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

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

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

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

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

Missing data in randomized controlled trials testing palliative interventions pose a significant risk of bias and loss of power: a systematic review and meta-analyses

Objectives To assess the risk posed by missing data (MD) to the power and validity of trials evaluating palliative interventions. Study Design and Setting A systematic review of MD in published randomized controlled trials (RCTs) of palliative interventions in participants with life-limiting illnesses was conducted, and random-effects meta-analyses and metaregression were performed. CENTRAL, MEDLINE, and EMBASE (2009-2014) were searched with no language restrictions. Results One hundred and eight RCTs representing 15,560 patients were included. The weighted estimate for MD at the primary endpoint was 23.1% (95% confidence interval [CI] 19.3, 27.4). Larger MD proportions were associated with increasing numbers of questions/tests requested (odds ratio [OR] , 1.19; 95% CI 1.05, 1.35) and with longer study duration (OR, 1.09; 95% CI 1.02, 1.17). Meta-analysis found evidence of differential rates of MD between trial arms, which varied in direction (OR, 1.04; 95% CI 0.90, 1.20; I 2 35.9, P = 0.001). Despite randomization, MD in the intervention arms (vs. control) were more likely to be attributed to disease progression unrelated to the intervention (OR, 1.31; 95% CI 1.02, 1.69). This was not the case for MD due to death (OR, 0.92; 95% CI 0.78, 1.08). Conclusion The overall proportion and differential rates and reasons for MD reduce the power and potentially introduce bias to palliative care trials

Palliative management of refractory dyspnea in COPD

COPD is a progressive illness with worldwide impact. Patients invariably reach a point at which they require palliative interventions. Dyspnea is the most distressing symptom experienced by these patients; when not relieved by traditional COPD management strategies it is termed “refractory dyspnea” and palliative approaches are required. The focus of care shifts from prolonging survival to reducing symptoms, increasing function, and improving quality of life. Numerous pharmacological and non-pharmacological interventions can achieve these goals, though evidence supporting their use is variable. This review provides a summary of the options for the management of refractory dyspnea in COPD, outlining currently available evidence and highlighting areas for further investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled furosemide, Heliox, rehabilitation, nutrition, psychosocial support, breathing techniques, and breathlessness clinics

Towards an expert consensus to delineate a clinical syndrome of chronic breathlessness

Copyright ©ERS 2017. Breathlessness that persists despite treatment for the underlying conditions is debilitating. Identifying this discrete entity as a clinical syndrome should raise awareness amongst patients, clinicians, service providers, researchers and research funders.Using the Delphi method, questions and statements were generated via expert group consultations and one-to-one interviews (n=17). These were subsequently circulated in three survey rounds (n=34, n=25, n=31) to an extended international group from various settings (clinical and laboratory; hospital, hospice and community) and working within the basic sciences and clinical specialties. The a priori target agreement for each question was 70%. Findings were discussed at a multinational workshop.The agreed term, chronic breathlessness syndrome, was defined as breathlessness that persists despite optimal treatment of the underlying pathophysiology and that results in disability. A stated duration was not needed for "chronic". Key terms for French and German translation were also discussed and the need for further consensus recognised, especially with regard to cultural and linguistic interpretation.We propose criteria for chronic breathlessness syndrome. Recognition is an important first step to address the therapeutic nihilism that has pervaded this neglected symptom and could empower patients and caregivers, improve clinical care, focus research, and encourage wider uptake of available and emerging evidence-based interventions

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