LDFA and IDFA suggests that although more stable immune function can be achieved by those methods in comparison with SDFA, it is recommendable to apply IDFA to avoid the side effects that might be observed using LDFA method. Key words: fentanyl, surgery, cytokines, NK cell cytotoxicity
January/February 2008; pages 34-40 Abstract Aim: Inadequate sedative techniques may adversely affect morbidity and mortality in the intensive care unit (ICU), and the search for the ideal sedative agent continues. Combinations of hypnotics and opiates have are commonly used for sedation. In this study, the authors aimed to assess whether or not the addition of a haloperidol, propofol, or midazolam infusion decreased the sufentanil requirements by using bispectral index (BIS). Material and Methods: The study involved 60 patients in the ICU. All patients received 0.5 ?g/kg sufentanil IV bolus. Immediately after, group S received 0.25 ?g/kg sufentanil infusion, group SH received sufentanil infusion + haloperidol 3 mg/h infusion, group SP received sufentanil infusion + propofol 25 ?g/kg/min infusion, and group SM received sufentanil infusion + midazolam 0.04 mg/kg/h infusion, for 6 hours. Average BIS values 61-80 and Ramsay Sedation Score 2-5 were kept at a range of by decreasing or increasing sufentanil levels in all groups and hourly sufentanil consumption was determined. Hemodynamic and biochemical parameters and arterial blood gases were determined at baseline and were repeated in study hours. Results: There was no significant difference in hemodynamic and biochemical parameters and arterial blood gases among the groups. Propofol, midazolam, haloperidol infusion, when added to sufentanil infusion, decreased the consumption of sufentanil in all the measured times (p < 0.001). Conclusions: The authors aimed to determine the effects of haloperidol, propofol, or midazolam infusion when added to sufentanil infusion in a short period of time. The authors found that propofol, midazolam, and haloperidol infusion decreased the sufentanil requirements in ICU patients. Key words: sedation, sufentanil, haloperidol, propofol, midazolam, bispectral index, intensive care unit
January/February 2008; pages 41-47 Abstract 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 (?2 = 52.98, p < 0.000) and Trail Making Test-A (?2 = 26.29, p < 0.000) and B (?2 = 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. Key words: buprenorphine, psychomotor effects, maintenance treatment, opioid dependence
January/February 2008; pages 49-53 Abstract The aim of this double-blind double-dummy randomized controlled trial was to investigate if there was any difference in analgesia between the maximum recommended doses of rectal diclofenac and iv parecoxib after laparoscopic sterilization. The authors studied 55 ASA I-II patients undergoing gynecological laparoscopy; each patient received either preoperative rectal diclofenac 100 mg and 2 mL of normal saline at induction of anesthesia, or preoperative placebo suppository and 2 mL of parecoxib 40 mg at induction. Pain intensity, sedation, and nausea were measured using a 100-mm visual analogue scale on awakening and at 1, 2, and 3 hour postoperatively. Median (interquartile range) pain intensity at rest on awakening and at 1, 2, and 3 hour postoperatively were 15 (0-40), 37 (10-56), 16 (6-29), and 13 (2-32) mm, respectively, in the parecoxib group, and 3 (0-34), 22 (5-45), 24 (6-37), and 10 (4-21) mm, respectively, in the diclofenac group. There was no significant difference in these scores. Furthermore, there was no significant difference between the two groups in sedation, nausea, rescue analgesia, or rescue antiemetic consumption. Preoperative rectal diclofenac 100 mg and parecoxib 40 mg iv at induction of anesthesia were found to have equianalgesic effects after laparoscopic sterilization. Both drugs appear to be useful after short anaesthetics. Key words: analgesics anti-inflammatory, cyclooxygenase- 2 inhibitors; analgesics nonopioid, diclofenac; analgesics nonopioid, parecoxib, randomized trial
January/February 2008; pages 54-56 Abstract 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. Key words: pain, sedation, opioids, tol Journal of Opioid Management March/April 2008, Volume 4, Number 2
March/April 2008; pages 63-71 Abstract Objective: The purpose of this study is to describe the sample characteristics and methods for a study of rural medical and nonmedical prescription opioid users with a history of OxyContin® use. Design and setting: Snowball sampling was used to recruit 221 rural Appalachian residents. Participants included those under medical supervision for pain (n = 101) as well as those self-reporting nonmedical use of prescription opioids (n = 120). Participants were given an interviewer-administered questionnaire. Outcome measures: Data relating to demographics, illicit and nonmedical prescription drug use, medical, legal, family, and psychiatric status, as well as pain history were collected. The primary outcomes of interest were differences in past 30 day prescription drug use between pain patients and nonmedical opioid users. Results: A significantly greater proportion of those treated for pain reported using oxycodone and hydrocodone prescribed by a physician in the prior 30 days (p < 0.001); however, more than third of pain participants also reported nonmedical use of OxyContin®, methadone, hydrocodone, benzodiazepines, and marijuana in the prior 30 days. Conclusions: A large proportion of rural opioid users who reported being treated for pain also reported nonmedical use of prescription drugs. Similarly, among the nonmedical users, half of those reported experiencing pain that interfered with their daily life. These results suggest that many rural prescription drug users are being either incorrectly or perhaps inadequately treated for chronic nonmalignant pain. Therefore, developing educational materials and training for rural physicians about pain treatment (including drug seeking behavior) is proposed. Key words: rural, Appalachia, pain, opioid
March/April 2008; pages 73-79 Abstract Objective: This study was designed to describe and compare individuals in rural Appalachia prescribed, abusing or diverting OxyContin® a region with high rates of prescription medication abuse and misuse. Setting and Participants: Fifty subjects treated for OxyContin® abuse, 34 subjects prescribed OxyContin® for pain and 50 subjects incarcerated due to OxyContin®-related charges from rural Appalachia. Interventions: The Addiction Severity Index, DSM-IV Checklist, and an investigator developed questionnaire were administered to all three groups. Results: All three groups included individuals prescribed OxyContin® for pain and demographic variables and psychiatric/medical histories failed to discriminate between the pain and substance abuse (SA) subjects. SA and criminal justice subjects were significantly more likely to have a current DSM-IV diagnosis of psychoactive abuse/dependence and more likely to be younger and unmarried. Conclusion: This study found that these groups are not distinct and in depth evaluations, including a detailed SA history, are needed to identify the pain patient at risk for abuse and/or diversion of prescribed opioids. Key words: prescription medication misuse and abuse, OxyContin (TM), pain patients, criminal justice, substance abuse
March/April 2008; pages 81-86 Abstract 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. Key words: HIV, AIDS, incarceration, Criminal Justice System, prison, opioids, buprenorphine, methadone, prisoners
March/April 2008; pages 87-97 Abstract 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. Key words: tramadol, back pain, disability, sleep
March/April 2008; pages 99-104 Abstract Background: There are no studies reported on pharmacokinetics of opioids in patients with hepatocellular carcinoma, the fifth most common cancer in the world. Methods: The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls. Plasma tramadol concentrations were measured in venous samples at intervals up to 12 hours by high-pressure liquid chromatography. All pharmacokinetic variables were evaluated using one-compartment model. Results: Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively). The area under the serum concentration-time curve increased significantly in patients with primary and metastatic cancer of liver than in control [1,933 ?g/h/L (SD = 41), 1,327 ?g/h/L (SD = 51), 1,138.5 ?g/h/L (SD = 31), respectively]. Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control. Reduced clearance and impaired elimination was significantly observed in patients with liver carcinoma than control. Clearance was reduced to 50 percent of control, and elimination halflife increased up to three folds in patients with primary liver carcinoma than that of control. Satisfactory pain relief with minimal side effects was observed all over study period. Conclusion: It is recommended to lengthen the dose interval of oral tramadol, if it is to be used in patients with liver cancer for analgesic purposes, to 50 mg every 12 hours as it is proved to be effective and safe. Key words: analgesics, opioid, tramadol, liver, carcinoma, pharmacokinetics
March/April 2008; pages 105-110 Abstract Background: Magnesium sulphate administration was initially reported to reduce postoperative analgesic requirements. Subsequent reports, though, were inconsistent. Specifically, we tested the hypotheses that intraoperative magnesium sulfate administration reduces postoperative requirement for opioids, secondary outcomes were intraoperative muscle relaxant, sevoflurane consumptions and postoperative pain. Methods: Fifty American society of anesthesiology status (ASA) I-II patients who gave a written informed consent were scheduled for elective lumbar disc surgery. The Institutional Review Board approved the study. Patients were randomly assigned to the placebo group (n = 25) or magnesium group (n = 25). Patients assigned to the magnesium group were given an initial infusion of 30 mg/kg (over 10 minutes) starting immediately after anesthesia and completed before intubation. The infusion was then continued at 10 mg/kg/hr throughout surgery. General anesthesia was induced with propofol, 2.5 mg/kg, and maintained with sevoflurane 2 percent in a 50 percent O2/50 percent N2O mixture. The sevoflurane concentration was adjusted to keep bispectral index (BIS) values between 45 and 60. Both groups were given atracurium, 0.6 mg/kg, and a remifentanil infusion at an initial dose of 0.1 mg/kg/h. The remifentanil infusion was adjusted to maintain heart rate and mean arterial pressure (MAP) within 20 percent of baseline values. Atracurium administration was repeated when the train of four (TOF) ratio exceeded 0.30. Intubation conditions were scored. At the end of surgery, the authors assessed recovery using early recovery criteria and Aldrete recovery scores. Postoperative analgesia was maintained with morphine via patient-controlled analgesia. Results: Heart rate, MAP, and pulse oximetry (SPO2) values were similar in the groups at all times. Intubating conditions were similar except that the increase in MAP was greater in the placebo group. Neither BIS values nor sevoflurane consumption differed between the groups; however, significantly less atracurium [95% CI = 4.1 (2.8, 5.5)] and remifentanil [95% CI = 0.14 (0.07, 0.20)] was used in the magnesium group. Side effects, Aldrete scores, and early recovery parameters were all similar in the groups. In the first 24 hours, visual analogue scale (VAS) values for pain were greater in the placebo than in the magnesium group. The magnesium group consumed significantly less morphine [95% CI = 11 (6, 16)]. Conclusion: Intraoperative magnesium administration significantly reduced muscle relaxant and opioid requirements; more importantly, it also reduced postoperative pain and opioid use. Key words: magnesium, postoperative, pain
March/April 2008; pages 111-115 Abstract Background: Chronic noncancer pain is often undertreated. Aims: To assess the efficacy of fentanyl transdermal therapeutic system (TTS) associated with oral transmucosal fentanyl citrate (OTFC) for breakthrough pain in patients with chronic noncancer pain. Methods: A total of 215 patients with chronic (= 6 months), severe (VAS = 8) noncancer pain participated in a 6-month prospective study. The starting dose of 12 ?g/h fentanyl TTS was titrated in 25 ?g/h increments to a visual analog scale (VAS) score = 4. OTFC was administered as single-unit doses of 400 ?g. Results: The mean (SD) VAS score decreased from 9.86 (0.35) at baseline to 2.05 (0.96) at 6 months. The percentage of patients with poor quality of sleep decreased from 99 percent at baseline to 2.8 percent at the end of the study. The percentage of patients with inadequate pain control decreased from 16.2 percent at month 1 to 2.3 percent at month 6. Pain control was achieved with the 50 ?g/h dose in 48 percent of patients, the 75 ?g/h dose in 18 percent, and the 100 ?g/h dose in 5 percent (only two patients required > 100 ?g/h). The daily use of single-unit doses of OTFC decreased from 4.64 at month 1 to 2.62 at month 6. Headache, nausea/vomiting, constipation, and somnolence of mild or moderate intensity were the most common side effects. Treatment was discontinued because of nausea/vomiting in seven patients, somnolence in three, and dermatitis in two. Conclusions: Fentanyl TTS associated with OTFC for breakthrough pain is a feasible and effective strategy in opioid naďve patients with severe chronic nonmalignant pain. Key words (MeSH terms): pain/drug therapy; fentanyl/ administration & dosage; fentanyl/adverse effects; chronic disease/drug therapy; analgesics/opioid Journal of Opioid Management May/June 2008, Volume 4, Number 3
May/June 2008; pages 123-130 Abstract 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. Key words: opioids, pain, opioid-induced hyperalgesia, intensivists
May/June 2008; pages 131-132 Abstract The treatment of chronic pain remains an enormous challenge in the United States. Opioid analgesics are an important component of pharmacotherapy for chronic pain and have proven efficacy in the management of cancer and noncancer chronic pain. The newest addition to oral opioid pharmacotherapy is oral oxymorphone, a semisynthetic opioid agonist that is now available in oral immediate-release (IR) and extended-release (ER) formulations. This review discusses the pharmacology, pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and clinical use of oral oxymorphone IR and ER formulations for the management of moderate to severe pain for different types of patients in a variety of settings. Two published studies evaluated the efficacy and safety of oxymorphone IR in patients with moderate to severe postoperative pain and demonstrated that it provides rapid and effective analgesia and is generally well tolerated. Six published randomized controlled trials and three published open-label studies evaluated the efficacy and safety of oxymorphone ER for chronic cancer or noncancer pain. These trials found analgesic efficacy and tolerability comparable to that provided by morphine controlled release (CR) or oxycodone CR; treatment effects with oxymorphone ER were durable for treatment periods of 12 weeks at the same dose or up to 1 year with little dose escalation. Titrated doses of oxymorphone ER were effective and generally well tolerated in both opioid-experienced and opioid-naďve patients. Aspects of oxymorphone metabolism and limited protein binding may simplify treatment in certain populations. Key words: opioids, analgesics, pain management, oxymorphone, pharmacokinetics, pharmacodynamics
May/June 2008; pages 145-152 Abstract Objective: To describe opioid pharmacy claims patterns in the United States among an insured population. Design: Information was obtained from the US insurance claims database, IMS Lifelink™, between 1997 and 2002. Descriptive statistics of opioid claims patterns were described with stratification by gender, age, and year of use. Results: The prevalence of insured people with opioid claims increased from 17.1 percent in 1997 to 18.4 percent in 2002. Among people with an opioid claim, 24 percent had =30 days and 10 percent had =90 days of days supplied based on the insurance claims. Prevalence varied by type of opioid; 56 percent of people with a claim received propoxyphene, 43 percent received codeine, 23 percent received oxycodone, and 17 percent received hydrocodone. Sustained-release opioids were found among 6 percent of those with a claim. With respect to the dose of opioids in the pharmacy claims (expressed as morphine equivalent total daily dose), 71 percent had claims for <50 mg, 55 percent had claims for 50-99 mg, and 24 percent had claims for =100 mg. Women, individuals with cancer, and older patients had significantly more pharmacy claims as well as claims for higher doses of opioids (p < 0.05). Internal medicine and family practice specialists were responsible for 22.4 percent and 20.9 percent of all opioid claims. Conclusions: Opioid pharmacy claims increased slightly over time. Older patients, women and patients with a cancer diagnosis had significantly more opioid claims and claims for higher doses than the younger patients, men, and those without cancer. Key words: opioid, epidemiology, pharmacy, insurance claims
May/June 2008; pages 153-162 Abstract 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. Key words: patient satisfaction, back pain, opioids, prescription medication, low back pain
May/June 2008; pages 163-166 Abstract 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. Key words: epidural haloperidol, epidural morphine, analgesia, epidural analgesics
May/June 2008; pages 167-171 Abstract 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. Key words: neuropathic face pain, opioid therapy, behavioral therapy, psychological treatment, opioid taper, appliance therapy
May/June 2008; pages 173-180 Abstract 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 patientcontrolled 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. Key words: pain, acute, oncologic, breakthrough; ketamine, opioids, tolerance, dependence Journal of Opioid Management July/August 2008, Volume 4, Number 4
July/August 2008; pages 187-191 Abstract 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. Key words: dexmedetomidine, withdrawal, Finnegan score
July/August 2008; pages 193-196 Abstract Background: Although opioid analgesics are effective therapeutic agents, gastrointestinal (GI) side effects represent a challenging consequence of treatment. In an elderly population, age-related physiological changes, such as decreased GI functioning and dehydration, may compound the adverse effects of opioids; therefore, appropriate prophylactic treatment, utilizing laxatives and/or acid suppressants, is particularly important in an elderly population. Aim: This study describes the prevalence of outpatient opioid dispensings and the concomitant dispensing of opioids and GI medications in a population 65 years or older enrolled in the Ontario Drug Benefit Program in 2005. Methods: Using a retrospective cohort design, dispensings of opioids, laxatives, and acid suppressants were identified using claims reimbursement data. Concurrent dispensings were defined as having at least one “GI medication-dispensed day” overlapping an “opioid-dispensed day.” Results: More than 18 percent of the elderly, drug plan population was dispensed an opioid in 2005. Women had more opioid dispensings and were dispensed opioids for extended periods of time as compared with men. Approximately half of patients with an opioid dispensing were concomitantly dispensed a GI medication; these medications were dispensed nearly twice as frequently among people with chronic opioid dispensings when compared with people with nonchronic opioid dispensings. Conclusions: Although laxatives are commonly recommended in patients taking opioids, only half of the older adults in Ontario who were dispensed an opioid also received a concomitant GI medication dispensing. As the elderly are more likely to develop opioid-induced constipation, the prophylactic use of laxatives and/or acid suppressant medications is often necessary to mitigate the side effects associated with their pain management. Key words: opioid, elderly, epidemiology, laxative, upper GI medication, dispensings, prevalence
July/August 2008; pages 201-211 Abstract 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. Key words: medical education, chronic nonmalignant pain, Internal Medicine, chronic noncancer pain
July/August 2008; pages 213-250 Abstract 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. Key words: opioid rotation/opioid switching/opioid substitution, guidelines/recommendations/decision making, cancer pain, morphine, genetic polymorphism/ intraindividual variability in response, alternative opioids, methadone, opioid rotation/outcome
July/August 2008; pages 251-254 Abstract Ultra low doses of opioid antagonists such as naloxone block excitatory opioid receptor pathways may paradoxically enhance morphine analgesia. This case study reports safety and efficacy of ultra low-dose intrathecal (IT) naloxone added to IT morphine for the treatment of severe refractory chronic low back pain. A 56-year-old man with a history of severe chronic low back pain (postlaminectomy syndrome) was evaluated. Extensive multidisciplinary therapies had all failed. Initial treatment at our clinic was a lumbar IT trial of morphine (unsuccessful) up to 50 mg/day. We administered an IT bolus of morphine 2 mg combined with IT naloxone of 20 ng with the patient’s consent and approval. The onset of pain relief was within 20 minutes and peaked at 1 hour with a 50 percent reduction in VAS pain score. There were no signs of adverse drug toxicity or hemodynamic compromise. An IT infusion of daily morphine 5 mg and naloxone 50 ng was started. Throughout the 3-year follow-up period, the patient maintained pain reduction of 60 to 80 percent, with a return to daily activities and no further hospitalizations. Key words: intrathecal naloxone, intrathecal morphine, analgesia, spinal analgesics
July/August 2008; pages 255-259 Abstract 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. Key words: edema, epidural hydromorphone infusion, epidural morphine infusion, intraspinal drug delivery, failed back surgery syndrome Journal of Opioid Management September/October 2008, Volume 4, Number 5
September/October 2008; pages 267-267
September/October 2008; pages 271-283 Abstract Objective: To assess the prevalence of opioid-related deaths in patients in an interventional pain management tertiary referral center. Methods: Patient deaths from March 2003 to February 2007 were evaluated. Results: From March 2003 to February 2007, 2,179 patients were receiving opioids in 2003, 2,445 in 2004, 2,804 in 2005, and 2,965 in 2006, respectively. Overall, 86 percent of the patients were referred by a physician and 90 percent of patients received interventional techniques. There were a total of 91 deaths, of which 60 were categorized as natural deaths, 25 were characterized as accidental deaths, and 6 were characterized as suicidal. Of the 18 drug poisoning deaths, 5 deaths were positively related to prescription drugs, 7 deaths were probably related to prescription drugs, and 6 deaths had no relation to the prescription drugs provided. Total opioid-related deaths were 12 over this 4-year period with 0.46 in 2003, 2.04 in 2004, 2.85 in 2005, and 1.35 in 2006 per 1,000 population. In contrast, deaths definitely related to prescription opioids were 5 (0.92 per 1,000) over a period of 4 years. In the suicidal group, there were a significantly higher proportion of patients with generalized anxiety disorder. Conclusions: In an interventional pain management practice (a tertiary referral center), the total prevalence of opioid-related deaths varied from 0.46 to 1.78 per 1,000 from 2003 to 2006 with a total of 12 deaths over a period of 4 years. The deaths definitely related to opioid prescriptions were 5 with a rate of 0 to 1.43 per 1,000 over a period of 4 years. Key words: drug poisoning deaths, opioids, benzodiazepines, nonmedical use of prescription drugs, psychotherapeutic drugs, hydrocodone, methadone
September/October 2008; pages 285-292 Abstract 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. Key words: acute, low back pain, tramadol, oncedaily, onset, clinical trial, pain relief, pharmacokinetic
September/October 2008; pages 293-304 Abstract 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. Key words: intrathecal drug delivery, cancer pain, chronic pain
September/October 2008; pages 305-309 Abstract 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. Key words: remifentanil, desflurane, pharmacology, drug interaction, surgery
September/October 2008; pages 311-319 Abstract 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. Key words: substance dependence, opioid, detoxification, withdrawal, prediction
September/October 2008; pages 321-327 Abstract Objective: To assess changes in hospital morbidity associated with heroin use from pre-initiation, recreational to dependent use, and changes following treatment. Design: Analysis of hospital admission data assessed over six, 6-month periods (before and after heroin initiation; two dependent heroin use periods; and post-oral and post-sustained release naltrexone treatment). Participants: A sequential cohort of 139 patients for whom date of initial heroin use, regular heroin use, and two periods of heroin dependence (prior to treatment with oral and implant naltrexone) were known. Outcome Measures: The West Australian Data Linkage System was used to assemble hospital admission data. Admissions were analyzed as follows: “all cause” admissions and then subgrouped as “mental health (MH) other,” “MH opioid related,” “MH non-opioid drug related,” and “opioid overdoses.” Results: The database identified 130 (94 percent) of the participants with 76 (59 percent) being male. The mean length of follow-up from first heroin use was 9.4 (SD 4.9) years. Significant increases in morbidity were not found in the periods pre-first and post-first heroin use, but were found from pre-heroin use to dependent use for “all cause,” “MH opioid related,” and “opioid overdose” admissions. A significant decline in these measures was observed from the first dependent period to the post-implant period. “MH opioid related” admissions declined from the first to the second period of dependent heroin use. Conclusions: Findings suggest that the movement to dependent heroin use increases hospital morbidity; that morbidity in the presence of treatment does not necessarily increase; and the treatment with a sustained release preparation may be more effective than oral naltrexone in arresting morbidity. Key words: heroin, hospital, naltrexone, morbidity Journal of Opioid Management November/December 2008, Volume 4, Number 6
November/December 2008; pages 335-344 Abstract Objective: To describe the pharmacokinetics of hydromorphone (HM) and its primary metabolite hydromorphone- 3-glucuronide (H3G) both on and off dialysis in relation to the pharmacodynamic measurements of pain. Design: Prospective, open-label, observational study. Setting: Canadian, university-based renal program. Participants: Twelve anuric hemodialysis patients with chronic pain, established on immediate-release HM. Main Outcome Measures: HM and H3G plasma concentrations were measured during and between hemodialysis treatments using a reverse-phase highperformance liquid chromatography assay with liquid chromatography/mass spectrometer/mass spectrometer detection. The McGill Pain Questionnaire (MPQ) and a Visual Analogue Scale (VAS) were used to measure pain. Noncompartmental analyses were conducted. Adverse effects were recorded. Results: HM did not substantially accumulate (accumulation factor R = 2.7 (1.6)), most likely due to the rapid conversion to H3G. Conversely, H3G accumulated between dialysis treatments (R = 12.5 (12.1)) but appeared to be effectively removed during hemodialysis (1.8 (0.7), p = 0.03). HM resulted in > 65 percent reduction in pain over dosing intervals. Mean MPQ pain scores decreased from 39.8 (18.2) to 12.3 (16.2) on dialysis and from 35.0 (18.5) to 15.5 (13.6) between dialysis treatments. Mean VAS pain scores decreased from 7.5 (2.5) to 3.0 (1.5) on dialysis and from 5.9 (3.2) to 4.4 (1.6) between dialysis treatments. No clinically significant opioid toxicity was observed. The accumulation of H3G between hemodialysis treatments was associated with greater sensory-type pain (r = 0.76, p < 0.0001) and reduced duration of analgesia. Conclusions: HM may be a safe and effective opioid for use in selected hemodialysis patients. Key words: kidney failure, dialysis, opioids, hydromorphone, hydromorphone-3-glucuronide, pharmacokinetics, pharmacodynamics, chronic pain
November/December 2008; pages 345-349 Abstract 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. Key Words: tramadol, perineural, nerve block, nerve conduction, electroneurography
November/December 2008; pages 351-360 Abstract 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. Key words: chronic spinal pain, facet joint pain, controlled diagnostic blocks, facet joint blocks, lidocaine, bupivacaine, prevalence, false-positive rates, opioids
November/December 2008; pages 361-368 Abstract 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. Key words: cancer pain management, WHO analgesic ladder, opioids
November/December 2008; pages 369-381 Abstract Opioid treatment programs (OTPs) dispense methadone and buprenorphine under specific federal regulations to individuals diagnosed with opioid dependence. OTPs can provide a comprehensive therapeutic milieu, often including primary medical care, psychosocial counseling, vocational rehabilitation, ongoing performance monitoring, and other vital services. Because of the high prevalence of infectious diseases, particularly hepatitis C virus infection, model OTPs are developing comprehensive care and treatment programs that integrate general medical and infectious disease-related medical care with substance abuse and mental health services. Integrating hepatitis care services in the substance abuse treatment settings fosters access to care for patients with multiple comorbidities, many who otherwise would not receive needed care. Improving health related outcomes for this patient population with complex medical problems requires an advanced integrated model of care for OTPs that can be exemplified through establishing resources needed to prevent hepatitis infection as standard of care. Outcomes management becomes possible through enhancing current capability of existing dispensing programs. This may serve as a national model for highly cost-efficient healthcare that has a measurable outcome of improved health. Key words: hepatitis, methadone, health services, opioid treatment programs
November/December 2008; pages 383-391 Abstract Objective: To describe the rationale behind the choice of fentanyl administration forms as reported by Danish nurses and physicians specializing in pain management. Methods: Sixty nurses and 60 physicians specializing in pain management in Denmark were contacted via an Internet survey system to perform two Delphi surveys. In the brainstorming phase, the main reasons for administering and not administering fentanyl patches and oral transmucosal fentanyl citrate (OTFC) were identified. In the second phase, the nursing and medical experts rated the importance of these reasons on an 11-point Numerical Rating Scale. Results: Responses from 10 pain nurses and 14 pain doctors were used for the final analysis. Impossible or difficult oral intake of analgesia was the most important reason to administer fenantyl patches, whereas patients’ dermatological problems and neuropathic pain origin were the most important reasons for not administering fenantyl patches in both panels. OTFC was presented as an alternative or second choice administration form for breakthrough cancer pain by both nurses and doctors. A damaged mouth, the high cost, and energy required for administration of this medication were reported as the main reasons why OTFC was only rarely prescribed to cancer pain patients in Denmark. Conclusions: The reasons for administering fentanyl in different administration forms reported by Danish pain nurses and pain specialists partly differed from those derived from the literature. Studies of pain management traditions could improve the understanding of the reasons for analgesic administration. Key words: fentanyl, administration forms, nurses, pain specialists, rationale, Delphi survey, Denmark |
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