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S Mercadante

Publications and source records attributed to S Mercadante.

At least 19 recordsLinked to original sources
PubMed2006

Use of antiepileptics and tricyclic antidepressants in cancer patients with neuropathic pain.

Using a large US health insurance claims database, we identified all persons aged > or =18 years with > or =2 medical encounters with diagnoses of cancer and > or =2 medical encounters with diagnoses of painful neuropathies in calendar year (CY) 2000; persons with seizure disorders or depression were excluded. We then examined the use of antiepileptics (AEDs), tricyclic antidepressants (TCAs) and other pain-related pharmacotherapy among these selected persons, as proxied by pharmacy dispenses. A total of 956 persons were identified who met all entry criteria; 17% received AEDs in CY2000 and 14% received TCAs. Gabapentin was the most widely used AED (92% of all AED patients); amitriptyline was the most widely used TCA (79% of all TCA patients). Patients who received AEDs and/or TCAs were similar in age, gender and the presence of metastases to those who had not received these medications; they were more likely to have received other pain-related therapies, however, including short-acting opioids (73% vs. 53%; P < 0.01) and long-acting opioids (23% vs. 8%; P < 0.01). Use of AEDs and TCAs appears to be relatively low among cancer patients with painful neuropathies. Further research is needed to better understand reasons for this finding, as well as its potential implications for pain management in this patient population.

Aged↗
PubMed2004

Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in glioma cells.

We have observed that treatment of human glioma cells with morphine in the nanomolar range of concentration affects the mitochondrial membrane potential. The effect is specific to morphine and is mediated by naloxone-sensitive receptors, and is thus better observed on glioma cells treated with desipramine; moreover, the mitochondrial impairment is not inducible by fentanyl or methadone treatment and is prevented by the nitric oxide (NO) synthase inhibitor L-NAME. We conclude that in cultured glioma cells, the morphine-induced NO release decreases the mitochondrial membrane potential, as one might expect based on the rapid inhibition of the respiratory chain by NO. The identification of new intra-cellular pathways involved in the mechanism of action of morphine opens additional hypotheses, providing a novel rationale relevant to the therapy and toxicology of opioids.

Adjuvants, Anesthesia↗
PubMed2004

Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.

Analysis of Variance↗
PubMed2003

Opioid plasma concentration during switching from morphine to methadone: preliminary data.

Opioid switching is often used to improve the opioid response in cancer patients experiencing poor analgesia or adverse effects. However, no data are available on plasmatic changes of opioids and their metabolites during these phases, and whether there exists a relationship with the clinical events. In a prospective study of 10 consecutive cancer patients on oral morphine but with uncontrolled pain (greater >4 on a numerical scale of 0 to 10) and/or moderate to severe opioid adverse effects (on a level of 2 and 3 of a verbal scale) and not responsive to adjuvant medications, switching to oral methadone was performed using a fixed ratio of 5:1, leaving extra-doses of 1/5 of the daily dose of methadone calculated as needed. Blood samples were obtained at the same hour for four days, before the switching, and then on day 1, 2, and 3. The intensity of pain and the adverse effects were assessed daily to calculate the switching score before and after switching. Completed blood samples were obtained in 9 patients. One patient was separately considered, because of his renal impairment. Significant improvements in pain intensity as well as adverse effects within an average period of 1-2 days were observed. Morphine, morphine-6-glucuronide, and morphine-3-glucuronide were progressively cleared from plasma to almost disappear within three days. Methadone rapidly achieved a stable concentration in 1-2 days. The doses of methadone were changed, but not significantly, and tended to decrease in the following days, according to the clinical situation. The results of this study confirm the need to stop rapidly morphine, and to use a priming dose of methadone, rather than using progressive decrements and increments of morphine and methadone, respectively, during opioid switching. This method allows for a rapid clearance of morphine and its metabolites are rapidly cleared, except in patients with renal failure. Opioid plasma changes substantially overlap the clinical changes observed in these patients, in terms of benefit between analgesia and adverse effects.

Administration, Oral↗
PubMed2002

A randomised controlled study on the use of anti-inflammatory drugs in patients with cancer pain on morphine therapy: effects on dose-escalation and a pharmacoeconomic analysis.

The role of non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain has been well established in the treatment of mild pain and in association with opioids in the treatment of moderate to severe pain. The aim of this study was to verify the effects of NSAIDs on morphine escalation in advanced cancer patients with pain followed-up at home and to assess the pharmacoeconomic implications. A prospective randomised controlled study was carried out in 156 consecutive advanced cancer patients with pain followed-up at home in the period December 1999-December 2000. In this group of patients, 47 were selected with pain progression after 1 week of opioid stabilisation. Patients were randomly assigned to one of two groups: group 'O' patients were treated with continuing opioid escalation according to their clinical needs; group 'OK' received ketorolac 60 mg/daily orally (p.o.) in three doses and then continued opioid escalation according to their clinical situation. Performance status, doses of morphine before and after starting treatment, mean weekly pain intensity (assessed by means of a numerical scale from 0 to 10), mean weekly symptoms intensity, adverse effects and pain mechanisms were recorded. Moreover, drug costs per day in both groups were calculated. Patients who received ketorolac in addition to morphine showed a better analgesia after a week in comparison to the group treated with morphine only (P=0.005). Thereafter, morphine escalation was slower and the maximum morphine dose was lower in the group treated with ketorolac. The incidence and the severity of gastric discomfort was more evident in patients treated with ketorolac, while constipation was significantly increased in patients who received morphine only. Drug costs per day were similar in both groups; statistical differences were observed in patients who started on lower morphine doses (<100 mg/daily) in the two groups (4.3 in the ketorolac-morphine group versus 3.4 in the morphine group; P=0.012). The use of NSAIDs reduces the need for an opioid dose escalation or allows the use of lower doses. Their use is associated with a more intense gastric discomfort, but results in less opioid-related constipation. The eventual additive cost for NSAIDs therapy is negligible, especially in patients taking high doses of morphine.

Aged↗
PubMed2001

Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study.

PURPOSE: To evaluate the clinical benefits of switching from morphine to oral methadone in patients who experience poor analgesia or adverse effects from morphine. PATIENTS AND METHODS: Fifty-two consecutive cancer patients receiving oral morphine but with uncontrolled pain and/or moderate to severe opioid adverse effects were switched to oral methadone administered every 8 hours using different dose ratios. Intensity of pain and adverse effects were assessed daily, and the symptom distress score (DS) was calculated before and after switching. RESULTS: Data were analyzed for 50 patients. Switching was considered effective in 80% of the patients; results were achieved in an average of 3.65 days. In the 10 patients who switched to methadone because of uncontrolled pain, a significant reduction in pain intensity (P <.005) and an average of a 33% increase in methadone doses necessary (P <.01) were found after an average of 3.5 days. DS significantly decreased from an average of 8.4 to 4.5 (P <.0005). In the 32 patients switching because of uncontrolled pain and morphine-related adverse effects, significant improvement was found in pain intensity (P <.0005), nausea and vomiting (P <.03), constipation (P <.001), and drowsiness (P <.01), but a significant increase in the methadone dose of an average of 20% (P <.004) was required. CONCLUSION: In most patients with cancer pain referred for poor pain control and/or adverse effects, switching to oral methadone is a valid therapeutic option. In the clinical setting of poor pain control, higher doses of methadone are necessary with respect to the equianalgesic calculated dose ratios previously published.

Administration, Oral↗
PubMed2001

Strategies to manage the adverse effects of oral morphine: an evidence-based report.

Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of definitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidence-based recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research NETWORK: These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options.

Administration, Oral↗
PubMed2001

Morphine and alternative opioids in cancer pain: the EAPC recommendations.

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.

Administration, Oral↗
PubMed2001

Clinical-practice recommendations for the management of bowel obstruction in patients with end-stage cancer.

The paper highlights a series of questions that doctors need to consider when faced with end-stage cancer patients with bowel obstruction: Is the patient fit for surgery? Is there a place for stenting? Is it necessary to use a venting nasogastric tube (NGT) in inoperable patients? What drugs are indicated for symptom control, what is the proper route for their administration and which can be administered in association? When should a venting gastrostomy be considered? What is the role of total parenteral nutrition (TPN) and parenteral hydration (PH)? A working group was established to review issues relating to bowel obstruction in end-stage cancer and to make recommendations for management. A steering group was established by the (multidisciplinary) Board of Directors of the European Association for Palliative Care (EAPC) to select members of the expert panel, who were required to have specific clinical and research interests relating to the topic and to have published significant papers on advanced cancer patients in the last 5 years, or to have particular clinical expertise that is recognised internationally. The final constitution of this group was approved by the Board of the EAPC. This Working Group was made up of English, French and Italian physicians involved in the field of palliative care for advanced and terminal cancer patients; and of English, American and Italian surgeons who also specialized in artificial nutrition (Dr. Bozzetti) and a professor of health economics. We applied a systematic review methodology that showed the relative lack of RCTs in this area and the importance of retrospective and clinical reports from different authors in different countries. The brief was to review published data but also to provide clinical opinion where data were lacking. The recommendations reflect specialist clinical practice in the countries represented. Each member of the group was allocated a specific question and briefed to review the literature and produce a position paper on the indications, advantages and disadvantages of each symptomatic treatment. The position papers were circulated and then debated at a meeting held in Athens and attended by all panel members. The group reviewed all the available data, discussed the evidence and discussed what practical recommendations could be derived from it. An initial outline of the results of the review and recommendations was produced. Where there were gaps in the evidence, consensus was achieved by debate. Only unanimous conclusions have been incorporated. Subsequently the recommendations were drawn together by Carla Ripamonti (Chairperson) and Robert Twycross (Co-Chair) and refined with input from all panel members. The recommendations have been endorsed by the Board of Directors of the EAPC. It was concluded that surgery should not be undertaken routinely in patients with poor prognostic criteria, such as intra-abdominal carcinomatosis, poor performance status and massive ascites. A nasogastric tube should be used only as a temporary measure. Medical measures such as analgesics, anti-secretory drugs and anti-emetics should be used alone or in combination to relieve symptoms. A venting gastrostomy should be considered if drugs fail to reduce vomiting to an acceptable level. TPN should be considered only for patients who may die of starvation rather than from tumour spread. PH is sometimes indicated to correct nausea, whereas regular mouth care is the treatment of choice for dry mouth. A collaborative approach involving both surgeons and physicians can offer patients an individualized and appropriate symptom management plan.

Humans↗
PubMed2001

Methadone in treatment of tenesmus not responding to morphine escalation.

Tenesmus is a painful sensation of incomplete evacuation of the bowel and is often associated with poorly localized perineal pain. We describe a 68-year-old man with locally advanced rectal carcinoma metastatic to lung and with unbearable rectal-perineal pain unresponsive to morphine and ketorolac. Treatment with oral methadone was successful and pain improved considerably. Methadone has been reported to improve pain relief in patients with morphine resistance, and it is lipophilic and exerts a lesser activity on opioid receptors in the gastrointestinal tract.

Aged↗
PubMed2001

The use of corticosteroids in home palliative care.

Evidence for the effectiveness of corticosteroids in palliative care is anecdotal, and more information is required. From January to December 1999 a total of 376 consecutive patients admitted to a home palliative care program were longitudinally surveyed. Patients who started a corticosteroid treatment after admission on the basis of common indications prescribed by their home care physicians were selected. Fifty patients were enrolled in the study. Dexamethasone, in doses ranging from 4 to 16 mg, was the drug of choice. Corticosteroids were found to be effective in anorexia, weakness, headache, and nausea and vomiting. The reduction of symptom intensity was achieved in less than 3 days on average. However, no great advantages were found in terms of controlling drowsiness or confusional states associated with advanced illness because of cerebral involvement. It can be concluded from this study that: (a) corticosteroids may be effective in controlling anorexia, weakness, headache, and nausea and vomiting associated with cerebral involvement or bowel obstruction; (b) they should be stopped if no therapeutic effect has become evident within 3-5 days; (c) the treatment is not useful when given in the presence of severe neurological impairment resulting from the advanced stage of disease; (d) the range of adverse effects was acceptable for limited periods and in the circumstances in which the preparations were used in this study; and (e) corticosteroids may have an adjuvant role in potentiation of analgesic drugs. These findings will be very useful in the planning of future controlled studies designed to yield evidence-based data on the role of corticosteroids in the relief of specific symptoms.

Aged↗
PubMed2001

Rifampicin in opioid-induced itching.

Pruritus is prevalent in 5-12% of palliative care patients. Rifampicin has been shown to be useful both as initial treatment and as salvage treatment after failure of other agents to control the pruritus associated with the cholestatic jaundice of malignancy. We report the case of a 65-year-old woman who complained of severe pruritus after morphine treatment. The use of rifampicin 300 mg twice a day by the i.v. route was successful, and after opioid switching it was no longer necessary to maintain rifampicin in the therapeutic regimen. Controlled clinical trials are warranted to confirm this preliminary observation.

Aged↗
PubMed2001

Gabapentin for opiod-related myoclonus in cancer patients.

Chronic opioid medication has been found to cause myoclonus in patients taking it for cancer pain. Gabapentin seemed a likely candidate for the treatment of this myoclonus and has indeed proved useful, as illustrated in this paper by two case histories.

Acetates↗