Assessment and Management of Sleep Disturbance in Palliative Care Settings.

Background: Sleep disturbances, including insomnia, sleep-disordered breathing, and circadian rhythm disorders with potential consequences including excessive daytime somnolence and worsening fatigue, are prevalent yet largely under-measured and therefore under-managed problems in people receiving palliative care. This has the potential to negatively affect the person's functioning and quality of life. Objectives: We aimed to review the current practice of assessment and management of sleep disturbances in people with life-limiting illnesses in Australian and New Zealand palliative care settings, and to define areas for improvement in assessment and management of sleep disturbances and further research. Design: A cross-sectional, online survey was conducted with palliative care health professionals (PCHPs) to explore current approaches to routine assessment of sleep disturbances and PCHPs' awareness of, and perceived access to, evidence-based resources for assessing and managing sleep disturbances in their local settings. Results: Fifty-four PCHPs responded to the survey, including allied health professionals (44%), palliative care nurses (26%), and physicians (19%). Over 70% of PCHPs endorsed routine verbal screening of sleep symptoms, and >90% recommended management with basic behavioral strategies. However, none of PCHPs used validated patient-reported outcome measures for sleep, and <10% of PCHPs demonstrated awareness or use of sleep-specific interventions (including medications). Only 40% reported they had access to sleep specialist services for patients. Conclusion: Our findings provide a useful snapshot of current approaches to managing sleep disturbances in palliative care. Gaps in current practice are highlighted, including the lack of structured, clinical assessment, referral pathways, and PCHPs' perceived lack of access to targeted interventions for sleep disturbances.

The complexity of multidisciplinary respiratory care in amyotrophic lateral sclerosis.

Motor neurone disease/amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with no known cure, where death is usually secondary to progressive respiratory failure. Assisting people with ALS through their disease journey is complex and supported by clinics that provide comprehensive multidisciplinary care (MDC). This review aims to apply both a respiratory and a complexity lens to the key roles and areas of practice within the MDC model in ALS. Models of noninvasive ventilation care, and considerations in the provision of palliative therapy, respiratory support, and speech and language therapy are discussed. The impact on people living with ALS of both inequitable funding models and the complexity of clinical care decisions are illustrated using case vignettes. Considerations of the impact of emerging antisense and gene modifying therapies on MDC challenges are also highlighted. The review seeks to illustrate how MDC members contribute to collective decision-making in ALS, how the sum of the parts is greater than any individual care component or health professional, and that the MDC per se adds value to the person living with ALS. Through this approach we hope to support clinicians to navigate the space between what are minimum, guideline-driven, standards of care and what excellent, person-centred ALS care that fully embraces complexity could be. Educational aims: To highlight the complexities surrounding respiratory care in ALS.To alert clinicians to the risk that complexity of ALS care may modify the effectiveness of any specific, evidence-based therapy for ALS.To describe the importance of person-centred care and shared decision-making in optimising care in ALS.

A Novel Approach to Managing Thirst and Dry Mouth in Palliative Care: A Prospective Randomized Cross-Over Trial.

CONTEXT: Thirst and xerostomia are significant and highly distressing symptoms experienced by patients receiving palliative and end-of-life care. OBJECTIVES: Determine a reduction of thirst intensity and perceptions of dry mouth on a numerical scale following both the experimental intervention (mini mint ice cubes) and control (plain ice chips). METHODS: Cross-over Randomized Controlled Trial (RCT) to assess the effectiveness of novel intervention in the treatment of dry mouth and the sensation of thirst in palliative care patients. RESULTS: Patients rated the severity of their symptoms of dry mouth and thirst using a numeric rating scale (NRS). On commencing the study and preintervention, all patients suffered severe dry mouth and thirst (≥5/10). Mint and plain ice cubes produced improvement of symptoms immediately after interventions. Results from dry mouth ratings show, a decrease of 1.6 points for plain ice cubes (P < 0.0001), on average, ratings for mint ice cubes decreased 3.7 (P < 0.0001). For the sensation of thirst, the plain ice cube intervention group rating decreased 1.7 points (P < 0.006), ratings for mint ice cubes decreased 3.4 points (P < 0.0001). The average decrease in dry mouth and thirst intensity scores from preintervention to postintervention were significantly greater for mint ice cubes (P < 0.05) and 86.6% of patients preferred mint ice cubes. CONCLUSION: This trial found that while usual mouth care and the intervention were both able to reduce the intensity of dry mouth and the sensation of thirst, the mint intervention had a greater response.

Relieving Perception of Thirst and Xerostomia in Patients with Palliative and End-of-life Care Needs: A Rapid Review.

CONTEXT: Thirst and dry mouth are interlinked symptoms that frequently cause significant distress for patients with life-limiting conditions. OBJECTIVES: The objective of this rapid review was to identify and synthesize effective interventions that relieve perceptions of thirst and dry mouth of patients with palliative care and end-of-life care needs. METHODS: Eligible studies were undertaken in clinical settings, with patients experiencing thirst-related distress and/or dry mouth. This review of peer-reviewed literature was conducted following aspects of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. The main outcomes of interest were: 1) efficacy of thirst and dry mouth interventions for patient, and 2) patient, caregiver, and staff acceptability and satisfaction of the interventions. Scientific journal articles were retrieved through searches in electronic databases of MEDLINE (Ovid), CINAHL (EBSCO), and AgeLine (EBSCO). RESULTS: Eleven studies were included for analysis and synthesis of the results. Most studies either focused on a dry mouth intervention or reported dry mouth outcomes within a broader thirst intervention (n = 9/11 studies). Standard oral care was the common intervention type (n = 5/11). All but one dry mouth intervention reported statistical improvement in outcomes of interest. All studies that reported on thirst were conducted in an Intensive Care Unit (ICU) setting (n = 4/4). No studies specifically addressed thirst in patients in specialist palliative care settings. CONCLUSION: Evidence from this review suggests that thirst interventions established within the ICU setting may prove effective for treatment of terminally ill patients receiving specialist palliative care.

Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain: a JORTC-PAL16 trial protocol.

INTRODUCTION: Management of neuropathic cancer pain (NCP) refractory to regular opioids remains an important challenge. The efficacy of pregabalin for NCP except chemotherapy-induced peripheral neuropathy (CIPN) has already been confirmed in two randomised controlled trials (RCTs) compared with placebo. Duloxetine offers the potential of analgesia in opioid refractory NCP. However, there are no RCT of duloxetine for the management of opioid-refractory NCP as a first line treatment. Both classes of drugs have the potential to reduce NCP, but there has been no head-to-head comparison for the efficacy and safety, especially given differing side effect profiles. METHODS AND ANALYSIS: An international, multicentre, double-blind, dose increment, parallel-arm, RCT is planned. Inclusion criteria include: adults with cancer experiencing NCP refractory to opioids; Brief Pain Inventory (BPI)-item 3 (worst pain) of ≥4; Neuropathic Pain on the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale of ≥12 despite of an adequate trial of regular opioid medication (≥60 mg/day oral morphine equivalent dose). Patients with CIPN are excluded.The study will recruit from palliative care teams (both inpatients and outpatients) in Japan and Australia. Participants will be randomised (1:1 allocation ratio) to duloxetine or pregabalin arm. Dose escalation is until day 14 and from day 14 to 21 is a dose de-escalation period to avoid withdrawal effects. The primary endpoint is defined as the mean difference in BPI item 3 for worst pain intensity over the previous 24 hours at day 14 between groups. A sample size of 160 patients will be enrolled between February 2020 and March 2023. ETHICS AND DISSEMINATION: Ethics approval was obtained at Osaka City University Hospital Certified Review Board and South Western Sydney Local Health District Human Research Ethics Committee. The results of this study will be submitted for publication in international journals and the key findings presented at international conferences. TRIAL REGISTRATION NUMBERS: jRCTs051190097, ACTRN12620000656932.

Health-related quality of life in patients with inoperable malignant bowel obstruction: secondary outcome from a double-blind, parallel, placebo-controlled randomised trial of octreotide.

BACKGROUND: This analysis aims to evaluate health-related quality of life (HrQoL) (primary outcome for this analysis), nausea and vomiting, and pain in patients with inoperable malignant bowel obstruction (IMBO) due to cancer or its treatments randomised to standardised therapies plus octreotide or placebo over a maximum of 72 h in a double-blind clinical trial. METHODS: Adults with IMBO and vomiting recruited through 12 services spanning inpatient, consultative and community settings in Australia were randomised to subcutaneous octreotide infusion or saline. HrQoL was measured at baseline and treatment cessation (EORTC QLQ-C15-PAL). Mean within-group paired differences between baseline and post-treatment scores were analysed using Wilcoxon Signed Rank test and between group differences estimated using linear mixed models, adjusted for baseline score, sex, age, time, and study arm. RESULTS: One hundred six of the 112 randomised participants were included in the analysis (n = 52 octreotide, n = 54 placebo); 6 participants were excluded due to major protocol violations. Mean baseline HrQoL scores were low (octreotide 22.1, 95% CI 14.3, 29.9; placebo 31.5, 95% CI 22.3, 40.7). There was no statistically significant within-group improvement in the mean HrQoL scores in the octreotide (p = 0.21) or placebo groups (p = 0.78), although both groups reported reductions in mean nausea and vomiting (octreotide p < 0.01; placebo p = 0.02) and pain scores (octreotide p < 0.01; placebo p = 0.03). Although no statistically significant difference in changes in HrQoL scores between octreotide and placebo were seen, an adequately powered study is required to fully assess any differences in HrQoL scores. CONCLUSION: The HrQoL of patients with IMBO and vomiting is poor. Further research to formally evaluate the effects of standard therapies for IMBO is therefore warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12608000211369 (date registered 18/04/2008).

A case series of suprascapular nerve block (with an historical comparator) for shoulder pain in motor neurone disease.

BACKGROUND: Shoulder pain is a distressing but under-reported and poorly managed symptom in people with motor neurone disease. OBJECTIVES: This study aimed to assess the efficacy of suprascapular nerve block for the management of shoulder pain in patients with motor neurone disease. METHODS: A total of 27 patients with motor neurone disease and shoulder pain were offered a suprascapular nerve block. Ten of these patients had bilateral shoulder pain and both were injected, making a total of 37 shoulders. The patients were followed up for a total of 3 months, or until death. Shoulder pain was measured using the pain scale (out of 100) of the shoulder pain and disability index and compared with baseline scores and a placebo control group from an earlier study using the same methodology (ACTRN12619000353190). RESULTS: Following the nerve block there was a significant improvement of pain scores from baseline (58.4) at week 1 (20.8, p < 0.000), week 6 (17.6, p < 0.000) and week 12 (30.4, p = 0.001) and a significant improvement compared with the control group across each time interval. CONCLUSION: Suprascapular nerve block is a safe, effective therapy for patients with chronic shoulder pain.

Isolating peripheral effects of endogenous opioids in modulating exertional breathlessness in people with moderate or severe COPD: a randomised controlled trial.

QUESTION ADDRESSED BY THE STUDY: Endogenous opioids (endorphins) have been reported to modulate exercise-induced breathlessness, but the relative contribution of peripheral opioid receptors has not been tested. MATERIALS PARTICIPANTS AND METHODS: This was a double-blind, randomised, three-arm, cross-over trial in outpatients with spirometry-verified moderate to severe chronic obstructive pulmonary disease. Participants undertook an incremental symptom-limited treadmill test followed by five endurance treadmill tests at 75% of their maximal work rate; two tests for familiarisation and three tests 30 min after intravenous injection of either methylnaltrexone 0.3 mg·kg-1 (blocking peripheral opioid receptors only) or naloxone 0.1 mg·kg-1 (blocking both central and peripheral opioid receptors) or normal saline, in randomised order. The primary end-point was the regression slope between breathlessness intensity (0-10 numerical rating scale) and oxygen consumption (V'O2 ) during the walk tests, comparing methylnaltrexone and placebo using a paired t-test. RESULTS: 17 participants completed the trial: median (range) 66 (55-82) years; 15 males; mean±sd forced expiratory volume (FEV1) 53.8±17.6% predicted; FEV1/forced vital capacity ratio 0.55±15.9. There was no statistically or clinically significant difference in the primary end-point (regression slope of breathlessness intensity and V'O2 ) for methylnaltrexone (p=0.498) or naloxone (p=0.804), compared to placebo. Secondary outcomes were similar between the three treatment groups, including peak and mean breathlessness intensity and unpleasantness, exercise capacity, endurance time and leg fatigue. ANSWER TO THE QUESTION: Blocking peripheral opioid receptors (methylnaltrexone) or peripheral and central opioid receptors (naloxone) did not appear to modulate breathlessness intensity nor exercise capacity when compared with placebo (no blockade).

Academic detailing of general practitioners by a respiratory physician for diagnosis and management of refractory breathlessness: a randomised pilot study.

BACKGROUND: Academic detailing (AD; also known as educational visiting) facilitates the translation of evidence into practice and has been widely adopted internationally to facilitate practice change. The potential of AD linked to a specific patient and delivered by a specialist physician to general practitioners has not been evaluated. This pilot study assessed the feasibility and acceptability of AD on the knowledge and confidence of GPs caring for people with advanced cancer who had breathlessness at the end of life. METHODS: In this randomised controlled pilot, 35 patient/GP dyads were randomised to AD or usual care. Key messages included: ensuring reversible causes were optimally treated; non-pharmacological and pharmacological treatments were considered; and oxygen considered for hypoxaemic patients. RESULTS: Acceptability: The majority of GPs randomised to AD agreed to participate, reporting benefits to practice. The majority of GPs in the control group requested a copy of academic detailing written materials at study completion. Feasibility: AD visits to GPs' offices could be timetabled reasonably easily, with 24 detailing visits occurring. Self-reported knowledge and beliefs: Ninety two percent of GPs reported the topics covered in the AD sessions were useful, with 83% reporting an increase in knowledge and confidence. AD sessions resulted in 58% of GPs reporting a change in their approach to the management of breathlessness. By contrast, 81% of the usual care group reported low confidence in the management and knowledge of breathlessness. CONCLUSION: AD was acceptable and feasible to participating GPs. This pilot supports proceeding to a fully powered study.

Breathlessness in motor neurone disease: a review of the current strategies and gaps in the evidence.

PURPOSE OF REVIEW: This review on breathlessness and motor neurone disease (MND) is important, as palliative care teams are increasingly becoming involved in the complex care of these patients at an earlier stage in their illness. Subtle cognitive and behavioural changes with MND may make management more challenging. Breathlessness is a distressing symptom, impacting on both patients and carers. Assessment and expectant management of breathlessness improves the quality of life (QoL) and may minimize hospital admission. RECENT FINDINGS: Low-dose opioids improve the sensation of breathlessness, with minimal side-effects. It is well established that noninvasive ventilation (NIV) improves survival in patients with MND and also improves health-related QoL of patients with minimal or no bulbar symptoms. Preparation of advance care plans is essential to the provision of care in the final stages of illness in patients with MND and NIV use. SUMMARY: Assessment of breathlessness and its successful management improves the QoL of patients with MND. Opioids in titrated doses may play a role in this. NIV improves survival in patients with respiratory failure with minimal or no bulbar symptoms and should be offered when appropriate. Preemptive education improves the uptake and understanding of the role of NIV.

The role of benzodiazepines in breathlessness: a single site, open label pilot of sustained release morphine together with clonazepam.

BACKGROUND: Breathlessness at rest or on minimal exertion despite optimal treatment of underlying cause(s) is distressing and prevalent. Opioids can reduce the intensity of chronic refractory breathlessness and an anxiolytic may be of benefit. This pilot aimed to determine the safety and feasibility of conducting a phase III study on the intensity of breathlessness by adding regular benzodiazepine to low-dose opioid. METHODS: This is a single site, open label phase II study of the addition of regular clonazepam 0.5 mg nocte orally to Kapanol(R) 10 mg (sustained release morphine sulphate) orally mane together with docusate/sennosides in people with modified Medical Research Council Scale ≥2. Breathlessness intensity on day four was the efficacy outcome. Participants could extend for another 10 days if they achieved >15% reduction over their own baseline breathlessness intensity. RESULTS: Eleven people had trial medication (eight males, median age 78 years (68 to 89); all had COPD; median Karnofsky 70 (50 to 80); six were on long-term home oxygen. Ten people completed day four. One person withdrew because of unsteadiness on day four. Five participants reached the 15% reduction, but only three went on to the extension study, all completing without toxicity. CONCLUSION: This study was safe, feasible and there appears to be a group who derive benefits comparable to titrated opioids. Given the widespread use of benzodiazepines for the symptomatic treatment of chronic refractory breathlessness and its poor evidence base, there is justification for a definitive phase III study.

Chronic refractory dyspnoea--evidence based management.

BACKGROUND: Chronic refractory dyspnoea is defined as breathlessness daily for 3 months at rest or on minimal exertion where contributing causes have been treated maximally. Prevalent aetiologies include chronic obstructive pulmonary disease, heart failure, advanced cancer and interstitial lung diseases. OBJECTIVE: To distil from the peer reviewed literature (literature search and guidelines) evidence that can guide the safe, symptomatic management of chronic refractory dyspnoea. DISCUSSION: Dyspnoea is mostly multifactorial. Each reversible cause should be managed (Level 4 evidence). Non-pharmacological interventions include walking aids, breathing training and, in chronic obstructive pulmonary disease, pulmonary rehabilitation (Level 1 evidence). Regular, low dose, sustained release oral morphine (Level 1 evidence) titrated to effect (with regular aperients) is effective and safe. Oxygen therapy for patients who are not hypoxaemic is no more effective than medical air. If a therapeutic trial is indicated, any symptomatic benefit is likely within the first 72 hours.

Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study.

CONTEXT: Randomized controlled trials can answer questions of efficacy, but long-term pharmacovigilance studies generate complementary safety data. OBJECTIVES: Level I evidence supports short-term efficacy of opioids in reducing chronic refractory dyspnea. This study aimed to determine the minimum effective once-daily dose of sustained-release morphine, and whether net clinical benefits are sustained safely. METHODS: In a Phase II dose increment study, 10mg daily of sustained-release morphine was administered, and increased in nonresponders by 10mg daily each week to a maximum of 30 mg daily. The participant was withdrawn if there were unacceptable side effects or no response to maximum dose. If participants had a 10% improvement in dyspnea over their own baseline, they joined a long-term Phase IV effectiveness/safety study at that dose. Complying with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, response and side effects are described, with demographic and clinical characteristics of responders. RESULTS: Eighty-three participants (53 males, mean age 75 years, 54% with chronic obstructive pulmonary disease) provided more than 30 patient-years of data. Fifty-two participants derived ≥ 10% benefit (on average 35% improvement over baseline), giving a response rate of 62% (number needed to treat of 1.6: number needed to harm 4.6); for 70%, this dose was 10mg/24h. Benefit was maintained at three months for 28 (33%) people. Ranking of breathlessness was reduced significantly (P<0.001), but constipation increased (P<0.001) despite laxatives. There were no episodes of respiratory depression or hospitalizations as a result of the sustained-release morphine. Overall, one in three people continued to derive benefit at three months. CONCLUSION: Ten milligrams of sustained-release oral morphine once daily is safe and effective for most people who respond.