[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of pain and symptom management 04/2009; 37(4):632-41. · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of pain and symptom management 12/2008; 37(5):771-9. · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 admission. All patients had laboratory tests and several instrumental examinations. Almost all patients were prescribed one or more opioids at significant doses, and different routes of administration, as well as medication as needed. 59 patients received blood cell transfusions and 34 interventional procedures. Only 40 patients died in the unit, 11 of them being sedated at the end of life. Treatment efficacy was considered optimal and mild in 264 and 226 patients respectively. A mean of 3019 euros for admission was reimbursed by the Health Care System. APCs are of paramount importance within an oncological department, as they provide effective and intensive treatments during the entire course of disease, providing a simultaneous and integrated approach. Our findings also suggest both a cost and quality incentive for oncological departments to develop APC.
Palliative Medicine 10/2008; 22(6):760-7. · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 trial, advanced cancer patients had to have diffuse bilateral leg edema unresponsive to common doses of diuretics. A solution of 60 mEq of NaCl, 250 mg of furosemide, and 150 mL of normal saline were infused over 20 minutes. The treatment was repeated twice a day for two days and eventually continued on the basis of the clinical outcome. Circumferences were measured at the foot, ankle, calf, and thigh before starting the treatment (T(0)) and at intervals of 24 hours (T(1) and so on). At the same intervals, diuresis was determined. Patients were asked to score their sensation of leg weakness/heaviness on a numerical scale from 0 to 10, before (T(0)) and after the treatment (T(end)). An appreciable improvement in the sensation of weakness/heaviness (score reduction of at least two points) was recorded in all the patients. A small decrease in leg circumferences at the different sites was found, and a mean of 3600 mL/day of diuresis was recorded. These observations suggest that high-dose furosemide and small-volume saline may be an effective strategy for the treatment of peripheral edema in patients with advanced cancer.
Journal of pain and symptom management 10/2008; 37(3):419-23. · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Advanced cancer patients with refractory ascites do not often respond to dietary sodium restriction and diuretics. While paracentesis is effective, the condition invariably recurs, necessitating repeated procedures. A continuous peritoneal drainage by an indwelling catheter has been reported to be hugely beneficial symptomatically, avoiding the hazards and disadvantages of multiple repeated procedures and direct and indirect costs.
Forty patients with advanced cancer patients admitted to an acute pain relief and palliative care unit, who presented symptomatic ascites, were recruited for continuous drainage of peritoneal fluid. A central venous catheter set for Seldinger technique was used. Technical failure was defined as an unsuccessful drainage of fluid through the catheter. Immediate and late complications, including hypotension, haemorrhage, tube blockage, dislodgment and sepsis were recorded. Record of daily drainage during admission were noted. At time of discharge, patients were asked to rate their global symptom burden as improved, unchanged or worsened. The follow-up was performed with frequent phone contacts or day-hospital admission in case of problems.
The mean patients' age was 68 years, and 21 were men. Patients were receiving unsuccessfully a mean dose of furosemide of 32 mg/day. The technique was not painful and was easily accepted by patients. Insertion was technically successful in almost all patients. Mean admission time was 5.5 days (range 2-14), and the mean drained volume during admission was 8,499 ml (range 800-20,700), 2,850 ml (300-4,200) being drained on the first 24 h. No immediate complications were recorded. Six patients died during admission. The mean survival was 38.9 days (range 1-120). Of the 34 patients who were discharged home, 22 patients stated that symptom burden had improved, while in 10 patients symptom burden did not change or worsened, probably due to the advanced status of diseases and multiple contributing factors. Five, two, and one patients required skin sutures at 1, 2 and 3 months, respectively. About one third of patients had mechanical problems, some of them requiring a catheter replacement. No infection was recorded.
In conclusion, a permanent peritoneal catheter was a valuable method to remove abdominal fluids and reduce symptom burden attributable to ascites and was also easy to use at home. Complication rate was acceptable and balanced by the benefits of the technique which avoided frequent paracentesis and associated complications.
Supportive Care Cancer 06/2008; 16(8):975-8. · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 (T15). Nurses were unaware of the aim of the study and just followed department policy. In total, 945 breakthrough events treated by IV-M were recorded and the mean number of events per patient per admission was eight (95% confidence interval (CI) 6.9-9.5). The mean dose of IV-M was 12mg (95% CI 9-14mg). In the 469 events (49.6%) with a complete assessment, a decrease in pain of more than 33% and 50% was observed in 287 (61.2%) and 115 (24.5%) breakthrough events, respectively. The mean pain intensity decreased from 7.2 (T0) to 2.7 (T15). In eight episodes, no changes in pain intensity were observed and a further dose of IV-M was given. The remaining patients did not require further interventions. No clinical events requiring medical intervention were recorded. In this confirmatory study, IV-M was administered for the management of breakthrough pain in doses proportional to the basal opioid regimen to all patients, including older patients and those requiring relatively large doses. This did not result in life-threatening adverse effects in a large number of patients and was effective in most cases. The role of nurses is of paramount importance in monitoring and collecting data and gathering information for audit purposes on the unit.
Journal of Pain and Symptom Management 04/2008; 35(3):307-13. · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to confirm that the concomitant presence of transdermal fentanyl (TTS FE) and buprenorphine (TTS BU) may be feasible without important consequences, using doses presumed to be equianalgesic. A prospective "N of 1" study was carried out in a sample of volunteers with cancer pain receiving stable doses of TTS FE or TTS BU, with adequate pain and symptom control. In the study design, each patient provided data before and after a switch from one opioid to the other and then back to the previous one. Sixteen patients receiving daily stable doses of 0.6 or 1.2mg of TTS FE were switched to TTS BU using an FE-BU ratio of 0.6-0.8. After three days, the TTS BU patch was removed and TTS FE patch was placed for another three days. Six patients receiving TTS BU were switched to TTS FE and then rotated back to TTS BU with the same dosing considerations. No statistical differences in changes in pain and symptom intensity during switching and between the two different sequences were observed. No significant changes in rescue doses of oral morphine were reported at the same intervals. Cancer patients receiving stable doses of TTS FE or TTS BU can be safely switched to the alternative transdermal opioid. Further studies should be performed to gather data about the use of TTS BU with other opioids, at different doses, and in different clinical conditions.
Journal of Pain and Symptom Management 12/2007; 34(5):532-8. · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 intensity decreased from a mean of 6.9 to 4.1 and to 2.4 at T1 and T2, respectively. Statistical differences between the two treatments were found at T1 (P=0.013), but not at T2 (P=0.059). Adverse effects were comparable and were not significantly related with the IV-MO and OTFC doses. Intravenous morphine and OTFC in doses proportional to the scheduled daily dose of opioids were both safe and effective, IV-MO having a shorter onset than OTFC. Future comparative studies with appropriate design should compare titration methods and proportional methods of OTFC dosing.
British Journal of Cancer 07/2007; 96(12):1828-33. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the clinical response to a combination of intrathecal morphine and levobupivacaine in advanced cancer patients who were highly opioid-tolerant, being previously treated with multiple opioid trials unsuccessfully. Initial intrathecal morphine dose was calculated from the previous opioid consumption using a morphine oral-intrathecal ratio of 100:1. Then, doses of both drugs were modified during the treatment according to the clinical needs and balanced with adverse effects. Fifty-five patients were assessed during admission, before starting the intrathecal treatment, during the titration phase, and followed up to death, by frequent phone contacts or visits, as available. Pain and symptom intensities were recorded before starting the intrathecal treatment (T0), at time of hospital discharge (T dis), and then at 1 month (T1), 3 months (T3), 6 months (T6) intervals, and the last observation, at least 1 week before death (T death). Fifty-five patients were selected for starting an intrathecal treatment. Thirty-two patients were males. The mean age was 60 years (95% CI 57-63), and 65.4% of patients were under 65 years. The most frequent indication was the presence of adverse effects and poor pain control. Complete data with adequate follow-up until death were available in 45 patients. Statistical differences in pain intensity were found at the different time intervals examined until death. Statistical decreases in the intensity of drowsiness and confusion were found until 1 month after starting intrathecal therapy. Statistical differences were found in daily intrathecal morphine doses, with a 3-fold increase at time of hospital discharge. Subsequently, further increases in doses were not significant. Conversely, systemic opioids, expressed as oral morphine equivalents, significantly decreased at all the intervals examined until death. Early complications included mild bleeding in 2 patients, without consequences, headache in 4 patients, bladder catheterization in 6 patients, reoperation for bleeding or changes of catheter position in 4 patients, unrelated death in 1 patient, and stroke in another 1. Late complications included local infection in 2 patients, and discontinuation of intrathecal therapy due to spinal compression. In patients who had received multiple trial of opioids and routes of administration, the intrathecal treatment started with an oral-intrathecal morphine conversion ratio of 100:1, and local anesthetics at the most convenient clinical doses provided a long-term improvement of analgesia, with a decrease in adverse effects and opioid consumption until death.
Clinical Journal of Pain 01/2007; 23(9):793-8. · 2.55 Impact Factor