Effects of low dose morphine on perceived sleep quality in patients with refractory breathlessness : a hypothesis generating study

© 2015 Asian Pacific Society of Respirology. Background and objective The management of chronic refractory breathlessness is one of the indications for regular low-dose (≤30 mg/24 h) oral sustained release morphine. Morphine may disrupt sleep in some conditions and improve sleep quality in others. This study aimed to determine any signal of regular, low-dose morphine on perceived sleep disruption due to breathlessness and perceived sleep quality. Methods This is a secondary analysis of data from 38 participants with refractory breathlessness (30 male; 33 with COPD) aged 76 ± 0.9 years who completed a double-blind, randomized, placebo-controlled, cross-over study in which they received 20 mg oral sustained release morphine daily and placebo for 4 days each. Participant ratings of sleep disruption due to breathlessness and perceived sleep quality were obtained daily throughout the 8-day trial. Results Perceived sleep disruption due to breathlessness over the 4-day period ranged between 13% and 32% of participants for placebo and 13% and 26% for morphine, decreasing by each day of the study during the morphine arm. Most participants reported 'very good' or 'quite good' sleep throughout the trial and were less likely to perceive poor sleep quality during the morphine arm (odds ratio = 0.55, 95% confidence interval: 0.34-0.88, P = 0.01). Participants who reported decreased breathlessness during the 4 days on morphine were also likely to report improved sleep quality with morphine (P = 0.039). Conclusion Four days of low-dose morphine improved perceived sleep quality in elderly participants with refractory breathlessness. Regular low-dose morphine targeted to reduce refractory breathlessness may yield associated benefits by reducing sleep disruption and improving sleep quality

Breathlessness in the elderly during the last year of life sufficient to restrict activity

OBJECTIVES: Breathlessness is prevalent in older people. Symptom control at the end of life is important. This study investigated relationships between age, clinical characteristics and breathlessness sufficient to have people spend at least one half a day in that month in bed or cut down on their usual activities (restricting breathlessness) during the last year of life. DESIGN: Secondary data-analysis SETTING: General community PARTICIPANTS: 754 non-disabled persons, aged 70 and older. Monthly telephone interviews were conducted to determine the occurrence of restricting breathlessness. The primary outcome was the percentage of months with restricting breathlessness reported during the last year of life. RESULTS: Data regarding breathlessness were available for 548/589 (93.0%) decedents (mean age 86.7 years (range 71 to 106; males 38.8%). 311/548 (56.8%) reported restricting breathlessness at some time-point during the last year of life but no-one reported this every month. Frequency increased in the months closer to death irrespective of cause. Restricting breathlessness was associated with anxiety, (0.25 percentage point increase in months breathlessness per percentage point months reported anxiety, 95% CI 0.16 to 0.34, P<0.001), depression (0.14, 0.05 to 0.24, P=0.002) and mobility problems (0.07, 0.03 to 0.1, P=0.001). Percentage months of restricting breathlessness increased if chronic lung disease was noted at the most recent comprehensive assessment (6.62 percentage points, 95% CI 4.31 to 8.94, P<0.001), heart failure (3.34, 0.71 to 5.97, P<0.01), and ex-smoker status (3.01, 0.94 to 5.07, P=0.002), but decreased with older age (─0.19, ─0.37 to ─0.02, P=0.03). CONCLUSION: Restricting breathlessness increased in this elderly population in the months preceding death from any cause. Breathlessness should be assessed and managed in the context of poor prognosis

One evidence base; three stories: do opioids relieve chronic breathlessness?

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. The efficacy of low-dose systemic opioids for chronic breathlessness was questioned by the recent Cochrane review by Barnes et al We examined the reasons for this conflicting finding and re-evaluated the efficacy of systemic opioids. Compared with previous meta-analyses, Barnes et al reported a smaller effect and lower precision, but did not account for matched data of crossover trials (11/12 included trials) and added a risk-of-bias criterion (sample size). When re-analysed to account for crossover data, opioids decreased breathlessness (standardised mean differences -0.32; -0.18 to -0.47; I2=44.8%) representing a clinically meaningful reduction of 0.8 points (0-10 numerical rating scale), consistent across meta-analyses

The independent association of overweight and obesity with breathlessness in adults: a cross-sectional, population-based study

Obesity is an independent risk factor for chronic breathlessness and should be assessed in people with this symptom

The complex relationship between household income of family caregivers, access to palliative care services and place of death : A national household population survey

BACKGROUND: Previous work shows that more affluent patients with cancer are more likely to die at home, whereas those dying from non-cancer conditions are more likely to die in hospital. Family caregivers are an important factor in determining place of death. AIM: To investigate associations between family caregivers' household income, patients' access to specialist palliative care and place of patients' death, by level of personal end-of-life care. DESIGN: A cross-sectional community household population survey. SETTING AND PARTICIPANTS: Respondents to the Household Survey for England. RESULTS: One-third of 1265 bereaved respondents had provided personal end-of-life care (caregivers) (30%). Just over half (55%) of decedents accessed palliative care services and 15% died in a hospice. Place of death and access to palliative care were strongly related ( p < 0.001). Palliative care services reduced the proportion of deaths in hospital ( p < 0.001), and decedents accessing palliative care were more likely to die at home than those who did not ( p < 0.001). Respondents' income was not associated with palliative care access ( p = 0.233). Overall, respondents' income and home death were not related ( p = 0.106), but decedents with caregivers in the highest income group were least likely to die at home ( p = 0.069). CONCLUSION: For people who had someone close to them die, decedents' access to palliative care services was associated with fewer deaths in hospital and more home deaths. Respondents' income was unrelated to care recipients' place of death when adjusted for palliative care access. When only caregivers were considered, decedents with caregivers from higher income quartiles were the least likely to die at home. Family caregivers from higher income brackets are likely to be powerful patient advocates. Caregiver information needs must be addressed especially with regard to stage of disease, aim of care and appropriate interventions at the end of life

Clinically important differences in the intensity of chronic refractory breathlessness

Context: Clinically important differences in chronic refractory breathlessness are ill defined but important in clinical practice and trial design. Objectives: To estimate the clinical relevance of differences in breathlessness intensity using distribution and patient anchor methods. Methods: This was a retrospective data analysis from 213 datasets from four clinical trials for refractory breathlessness. Linear regression was used to explore the relationship between study effect size and change in breathlessness score (0-100 mm visual analogue scale) and to estimate the change in score equivalent to small, moderate, and large effect sizes. Pooled individual blinded patient preference data from three randomized controlled trials were analyzed. The difference between the mean change in Day 4 minus baseline scores between preferred and non-preferred arms was calculated. Results: There was a strong relationship between change in score and effect size (P = 0.001; R 2 = 0.98). Values for small, moderate, and large effects were -5.5, -11.3, and -18.2 mm. The participant preference change in score was -9 mm (95% CI, -15.8, -2.1) (P = 0.008). Conclusion: This larger dataset supports a clinically important difference of 10 mm. Studies should be powered to detect this difference

Blinded patient preference for morphine compared to placebo in the setting of chronic refractory breathlessness – an exploratory study

Context Patients’ preference for morphine therapy has received little attention in the setting of chronic refractory breathlessness. However, this is one important factor in considering longer term therapy. Objectives The aim of this secondary analysis is to explore blinded patient preference of morphine compared to placebo for this indication and to define any predictors of preference. Methods Data were pooled from three randomized, double-blind, crossover, placebo-controlled studies of morphine (four days each) in chronic refractory breathlessness. Blinded patient preferences were chosen at the end of each study. A multivariable regression model was used to establish patient predictors of preference. Results Sixty-five participants provided sufficient data (60 males; median age 74 years; heart failure 55%, chronic obstructive pulmonary disease 45%; median Eastern Cooperative Oncology Group performance status 2). Forty-three percent of participants preferred morphine (32% placebo and 25% no preference). Morphine preference and younger age were strongly associated: odds ratio = 0.85, 95% confidence interval 0.78, 0.93;

Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?

© 2015, BMJ Publishing Group. All rights reserved. Objectives: Opioids modulate the perception of breathlessness with a considerable variation in response, with poor correlation between the required opioid dose and symptom severity. The objective of this hypothesis-generating, secondary analysis was to identify candidate single nucleotide polymorphisms (SNP) from those associated with opioid receptors, signalling or pain modulation to identify any related to intensity of breathlessness while on opioids. This can help to inform prospective studies and potentially lead to better tailoring of opioid therapy for refractory breathlessness. Setting: 17 hospice/palliative care services (tertiary services) in 11 European countries. Participants: 2294 people over 18 years of age on regular opioids for pain related to cancer or its treatment. Primary outcome measures: The relationship between morphine dose, breathlessness intensity (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; EORTCQLQC30 question 8) and 112 candidate SNPs from 25 genes (n=588). Secondary outcome measures: The same measures for people on oxycodone (n=402) or fentanyl (n=429). Results: SNPs not in Hardy-Weinberg equilibrium or with allele frequencies ( < 5%) were removed. Univariate associations between each SNP and breathlessness intensity were determined with Benjamini-Hochberg false discovery rate set at 20%. Multivariable ordinal logistic regression, clustering over country and adjusting for available confounders, was conducted with remaining SNPs. For univariate morphine associations, 1 variant on the 5-hydroxytryptamine type 3B (HTR3B) gene, and 4 on the β-2-arrestin gene (ARRB2) were associated with more intense breathlessness. 1 SNP remained significant in the multivariable model: people with rs7103572 SNP (HTR3B gene; present in 8.4% of the population) were three times more likely to have more intense breathlessness (OR 2.86; 95% CIs 1.46 to 5.62; p=0.002). No associations were seen with fentanyl nor with oxycodone. Conclusions: This large, exploratory study identified 1 biologically plausible SNP that warrants further study in the response of breathlessness to morphine therapy

Caregivers' perceived adequacy of support in end-stage lung disease: results of a population survey.

BACKGROUND: End-stage lung disease (ESLD) is a frequent cause of death. What are the differences in the supports needed by caregivers of individuals with ESLD at end of life versus other life-limiting diagnoses? METHODS: The South Australian Health Omnibus is an annual, random, face-to-face, cross-sectional survey. In 2002, 2003 and 2005-2007, respondents were asked a range of questions about end-of-life care; there were approximately 3000 survey participants annually (participation rate 77.9%). Responses were standardised for the whole population. The families and friends who cared for someone with ESLD were the focus of this analysis. In addition to describing caring, respondents reported additional support that would have been helpful. RESULTS: Of 1504 deaths reported, 145 (9.6%) were due to ESLD. The ESLD cohort were older than those with other 'expected' causes of death (> 65 years of age; 92.6% versus 70.6%; p < 0.0001) and were less likely to access specialised palliative care services (38.4% versus 61.9%; p < 0.0001). For those with ESLD, the mean caring period was significantly longer at 25 months (standard deviation (SD) 24) than for 'other diagnoses' (15 months; SD 18; p < 0.0001). Domains where additional support would have been useful included physical care, information provision, and emotional and spiritual support. CONCLUSIONS: Caregiver needs were similar regardless of the underlying diagnosis although access to palliative care specialist services occurred less often for ESLD patients. This was despite significantly longer periods of time for which care was provided.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Pharmacovigilance in hospice/palliative care: rapid report of net clinical effect of metoclopramide

Background: Understanding the performance of prescribed medications in day-to-day practice is important to minimize harm, maximize clinical benefits, and, eventually, better target the people who are most likely to benefit, especially in hospice/palliative care where there may be limited time to optimize prescribing. Metoclopramide, a benzamide prokinetic antiemetic, is widely used for a number of indications including nausea, vomiting, hiccups, and reflux. It has recently had a new ‘‘black box’’ warning issued by the Food and Drug Administration in relation to tardive dyskinesia to limit use to 12 weeks. Methods: A consecutive cohort of patients from 12 participating centers in two countries who were having metoclopramide initiated had data collected at three time points—baseline, 2 days (clinical benefit), and day 7 (clinical harm). Additionally, harms could be recorded at any time. Results: Of the 53 people included in the cohort, 23 (43%) reported benefit at 48 hours, but only 18 (34%) of these people were still using it one week after commencing it. For the other 5, the medication was ceased due to harms. The most frequent harms were akathisia (n = 4), headache (n = 4), and abdominal pain (n = 4). Nine people (17%) had no clinical benefit and experienced harms. Conclusion: Overall, one in three people gained net clinical benefit at one week. Limiting effects include sideeffects that need to be sought actively in clinical care