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) by telephone contact or visit. Well-being, fatigue, and dyspnea were measured on a numerical scale of 0-10. Sixty-one patients were recruited in the period of study. One hundred thirty-three units of red blood cells were transfused (mean 2.18, 95% confidence interval [CI] 0.6). Complete data were available for 40 patients. Hemoglobin values and well-being significantly increased after transfusion (T1), maintaining acceptable values 15 days afterward (T2). Significant changes in fatigue and dyspnea were found immediately after transfusion, although the effect was partially lost 15 days after transfusion. No statistical differences were found between patients with different survival times. Fatigue was significantly lower in patients with longer survival times in comparison with patients with shorter survival times (p = 0.04). Blood transfusion in patients with hemoglobin values of approximately 8 g/dL improved anemia-related symptoms on a short-term basis. This benefit is independent of the stage of disease and survival. However, the effects on dyspnea and fatigue tend to decrease within 15 days, despite the maintenance of hemoglobin values attained after transfusions, suggesting that other factors may play a role.

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

PURPOSE: 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. PATIENTS AND METHODS: 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 intervals for 4 weeks. Costs of opioid therapy, supportive drugs, and other analgesic drugs were also evaluated. RESULTS: Seventy patients completed the 4 weeks period of study. Five, five, and four patients, treated with oral morphine, transdermal fentanyl, and oral methadone, respectively, required opioid switching. No differences in pain and symptom intensity were observed. Opioid escalation index was significantly lower in patients receiving methadone (p<0.0001), although requiring up and down changes in doses. At the doses used, methadone was significantly less expensive (p<0.0001), while the use and costs of supportive drugs and other analgesics were similar in the three groups. No relevant differences in adverse effects were observed among the groups during either the titration phase and chronic treatment. CONCLUSION: All the three opioids used as first-line therapy were effective, well tolerated, and required similar amounts of symptomatic drugs or co-analgesics. Methadone was significantly less expensive, but required more changes, up and down, of the doses, suggesting that dose titration of this drug requires major clinical expertise.

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 (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.

Intrathecal treatment in cancer patients unresponsive to multiple trials of systemic opioids.

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.

Injustifiable use of gastroprotection in advanced cancer patients.

The aim of this survey was to prospectively collect data about gastroprotector prescription at admission of an acute pain relief and palliative care unit. An observational survey was performed on three-hundred consecutive patients. Reasons for admission, concomitant treatment and use of drugs were recorded at admission. About 60.6% patients had been prescribed proton pump inhibitors or anti-H2 receptors agents. Of these patients, possible risk factors were nonsteroidal anti-inflammatory drugs (41, 22.5%), corticosteroids (43, 23.6%), age > 75 years (27, 14.8%). In only 25 admissions (13.7%) prescription corresponded to Italian drug agency recommendations with an odds ratio of an off-label prescription of 7.28. In a relatively high percentage of admissions (55%), patients receiving gastroprotectors were on chemotherapy, with an odds ratio of 1.42. This survey showed that gastroprotectors are often prescribed regardless of Health Care System regulations, as only a minority of patients satisfied the requirements of an appropriate and refundable prescription. The attitudes of oncologists who prescribe gastroprotectors for a putative protective effects are not supported by evidence. Health Care Service in Italy should be aware of these problems to improve the strategies of budgeting the drug expense in a better way or providing further guidelines based on studies able to demonstrate the real cost-benefit ratio of this class of drugs.

Switching from transdermal drugs: an observational "N of 1" study of fentanyl and buprenorphine.

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.