Opioid prescription in Italy: new law, no effect.
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Biomedical subjects
Publications and source records attributed to Sebastiano Mercadante.
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BACKGROUND: Cancer pain emergencies presenting with severe excruciating pain require a rapid application of powerful analgesic strategies. The aim of the current study was to evaluate a method of rapid titration with intravenous morphine to achieve relief of cancer pain of severe intensity. METHODS: Forty-nine consecutive patients admitted to a Pain Relief and Palliative Care Unit for severe and prolonged pain were enrolled in the study. Pain was evaluated on a numeric scale of 0-10 (0 indicated no pain and 10 indicated excruciating pain). After the initial assessment (T0), an intravenous line was inserted and boluses of morphine (2 mg every 2 minutes) were given until the initial signs of significant analgesia were detected or severe adverse effects occurred (T1). A continuous reassessment was warranted and the effective total dose administrated intravenously was assumed to last approximately 4 hours and was calculated for 24 hours. The dose immediately was converted to oral morphine (a 1:3 ratio for low doses and a 1:2 ratio for high doses). RESULTS: Data from 45 patients was analyzed. A significant decrease in pain intensity was achieved in a mean of 9.7 minutes (95% confidence interval [95% CI], 7.4-12.1 minutes), using a mean dose of intravenous morphine of 8.5 mg (95% CI, 6.5-10.5 mg). The doses administered rapidly were converted to oral morphine and pain control was maintained until the patient's discharge, which occurred in a mean of 4.6 days (95% CI, 4.1-5.2 days). The incidence of adverse effects was minimal. CONCLUSIONS: The results of the current study demonstrate that cancer pain emergencies can be treated rapidly in the majority of cancer patients with an acceptable level of adverse effects. Intravenous administration of morphine requires initial close supervision and continuity of medical and nursing care.
BACKGROUND: Breakthrough pain is transitory exacerbation of pain that occurs in addition to otherwise stable persistent pain. The wide differences in estimation of incidence reported in literature are probably because of different settings and meanings attributed to the definition of breakthrough pain. METHODS: A panel of experts met to establish the actual knowledge on breakthrough pain, according to the evidence in literature and experience. They agreed that episodic or transient pain could be a more simple and adequate term in most languages, including English, French, Italian, and Spanish. RESULTS: A specific assessment and precise pain characterization are essential to plan the most appropriate treatments. Despite the relevance of this temporal pain pattern for the influence on the outcome and quality of life, few controlled studies have been performed to give evidence of a specific approach. Several experiences have reported the possible efficacy of different drugs, route of administration, and modalities of administration in different circumstances. CONCLUSIONS: Prospective studies with previous treatments using similar terminologies are necessary to find the most convenient therapeutic intervention, according to the temporal pattern characteristics and the pain mechanism involved.
Improved understanding of the pathophysiology of prostate cancer-induced metabolic bone disease implies that bisphosphonates may have a role in the treatment of this disorder. Although prostate cancer cells stimulate osteoblasts, resulting in a marked increase in bone volume and the classic radiologic aspect of sclerotic metastases, accelerated bone resorption has been reported by histomorphometric and biochemical studies. The significant relationship between the biochemical parameters of bone resorption and formation suggests a coupling between these two processes in metastatic prostate cancer. Several studies have demonstrated that administration of bisphosphonates is one of the most cost-effective palliative treatments for patients with prostate carcinoma and bone metastases, both as first-line and long-term therapy. With appropriate doses, a large proportion of patients can be maintained free of bone pain until death. Studies of the efficacy of lower doses to prevent skeletal morbidity in patients without metastases or with asymptomatic bone lesions are warranted.
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Epidural and intrathecal techniques are well established techniques in cancer pain. However, several questions remain unresolved. The several problems of long-term spinal opioid treatment in advance cancer patients were reviewed. Indications for the use of spinal opioids include patients treated by systemic opioids with effective pain relief but with unacceptable side effects, or unsuccessful treatment with sequential strong opioid drug trials despite escalating doses. Therefore, the previous aggressive treatment with systemic opioids would leave as failures patients with difficult pain syndromes unresponsive to opioids. The choice of external or totally implanted delivery systems is based on different clinical considerations. The use of externalized tunneled intrathecal catheters has not been associated with higher rates of complications and is easier to place and use at home in debilitated patients late in the course of their disease. The intrathecal administration has a lower incidence of catheter occlusion, lower malfunctioning rate, lower dose requirement, and more effective pain control. Due to the lower daily doses and volumes, intrathecal treatment proved to be more suitable for treatment at home by a continuous infusion than the epidural treatment. Advantages of infusion techniques are more evident when using local anesthetics, since intermittent administration of bupivacaine often results in motor paralysis and hemodynamic instability. Morphine is the opioid of choice. An epidural dose of 10% of the systemic dose is often used. However, intrathecal administration of opioids and bupivacaine may substantially improve pain relief in patients unresponsive to high epidural doses of these drugs, Bupivacaine-induced adverse effects, including sensory deficits, motor complaints, signs of autonomic dysfunction or neurotoxicity have been reported to not occur with bupivacaine doses less than 30-60 mg/day. Adjuvant drugs may further improve analgesia. Different ranges of technical complication rates have been reported in the literature, most of them being associated with epidural catheters. Subcutaneous tunneling and fixation of the catheter, bacterial filters, minimum changes of tubings, careful exit site care weekly, site protection and monitoring of any sign of infection to prevent infection, and training for family under supervision, are recommended. Areas for additional research include the use of spinal adjuvants, the ideal spinal morphine-bupivacaine ratio. methods to improve spinal opioid responsiveness and long-term catheter management with appropriate home care programs.
Prolonged and severe diarrhoea after alcohol celiac plexus block is a rare, but life-threatening, complication if not recognized. This type of diarrhoea may be considered an autonomic neuropathy due to sympathetic denervation. A 65-year-old pancreatic cancer patient developed serious diarrhoea after celiac plexus block which was unresponsive to traditional treatment such as loperamide, dyphenoxylate and opioids. Subcutaneous octreotide, 0.1 mg twice a day, achieved a complete resolution of the symptom. This drug was maintained at the same dosage and was well tolerated for 4 months until death. Octreotide, an analogue of somatostatin, reduces diarrhoea by suppression of intestinal motility and secretion and offers a useful option in the treatment of this complication of celiac plexus block.
Sixty consecutive lung cancer patients referred to a palliative care service were followed until death to obtain specific information about the prevalence, characteristics and localization of pain. To determine the course of treatment, an Opioid Escalation Index and Effective Analgesic Score were calculated. The prevalence of pain was almost 90%. Chest and lumbar pain were the most common sites with a clear correlation between site and metastases for the chest. Somatic incident pain did not achieve good pain relief while patients with neuropathic pain did not show any particular disadvantage compared to those exhibiting somatic or visceral pain. Mean Opioid Escalation Index and percentage of pain control observed in lung cancer patients were similar to those recorded in the general cancer population.
Twenty pancreatic cancer patients were studied to assess the effectiveness and duration of celiac plexus block compared to traditional treatment with analgesics by considering the previous and subsequent consumption of narcotics until their death. After 1 week of therapy with NSAID-narcotic sequence according to the WHO method, 10 patients were continued on this treatment, while the other 10 patients underwent celiac plexus block. Subsequently analgesics were administered as in the patients not treated by the block. A visual analogue score and opioid consumption were used to calculate the effective analgesic dose at weekly intervals until death. Celiac plexus block made pain control possible with a reduction in opioid consumption for a mean survival period of about 51 days. Administration of only analgesics resulted in an equal reduction in VAS pain score until death, but with more unpleasant side effects than when using celiac plexus block.
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Analgesic response, incidental pain and pain mechanism were evaluated in order to predict the chances of pain relief in advanced cancer patients. In an observation period of about 2 months, 130 patients were followed at home until death using only a pharmacological approach to control pain according to the WHO ladders. Ninety-eight patients were considered. Pain relief was considered good if less than moderate. Pain was assessed during the course of examinations (2-3 a week) by independent observers. If other techniques were needed the result was considered negative. The patients were tested with an NSAID (Diclofenac) and assigned to group 1 if the pain became slight in 3 days. If the response was negative, a 4-day trial with opioids was started. If the pain was slight the patient was included in group 3, otherwise in group 5. Every patient belonging to these groups but with incidentical pain was included in groups 2, 4 and 6, respectively. For each group a subdivision was made according to the pain characteristics. There was a progressive worsening in pain relief in groups 4, 5 and 6, suggesting a good correlation between response to the drugs and future chances of pain control in a period of 2 months. This study demonstrates that incidental pain reduces the possibility of pain control (50%) with the exclusive administration of analgesics in patients with a mean life expectation of about 2 months. This negative influence is counterbalanced by the possible individual response to analgesics administered sequentially during a 1-week period (85.8% good pain relief with NSAID, 74% with opioids).(ABSTRACT TRUNCATED AT 250 WORDS)
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AIMS AND BACKGROUND: Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain. METHODS: Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded. RESULTS: No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of amitriptyline were slight and associated with adverse effects. CONCLUSIONS: In light of the results obtained in the study, the extensive use of the drug for cancer pain should be questioned.
AIMS AND BACKGROUND: There is controversy about the role of neurolytic sympathetic blocks in advanced cancer, when pain syndromes may assume other characteristics, with a possible involvement of structures other than visceral. The aim of the present study was to assess the pain characteristics and the analgesic response of a consecutive sample of home care patients with pancreatic and pelvic pain, which would have possible indications for a celiac plexus block and a superior hypogastric block, respectively. METHODS: From January 1999 to December 1999, 400 consecutive advanced cancer patients were surveyed for a prospective longitudinal survey. We considered only patients who had pancreatic cancer or pelvic cancer with pain. RESULTS: Thirty-six patients were surveyed: 22 patients had pelvic cancers and 14 had pancreatic cancer. Patients with pelvic cancers showed a longer survival than those with pancreatic cancer (P = 0.019). Patients with pelvic cancers more frequently showed a neuropathic component associated with a visceral or somatic mechanism than patients with pain due to pancreatic cancer (P = 0.019). When the pain mechanism was taken into consideration, patients with pelvic cancers with a neuropathic component showed worse pain relief than patients with pain due to pancreatic cancer (P = 0.040). CONCLUSIONS: Sympathetic procedures for pain conditions due to pancreatic and pelvic cancers should be intended as adjuvant techniques to reduce the analgesic consumption, and not as a panacea, given that multiple pain mechanisms are often involved because progression of disease is able to change the underlying pain mechanisms. Pancreatic pain seems to maintain visceral characteristics amenable to sympathetic block more than pain due to pelvic cancer.