0000000000122506

AUTHOR

Patrizia Villari

Supportive care services in hemato-oncology centers: a national survey

Background: In the field of hemato-oncology, there is paucity of data assessing models of integration between hemato-oncology and other partner specialties. The aim of this national survey was to gather information about the status of the integration of this kind of activity in hemato-oncologic units existing in Italy. Methods: A national telephone survey was conducted to gather information about the status of the integration of hemato-oncologic and supportive care/anesthesiological services. From the national registry of hemato-oncology units, 149 centers were contacted by phone and a dedicated doctor was identified to gather information about the center through a telephone interview. Resu…

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Opioid Plasma Concentrations during a Switch from Transdermal Fentanyl to Methadone

Opioid switching is often used to improve the opioid response in patients with cancer experiencing poor analgesia or adverse effects. When switching between drugs with delayed effect because of pharmacokinetics or type of delivery, concerns exist about the correct timing of introducing the second drug after stopping the previous one. The aim of this study was to assess plasmatic changes of fentanyl and methadone underlying the clinical events occurring during opioid switching. Eighteen patients with cancer receiving transdermal fentanyl with uncontrolled pain and/or moderate to severe opioid adverse effects, were switched to oral methadone using an initial fixed ratio of 1:20. Fentanyl patc…

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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 …

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An Italian survey on the attitudes in treating breakthrough cancer pain in hospice.

As recognition and treatment of breakthrough cancer pain (BcP) depend on the education and knowledge of palliative care physicians, it is important to systematically explore the attitudes of palliative care physicians in hospices or palliative care units. The aim of this study was to assess the knowledge and attitudes of hospice physicians in Italy regarding BcP and its treatment. All hospices existing in Italy were interviewed to gather information about provision of BP medication, drugs of choice, preferred route of administration, methods to choose the dose, and choice of BcP medication based on opioid administered for background analgesia. Of 158 hospices registered, 122 centers agreed …

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The use of pilocarpine in opioid-induced xerostomia

Oral dryness can be a symptom of asystemic disease, an adverse effect of anticholin-ergic, antiadrenergic or cytotoxic drug treatment, orit can be due to local radiotherapy. Opioid use isstrongly associated with xerostomia, although themechanism for this remains unclear; in one studypatients receiving morphine were four times morelikely to have a dry mouth than patients taking otherdrugs known to cause xerostomia.

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Low morphine doses in opioid-naive cancer patients with pain

Cancer pain can be managed in most patients through the use of the analgesic ladder proposed by the World Health Organization. Recent studies have proposed to skip the second "rung" of the ladder by using a so-called "strong" opioid for moderate pain. However, usual doses of strong opioids commonly prescribed for the third rung of the analgesic ladder may pose several problems in terms of tolerability in opioid-naive patients. The aim of this multicenter study was to evaluate the efficacy and tolerability of very low doses of morphine in advanced cancer patients no longer responsive to nonopioid analgesics. A sample of 110 consecutive opioid-naive patients with moderate-to-severe pain were …

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The use of opioids for breakthrough pain in acute palliative care unit by using doses proportional to opioid basal regimen.

OBJECTIVES: To determine the efficacy and safety of different opioids used in doses proportional to the basal opioid regimen for the management of breakthrough pain (BP). METHODS: In 66 patients consecutive patients admitted to a pain relief and palliative care unit, the efficacy and safety of different opioids used in doses proportional to the basal opioid regimen for the management of breakthrough pain (BP) were assessed. The choice of the opioid to be administered as rescue medication was based on the characteristics of patients, clinical stability, compliance, preference, and so on. For each episode, nurses were instructed to routinely collect changes in pain intensity and emerging prob…

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Clinical and financial analysis of an acute palliative care unit in an oncological department

The aim of this article is to describe the clinical activity and medical intervention of an acute model of palliative care unit (APC), as well as the reimbursement procedures and economic viability. A sample of 504 patients admitted at an APC in 1 year was surveyed. Indications for admission, pain and symptom intensity, analgesic treatments, procedures, instrumental examinations and modalities of discharge were recorded. For each patient, tariff for reimbursement was calculated according to the existent disease related grouping (DRG) system. The mean age was 62 years, and 246 patients were males. The mean hospital stay was 5.4 days. Pain control was the most frequent indication for admissi…

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Naloxone in Treating Central Adverse Effects During Opioid Titration for Cancer Pain

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Opioid escalation in patients with cancer pain: the effect of age.

Elderly people are commonly considered more susceptible to opioid effects. However, no data regarding the need for opioid escalation in patients already receiving opioids for the management of chronic pain are available. The purpose of this study was to evaluate the differences between younger and older patients during the crucial phase of opioid titration. One hundred consecutive patients with cancer pain requiring further opioid dose refinement were recruited for this cohort study. Pain intensity, dose of opioids, number of opioids used (need to switch), routes of administration used, and opioid-related symptoms were measured from admission until dose stabilization. Opioid escalation inde…

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Controlled sedation for refractory symptoms in dying patients.

Terminally ill cancer patients near the end of life may experience intolerable suffering refractory to palliative treatment. Although sedation is considered to be an effective treatment when aggressive efforts fail to provide relief in terminally ill patients, it remains controversial. The aim of this study was to assess the need and effectiveness of sedation in dying patients with intractable symptoms, and the thoughts of relatives regarding sedation. A prospective cohort study was performed on a consecutive sample of dying patients admitted to an acute pain relief and palliative care unit within a cancer center. Indications for sedation, opioid and midazolam doses, level of delirium and s…

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Optimization of opioid therapy for preventing incident pain associated with bone metastases

Breakthrough pain is a transitory flare of Pain superimposed on an otherwise stable pain pattern in patients treated with opioids. One form of breakthrough pain is incident pain, which is due to movement and is commonly associated with bone metastases. The development of this pain is rapid and no medication, administered "as needed," has such a rapid onset that it parallels this temporal Pattern of Pain. This study used a construct based on the prevention of this event, and implemented a new experimental paradigm. Specifically, the study determined whether increasing the opioid doses above those sufficient to control pain at rest would. reduce the occurrence of these pains. Twenty-five cons…

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Amitriptyline in neuropathic cancer pain in patients on morphine therapy: A randomized placebo-controlled, double-blind crossover study

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, patient…

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Frequency, indications, outcomes, and predictive factors of opioid switching in an acute palliative care unit.

The aim of this study was to prospectively evaluate the frequency, indications, outcomes, and predictive factors associated with opioid switching, using a protocol that had been clinically applied and viewed as effective for many years. A prospective study was carried out on a cohort of consecutive cancer patients who were receiving opioids but had an unacceptable balance between analgesia and adverse effects, despite symptomatic treatment of side effects. The initial conversion ratio between opioids and routes was as follows (mg/day): oral morphine 100=intravenous morphine 33=transdermal fentanyl 1=intravenous fentanyl 1=oral methadone 20=intravenous methadone 16=oral oxycodone 70=transder…

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Frequency and Indications of Parenteral Nutrition in an Acute Palliative Care Unit

The aim of this study was to estimate the use of parenteral nutrition (PN) in advanced cancer patients enrolled in an acute pain relief and palliative care unit of a comprehensive cancer center and the appropriateness of the criteria to select patients for PN. Fourteen out of 750 patients (1.8%) admitted to an acute palliative care unit were administered PN. Patients were referred from various settings. The mean age was 58 yr (range 37-79), and 9 were males. The mean hospital stay was 7.7 days (range 3-14), and the mean Karnofsky level was 35 (range 10-50). The principal indication was bowel obstruction. Ten patients (71%) were already receiving PN before admission, and 2 of them discontinu…

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Low doses of transdermal buprenorphine in opioid-naive patients with cancer pain: A 4-week, nonrandomized, open-label, uncontrolled observational study

OBJECTIVE: The aim of this study was to evaluate the effect and tolerability of low doses of transdermal (TD) buprenorphine patches in opioid-naive patients with cancer pain. METHODS: This was a nonrandomized, open-label, uncontrolled study in consecutive opioid-naive patients with advanced cancer and moderate pain. TD buprenorphine was initiated at a dose of 17.5 microg/h (0.4 mg/d), with patch changes every 3 days. Doses were then adjusted according to the clinical response. Pain intensity, opioid-related adverse effects, TD buprenorphine doses, and quality of life were monitored over 4 weeks. The time to dose stabilization and indexes of dose escalation were also calculated. RESULTS: Thi…

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Methadone versus morphine for postoperative pain in patients undergoing surgery for gynecological cancer: A randomized controlled clinical trial.

Abstract Study objective The aim of this study was to compare methadone and morphine for the management of postoperative. Design Open, controlled study. Setting Postoperative recovering area, ward. Patients Sixty-four patients, ASA I-III, undergoing gynecological surgery for cancer. Interventions Morphine or methadone 0.15 mg/kg given preoperatively. After operation an intravenous morphine or intravenous methadone infusion at doses of 12 mg/day was started. Measurements Pain intensity and opioid consumption. Main results Methadone infusion provided a better analgesia in comparison with morphine infusion on the second day. Opioid consumption was significantly lower in the methadone group. No…

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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…

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A Randomized-Controlled Study of Intrathecal Versus Epidural Thoracic Analgesia in Patients Undergoing Abdominal Cancer Surgery

Background. We sought to determine the effectiveness of continuous intrathecal thoracic analgesia (ITA) in comparison with continuous epidural thoracic analgesia (ETA) for the management of postoperative pain after abdominal cancer surgery in a randomised controlled study. Materials and methods. Catheters were inserted at T8-10 level for both techniques. Sixty patients were randomized to receive ITA providing levobupivacaine 0.25%, at 0.5-0-7 ml/h, associated with a single bolus of morphine 0.15 mg, or ETA with levobupivacaine 0.25% 4-6 ml/h and a single bolus of epidural morphine 2-3 mg. Data were collected before discharging from recovery room to the surgical ward, 1, 2, 3, 8, 12, 24 h, a…

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High-dose furosemide and small-volume hypertonic saline solution infusion for the treatment of leg edema in advanced cancer patients.

Peripheral edema is a common feature in populations with advanced cancer, although it is seldom recognized. Diuretics are commonly employed and may show some benefit, but there are insufficient clinical trial data to draw useful conclusions about their clinical use. The aim of this prospective study was to evaluate the efficacy and tolerability of high-dose furosemide and small-volume hypertonic saline solution infusion in reducing leg edema in patients with advanced cancer treated unsuccessfully with diuretics. A prospective study was performed in a consecutive sample of 24 patients admitted to a pain relief and palliative care unit over a period of 18 months. To be eligible to enter the t…

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Sustained-release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management.

The aim of this study was to compare the analgesic and adverse effects, doses, as well as cost of opioid drugs, supportive drug therapy and other analgesic drugs in patients treated with oral sustained-release morphine, transdermal fentanyl, and oral methadone.One hundred and eight cancer patients, no longer responsive to opioids for moderate pain, were selected to randomly receive initial daily doses of 60 mg of oral sustained-release morphine, 15 mg of oral methadone, or 0.6 mg (25 microg/h) of transdermal fentanyl. Oral morphine was used as breakthrough pain medication during opioid titration. Opioid doses, pain intensity, adverse effects, symptomatic drugs, were recorded at week interva…

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Withdrawal Acute Psychosis After Corticosteroid Discontinuation

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Refractory Death Rattle: Deep Aspiration Facilitates the Effects of Antisecretory Agents

Anticholinergic drugs, including atropine, hyoscine butylbromide, and scopolamine, have been shown to be equally effective in the treatment of death rattle. However, anticholinergic drugs may only be effective in reducing the production of further secretions, rather than eliminating the existing ones. A case is described in which a preventive procedure was undertaken to carefully eliminate secretions before starting anticholinergic drugs. Airway aspiration under light anesthesia removed secretions before starting anticholinergic drugs. Low doses of propofol were given intravenously to make a laryngoscopy feasible, allowing the complete aspiration of large amounts of tracheal secretions. No …

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Safety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphine.

Supplemental dosing of an opioid is the main treatment suggested to manage breakthrough pain in cancer patients. The intravenous route has been proven to be safe and effective, providing rapid analgesia in patients receiving oral morphine. Transdermal buprenorphine (TTS-BUP) is increasingly used in cancer pain management, but this drug has been labeled as a difficult drug to use in combination with other opioids. The aim of this open-label study was to verify the safety and effectiveness of intravenous morphine (IV-MO) for the treatment of episodic pain in cancer patients receiving TTS-BUP. A consecutive sample of 29 cancer patients, who were treated with TTS-BUP, reported an acceptable bas…

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Opioid-induced or pain relief-reduced symptoms in advanced cancer patients?

Abstract Background While opioids in increasing doses may produce adverse effects, the same adverse effects may be associated with poor pain control. Moreover, in the clinical setting symptomatic treatment and illness may balance the outcome of opioid titration. Some adverse effects may tend to disappear continuing the treatment in a long-term period. Aims The aim of this study was to monitor the effects of a rapid opioid titration combined with symptomatic treatment in patients with poor relief and to monitor these changes in the following period of 20 days. Methods A consecutive sample of 35 patients admitted to an acute Pain Relief and Palliative Care Unit were titrated with opioids, acc…

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Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversion

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 si…

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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…

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Clinical Problems with Transdermal Fentanyl Titration from 25 to 50 μg/hr

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Intravenous morphine for breakthrough (episodic-) pain in an acute palliative care unit: a confirmatory study.

The aim of this prospective cohort study was to confirm the safety of intravenous morphine (IV-M) used in doses proportional to the basal opioid regimen for the management of breakthrough pain and to record the nurse compliance on regularly recording data regarding breakthrough pain treated by IV-M. Over a one-year period, 99 patients received IV-M for breakthrough pain during 116 admissions. The IV-M dose was 1/5 of the oral daily dose, converted using an equianalgesic ratio of 1/3 (IV/oral). For each episode, nurses were instructed to routinely collect changes in pain intensity and emerging problems when pain became severe (T0), and to reassess the patient 15minutes after IV-M injection (…

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Rapid Switching Between Transdermal Fentanyl and Methadone in Cancer Patients

Purpose The aim of this study was to examine the clinical effects of switching from transdermal (TTS) fentanyl to methadone, or vice versa, in patients with a poor response to the previous opioid. Patients and Methods A prospective study was carried out on 31 patients who switched from TTS fentanyl to oral methadone, or vice versa, because of poor opioid response. A fixed conversion ratio of fentanyl to methadone of 1:20 was started and assisted by rescue doses of opioids, and then doses were changed according to clinical response. Pain and symptom intensity, expressed as distress score, were recorded before switching doses of the two opioids and after subsequent doses. The number of change…

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Noninvasive Ventilation for the Treatment of Dyspnea as a Bridge from Intensive to End-of-Life Care

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Switching from oxycodone to methadone in advanced cancer patients

The aim of this study was to prospectively evaluate the outcomes and the conversion ratio of switching from oxycodone to methadone in advanced cancer patients admitted to an acute palliative care unit.A prospective study was carried out on a cohort of consecutive sample of patients receiving oxycodone, who were switched for different reasons mainly because of an inconvenient balance between analgesia and adverse effects. An initial conversion ratio between oxycodone and methadone was 3.3:1. Intensity of pain and symptoms associated with opioid therapy were recorded, and a distress score (DS) was also calculated as a sum of symptom intensity. A successful switching was considered when the in…

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Effects of red blood cell transfusion on anemia-related symptoms in patients with cancer.

The aim of this study was to assess the effects of red blood cell transfusion, and the subsequent increase in hemoglobin values, on anemia-related symptoms in a cohort of patients with cancer with different survival times. A red blood cell transfusion was recommended to a consecutive sample of patients with hemoglobin levels of 8 +/- 0.5 g/dL. The number of units to be ordered was decided according the hemoglobin values with a mean target of increasing the hemoglobin values by approximately 2 g/dL. Hemoglobin values, anemia-related signs and symptoms, including well-being, fatigue, and dyspnea, were recorded at admission (T0), 1 day after the last transfusion (T1), and 15 days afterward (T2…

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Long-term efficacy and tolerability of intranasal fentanyl in the treatment of breakthrough cancer pain

Purpose: The aim of the present study was to assess the long-term tolerability and efficacy of intranasal fentanyl (INFS) in opioid-tolerant patients with breakthrough cancer pain (BTP).Patients and methods: A 6 months, observational, prospective, cohort study design was employed to follow advanced cancer patients with BTP receiving INFS under routine clinical practice. Eligible adult cancer patients suffering from BTP had been prescribed INFS at effective doses. Data were collected at T0 and at month intervals for six months. The principal outcomes were the evaluation of possible serious adverse effects with prolonged use of INFS, the efficacy of BTP treatment with INFS, the quality of sle…

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Aggressive Pharmacological Treatment for Reversing Malignant Bowel Obstruction

Early and intensive pharmacological treatment not only may reduce gastrointestinal symptoms but also reverse malignant bowel obstruction. Fifteen consecutive advanced cancer patients with inoperable bowel obstruction received a combination of drugs including metoclopramide, octreotide, dexamethasone and an initial bolus of amidotrizoato. Recovery of intestinal transit was reported within 1-5 days in fourteen patients, who continued this treatment without presenting symptoms of bowel obstruction until death. This case series establishes that the combination of propulsive and antisecretive agents can act synergistically to allow a fast recovery of bowel transit without inducing unpleasant col…

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Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic-breakthrough pain

The use of supplemental doses of opioids is commonly suggested to manage breakthrough pain. A comparative study of intravenous morphine (IV-MO) and oral transmucosal fentanyl citrate (OTFC) given in doses proportional to the basal opioid regimen was performed in 25 cancer patients receiving stable opioid doses. For each episode, when it occurred and 15 and 30 min after the treatment, pain intensity and opioid-related symptoms were recorded. Fifty-three couples of breakthrough events, each treated with IV-MO and OTFC, were recorded. In episodes treated with IV-MO, pain intensity decreased from a mean of 6.9 to 3.3 and to 1.7 at T1 and T2, respectively. In episodes treated with OTFC, pain int…

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Local anesthetic switching for intrathecal tachyphylaxis in cancer patients with pain.

IMPLICATIONS Switching from bupivacaine to lidocaine may improve intrathecal morphine analgesia in advanced cancer patients, possibly because of different spinal mechanisms limiting the hyperalgesic processes.

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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…

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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…

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Alternative treatments of breakthrough pain in patients receiving spinal analgesics for cancer pain.

Patients who experience a poor response to different systemic opioid trials (oral and intravenous) are candidates for spinal treatment. Breakthrough pain occurring in this group of patients is challenging for physicians. This phenomenon has never been described in this context and the treatment is quite difficult, as patients already demonstrated a poor response to systemic opioids. We report a preliminary experience of alternative methods, including the intrathecal injection of local anesthetic boluses as needed, or alternatively, the use of sublingual ketamine. Twelve consecutive patients with advanced cancer and pain were selected for intrathecal treatment after receiving different trial…

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