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Biomedical subjects

S Mercadante

Publications and source records attributed to S Mercadante.

At least 91 records · Page 5Linked to original sources

Ineffectiveness of dextromethorphan in cancer pain.

Experimental studies have indicated that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective analgesics in a wide variety of chronic pain states. The mechanism is presumed to be related to decreased firing of dorsal horn neurons after constant repeated C-fiber stimulation. Dextromethorphan (DM), a potent NMDA antagonist with a good safety profile, may be a promising agent for the treatment of persistent pain. An open-label randomized trial was designed to examine the effects of combining DM with NSAIDs, dextropropoxyphene, or morphine in cancer patients with pain. Patients who required a change in the step of the World Health Organization's (WHO) analgesic ladder because of a pain level of 4 or more on a numerical pain scale were randomly allocated to receive DM 30 mg three times a day (30 patients) or conventional treatment (30 patients). There were 20 patients randomized for each step of the analgesic ladder. Pain mechanisms, pain intensity (numerical 0-10 scale), symptoms more frequently present in advanced cancer patients or associated with opioid therapy (graded on a 0-3 scale--not at all, slight, a lot, awful), opioid escalation index, days on opioid treatment, and adverse effects were recorded. After 2 days 75%, 80%, and 100% of patients treated with DM in steps 1, 2, and 3, respectively, required conventional treatment, because adequate pain relief had not been achieved (pain scale > 4). Failure of this treatment was equally observed in neuropathic pain or nociceptive pain syndromes. Four patients treated with DM who did not require the conventional treatment immediately did require this change after some days, due to poor pain control. A highly significant reduction in pain was observed in patients directly treated with the conventional treatment in all the three steps of the analgesic ladder. No significant analgesic effects could be found when DM at this dose was combined with NSAIDs, dextropropoxyphene, or morphine.

Analgesics, Opioid↗

The SAMOT supportive care programme in southern Italy.

Since 1988 a palliative care programme has been in development in Palermo, a large town in Southern Italy. The main objective is to provide home palliative care in conditions in which no other facility exists to meet the needs and reduce the distress of terminal cancer patients. This programme has been implemented and extended to other cities and villages in Sicily. A team composed of physicians, nurses, social workers and volunteers looks after patients at home. This model has been recognized as highly effective. The activities, the problems related to the development of such programme, including those concerned with the sociocultural environment and the family doctor, the needs of specific hospital departments, and the scientific and educational activities, are pointed out.

Culture↗

Treatment of pain in chronic bowel subobstruction with self-administration of methadone.

Chronic treatment with opioids in cancer patients with chronic intestinal obstruction is hazardous, as uncontrolled constipation may result in definitive bowel obstruction. Intermittent use of opioids adjusted for fluctuating pain levels may enable patients to take the lowest opioid doses that will have sufficient effect, with a consequently lower risk of intestinal side effects. Methadone has many pharmacokinetic characteristics that fit it for use in this clinical situation. In two patients with recurrent episodes of bowel obstruction, methadone used at low doses and at flexible intervals regulated by the patients according to their pain level avoided the occurrence of new episodes of intestinal obstruction. Oral patient-controlled analgesia with methadone may be a simple, safe and cheap method of treating patients with pain associated with subtotal intestinal obstruction.

Adult↗

Malignant bone pain: pathophysiology and treatment.

The presence of bone metastases predicts the presence of pain and is the most common cause of cancer-related pain. Although bone metastases do not involve vital organs, they may determine deleterious effects in patients with prolonged survival. Bone fractures, hypercalcaemia, neurologic deficits and reduced activity associated with bone metastases result in an overall compromise in the patient's quality of life. A metastasis is a consequence of a cascade of events including a progressive growth at the primary site, vascularization phase, invasion, detachment, embolization, survival in the circulation, arrest at the site of a metastasis, extravasion, evasion of host defense and progressive growth. Once cancer cells establish in the bone, the normal process of bone turnover is disturbed. The different mechanisms responsible for osteoclast activation correspond to typical radiologic features showing lytic, sclerotic or mixed metastases, according to the primary tumor. The release of chemical mediators, the increased pressure within the bone, microfractures, the stretching of periosteum, reactive muscle spasm, nerve root infiltration and compression of nerves by the collapse of vertebrae are the possible mechanisms of malignant bone pain. Pain is often disproportionate to the size or degree of bone involvement. A comprehensive assessment including a trusting relationship with the patient, taking a careful history of the pain complaint, the characteristics of the pain, the evaluation of the psychological status of the patient, neurological examination, the reviewing of diagnostic studies and laboratory findings, and individualization of the therapeutic approach, should precede any treatment. Radiotherapy is the cornerstone of the treatment. Low doses given in a single session are safe and effective, and reduce distress and inconvenience associated with repeated session. Radioisotopes are more imprecise in delivering specific doses of radiation, but have less toxicity and easy administration as well as effectiveness in subclinical sites of metastases, although storage, dispensing and administration should be under strict control. Chemotherapy and endocrine therapy are difficult to measure in terms of pain relief. Prophylactic fixation surgery can lead to improved survival and quality of life of patients with bone metastases. Surgical treatment should be undertaken when fracture occurs. Careful selection of patients for surgical spinal decompression is required. The potential benefits of surgical interventions have to be tempered with patient survival. The use of analgesics according to the WHO ladder is recommended. There is no clear evidence that non-steroidal anti-inflammatory drugs (NSAIDs) have a specific efficacy in malignant bone pain. The difficulty with incident pain is not a lack of response to systemic opioids, but rather that the doses required to control the incidental pain produce unacceptable side-effects at rest. Alternative measures are often required. The inhibition of bone resorption and hypercalcaemia can be reduced by the use of bisphosphonates. This class of drugs potentiate the effects of analgesics in improving metastatic bone pain. Invasive techniques are rarely indicated, but may provide analgesia in the treatment of pain resistant to the other modalities. Neural blockade should never be used as the sole modality for malignant bone pain, but should be considered as a helpful in specific pain situations. Careful appraisal and the application of a correct approach should enable the patient with bone metastases to obtain an acceptable pain relief despite the advanced nature of their malignant disease.

Animals↗

Monitoring of opioid therapy in advanced cancer pain patients.

Until now, there have not been any parameters to monitor opioid therapy in cancer patients with pain. In this study, 325 consecutive advanced cancer patients were scheduled for a prospective longitudinal survey. After exclusions, 67 patients were surveyed. All included patients were advanced cancer patients with pain that required opioid therapy for more than 6 weeks before death. Opioid escalation, symptoms associated with opioid therapy, pain mechanism, and pain intensity were recorded. Indices were calculated to categorize the response to opioids. The opioid escalation index (OEI) was used to index the mean increase of the starting opioid dosage, expressed as a percentage or in mg. The length of the period of stable dose (MLD) and the effective analgesic score (EAS), that is, the analgesic consumption/pain relief ratio calculated at fixed intervals, were also used. Patients with a mean visual analogue scale score (VAS) of less than 4 and regular OEI and EAS were considered responsive; patients with a mean VAS less than 4 but with an OEI more than 5 or increases of more than 100% of EAS when compared to that calculated the week before were considered mildly responsive; and patients with a mean VAS more than 4 were considered unresponsive. Advanced age, female gender, and previous chemotherapy were all factors reducing OEI. Head and neck cancer was associated with a higher OEI. Regarding the influence of the opioid-related symptoms, an increased OEI was associated with the presence of confusion. Moreover the presence of confusion was associated with neuropathic pain. Neuropathic pain taken alone, however, did not influence this score. Gender-specific cancer, such as breast cancer, influenced the gender differences reported for MLD (significantly longer than that reported for males and other primary tumor). Good responsiveness was observed in 28 patients, partial responsiveness in 33 patients, unresponsiveness in six patients. Psychological factors were associated with poor pain relief, probably reducing the patient's compliance. The tools used in this study may be useful in monitoring the effects of opioid therapy in cancer pain patients. Simple numbers are easy to compare and make it possible to profile opioid responsiveness and differences among patients.

Aged↗

Opioid-sparing effect of diclofenac in cancer pain.

This study investigated the opioid-sparing effect of diclofenac using patient-controlled analgesia with oral methadone. Fifteen patients with advanced cancer participated. After achieving adequate analgesia with regular dosing of oral methadone (T1), patient-controlled analgesia with methadone was administered for 3 days (T2). Intramuscular diclofenac 75 mg twice daily was then added to this regimen for 3 days (T3). Compared to T2 values, methadone dose was significantly reduced at T2 and T2, and pain report (recorded on a visual analogue scale) was significantly reduced at T3. A reduction in methadone plasma concentration was also observed at T2 and T3, although it did not attain statistical significance. Significant decreases in the intensity of several symptoms other than pain were also found at T2 and T3. Diclofenac appears to have a relevant opioid-sparing effect when using patient-controlled analgesia with oral methadone.

Aged↗

Subcutaneous fentanyl infusion in a patient with bowel obstruction and renal failure.

Inoperable bowel obstruction in patients with renal failure is a difficult clinical situation. In the last days of life, an accumulation of morphine metabolites in patients with impaired renal function may cause opioid toxicity, including terminal agitation. The use of an alternative drug may prevent morphine metabolite accumulation in uremic patients. Fentanyl may be an alternative to morphine. It has a large apparent volume of distribution, a short plasma half-life, and extensive biotransformation without active metabolites. A patient with acute renal impairment and bowel obstruction was successfully treated with a subcutaneous continuous infusion of fentanyl (25 micrograms/hr) and boluses of 12.5 micrograms for the last 2 days of life, limiting the worsening of the dramatic clinical picture of bowel obstruction combined with renal impairment. No local toxicity was evidenced.

Aged↗

The inappropriate use of the epidural route in cancer pain.

There continues to be controversy concerning the optimal use of the epidural route in cancer pain. Although spinal opioids undoubtedly give long-lasting analgesia with low doses, indiscriminate use cannot be recommended. Inappropriate indications for the epidural route are reported in three patients who required home palliative care. In contrast to epidural treatment, which caused severe clinical problems, simpler measures, including oral and subcutaneous opioids, were able to give adequate analgesia and a better quality of life. Education of nursing staff and family is necessary when using opioid epidural analgesia at home. Wide dissemination of World Health Organization (WHO) guidelines among doctors and health-care workers can avoid the use of unnecessary and complicated techniques and improve the treatment of terminally ill patients suffering from cancer pain.

Aged↗

Octreotide may prevent definitive intestinal obstruction.

Partial bowel obstruction is indistinguishable from definitive obstruction at the onset of symptoms. No consensus exists regarding the treatment of potentially reversible states of bowel obstruction. On the basis of previous experience, octreotide was used in two patients with chronic intestinal obstruction, resulting in good control of intestinal symptoms and maintenance of a prolonged adequate intestinal transit, preventing the occurrence of definitive bowel obstruction. The results observed stress the early use of octreotide in such delicate clinical situations.

Aged↗

Methadone in cancer pain.

Methadone is often considered as a second-choice drug alternative to morphine in cancer pain treatment. A lack of information regarding methadone's pharmacokinetic/pharmacodynamic relationships has contributed to limitation in its use in analgesic treatments. However, it has been recently re-evaluated in light of better knowledge of its pharmacological characteristics and wider experience. Concern about the safety of methadone therapy arising because of its long and unpredictable half-life should not deter clinicians from its appropriate use. Methadone is a very useful drug in cancer pain because of its low cost, lack of known metabolites, high oral bioavailability, rapid onset and time to peak analgesic effect, and the long duration of activity which allows for longer intervals between doses. Moreover, methadone has been demonstrated to have a high receptor reserve and to exert some NMDA receptor antagonist effect. A shift from one opioid to methadone is recommended when the side-effect/analgesic balance is unfavourable, as symmetrical patterns of cross-tolerance of opioid agonists have been demonstrated. Different approaches, including the oral PCA, have been proposed to circumvent problems related to its pharmacokinetic properties.

Journal Article↗

Nutrition in cancer patients.

Many factors can modify nutritional status in cancer patients, including cachexia, nausea and vomiting, decreased caloric intake or oncologic treatments capable of determining malabsorption. Cachexia is a complex disease characterized not only by a poor intake of nutrients or starvation, but also by metabolic derangement. Nausea and vomiting may limit the nutrient intake and are most often the consequences of oncologic treatments or opioid chronic therapy. Decreased caloric intake is considered to be one of the major causes of malnutrition, although the causes of anorexia remain unclear. Malabsorption is generally attributed to the consequences of oncologic treatments reducing the gastrointestinal absorption. Biochemical measurements and immunological tests may be not reliable indicators of nutritional status in cancer patients. Therefore, medical history, physical examination, estimates of daily oral intake, weight changes and an appropriate consideration of the nutritional requirements according to the stage of disease must still be assessed. The therapeutic approaches should be individualized and realistic. Whenever possible, oral nutrition is the method of choice, with due consideration for specific dietary needs. Nausea and anorexia can be reduced by different kinds of drugs. A careful decision based on good clinical judgement is necessary before deciding to start either enteral or parenteral nutrition, to avoid a useless, costly and difficult treatment. In choosing the route for administration of nutrients, availability of and access to a functioning gastrointestinal tract, compliance and comfort of the patient, gastrointestinal toxicity due to chemotherapy or radiotherapy fields, different costs, duration and place of treatment should be considered rather than the different capacity of parenteral versus enteral nutrition. However, postoperative periods after massive intestinal resection often require prolonged parenteral nutrition. The benefits of parenteral nutrition are not often demonstrable in patients with bowel obstruction. Different ethical aspects are presented. Flexibility in attempting to meet the nutrition needs of each patient is probably the most useful guide.

Cachexia↗

Cancer pain knowledge in Southern Italy: data from a postgraduate refresher course.

A survey of Italian physicians was conducted to assess knowledge, attitudes, and beliefs on cancer pain. Physicians attending a refresher course on cancer pain and symptom relief were given a questionnaire composed of 28 questions before starting the lectures. The physicians represented the different centers treating cancer pain, or were going to deal with cancer pain, and were from all the provinces of Sicily, a southern region of Italy. Insufficient knowledge and education of the physicians regarding the management of cancer pain was evidenced. Limited experience may be the principal reason. Most participants had difficulties in prescribing opioids (23%). Analgesics were frequently administered intramuscularly (46%), although the oral route was suggested by 86% of the physicians as the route of choice for opioids. Opioids were used in more than 75% of the patients by only 33% of the physicians. Opioid treatment was considered effective in more than 75% of the patients by only 63% of the physicians. An arbitrary maximum dose of opioids was reported by 35% of the respondents. Opioid spinal administration was mainly considered the most effective route, the first-choice route to start opioid therapy by 4% of the physicians, and the alternative route to the oral one in 29% of cases. Nausea and vomiting, and tolerance were considered the principal problem during opioid therapy. Antidepressants were the most common adjuvants associated with opioid therapy, and laxatives and antiemetics were frequently used to limit the side effects. Incident pain was rarely reported as a challenging pain syndrome. Examples of cancer pain syndromes were mainly reported correctly, although some definitions were disputable. Inadequate knowledge about cancer pain management limits appropriate treatment. Greater efforts should be made to improve medical education.

Education, Medical, Continuing↗

Patient-controlled analgesia with oral methadone in cancer pain: preliminary report.

BACKGROUND: Methadone is a very useful drug in cancer pain because of its low cost, lack of active metabolites, high oral availability, and the rapid onset of its analgesic effect. It seems to be well tolerated in patients with difficult pain syndromes who are receiving high doses of opioids, and it may deter the development of tolerance, but a high individual variation in terminal elimination half-life can result in different rates and extents of drug accumulation. For this reason, oral patient-controlled analgesia with methadone was used in 24 advanced-disease patients with pain. PATIENTS AND METHODS: A regimen of self-administered oral methadone at fixed doses and flexible patient-controlled dosage intervals to achieve adequate analgesia, while avoiding toxic effects of methadone accumulation, was used in 24 patients requiring opioid therapy. After a priming period of three days with fixed doses of 3-5 mg three times a day for naïve patients and 50% of the morphine equivalent of methadone in patients switched from morphine, patients and relatives were instructed to maintain the night-time dose and to administer a second dose when the pain recurred. When more than four doses of methadone a day were used, an increase of the dosage was prescribed. Continuous pain assessment and monitoring of symptoms were offered. RESULTS: The majority of patients achieved good pain relief until death, and three were switched to very low doses of subcutaneous morphine in their final days. The methadone escalation index was about 2% a day, with a mean dosage increase of 0.3 mg a day for an average of 60 days of treatment at doses ranging from 9 to 80 mg. The plasma concentration in 14 patients ranged from 0.013 to 0.273 mcg/ml with dosages of 20-80 mg during chronic treatment. A mean of 2.4 doses a day was reported, including the fixed night-time dose. The extent of side effects was considered acceptable. CONCLUSION: Patient-administered analgesia with oral methadone appears to be a simple, cheap and relatively safe technique for controlling cancer pain, permitting individualization by the patient him- or herself and avoiding the risk of accumulation. Continuous assessment is necessary.

Administration, Oral↗

Ketamine in cancer pain: an update.

Ketamine has been shown to have potent analgesic properties at low dosages. Bioavailability is high when it is given parenterally, but low after oral or rectal administration. Active metabolites should account for part of the analgesic effect of ketamine during long-term oral administration. NMDA receptor inhibition by ketamine may reflect a wind-down phenomenon, and should alleviate NMDA-related neuropathic pain, reversing the rightward shift of the opioid-response curve. A synergistic effect between ketamine and opioids has been observed in cancer pain patients who have lost an analgesic response to high doses of morphine. Further studies need to be carried out to confirm the benefits of ketamine in cancer pain, and to determine the best route of administration, dosages and the incidence of side effects.

Analgesics, Opioid↗

A circular diagram for representing symptom status in advanced cancer patients.

Symptom relief is the major goal of palliative care. Its assessment is essential and several methods have been described. To evaluate immediately the clinical situation, a circular diagram for a visual representation of the physical symptoms is proposed. Particular patterns derived from the given data emerge from the diagrams. Certain critical situations often observed in palliative care, especially in the last weeks of life, show specific patterns that are easily distinguished. Effective treatments may change the appearance of different pictures.

Audiovisual Aids↗