Strong Analgesics Research Articles

A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Study to Assess the Effects of Long-Term Opioid Drug Consumption and Subsequent Abstinence in Chronic Noncancer Pain Patients Receiving Controlled-Release Morphine

The long-term use of strong opioid analgesics among chronic noncancer pain (CNCP) patients remains controversial because of concerns over problematic drug use. However, previous surveys suggest that this is not necessarily the case. Therefore, we designed a controlled study to generate evidence in support of these findings. Ten CNCP patients attending the pain clinic in a district general hospital had been taking an average daily dose of 40 mg controlled-release morphine sulphate (mean 40, range 10-90, SD 21 mg), for an average of 2 years (mean 2.175, range 2-2.25, SD 0.2 years). Randomized, double-blind, placebo controlled cross-over study. The study was based on the premise that abrupt cessation of opioid drugs is most likely to highlight problematic use and the consequent inability to stop using opioids. Morphine was substituted with placebo for 60-hour periods to compare the effects of abstinence with those of continued use. Assessment of morphine cessation and abstinence effects was through direct observation, physiological measurements, questionnaire responses, and Brief Pain Inventory scores. Following cessation and abstinence, there were no indications of psychological dependence or drug craving, but there was evidence of the detrimental effects of pain intensity on activity, mood, relationships, sleep, and enjoyment of life. Three patients (30%) reported opioid drug withdrawal symptoms. Pharmacokinetic data demonstrated compliance with abstinence by all patients. The results suggest the existence of a group of CNCP patients whose long-term opioid consumption can be beneficial and remain moderate without them suffering from the consequences of problematic opioid drug use.

Successful Treatment of Buerger's Disease with Intramedullary K-wire: The Results of the First 11 Extremities

Objective This study describes a new technique for treatment of Buerger's disease, developed to stimulate angiogenesis, using a Kirschner wire placed in the medullary canal of the tibia. The aim of the study was to evaluate clinical and radiological effects of this technique in patients where medical and surgical therapy had failed. Material and methods Eleven extremities (six patients) with Buerger's disease were treated with the intramedullary Kirschner wire technique. Inclusion criteria were chronic critical ischemia, Rutherford Grade II or III, with major arterial occlusion shown by Doppler examination and angiography; failure to respond to non-surgical and surgical treatment; and the need for strong analgesics. Results The mean follow-up time was 19 months (range, 13–25 months). Satisfactory remission in each patient was obtained within 6 weeks of intervention. A significant improvement in clinical manifestations including reduced rest pain and increased claudication distance was observed. Foot ulcers completely healed after Kirschner wire intervention. Conclusion Despite short-term follow-up and small patient series, the intramedullary Kirschner wire technique can be expected to achieve relief of pain and a decrease in major amputations in patients with Buerger's disease in whom medical and surgical therapy had failed. However, comparative studies with longer follow-up should be done to confirm the benefits of this new treatment.

Intermittent Subcutaneous Methadone Administration in the Management of Cancer Pain

Methadone is a strong opioid analgesic that has been used successfully in cancer pain management. The oral route of administration is generally preferred for opioid analgesics. However that route sometimes cannot be used. Experience with continuous subcutaneous methadone infusions has produced local intolerance. The aim of this study was to analyze the use of intermittent subcutaneous methadone injections. Ten patients whose pain was well-controlled with oral methadone (average dose 30 mg, range 10 to 120 mg) participated in the study. A subcutaneous small vein needle (butterfly) was used exclusively for administration of methadone. Over a period of seven days the local discomfort of each injection was evaluated by means of a Verbal Numerical Rating Scale (NRS) and the site of infusion was observed. When any degree of erythema or inflammation was seen, the infusion site was changed. The initial subcutaneous dose was the same as the previously administered oral dose. A daily record was kept of the dose used, level of pain, and toxicity symptoms. This close vigilance was aimed at avoiding dosage errors due to variations among individuals in acceptance to previous oral medication. Changes in dosage were allowed according to standard medical criteria. Two patients were withdrawn from the study due to non-painful irritation at the infusion point. Another eight patients tolerated repeated administration of subcutaneous methadone over seven days. Any local irritation from subcutaneous methadone that occurred was managed satisfactorily by changing the infusion site and limiting doses to 30 mg. In seven of 182 repeat administration, injection site changes were necessitated by local irritation. The NRS for local discomfort was 2/10. The two patients who were intolerant of the subcutaneous injections were receiving injected doses which were significantly higher than the others (42 mg as compared to 25 mg). Dose adjustments needed when changing from the oral to the subcutaneous methadone route were minimal. Subcutaneous intermittent administration of methadone appears to be a useful alternative to oral administration in selected clinical situations when oral administration is not feasible.

Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: A single-center, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model

Background: The combination of tramadol and acetaminophen has demonstrated good efficacy in various clinical pain models. However, there is a need for comparisons of the onset of analgesia and other measures of analgesic efficacy with this combination and other strong combination analgesics for the management of acute pain.Objective: The goal of this study was to compare the time to onset of analgesia and other measures of analgesic efficacy with tramadol/acetaminophen 75/650 mg (Tr/Ac) and codeine/acetaminophen/ibuprofen 20/500/400 mg (Co/Ac/Ib) in the management of acute pain after oral surgery.Methods: This was a single-center, single-dose, randomized, active-controlled, parallel-group study in healthy subjects who had undergone surgical extraction of ≥1 impacted third molar requiring bone removal. When patients reported at least moderate pain after dental surgery (score ≥5 on a 10-point scale), they were randomized to 1 of 2 treatment groups. The time to onset of analgesia was measured using a 2-stopwatch technique. The time to the onset of perceptible and meaningful pain relief, pain intensity, pain relief, patient's overall assessment, and adverse events were recorded for 6 hours after dosing.Results: One hundred twenty-eight subjects participated in the study, 64 in each treatment group. The 2 groups were similar in terms of baseine pain severity and demographic characteristics (mean age, 23.7 and 23.4 years in the Tr/Ac and Co/Ac/Ib groups, respectively; mean body weight, 58.5 and 60.3 kg). The median times to the onset of perceptible pain relief were a respective 21.0 and 24.4 minutes, and the median times to the onset of meaningful pain relief were 56.4 and 57.3 minutes. Mean total pain relief and the sum of pain intensity difference were also similar in the early period after dosing (0–4 hours). However, between 4 and 6 hours, Co/Ac/Ib was associated with significant differences in both variables compared with Tr/Ac (P < 0.05). Although similar through the 4-hour assessment, mean pain intensity difference was significantly greater with Co/Ac/Ib at 5 to 6 hours. The proportion of patients assessing their assigned treatment as good or better was significantly greater with Co/Ac/Ib compared with Tr/Ac (P < 0.05). The safety profile of Tr/Ac was comparable to that of Co/Ac/Ib.Conclusions: In this small and selected group of subjects, the onset of analgesia and analgesic efficacy of Tr/Ac was comparable to that of Co/Ac/Ib. Tr/Ac provided rapid and effective analgesia for acute postoperative dental pain in this population.

Low doses of fentanyl block central sensitization in the rat spinal cord in vivo.

mu-Opioid receptor agonists are strong analgesics. However, their usefulness for preemptive analgesia is controversial. The authors tested antinociceptive and preemptive properties of fentanyl as a mu-opioid receptor agonist in a model of spinal nociception in vivo. C fiber-evoked potentials were recorded in the superficial laminae I-II of the rat lumbar spinal cord with glass microelectrodes in response to electrical stimulation of the sciatic nerve. High-frequency stimulation was applied on the sciatic nerve to induce long-term potentiation of C fiber-evoked field potentials, a form of central sensitization. To test the effect of fentanyl on acute nociception, fentanyl was infused intravenously at increasing doses (6-192 microg.kg(-1).h(-1)). One hour after start of infusion, high-frequency stimulation was applied to evaluate effects of fentanyl on the induction of long-term potentiation. In the absence of fentanyl, high-frequency stimulation potentiated C fiber-evoked field potentials to 149 +/-12% of controls (mean +/-SEM; n = 6) for at least 1 h. Increasing doses of fentanyl led to a significant reduction of C fiber-evoked potentials in a dose-dependent manner. The induction of long-term potentiation was blocked by low doses of fentanyl (infusion 12-48 microg.kg(1).h(-1)). At high doses, fentanyl did not block the induction of long-term potentiation (infusion 96-192 microg.kg(-1).h(-1)). : Low doses of fentanyl block the synaptic form of central sensitization in the rat spinal cord in vivo, but higher doses do not have this effect.

Variability in emergency physician decisionmaking about prescribing opioid analgesics

Study objective The purpose of this study is to determine what factors influence emergency physicians' decisions to prescribe an opioid analgesic for 3 common, painful conditions. Methods We developed items thought to influence the decision to prescribe an opioid analgesic through a review of the literature, expert consultation, and interviews with practicing emergency physicians. We developed a baseline vignette and items expected to influence the decision for each of the 3 conditions: migraine, back pain, and ankle fracture. We surveyed 650 physicians randomly selected from the American College of Emergency Physicians. The influence of individual items was explored through a univariate analysis of the response distribution. Patterns were assessed by analytically creating scales. Results We received responses from 398 (63%) of the 634 eligible physicians. Physicians' likelihoods of prescribing an opioid showed marked variability, with at least 10% of physicians saying they were unlikely and 10% of physicians saying they were likely to prescribe for each condition. Physician responses to individual pieces of clinical information, such as the patient requesting “something strong” for the pain, were also highly variable, with at least 10% of physicians saying they would be negatively influenced by this request and at least 10% saying they would be positively influenced by it. Conclusion Even when faced with identical case scenarios, physicians' decisions to prescribe opioid analgesics are highly variable. Moreover, the same clinical information, such as a patient requesting a strong analgesic, changes the likelihood of prescribing opioids in opposite directions for different physicians.

Functional inhibition by methadone of N-methyl-D-aspartate receptors expressed in Xenopus oocytes: stereospecific and subunit effects.

Methadone is a strong opioid analgesic that is finding increasing use in chronic pain therapeutics. We explored its reported efficacy for inhibiting N-methyl-D-aspartate (NMDA) receptors in a functional electrophysiologic assay (Xenopus laevis oocyte expression). Racemic methadone inhibited all subtypes of rat NMDA receptors with derived 50% inhibitory concentrations in the low micromolar range. These concentrations overlap with clinically achievable concentrations reported in pharmacokinetic studies. In contrast, morphine inhibited these functional ion channels only at 8-16 times larger concentrations. The NR1/2A and NR1/2B subtype combinations were in general significantly more sensitive to inhibition by methadone and morphine compared with the NR1/2C and NR1/2D subtypes. In the presence of racemic methadone, the maximum NMDA-stimulated currents were markedly decreased, but the NMDA concentration producing 50% of maximal activation was altered only slightly, indicating that methadone blocks by a noncompetitive mechanism. Although stereoisomers of methadone showed minimal stereoselectivity in most subtypes, R(-) methadone was highly selective in its inhibition of the NR1/2A combination. These results provide further functional data describing the NMDA receptor inhibitory actions of methadone and support the hypothesis that methadone acts through both opioid and NMDA receptor mechanisms. At clinically achievable concentrations, methadone inhibits functional N-methyl-D-aspartate receptors. These results indicate a unique mode of action by this opioid that may enhance its ability to treat chronic pain and to limit opioid tolerance.

Use of transdermal fentanyl without prior opioid stabilization in patients with cancer pain

SUMMARYObjective: To determine the safety and efficacy of transdermal fentanyl for pain relief in cancer patients and to compare the effects on patients according to whether they had previously received strong opioids, weak opioids or non-opioid analgesia.Methods: Cancer patients requiring strong analgesia were recruited into an open-label, multicentre study, conducted in eight countries. Patients received transdermal fentanyl treatment for 28days. Pain severity, overall satisfaction with pain control, convenience of use of patches and treatment preferences were recorded daily.Results: Of the 292 participants, 135 had previously received a strong opioid, 84 had previously received a weak opioid and 73 had received no regular opioids. Thirty-eight patients did not complete the study, mainly due to adverse events. For all groups the proportion of patients with ‘good to excellent’ pain control increased after transdermal fentanyl treatment. Transdermal fentanyl was well tolerated, with the most common treatment-related adverse events being nausea, vomiting and constipation. The percentage of strong-opioid-tolerant patients with constipation decreased following transdermal fentanyl treatment and increased slightly in the strong-opioid-naïve groups. Most patients rated the convenience of the patches as ‘good to excellent’, and most preferred transdermal fentanyl to their previous therapy.Conclusions: Transdermal fentanyl is an effective and well-tolerated treatment for cancer-related pain for patients regardless of whether they have previously received opioids. Previous guidelines have often advocated initial dose finding with short-acting opioids but this study demonstrates that such a complex titration and conversion schedule may not be necessary, and that treatment may be initiated directly with long-acting formulations such as transdermal fentanyl when previous analgesic therapy fails to provide adequate relief.

Drug prescription for adult frequent attenders in Danish general practice: a population-based study.

To analyse the association between daytime frequent attendance in general practice and drug use, i.e. type of drug used and prevalence of polypharmacy. A population-based cross-sectional study of individual face-to-face contacts with 179 Danish general practices (320 general practitioners, GPs) in the county of Northern Jutland, Denmark and the drug use of the 371 897 inhabitants aged 20 and over. Data on contacts and reimbursed drugs were obtained during the year of 1997 from the Health Insurance Registry. Frequent attenders (FAs) were defined as the 10% most FAs in 12 months. We measured the prevalence difference (PD) and the prevalence ratio (PR) of drug use and polypharmacy (drugs from five or more ATC groups) among FAs. FAs received prescriptions in 95% of the cases and utilised 27% of all prescribed drugs. Compared with the 50% least attending patients, the highest absolute prevalence of drug use among FAs was found for antibiotics (PD: 22.6-34.5), strong analgesics and psychotropics (PD: 16.0-38.5) and cardiovascular (PD: 4.2-46.2), musculoskeletal (PD: 16.3-29) and gastrointestinal drugs (PD: 10.8-39.9). The FAs had an increased PR for receiving a drug (1.1-1.6) and their polypharmacy PD was high (4.0-46.3). The association between frequent attendance and the prevalence of polypharmacy was strong (PR = 6.7-36.7). Frequent attendance in general practice is strongly associated with drug use and polypharmacy. FAs account for a high proportion of the prescription workload, and some disease groups are very common among FAs.

Comment with regard to: Outcomes of a prospective cohort study on peri-radicular infiltration for radicular pain in patients with lumbar disc herniation and spinal stenosis (L. Ng et al.)

In a patient presenting with clear-cut radicular pain, it is tempting to pursue non-surgical therapies directed towards the affected nerve. This would seem to be logical, especially in view of the increasing evidence that the genesis of such pain is not just nerve compression [1]. Amongst the techniques favoured in radicular pain syndromes is the injection of local anaesthetic and steroid around the nerve root, variously called peri-radicular infiltration, paravertebral block or nerve root block, a technique performed by anaesthetists as well as spinal surgeons. Whilst many practitioners can provide anecdotal evidence of efficacy, the literature is of little help: there are no controlled studies of reasonable quality. The study of Ng et al. in this issue is of interest because it does include carefully collected outcome data not only of pain and general function (Oswestry and Low Back Outcome Score), but also of the Dram score (Zung Depression Inventory and Modified Somatic Perceptions Questionnaire), in two cohorts of patients undergoing peri-radicular infiltrations for nerve root pain due either to lumbar disc herniation or spinal stenosis. The data provide details of the outcome that can be expected from the performance of a nerve root injection using a small volume of bupivacaine with 40 mg methyl prednisolone, on pain, distress and general function. Both groups get better, but this is much more marked in the disc herniation group. The improvement seen in the spinal stenosis group is minimal, with only a two-point reduction in ODI and 7 mm on VAS at 6 weeks with some further improvement (to 6 and 12, respectively), on the VAS at 12 weeks. Given that the patients started off with VAS scores of 77 a reduction to 70 after 7 weeks is not satisfactory pain management. It has been estimated that one needs a 13-point change to detect clinically relevant pain relief [3]. The disc herniation group fare somewhat better, with VAS changes of 11 at 6 weeks and 20 and 12 weeks, but this is a condition with a natural history of resolution, and the fundamental question of whether the injection aided this recovery is not answered due to lack of controls. Herewith, the major problem with the study: the lack of a control group ultimately limits its value. The authors refer to the literature on epidural steroids, which, although by no means categorical, is supportive of an effect in acute lumbar disc herniation. The authors added contrast medium to the injectate and only used a small volume. They do not report on epidural spread, but spread of injectate into the epidural space has been described during injections of this type [2] which raises the question as to the site of action of the drug. If one makes the charitable assumption that the authors injections do provide some benefit to patients with lumbar disc herniation, the question then arises as to whether this technique is easier to perform, cheaper, or more effective than epidural injection. One aspect that the literature on epidurals in acute disc prolapse does not adequately address is the short-term acute pain relief obtainable from such injections. The pain of an acute disc can be terrible and because of its neuropathic nature difficult to control even with strong analgesics. Effective relief of this pain is a rational end point of treatment even if the long-term outcome is unchanged. We thus do not need evidence of long-term benefit to justify a treatment if it can be shown to provide high-quality pain relief in the acute phase. Unfortunately, this study does not help in this respect. As always, there are more questions than answers: controlled studies are urgently needed.

INFLUENCE OF A COMPLEX MAGNETIC FIELD APPLICATION IN RATS UPON THERMAL NOCICEPTIVE THRESHOLDS: THE IMPORTANCE OF POLARITY AND TIMING

The application of a weak (1 microTesla) complex magnetic field pattern with a relevant electrophysiological signature produced an analgesic response in rats to thermal stimuli when the pattern was presented once every 4 sec for 30 min through iron-core solenoids. In one experiment, the burst-firing pattern was presented once every 4 s for 30 min and restricted to the positive polarity, negative polarity or a bipolar equivalent. The strongest analgesia occurred when the burst-firing pattern was presented with positive polarity or as the typical bipolar signal. Administrations of the burst-firing pattern once per week for four consecutive weeks produced analgesia that was clearly evident during the first, third, and fourth weeks but not during the second week of treatment. A telephone sensor coil (that can be readily obtained from local electronic shops) was then used instead of the solenoids along with an audio (.wav) file to generate the magnetic field; the analgesia was still apparent. However, when the magnetic pattern was generated from a compact disc source the analgesia was not evoked. The current results suggest that these fields can be generated through simple commercial devices controlled by available computer software.

Use of Opioids in the Treatment of Severe Pain in Terminally Ill Patients—Dying Should Not Be Painful

Pain is a common symptom at the end of life. The vast majority of pain can be readily managed if simple principles of practice are followed. Chronic pain requires continuous analgesia, and severe pain requires use of strong analgesics, most commonly the opioids. In addition to drugs administered continually, short-acting medications must be available for "breakthrough" pain. This article reviews the principles of pain management in terminally ill patients, using a case-based demonstration.

Factors determining the return to normal activity after appendicectomy.

The ability of a patient to return to their normal activities is an important outcome of an operation. The present study was designed to identify and rank factors that are important in determining this return to normal activity (RTNA) after appendicectomy. Consecutive patients were identified prospectively following appendicectomy at North Shore Hospital between February and April 2000. Data regarding 25 different factors were obtained by a structured patient interview before and after discharge from hospital and by review of the medical records. Statistical analysis involved analysis of variance and logistic regression analysis. There were 98 patients (median age 28, range 15-69 years, male : female ratio 48:50) who had an appendicectomy. An open appendicectomy was performed in 74 patients, a laparoscopic appendicectomy in 22 patients and a laparotomy in two patients. This includes the 16 patients who were converted from laparoscopic to open appendicectomy (conversion rate 42% 16/38). Acute appendicitis was confirmed by histology in 67 (68%) patients. The significant independent variables identified by anova were ranked by logistic regression analysis. The most important determinant for the time to RTNA was what the doctor advised (chi-squared 43.7, P < 0.0001). The other determinants were the physical activity of their primary occupation (chi-squared 21.5, P < 0.017), the need for strong postdischarge analgesia (chi-squared 21.1, P < 0.13), the American Society of Anesthesiologists (ASA) category (chi-squared 13.6, P < 0.018) and the total sick leave obtained (chi-squared 9.6, P < 0.08). It has been shown that the most significant factor in determining the RTNA after appendicectomy was the advice given by the doctor, and that this was more important than the surgical approach, pathology, complications, age or occupation of the patient.

Breakthrough strong opioid analgesia prescription in patients using transdermal fentanyl admitted to a hospice.

Durogesic (fentanyl) patches have revolutionized pain relief, but patients still require breakthrough medication. A retrospective analysis of in-patient admission notes at a 25-bed hospice over a six-month period was carried out. Details of analgesia being used on admission for both background and breakthrough pain were obtained, and the appropriateness of the breakthrough dose for those patients using transdermal fentanyl was determined. During the study period 278 patients were admitted to the hospice and 56 (20 percent) were using transdermal fentanyl. Of these, 35 (62 percent) were prescribed strong opioid analgesia--the dose of breakthrough medication prescribed was appropriate in 11 patients (31 percent). Rescue dosing was less than recommended, in relation to prescribed transdermal fentanyl strength in 21 patients (60 percent) and greater than recommended in one patient (3 percent). In this study, short-acting strong opioid analgesia was not always prescribed for patients using transdermal fentanyl, and when they were prescribed, this was in the appropriate dose range in less than a third of patients.

Pharmacotherapy for regional musculoskeletal pain.

Studies performed on drug therapy in regional musculoskeletal pain conditions are of varying quality, and this is related to several methodological problems. The efficacy of analgesic medications is well established from clinical practice. However, both weak and especially strong opioid analgesics are associated with adverse reactions and also with dependency and abuse. The use of anti-depressants and skeletal muscle relaxants is only weakly supported by results from controlled clinical trials. The efficacy of both systemic and topical non-steroidal anti-inflammatory drugs (NSAIDs) has been examined in several Cochrane reviews of various regional musculoskeletal pain conditions. Studies of COX-2 selective NSAIDs have not been performed in conditions with regional musculoskeletal pain, but it is assumed that COX-2 selective inhibitors will not differ from dual COX inhibitors regarding efficacy. Therefore, some of the recent controversies related to gastrointestinal safety and possible risk of myocardial infarctions are also discussed.

Breakthrough strong opioid analgesia prescription in patients using transdermal fentanyl admitted to a hospice

Durogesic ® (fentanyl) patches have revolutionized pain relief, but patients still require breakthrough medication. A retrospective analysis of in-patient admission notes at a 25-bed hospice over a six-month period was carried out. Details of analgesia being used on admission for both background and breakthrough pain were obtained, and the appropriateness of the breakthrough dose for those patients using transdermal fentanyl was determined. During the study period, 278 patients were admitted to the hospice and 56 (20 percent) were using transdermal fentanyl. Of these, 35 (62 percent) were prescribed strong opioid analgesia—the dose of breakthrough medication prescribed was appropriate in 11 patients (31 percent). Rescue dosing was less than recommended, in relation to prescribed transdermal fentanyl strength, in 21 patients (60 percent) and greater than recommended in one patient (3 percent). In this study, short-acting strong opioid analgesia was not always prescribed for patients using transdermal fentanyl, and when they were prescribed, this was in the appropriate dose range in less than a third of patients.

&lt;b&gt;Cancer pain management with transdermal fentanyl patch &lt;/b&gt;

Introduction: For decades, morphine was the only strong opioid for the treatment of cancer pain in Japan. From March 2002, transdermal fentanyl patch has been applied to cancer patients previously treated with morphine. As a consequence, opioid rotation from morphine to fentanyl patch (DurotepTM patch) became major concern for physicians to control cancer pain in our country. In this article, we would like to introduce why and how we rotate the opioid, incidence of side efffects, and how we control breakthrough pain in our hospital. Patients: During the period of March 2002 to July 2002, 12 patients were entrusted to the anesthesiology pain service from difficulty in controlling morphine side effects. Primary cancer of the patients were 4 stomach, 2 gallbladder, 1 liver, 1 pancreas, 1 ovarian, 1 breast, 1 thyroid, and 1 lingual cancer. All patients were given morphine either orally, rectally, or intravenously and were scheduled for opioid rotation. They were all suffering from intractable side effect of morphine, possible digestive tract obstruction, and/or pruritis. Methods: Direct conversion from oral morphine to transdermal fentanyl with the ratio of 100:1 was basical­ly enforced, however, varied depending on patient status. We also gave intravenous morphine using patient controlled analgesia (PCA) for rescue in several patients with severe breakthrough pain. Numeric rating scale (NRS), nausea score and drowsiness score was obtained for 72 hours during the rotation. Constipation was not evaluated as this study was designed for only 72 hours. Results: The median Numeric rating scale (NRS) at rest decreased from 4.5 to 3.0 at 72 hours after the rotation, however not significant. Nausea was present in 10 patients, and resolved completely in 6 patients. There were no significant increase in drowsiness score. One patient with pruritis, possibly due to morphine, dis­appeared soon after the end of rotation. Conclusion: Opioid rotation to transdermal fentanyl patch, under discreet assessment and rotation planning, is beneficial for cancer pain relief in patients requiring strong opioid analgesics if they were naive to previously given morphine.

Single dose dipyrone for acute renal colic pain.

Renal colic pain is extremely painful and requires immediate treatment with strong analgesics. Dipyrone is the most popular non-opioid first line analgesic in many countries but in others it has been banned (e.g. USA, UK) because of its association with blood dyscrasias such as agranulocytosis. Since dipyrone is used in many countries (e.g. Brazil, Spain) there is a need to determine the benefits and harms of its use to treat renal colic pain. To assess quantitatively the analgesic efficacy and adverse effects of single-dose dipyrone in adults with moderate to severe renal colic pain. Published reports were identified from electronic databases (MEDLINE, EMBASE, the Cochrane Library, LILACS) and additional studies were identified from the reference lists of retrieved reports. Date of the most recent search: January 2000. Inclusion criteria were: full journal publication; RCT with a double-blind design; adult patients with baseline renal colic pain of moderate or severe intensity; treatment arms which included dipyrone (oral, intramuscular or intravenous administration) and a control; single dose data. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief over 15-30 minutes, 1-2 hours and six hours. The proportion of patients with at least 50% pain relief was calculated. Single dose adverse effect data were collected. Eleven studies with 1053 patients (550 on dipyrone) met the inclusion criteria. Unfortunately, few data were available for analysis; most analyses were based on the results of single, small trials and statistical pooling of the results was inappropriate. Efficacy estimates were calculated as the weighted mean percent of patients achieving at least 50% pain relief with the range of values from trials contributing to the analysis. However, these estimates were not robust. Commonly reported adverse effects with intravenous dipyrone were dry mouth and somnolence, and one study reported pain at the injection site. Insufficient information was available for safety analyses to be conducted. Limited available data indicated that single dose dipyrone was of similar efficacy to other analgesics used in renal colic pain, although intramuscular dipyrone was less effective than diclofenac 75 mg. Combining dipyrone with antispasmolytic agents did not appear to improve its efficacy. Intravenous dipyrone was more effective than intramuscular dipyrone. Dry mouth and somnolence were commonly reported with intravenous dipyrone. None of the studies reported agranulocytosis.

The effect of standard care, ibuprofen, and distraction on pain relief and patient satisfaction in children with musculoskeletal trauma

Introduction: The purpose of this study was to determine the effectiveness of nursing interventions in decreasing pain for children with minor musculoskeletal trauma and moderate pain and to examine patient satisfaction. Methods: Children were assigned to 1 of 3 intervention groups: (1) standard care (ice, elevation, and immobilization) only; (2) standard care and ibuprofen; or (3) standard care and distraction. Children were monitored for pain ratings for 60 minutes. Children who sustained minor musculoskeletal trauma within the past 24 hours and presented with pain ratings of 2 or greater using the 0-5 Wong/Baker faces scale were included. Two patient satisfaction questions were asked of parents upon their child's discharge from the emergency department. Results: A statistically significant decrease in pain for all patients (76) occurred at 30 minutes (F = 4.39, P <.05) and was maintained at 60 minutes. The distraction group demonstrated a statistically significant reduction in pain compared with the other groups at 30 minutes; this reduction was maintained at 60 minutes (F = 47.07, P <.05). Parents of only 6 children expressed dissatisfaction with overall pain management. Twelve percent of children who were not in the group receiving medication received analgesics while in the emergency department. At discharge, only 37% of children with fractures and/or sprains had received medications for pain. Discussion: Children with musculoskeletal trauma may be undermedicated. Distraction techniques can be an effective adjunct to analgesia for children with musculoskeletal pain in the emergency department and should be made available. Ibuprofen may not be an effective analgesic for children with these injuries; stronger analgesics may be required.

Biochemical characterisation of newly developed β-etorphine and β-dihydroetorphine derivatives

The highly potent synthetic narcotic compound etorphine is known to cause strong analgesia, catatonia and blockade of conditioned reflexes in laboratory animals and is widely used for the immobilisation of game animals. In this study, a number of new structural analogues of etorphine, including C18-β-structures, 3- O-methylether derivatives and saturated C7–C8 dihydro-compounds, were synthesised and examined in in vitro ligand binding experiments. Opiate receptor-mediated activation of G-proteins by these derivatives was also investigated using the [ 35S]GTPγS binding assay. The receptor binding affinity constant and G-protein stimulatory potency of the novel β-etorphins were compared with those of the corresponding C18-α-derivatives. In rat brain membrane preparations, all the compounds tested displayed high affinity ( K i's ranging 0.4–22 nM) using [ 3H]naloxone in competition assays. The α-etorphines had somewhat higher affinity in comparison with the β-structures. Methylether derivatives were consistently weaker than the corresponding phenolic compounds. Dihydroetorphine and β-dihydroetorphine, which have a partially saturated ring structure, showed as good potency in the binding assays as did etorphine and β-etorphine with C7–C8 double bonds. The etorphine derivatives were potent but naloxone-reversible activators of G-proteins in the [ 35S]GTPγS functional tests. It was also found that the C3 phenolic group is favourable for G-protein activation. On the basis of our experimental results, neither the configuration of C18 nor the saturation of the C7–C8 double bond appears to play a critical role in the biological activity of etorphines.