[Opioids. Old myths, new myths and the future].
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Biomedical subjects
Publications and source records attributed to M Zenz.
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INTRODUCTION: The intrathecal application of opioids is promoted as a safe and cost-efficient method to treat chronic pain of nonmalignant origin. But the way of application could trigger the appearance of otherwise rare side-effects. One of those side-effects could be the alteration of androgen hormones. Can a long-time-application of intrathecal opioids result in gynecomastia? METHODS: Case-report of a 49 year old with chronic back and limb pain. Research for publications. RESULTS: The close link between the begin of intrathecal application of opioids and the onset of gynecomastia in this patient refers to a causal correlation. Historic publications and new findings from animal research are supporting our hypothesis. CONCLUSIONS: Further research is needed to support the clinical suspicion of a correlation between intrathecal opioids and gynecomastia. In case of a opioid-produced gynecomastia tests of the oestrogen-testosterone-ratio should be performed. An early substitution of testosterone could prevent a full fledged gynecomastia.
Thalidomide was introduced as a sedative and antiemetic agent to the European market in the late 1950s. However, it soon became clear that a hitherto unheard-of incidence of severe birth defects was due to the maternal use of thalidomide and the drug was withdrawn from the market. Despite its teratogenesis, thalidomide is currently being rediscovered because of its known spectrum of anticachectic, antiemetic, mildly hypnotic, anxiolytic, anti-inflammatory, antiangiogenic, and analgesic properties. The mechanism of action of thalidomide is probably based on its immunomodulatory effect, namely the suppression of production of tumor necrosis factor alpha and the modulation of interleukins. A striking but not well-known finding is the effectiveness of thalidomide as an analgesic or analgesic adjuvant. During the early era of thalidomide use, the drug was shown to enhance the analgesic efficacy of a combined treatment with acetylsalicylic acid, phenacetin, and caffeine (APC) by testing "normal volunteers, using electrical stimulation of teeth." The combination of thalidomide and APC was superior to other combinations (APC alone, APC and codeine) with respect to both the total analgesic effect and the duration of this analgesic effect. In 1965 thalidomide was found to be effective in treating the painful subcutaneous manifestations of the leprosy-associated erythema nodosum leprosum, a condition for which it eventually was approved by the United States Food and Drug Administration in 1998. In an animal model of neuropathic pain (chronic constriction injury), thalidomide was shown to reduce both mechanical allodynia and thermal hyperalgesia. Recent studies documented the analgesic efficacy of thalidomide in treating painful mucocutaneous aphthous ulcers associated with HIV syndrome and Behcet's disease.However, to date there are no recent clinical trials that are specifically designed to explore the analgesic potential of thalidomide. In view of the current basic research and clinical findings,we suggest to investigate the potential benefits of thalidomide in severe pain conditions that respond poorly to common pain management approaches such as neuropathic pain, postherpetic neuralgia, or central pain phenomena. Because its mechanism of action is distinct from that of other drugs such as steroids, thalidomide offers the possibility of a combined treatment with other agents with nonoverlapping toxicities. We conclude that thalidomide, when used properly,may enrich the therapeutic regimen in the management of some pain-related conditions.
OBJECTIVES: The aim of our study was to determine the role of N-methyl-d-aspartate (NMDA)-mediated mechanisms in cortical excitability changes after limb amputation, and their possible relationship to phantom pain. MATERIALS AND METHODS: Sixteen upper limb amputees who were suffering from chronic phantom pain received the NMDA-antagonist memantine or placebo for 3 weeks. Intracortical inhibition (ICI) and intracortical facilitation (ICF) were determined at baseline and on day 21 using transcranial magnetic stimulation. Simultaneously, phantom pain intensity was assessed. RESULTS: Memantine reduced ICF and enhanced ICI to roughly the same extent as seen in healthy subjects in a previous study. These changes were not correlated to the reduction of phantom pain. CONCLUSION: We therefore conclude that NMDA-mediated mechanisms influence changes of ICI and ICF occurring after limb amputation. However, our results suggest that these cortical excitability changes and phantom pain are independent of each other.
UNLABELLED: The purpose of the study was to investigate the effect of intraoperative hyperventilation on postoperative cognitive functions. METHODS: A total of 120 patients (60 older and 60 younger than 65 years old) were allocated randomly to group I "hyperventilation" (p(et)CO(2)=30 mmHg) or group II "normoventilation" (p(et)CO(2)=45 mmHg). Before the operation and on days 1, 3 and 6 after the operation, a battery of neuropsychological tests was performed (concentration endurance test d2, number connection test, digit symbol test). A decline of 20% in at least one test was regarded as postoperative cognitive deficit (POCD). Anaesthesia was maintained with isoflurane in nitrous oxide/oxygen supplemented with fentanyl. RESULTS: In all patients pooled, POCD was present in 26 patients (22%). In patients older than 65 years, POCD was present in 3 cases after hyperventilation and 13 cases after normoventilation ( p<0.01). In younger subjects, 5 cases of POCD were diagnosed in each ventilation group. Furthermore, POCD was more severely pronounced in older patients after normoventilation. CONCLUSION: In older patients, POCD occurred more frequently after intraoperative normoventilation. We assume that a reduced amount of noxious substances reach the brain after hyperventilation, because hyperventilation reduces the cerebral blood flow.
BACKGROUND: S-100 protein serum concentration (S-100) serves as a marker of cerebral ischemia in cardiac surgery, head injury and stroke. In these circumstances S-100 corresponds well with the results of neuropsychological tests. The aim of the present study was to investigate the value of S-100 and neuron specific enolase (NSE) in reflecting postoperative cognitive deficit (POCD) after general surgical procedures. METHODS: One hundred and twenty patients undergoing vascular, trauma, urological or abdominal surgery were investigated. Serum values of S-100 and NSE were determined preoperatively and 0.5, 4, 18 and 36 h postoperatively. Neuropsychological tests for detecting POCD were performed preoperatively and on day 1, 3, and 6 after the operation. A decline of more than 10% in neuropsychological test results was regarded as POCD. Furthermore, we retrospectively compared the S-100 in patients with and without POCD in different types of surgery. RESULTS: According to our definition, forty-eight patients had POCD (95% confidence interval: 37.5-58.5). These patients showed higher serum concentrations of S-100 (median 024 ng/ml; range 0.01-3.3 ng/ml) compared with those without POCD (n=69; median 0.14 ng/ml; range 0-1.34 ng/ml) 30 min postoperatively (P=0.01). Neuron specific enolase was unchanged during the course of the study. Differences of S-100 in patients with and without POCD were found in abdominal and vascular surgery but not in urological surgery. CONCLUSION: When all patients are pooled, S-100 appears to be suitable in the assessment of incidence, course and outcome of cognitive deficits. We suspect that in some surgical procedures, such as urological surgery, S-100 appears to be of limited value in detecting POCD. Neuron specific enolase did not reflect neuropsychological dysfunction after noncardiac surgery.
OBJECTIVES: Delirium is the most common acute organic psychosis postoperatively, and occurs more frequently in the elderly than anticipated. The abbreviated mental test (AMT) is a widely used cognitive test in Great Britain. The present study assessed the AMT in a German version for diagnosis of postoperative delirium. METHODS: 40 patients (older than 65 years), scheduled for total knee or hip replacement, were tested repeatedly for delirium according to the ICD-10. These patients were investigated with the AMT simultaneously by a second investigator. RESULTS: Delirium was present in four orthopaedic patients (10 %) and was diagnosed correctly in these patients by the AMT. All but one patient without delirium showed no deterioriation in AMT score. CONCLUSION: As in Great Britain, the AMT in its German version is useful in diagnosing delirium. We recommend the use of the AMT preoperatively in elderly patients at risk for delirium.
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Today, a wide range of efficient analgesic and non-analgesic drugs for the treatment of back pain are available. However, drugs should never be the only mainstay of a back pain treatment program. Non-steroidal antiinflammatory drugs (NSAID) are widely used in acute back pain. NSAIDs prescribed at regular intervals are effective to reduce simple back pain. The different NSAIDs are effective for the reduction of this pain. They have serious adverse effects, particularly at high doses, in the elderly, and on long-term administration. The new cyclooxygenase II-inhibitors have less gastrointestinal complications. But the long-term experiences are limited up to now. Considerable controversy exists about the use of opioid analgesics in chronic noncancer pain. Many physicians are concerned about the effectiveness and adverse effects of opioids. Other clinicians argue that there is a role for opioid therapy in chronic noncancer pain, e. g. especially in chronic low back pain. There is a low incidence of organ toxicity in patients who respond to opioids. The incidence of abuse and addiction is likewise relatively low. The potential for increased function and improved quality of life seems to outweigh the risks. However, there is a lack of randomised controlled trials (RCT) on opioid therapy in a multimodal pain treatment approach. Clinical experience and some studies suggest administration of sustained release opioids because of better comfort for the patient and less risks for addiction. The opioids should be selected due to the specific side effects of the different drugs. For patients with pre-existing constipation transdermal fentanyl should be preferred. Antidepressant medications have been used for the treatment of chronic back pain, though there is only little scientific evidence for their effectiveness. There is no evidence for the use of antidepressants in acute low back pain. Trials of muscle relaxants for patients with acute back pain have used a wide range of agents, e. g. benzodiazepines. They mostly reduce acute back pain, but they have significant adverse effects including drowsiness and psychological and physical dependence even after relatively short treatment. Benzodiazepines are not indicated in the treatment of chronic back pain. Drugs are sometimes necessary for the patients to begin and persevere a multimodal treatment program. Drug therapy should be terminated as soon as other treatment strategies succeed. Unfortunately, no studies exist evaluating the place of analgesics within a multimodal treatment program.
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OBJECTIVE: We wanted to investigate plastic changes occurring in the motor and somatosensory cortex after upper limb amputation, and their possible relationship to phantom pain. METHOD: To assess these plastic changes, we used transcranial magnetic stimulation (TMS) and source localization of somatosensory evoked potentials (SEP). Eleven patients with upper limb amputation were investigated. The phantom pain intensity was assessed by visual analogue scaling (VAS). RESULTS: Using TMS mapping, we found a significant lateralization of the amplitude-weighted centre of gravity (P<0.01) and an enlargement of the excitable area (P<0.05) on the hemisphere contralateral to the amputation. SEP mapping showed a significant medialization of the N20 dipole (P<0.05) on this side. None of these changes correlated with the phantom pain intensity. CONCLUSIONS: We conclude that after limb amputation, the relationship between plastic changes occurring in the sensorimotor cortex and phantom pain seems to be more complex than previously believed.