Andrew Wilcock

Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial

BACKGROUND Palliative oxygen therapy is widely used for treatment of dyspnoea in individuals with life-limiting illness who are ineligible for long-term oxygen therapy. We assessed the effectiveness of oxygen compared with room air delivered by nasal cannula for relief of breathlessness in this population of patients. METHODS Adults from outpatient clinics at nine sites in Australia, the USA, and the UK were eligible for enrolment in this double-blind, randomised controlled trial if they had life-limiting illness, refractory dyspnoea, and partial pressure of oxygen in arterial blood (PaO(2)) more than 7.3 kPa. Participants were randomly assigned in a 1:1 ratio by a central computer-generated system to receive oxygen or room air via a concentrator through a nasal cannula at 2 L per min for 7 days. Participants were instructed to use the concentrator for at least 15 h per day. The randomisation sequence was stratified by baseline PaO(2) with balanced blocks of four patients. The primary outcome measure was breathlessness (0-10 numerical rating scale [NRS]), measured twice a day (morning and evening). All randomised patients who completed an assessment were included in the primary analysis for that data point (no data were imputed). This study is registered, numbers NCT00327873 and ISRCTN67448752. FINDINGS 239 participants were randomly assigned to treatment (oxygen, n=120; room air, n=119). 112 (93%) patients assigned to receive oxygen and 99 (83%) assigned to receive room air completed all 7 days of assessments. From baseline to day 6, mean morning breathlessness changed by -0.9 points (95% CI -1.3 to -0.5) in patients assigned to receive oxygen and by -0.7 points (-1.2 to -0.2) in patients assigned to receive room air (p=0.504). Mean evening breathlessness changed by -0.3 points (-0.7 to 0.1) in the oxygen group and by -0.5 (-0.9 to -0.1) in the room air group (p=0.554). The frequency of side-effects did not differ between groups. Extreme drowsiness was reported by 12 (10%) of 116 patients assigned to receive oxygen compared with 14 (13%) of 108 patients assigned to receive room air. Two (2%) patients in the oxygen group reported extreme symptoms of nasal irritation compared with seven (6%) in the room air group. One patient reported an extremely troublesome nose bleed (oxygen group). INTERPRETATION Since oxygen delivered by a nasal cannula provides no additional symptomatic benefit for relief of refractory dyspnoea in patients with life-limiting illness compared with room air, less burdensome strategies should be considered after brief assessment of the effect of oxygen therapy on the individual patient. FUNDING US National Institutes of Health, Australian National Health and Medical Research Council, Duke Institute for Care at the End of Life, and Doris Duke Charitable Foundation.

Management of venous thromboembolism in patients with advanced cancer: a systematic review and meta-analysis

Venous thromboembolism is common in patients with cancer. However, no management guidelines exist for venous thromboembolism specific to patients with advanced progressive cancer. To help develop recommendations for practice, we have done a comprehensive review of anticoagulation treatment in patients with cancer, with particular focus on studies that included patients with advanced disease. Data from 19 publications, including randomised, prospective, and retrospective studies suggest that: long-term full-dose low-molecular-weight heparin (LMWH) is more effective than warfarin in the secondary prophylaxis of venous thromboembolism in patients with cancer of any stage, performance status, or prognosis; warfarin should not be used in patients with advancing progressive disease; and in patients at high risk of bleeding, full-dose LMWH for 7 days followed by a long-term decreased fixed dose long term can be considered. The optimum treatment duration is unclear, but because the prothrombotic tendency will persist in patients with advanced cancer, indefinite treatment is generally recommended. For patients with contraindications to anticoagulation, inferior-vena-caval filters can be considered, but their use needs careful patient selection. Ultimately, the decision to initiate, continue, and stop anticoagulation will need to be made on an individual basis, guided by the available evidence, the patients circumstances, and their informed preferences.

The Safety and Efficacy of a Single Dose (500 mg or 1 g) of Intravenous Magnesium Sulfate in Neuropathic Pain Poorly Responsive to Strong Opioid Analgesics in Patients with Cancer

Neuropathic pain may respond poorly to morphine and is often difficult to relieve. Recent attention has been drawn to the role of the N-methyl-D-aspartate (NMDA) receptor in the potentiation of neuropathic pain. Magnesium is known to block the NMDA receptor. It reduces the neuropathic pain response in animals, and attenuates postoperative pain and migraine in humans. We have examined the safety, tolerability, and efficacy of two intravenous doses of magnesium sulfate in 12 patients with neuropathic pain due to malignant infiltration of the brachial or lumbosacral plexus. The first six patients received 500 mg, the remainder 1 g. Apart from a mild feeling of warmth at the time of the injection, both doses were well tolerated. After receiving 500 mg, three patients experienced complete pain relief and two experienced partial pain relief for up to 4 hours duration; pain was unchanged in one patient. After receiving 1 g, one patient experienced complete relief and four experienced partial pain relief of similar duration; pain was unchanged in one patient. Intravenous magnesium sulfate in these doses appears to be safe and well tolerated. A useful analgesic effect may be obtained in some patients and further evaluation is warranted.

Researching breathlessness in palliative care: consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup.

Breathlessness is common in advanced disease and can have a devastating impact on patients and carers. Research on the management of breathlessness is challenging. There are relatively few studies, and many studies are limited by inadequate power or design. This paper represents a consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup. The aims of this paper are to facilitate the design of adequately powered multi-centre interventional studies in breathlessness, to suggest a standardised, rational approach to breathlessness research and to aid future ‘between study’ comparisons. Discussion of the physiology of breathlessness is included.

Does aromatherapy massage benefit patients with cancer attending a specialist palliative care day centre

A randomised controlled pilot study was carried out to examine the effects of adjunctive aromatherapy massage on mood, quality of life and physical symptoms in patients with cancer attending a specialist unit. Participants were randomised to conventional day care alone or day care plus weekly aromatherapy massage using a standardised blend of oils for four weeks. At baseline and at weekly intervals, patients rated their mood, quality of life and the intensity and bother of two symptoms most important to them. Forty-six patients were recruited to the study. Due to a large number of withdrawals, only 11 of 23 (48%) patients in the aromatherapy group and 18 of 23 (78%) in the control group completed all four weeks. Mood, physical symptoms and quality of life improved in both groups. There was no statistically significant difference between groups in any of the outcome measures. Despite a lack of measurable benefit, all patients were satisfied with the aromatherapy and wished to continue. Whilst this pilot study has shown that a randomised controlled trial of complementary therapy is feasible, it has also identified several areas that would require further consideration when designing future studies, e.g., the recruitment and retention of appropriate numbers of patients and the outcome measures used.

Is exercise an acceptable and practical therapy for people with or cured of cancer?: A systematic review

INTRODUCTION Therapeutic exercise, although potentially beneficial, does not appear acceptable to many cancer patients. A greater understanding of the reasons for this is required. We have systematically reviewed the use of exercise in this group, identifying rates of uptake, adherence and completion along with factors influencing acceptability. METHODS Searches were completed using relevant key words. Data on study design, patient group, exercise intervention, patient flow data and reasons for declining or withdrawing from a programme were independently extracted by two researchers. Rates of study uptake, completion and adherence were compared according to dichotomised patient or programme characteristics using Mann Whitney U test (p=0.05). Reasons provided when declining or withdrawing from a study were categorised. RESULTS Sixty five studies were included. The majority contained groups made up entirely or predominantly of patients with breast cancer offered an aerobic or resistance exercise programme. The median [IQR] rates of uptake, adherence and completion were 63 [33-80]%, 84 [72-93]% and 87 [80-96]%, respectively. No characteristic influenced the proportion of patients taking up or completing a programme. The main reasons for refusal were disinterest or the impracticality of undertaking the programme and for withdrawal, medical complication or deterioration. CONCLUSIONS The invitation to undertake a programme of therapeutic exercise is accepted by about two-thirds of patients. Rates of adherence and completion are relatively high, but overall, only about half of patients offered a programme complete one. There is a need to modify exercise programmes if they are to be acceptable for the majority of patients.

Validity of three accelerometers during treadmill walking and motor vehicle travel

Objective To determine the relative accuracy during treadmill walking and motor vehicle travel of the ActivPAL, PALlite and Digi-Walker accelerometers. Methods Forty healthy volunteers wearing all accelerometers undertook either five treadmill walks (n=20) at speeds ranging between 0.6 and 1.4 m/s or a 15 min motor vehicle journey (n=20). Step counts recorded by each accelerometer were compared with the actual step count determined by video analysis (treadmill walking) or with an actual step count of zero (motor vehicle). Mean percentage measurement error was calculated and compared between devices by one-way ANOVA and Student t test. Results For treadmill walking, the measurement error was lowest for the ActivPAL, with no significant differences between the ActivPAL and the PALlite monitors. The measurement error was significantly higher for the Digi-Walker at speeds of ≤1 m/s. During vehicle travel erroneous steps were recorded by the PALlite (254 steps) and Digi-Walker (25 steps), but not the ActivPAL monitor (0 steps). Conclusions The ActivPAL accelerometer accurately measures step count over a range of walking speeds and, unlike the other accelerometers tested, is not falsely triggered by motor vehicle travel.

Pilot study of nasal morphine-chitosan for the relief of breakthrough pain in patients with cancer.

Breakthrough pain in patients with cancer is common, often unpredictable, and can rapidly become severe. Treatment using the oral administration of opioids is not optimal due to the slow onset of pain relief. Nasal administration of analgesics potentially offers more rapid pain relief. This study investigates the tolerability and efficacy of a novel morphine-chitosan formulation. Twenty episodes of breakthrough pain were observed in 14 patients with cancer who received 5-80 mg of nasal morphine-chitosan. Nasal symptoms, sedation, giddiness, nausea, and other volunteered symptoms, along with pain scores (pain intensity and pain relief), were recorded at baseline and at regular intervals up to 4 hours after administration, together with an overall satisfaction rating. The formulation was acceptable to patients, generally well tolerated, and had an onset of pain relief 5 minutes after dosing. This formulation warrants further study.

Descriptors of Breathlessness in Patients With Cancer and Other Cardiorespiratory Diseases

The objective of this study was to examine the relationship between descriptors of breathlessness and its underlying cause in patients with lung cancer and cardiopulmonary diseases to see whether descriptors might be used to help determine the cause of breathlessness, particularly in patients with lung cancer. We studied 131 patients with primary or secondary lung cancer, whose breathlessness was attributed to tumor mass, pleural effusion, lung collapse, metastases, pleural thickening or lymphangitis carcinomatosis, and 130 patients with breathlessness attributed to asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease or cardiac failure. Patients selected statements (descriptors) that described the quality of their breathlessness from a 15-item questionnaire and the relationship between the descriptors and the attributed cause of breathlessness was evaluated by cluster analysis. All patient groups were characterized by more than one cluster and several clusters were shared between groups. Specific sets of clusters were associated with breathlessness due to asthma, COPD and cardiac failure, and to cancer causing collapse, metastases or pleural thickening. The association of different sets of clusters with the different diagnostic groups suggests that patients are describing qualitatively different experiences of breathlessness, but the relationship does not appear to be sufficiently robust for the questionnaire to aid differential diagnosis.

Audit of three antimuscarinic drugs for managing retained secretions.

Clinical experience suggests that noisy retained secretions or ‘death rattle’ are commonplace in patients with cancer in the last few days of life. Retrospective reviews suggest an incidence of 34–70%, with most patients receiving either intermittent injections or a continuous infusion of hyoscine hydrobromide.1–4 Other antimuscarinic drugs such as hyoscine butylbromide and glycopyrrolate are used, as are repositioning and suction.5,6 There are no prospective studies published of the efficacy of any of these measures. Treatment is thus largely pragmatic and can vary even within a single centre. Nurses have expressed a desire for consistent clinical guidelines.6 We have therefore audited the effect of guidelines based upon the use of three different antimuscarinic drugs emphasizing the support of those in attendance.