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Sebastiano Mercadante

Publications and source records attributed to Sebastiano Mercadante.

At least 19 recordsLinked to original sources

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans↗

Dialogues on complex analgesic strategies for difficult pain syndromes.

Although the use of oral analgesics for the control of cancer pain has been demonstrated to be successful in most patients, some patients will fail to respond to pharmacological therapy or will suffer unacceptable adverse effects. Experience is accumulating that when adverse effects prevail with oral opioid administration, the analgesic response may be improved by changing the drug and/or the route of administration. Switching to an alternative opioid may further improve the balance between analgesia and adverse effects. Despite optimal systemic opioid treatment, in some complicated circumstances it is necessary to find different solutions, including the neuraxial administration of multiple drugs with different characteristics, which are difficult to manage. Three case reports illustrate how complex could be the analgesic approach using multiple analgesic regimens and different routes of administration to effectively manage complex pain syndromes commonly defined as unresponsive.

Administration, Oral↗

Sleep disorders in advanced cancer patients: prevalence and factors associated.

GOALS OF WORK: Sleep disorders have been invariably reported in cancer population. However, the prevalence of this problem in advanced cancer patients has never been assessed. The aim of this study was to evaluate the frequency of sleep disturbances in terms of quantity and quality, and possible associated factors. PATIENTS AND METHODS: A consecutive sample of patients admitted to a pain relief and palliative care unit were surveyed. Patients with severe cognitive problems or who were too ill were excluded. Epidemiological and clinical data, including the performance status, habits, relevant symptoms, and drug use were recorded. Patients were asked to answer a small questionnaire regarding their sleep, and duration and characteristics (nocturnal and diurnal hours slept, falling asleep, awaking, getting back to sleep, early awaking, restoring sleep, nightmares, feeling depressed or anxious). The level of information about the illness was also assessed. MAIN RESULTS: Among the causes of admission, pain control was the main indication (about 58%). Of 123 patients surveyed, 30% slept less than 5 h. Women significantly slept more hours than men (p=0.042). Anxiety (p=0.045), falling asleep (p=0.003), awaking (p=0.035), early awaking (p=0.001), getting beck to sleep (p=0.021), and nightmares (p=0.034), were significantly associated with less hours slept. This relationship was highly significant for less restoring sleep, fatigue, and drowsiness ( p<0.0005). No differences were found for age (p=0.294), primary tumor (p=0.225), level of information ( p=0.529), Karnofsky status (p=0.539), depression (p= 0.095), confusion (p=0.074), possible causes of awaking (p= 0.881), use of opioids (p= 0.798), use of hypnotics (p= 0.197), other morbidities ( p=0.460), or use of alcohol or coffee (p= 0.141). Patients admitted for pain control and/or those receiving opioids more frequently had drowsiness (p=0.01) Patients with lower Karnofsky scores had more drowsiness and diurnal hours slept (p=0.01). Anxiety created more difficulties in falling asleep, produced a less restoring sleep, and nightmares. Depression was associated with early awaking, nonrestorative sleep, fatigue, and nightmares. Confusion was associated with fatigue and nightmares. CONCLUSION: Sleep problems appear to be a significant issue for advanced cancer patients. Attention to sleep disturbance needs to be incorporated into the routine practice in palliative care evaluation.

Female↗

Addition of a second opioid may improve opioid response in cancer pain: preliminary data.

Recent experimental data suggest a possible use of an opioid combination to improve analgesia. In cancer patients, a rapid opioid escalation due to either worsening of the pain condition or the development of tolerance is a critical phase, as this condition is associated with a negative prognosis. The aim of this study was to assess the effects of adding a second opioid at low doses in patients with a poor analgesic benefit after dose escalation. Fourteen patients receiving strong opioids who had increased their dosage more than 100% in the last week unsuccessfully were randomly chosen to add a second opioid to the first using an initial equivalent dosage of 20% of the previous therapy. The dose of the second opioid was then changed according to the clinical situation to obtain an acceptable pain control with minimal adverse effects. Pain and symptoms associated with opioid therapy were assessed, and an opioid escalation index (OEI) was calculated at weekly intervals. OEI significantly decreased after adding the second opioid, and this trend was also maintained for the following weeks. Similarly, pain intensity was significantly improved and maintained at acceptable levels for the following weeks. The second opioid did not induce significant opioid-related adverse effects. The opioid combination was able to break opioid escalation in patients with pain syndromes with a poor response to the previous opioid. It allowed for a regaining of analgesia, regardless of the opioid combination used. These preliminary observations should be confirmed in further studies.

Adult↗

Opioids and renal function.

UNLABELLED: Opioids, both endogenous and exogenous, have a strong influence on the renal function through different mechanisms, producing changes in the renal excretion of water and sodium. Several studies have demonstrated that opioids influence renal function, according to the agonist profile used. Mu, kappa, and delta agonists produce different renal effects, although the mechanisms remain unclear. Experimental data have given the input for a possible therapeutic role of kappa agonists for some specific conditions, for example, in treating water retention or hyponatremia occurring in patients who have hepatic cirrhosis with ascites. On the other hand, changes in renal function might strongly condition the use of opioids in the clinical setting, and the knowledge of the relationship between opioids and renal function is mandatory for a tailored approach to accommodate the individual responses in terms of pain intensity, tolerance, and adverse effects experienced by these groups of patients. The influence of renal function when using different opioids in the clinical setting is reviewed, as well as problems related to transplantation, renal damage induced by opioid addiction, and problems related to the use of opioid antagonists in such conditions. PERSPECTIVE: Endogenous opioids exert physiologic effects on renal function, and the use of opioids may have an influence on renal activity. Renal impairment has a serious impact on the clearance of most opioids used in the clinical setting. Biochemical and clinical monitoring is mandatory to prevent serious complications.

Analgesics, Opioid↗

Safety and effectiveness of intravenous morphine for episodic (breakthrough) pain using a fixed ratio with the oral daily morphine dose.

Breakthrough pain is normally severe in intensity and has a rapid onset. The availability of supplemental doses of opioids (rescue medication) in addition to the continuous analgesic medication is the main treatment suggested to manage these pain flares. The intravenous (i.v.) route may provide analgesia fast enough, but has never been assessed in clinical studies. The aim of this open-label study was to verify the safety and effectiveness of an i.v. dose equal to one-fifth the calculated equianalgesic total daily dose in advanced cancer patients with episodic pain. A consecutive sample of 48 cancer patients treated with oral morphine, who reported an acceptable basal analgesia and reported episodic pains, were selected for the study. The intravenous dose of morphine was one-fifth of the oral daily dose, converted into an i.v. dose using an equianalgesic ratio of 1/3 (i.v./oral). Written orders were given and intravenous morphine (i.v.-M) was administered by nurses. For each episode, pain intensity and opioid-related symptoms were recorded at the start (T0), after achieving maximum pain relief (T1), and one hour after (T2). In five patients, blood samples were taken at the time intervals described for measuring plasma concentrations of morphine and related glucuronated metabolites. One hundred seventy-one breakthrough pains were recorded during admission. In 162 episodes, a reduction of pain intensity of more than 33% was obtained within a mean of 17.7 minutes, from a mean intensity of 7.9 (on a 0-10 numeric scale) to 3. One hundred thirty-six episodes had more than a 50% pain intensity decrease after the i.v.-M within a mean of 16.6 minutes, from a pain intensity of 7.9 to 2.6. No differences in age, sex, pain mechanism, and time of events were found. There was a trend but no statistically significant differences between the groups receiving different basal doses and time to reach the maximum effect. Twenty episodes in ten patients required an additional dose within 2 hours. Adverse effects were uncommon and were significantly related to the basal dose, and as a consequence, with the i.v.-M dose. Morphine concentration significantly increased at the time of pain intensity reduction, and then decreased. These observations suggest that i.v.-M at a dose equivalent to 20% of the basal oral dosage is safe and effective in the majority of patients experiencing pain exacerbation. This treatment is inexpensive and can be used at little risk to patients.

Analgesics, Opioid↗

Factors involved in gastrointestinal bleeding in advanced cancer patients followed at home.

There is a lack of information on the frequency of symptomatic gastrointestinal bleeding in patients with advanced cancer. This group of patients presents several risk factors for developing gastrointestinal bleeding. The aim of this multicenter longitudinal survey was to assess the frequency of gastrointestinal bleeding and possible factors implicated in advanced cancer patients followed at home. A consecutive sample of 439 patients who referred to home palliative care program entered the study. Age, gender, primary cancer and known metastases, possible associated pathologies, history of peptic disease, use of previous or actual nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids, drugs used to prevent gastric complications, the occurrence of hematemesis or melena, significant anemia requiring blood transfusion, and mortality associated with the hemorrhagic event were recorded. Of 377 patients who completed the study, 18 reported gastrointestinal bleeding, and five had significant anemia requiring blood transfusion in three cases. Death was found to be related to bleeding in three patients. NSAIDs, steroids, and gastroprotectors were frequently used, either before or during home care. However, no clear relationship between age, gender, and the use of offender drugs with gastrointestinal bleeding was found. Liver involvement was frequently associated with the risk of developing gastrointestinal bleeding.

Anti-Inflammatory Agents, Non-Steroidal↗

Celiac plexus block for pancreatic cancer pain: factors influencing pain, symptoms and quality of life.

Neurolytic celiac plexus block (NCPB) is claimed to be an effective method of pain control for pancreatic cancer pain. However, the factors that may influence long-term analgesia, adverse effects, and quality of life after performing NCPB have never been determined. In a prospective multicenter study, 22 patients who underwent NCPB were followed until death. Numerous parameters other than pain and symptom intensity were evaluated, including age, gender, initial site of cancer, sites of pain, possible peritoneal involvement, technique, and oncologic interventions. Indices were calculated to determine the opioid consumption ratio (EAS) and the trend of opioid escalation (OEI). NCPB was effective in reducing opioid consumption and gastrointestinal adverse effects for at least 4 weeks. In the last four weeks prior to death, there was the typical trend of increasing symptom intensity common to the terminal cancer population. None of the factors studied influenced the analgesic effectiveness of NPCB. NPCB, performed by skilled clinicians, regardless of the technique chosen, is a safe and useful means that should be considered as an adjuvant to common analgesic regimens at any stage, as it may allow the reduction of the visceral component of pancreatic pain that may prevail in certain phases of the illness. The analgesic and symptomatic effect of NCPB is presumably advantageous for about four weeks. A possible factor interfering with long-term outcome includes the capacity of cancer to involve the celiac axis, which can distort the anatomy and prevent neurolytic spread, or modify the pain mechanisms. Outcomes are strongly based on individual variation.

Analgesics, Opioid↗

Hyperalgesia: an emerging iatrogenic syndrome.

Clinical reports suggest that opioids, intended to abolish pain, can unexpectedly produce hyperalgesia. This paradoxical effect may be mechanistically related to tolerance induced by increasing doses of opioids. Two case reports illustrate a syndrome characterized by increasing pain pursued by escalating opioid doses, which results in a worsening of the clinical picture. Several experimental data may help explain the course of this challenging clinical condition. In escalating opioid doses rapidly, a risk of opioid-induced hyperalgesia should be recognized, as higher doses of opioids may stimulate rather than inhibit the central nervous system by different mechanisms. Alternative procedures should be taken into consideration to break this cycle, should it occur. More data are needed to detect this condition, as currently no diagnostic information on specific markers, clinical or biochemical, exists.

Analgesics, Opioid↗

A model of acute symptom control unit: Pain Relief and Palliative Care Unit of La Maddalena Cancer Center.

Palliative care in Italy was provided solely on a home care basis until a couple of years ago. In recent years different realities have been created according to personal experience, quite apart from new resources provided by the National Health System. The first Pain Relief and Palliative Care Unit in Sicily, the largest region in Italy, was established in March 1999. Most members of the regular staff of this Unit have a background in anesthesiology. Activity in the Unit has grown progressively, with 460 admissions in the last year. The characteristics of the first 1,000 patients admitted, the principal protocols for diagnostic and therapeutic procedures, such as those for hitherto intractable pain, nutrition and hydration, interventional procedures for symptom control, and emerging problems, a project called "Island with no pain," and activities in the fields of formation and research are described.

Cancer Care Facilities↗