Alessandra Casuccio

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.

Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial.

Bowel obstruction may be an inoperable complication in patients with end-stage cancer. Scopolamine butylbromide (SB) and octreotide (OCT) have been successfully used with the aim of reducing gastrointestinal (GI) secretions to avoid placement of a nasogastric tube (NGT); however, there have been no comparative studies concerning the efficacy of these drugs. Furthermore, there is little information about the role played by parenteral hydration in symptom control of these patients. In a prospective trial that involved all 17 inoperable bowel-obstructed patients presenting to our services with a decompressive NGT, patients were randomized to OCT 0.3 mg/day or SB 60 mg/day for 3 days through a continuous subcutaneous infusion. Clinical data, survival time, and the time interval from the first diagnosis of cancer to the onset of inoperable bowel obstruction were noted. The intensity of pain, nausea, dry mouth, thirst, dyspnea, feeling of abdominal distension, and drowsiness were assessed by means of a verbal scale before starting treatment with the drugs under study (T0) and then daily for 3 days (T1, T2, T3). Moreover, daily information was collected regarding the quantity of GI secretions through the NGT, the oral intake of fluids, the quantity of parenteral hydration, and the analgesic therapy used. The NGT could be removed in all 10 home care and in 3 hospitalized patients without changing the dosage of the drugs. OCT significantly reduced the amount of GI secretions at T2 (P = 0.016) and T3 (P = 0.020). Compared to the home care patients, the hospitalized patients received significantly more parenteral hydration (P = 0.0005) and drank more fluids (P = 0.025). There was no difference in the daily thirst and dry mouth intensity in relation to the amount of parenteral hydration or the treatment provided (OCT or SB). Independent of antisecretory treatment, the patients receiving less parenteral hydration presented significantly more nausea (T0 P = 0.002; T1 P = 0.001; T2 P = 0.003; T3 P = 0.001) and drowsiness at T3 (P < 0.5). Pain relief was obtained in all 17 patients and only two patients required an increase in morphine dose at T1. All patients with inoperable malignant bowel obstruction should undergo treatment with antisecretory drugs so as to evaluate the possibility of removing the NGT. When a more rapid reduction in GI secretions is desired, OCT should be considered as the first choice drug. Parenteral hydration over 500 ml/day may reduce nausea and drowsiness.

Comparison of octreotide and hyoscine butylbromide in controlling gastrointestinal symptoms due to malignant inoperable bowel obstruction

Abstract In advanced cancer patients with inoperable bowel obstruction, the administration of antisecretive and antiemetic drugs has proved to be effective in controlling gastrointestinal symptoms caused by bowel obstruction. However, controlled studies concerning the most effective antisecretive drug are lacking. The aim of this randomized controlled study was to determine whether octreotide or hyoscine butylbromide was the more effective antisecretive drug for use in states of inoperable bowel obstruction. Eighteen patients with inoperable bowel obstruction randomly received octreotide 0.3 mg daily (n=9) or hyoscine butylbromide (HB) 60 mg daily (n=9) s.c. The following parameters were measured: episodes of vomiting, nausea, drowsiness, continuous and colicky pain, using a Likert scale corresponding to a numerical value: (none 0, slight 1, moderate 2, severe 3) recorded before starting the treatment (T0) and 24 h (T1), 48 h (T2) and 72 h after (T3), and the mean daily amounts of fluids administered i.v. or s.c. during the period of study. Three patients dropped out of the study because data were incomplete. Octreotide treatment induced a significantly rapid reduction in the number of daily episodes of vomiting and intensity of nausea compared with HB treatment at the different time intervals examined. No relevant changes were found in dry mouth, drowsiness and colicky pain. Lower levels of hydration were associated with nausea regardless of the treatment. At the doses used in this study, octreotide was more effective than HB in controlling gastrointestinal symptoms of bowel obstruction. Further studies are necessary to understand the role of hydration more clearly in such a clinical situation.

The Course of Symptom Frequency and Intensity in Advanced Cancer Patients Followed at Home

Four hundred consecutive patients who were referred to a home palliative care program were prospectively surveyed to estimate the prevalence and severity of common symptoms according to the changes in the performance status. Patients were admitted for the presence of different symptoms and psychosocial support. Common symptoms included in a standard form were rated for severity (absent 0, mild 1, moderate 2, severe 3) for each visit. Pain intensity was rated on a numerical scale (0-10). For each level of Karnofsky performance score (K), the frequency and the worse symptom intensity were recorded until patients death. Data from 370 patients were analyzed. Pain was effectively controlled. In the final stage, it was also less frequently observed, despite the use of lower analgesic doses in the last days of life. The peak of opioid consumption and symptom frequency and severity was found at K40. This was also the most frequent K level at admission. Some symptoms, such as nausea and vomiting, dry mouth, gastric pyrosis, and diarrhea reached a peak in frequency and severity, then decreased with the advanced stage of the disease. Other symptoms, such as dyspnea, drowsiness, weakness, and confusion tended to further increase and to have a peak at the lowest levels of K. Dysphagia and constipation progressively increased in frequency and intensity, but decreased at the end. These findings clarify the actual frequency and intensity of symptoms in a non-selected home care population with advanced cancer.

Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis : the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study

Residual vein thrombosis (RVT) indicates a prothrombotic state and is useful for evaluating the optimal duration of oral anticoagulant treatment (OAT). Patients with a first episode of deep vein thrombosis, treated with OAT for 3 months, were managed according to RVT findings. Those with RVT were randomized to either stop or continue anticoagulants for 9 additional months, whereas in those without RVT, OAT was stopped. Outcomes were recurrent venous thromboembolism and/or major bleeding. Residual thrombosis was detected in 180 (69.8%) of 258 patients; recurrent events occurred in 27.2% of those who discontinued (25/92; 15.2% person-years) and 19.3% of those who continued OAT (17/88; 10.1% person-years). The relative adjusted hazard ratio (HR) was 1.58 (95% confidence interval [CI], 0.85-2.93; P = .145). Of the 78 (30.2%) patients without RVT, only 1 (1.3%; 0.63% person-years) had a recurrence. The adjusted HR of patients with RVT versus those without was 24.9 (95% CI, 3.4-183.6; P = .002). One major bleeding event (1.1%; 0.53% person-years) occurred in patients who stopped and 2 occurred (2.3%; 1.1% person-years) in those who continued OAT. Absence of RVT identifies a group of patients at very low risk for recurrent thrombosis who can safely stop OAT. This trial was registered at http://www.ClinicalTrials.gov as no. NCT00438230.

Rapid Switching From Morphine to Methadone in Cancer Patients With Poor Response to Morphine

PURPOSE The aim of this study was to evidence the clinical effects of an abrupt substitution of morphine with methadone using a fixed ratio of 1:5 in patients for whom limiting adverse effects occurred before adequate analgesia was achieved with oral morphine. PATIENTS AND METHODS A cross-sectional prospective study was carried out on 24 consecutive patients who were switched from oral morphine to oral methadone because they experienced substantial adverse effects that limited further increase in morphine dose. A fixed conversion morphine-to-methadone ratio of 5:1 was chosen. Subsequently, doses were changed according to clinical need, with frequent visits or phone contacts. Pain and symptom intensity, preswitching doses of morphine, initial and subsequent doses of methadone, and survival were recorded. RESULTS A significant decrease in pain and symptom intensity was found within 24 hours after the substitution took place. The switching was effective in most patients (19 of 24), although five patients required alternative treatments. No significant changes in methadone dose were reported in the 3 days after switching. Methadone dose was significantly higher in patients who had lower preswitching doses of morphine and vice versa. No relevant complications were reported. CONCLUSION A rapid substitution of morphine with methadone using an initial fixed ratio of 5:1 is a safe and effective method for improving the balance between analgesia and adverse effects in cancer patients with poor morphine response. An appropriate system of patient monitoring is necessary, because further changes in dose may be required according to clinical needs.

Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home.

PURPOSE The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine. PATIENTS AND METHODS A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals. RESULTS differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups. CONCLUSION Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain.

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=transdermal buprenorphine 1.3. The switch was assisted by opioids used as needed, and doses were changed after the initial conversion according to clinical response in an acute care setting. Intensity of pain and symptoms associated with opioid therapy were recorded. A distress score (DS) was calculated as a sum of symptom intensity. A switch was considered successful when the intensity of pain and/or DS, or the principal symptom necessitating the switch, decreased to at least 33% of the value recorded before switching. One hundred eighteen patients underwent opioid substitutions. The indications for opioid switching were uncontrolled pain and adverse effects (50.8%), adverse effects (28.8%), uncontrolled pain (15.2%), and convenience (4.2%). Overall, 103 substitutions were successful. Ninety-six substitutions were successful after the first switching, and a further substitution was successful in seven patients who did not respond to the first switch. The mean time to achieve dose stabilization after switching was 3.2 days. The presence of both poor pain control and adverse effects was related to unsuccessful switching (P<0.004). No relationship was identified between unsuccessful switching and the opioid dose, opioid sequence, pain mechanism, or use of adjuvant medications. Opioid switching was an effective method to improve the balance between analgesia and adverse effects in more than 80% of cancer patients with a poor response to an opioid. The presence of both poor pain relief and adverse effects is a negative factor for switching prognosis, whereas renal failure is not.

Deep sclerectomy versus punch trabeculectomy with or without phacoemulsification: a randomized clinical trial.

Purpose:To compare the efficacy of non-penetrating deep sclerectomy without implant with Crozafon-De Laage punch trabeculectomy, and to evaluate the effect of simultaneous temporal approach phacoemulsification on both techniques. Patients and Methods:Setting: Department of Ophthalmology of the University of Palermo. Design:Prospective randomized clinical trial. Patients and intervention procedures: Sixty-five patients (65 eyes) with primary open angle glaucoma (POAG) or pseudoexfoliative glaucoma (PEXG): 32 eyes underwent non-penetrating deep sclerectomy (NPDS), 17 as single procedure and 15 combined with phacoemulsification (phaco-NPDS), and 33 eyes underwent punch trabeculectomy (PT), 18 single and 15 with phaco (phaco-PT). The patients were randomly assigned to each procedure. No adjuvants, such as Nd: YAG laser goniopuncture, laser suturelysis, and antimetabolites were used. Main Outcome Measures: Postoperative complications, number of antiglaucoma medications, and IOP level were checked at each control. Complete success indicated the achievement of the target IOP without antiglaucoma medications, while qualified success indicated the same goal with or without medications. These categories were assessed at two target IOP levels, namely ≤21 mm Hg and ≤17 mm Hg in all four groups. Results:The mean follow-up period was 22.5 ± 2.5 months. The mean preoperative IOP was 30.2 mm Hg in NPDS eyes, 26.8 in phaco-NPDS eyes, 32.1 in PT eyes, and 27.0 in phaco-PT ones, without significant intergroup difference. At the end point the mean IOP was 17.7 ± 0.8, 15.7 ± 0.9, 14.2 ± 1.1, and 13.8 ± 1.1 mm Hg respectively with postoperative IOP significantly lower (P = 0.005) than preoperative IOP in all groups. No difference was observed among groups at any observation time when simple and combined surgery were compared. Significant difference at the end point was found between NPDS and PT (P = 0.030). As for complete and qualified success with a ≤21 and ≤17 mm Hg target IOP no significant differences were noticed in all groups. Among postoperative complications, hypotony was significantly more frequent in both PT groups when compared with the NPDS groups. The same was true, but relating only to the single procedures, for shallow anterior chamber and choroidal detachment. The Kaplan-Meier cumulative survival curves relating to the qualified success rate in the four surgical groups for a ≤21 mm Hg target IOP (log rank, P = 0.564) and for a ≤17 mm Hg target IOP (log rank, P = 0.591) showed no significant intergroup differences. When the ≤21 mm Hg target IOP was considered, a mild positive trend in combined procedures (both phaco-NPDS and phaco-PT) was found in comparison with simple procedures. At lower IOP target (ie, ≤17 mm Hg) a better trend was found in favor of simple or combined PT procedure. Conclusions:Both techniques, NPDS and PT, without enhancements (ie, implants or antimetabolites) control IOP efficaciously at our end point. Phacoemulsification combined with penetrating and non-penetrating procedures does not seem to interfere with final results. When a lower target IOP and probability of success over time are considered, PT, single or combined, exhibits a better trend. PT, therefore, could be more suitable for higher IOP levels or longer life expectancies.

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 sedation, nutrition, hydration, rattle, inability to cough and swallow, pharyngeal aspiration, duration of sedation and survival, and use of anticholinergics or other drugs were recorded. Family members were interviewed. Forty-two of 77 dying patients were sedated, and had a longer survival than those who were not sedated (P=0.003). Prevalent indications for sedation were dyspnea and/or delirium. Twelve patients began with an intermediate sedation, and 38 patients started with definitive sedation. The median sedation duration was 22 hours. Opioid doses did not change during sedation. Agitated delirium significantly decreased with increasing doses of midazolam, whereas the capacity to communicate concomitantly decreased. Interviewed relatives were actively involved in the process of end-of-life care, and the decision to sedate, and the efficacy of sedation, were considered appropriate by almost all relatives. Controlled sedation is successful in dying patients with untreatable symptoms, did not hasten death, and yielded satisfactory results for relatives. This study also points to the importance of palliative care and the experience of professionals skilled in both symptom control and end-of-life care.