Elsevier

The Lancet Oncology

Volume 14, Issue 3, March 2013, Pages 219-227
The Lancet Oncology

Articles
Palliative use of non-invasive ventilation in end-of-life patients with solid tumours: a randomised feasibility trial

https://doi.org/10.1016/S1470-2045(13)70009-3Get rights and content

Summary

Background

Despite best-possible medical management, many patients with end-stage cancer experience breathlessness, especially towards the end of their lives. We assessed the acceptability and effectiveness of non-invasive mechanical ventilation (NIV) versus oxygen therapy in decreasing dyspnoea and the amount of opiates needed.

Methods

In this randomised feasibility study, we recruited patients from seven centres in Italy, Spain, and Taiwan, who had solid tumours and acute respiratory failure and had a life expectancy of less than 6 months. We randomly allocated patients to receive either NIV (using the Pressure Support mode and scheduled on patients' request and mask comfort) or oxygen therapy (using a Venturi or a reservoir mask). We used a computer-generated sequence for randomisation, stratified on the basis of patients' hypercapnic status (PaCO2 >45 mm Hg or PaCO2 ≤45 mm Hg), and assigned treatment allocation using opaque, sealed envelopes. Patients in both groups were given sufficient subcutaneous morphine to reduce their dyspnoea score by at least one point on the Borg scale. Our primary endpoints were to assess the acceptability of NIV used solely as a palliative measure and to assess its effectiveness in reducing dyspnoea and the amount of opiates needed compared with oxygen therapy. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00533143.

Findings

We recruited patients between Jan 15, 2008, and March 9, 2011. Of 234 patients eligible for recruitment, we randomly allocated 200 (85%) to treatment: 99 to NIV and 101 to oxygen. 11 (11%) patients in the NIV group discontinued treatment; no patients in the oxygen group discontinued treatment. Dyspnoea decreased more rapidly in the NIV group compared with the oxygen group (average change in Borg scale −0·58, 95% CI −0·92 to −0·23, p=0·0012), with most benefit seen after the first hour of treatment and in hypercapnic patients. The total dose of morphine during the first 48 h was lower in the NIV group than it was in the oxygen group (26·9 mg [37·3] for NIV vs 59·4 mg [SD 67·1] for oxygen; mean difference −32·4 mg, 95% CI −47·5 to −17·4). Adverse events leading to NIV discontinuation were mainly related to mask intolerance and anxiety. Morphine was suspended because of severe vomiting and nausea (one patient in each group), sudden respiratory arrest (one patient in the NIV group), and myocardial infarction (one patient in the oxygen group).

Interpretation

Our findings suggest that NIV is more effective compared with oxygen in reducing dyspnoea and decreasing the doses of morphine needed in patients with end-stage cancer. Further studies are needed to confirm our findings and to assess the effectiveness of NIV on other outcomes such as survival. The use of NIV is, however, restricted to centres with NIV equipment, our findings are not generalisable to all cancer or palliative care units.

Funding

None.

Introduction

Respiratory symptoms and dyspnoea are commonly reported in patients with solid tumours, with a prevalence ranging from 20% to 80%.1 Despite best-possible medical management, many patients are often breathless, especially in the latter stages of their life.2 Opioids provide symptomatic improvement in patients with less advanced disease—when acute respiratory distress is not yet present3—but little research has been done into the effect of oxygen in patients with cancer with refractory dyspnoea.4 There are some suggestions, however, that non-invasive ventilation (NIV) might be an alternative option to relieve dyspnoea in patients with end-stage cancer, including those with solid tumours.5 For this reason, the Society of Critical Care Medicine set up a task force to examine and potentially justify the use of NIV for patients in the palliative care setting.6 The members of the task force stated that most patients and their relatives are interested in ensuring comfort in the later stages of their disease, but some might also want to maintain cognition and the ability to communicate.6 In this context, NIV would be effective if it improves breathlessness and respiratory distress without having other negative consequences, such as discomfort from a tight-fitting face mask or an undue delay in the time of death. Studies on the effect of pharmacological treatments such as oxygen4 and morphine3 to relieve the burden of refractory dyspnoea in patients with end-stage cancer have not included people with severe respiratory distress—those who are most burdened by the symptom. Similarly, non-pharmacological treatments, such as NIV, have not been systematically studied.

The main objectives of this study were to assess the acceptability of NIV (used solely as a palliative measure) versus oxygen therapy and its effectiveness in reducing dyspnoea, the amount of opiates needed during NIV treatment, the recruitment and consent rate in a trial of NIV, and the variability of dyspnoea and morphine use to calculate sample sizes for future definitive studies.

Section snippets

Patients

In this multicentre, stratified, randomised feasibility study, designed according to the recommendations for good practice,7 done in five respiratory intensive care units and two critical care units of emergency departments (in Italy, Spain, and Taiwan), we enrolled consecutive patients who had end-stage cancer and solid tumours admitted to hospital because of acute respiratory failure and distress, and who had chosen to forego all life support and receiving only palliative care. The definition

Results

Between Jan 15, 2008, and March 9, 2011, 441 consecutive patients with cancer and acute respiratory failure were screened for eligibility for the trial. 234 patients were eligible for recruitment, of whom 200 (85%) were randomly allocated to treatment (all 234 eligible patients underwent the NIV run-in demonstration; figure 1). Baseline characteristics were much the same between individuals who received NIV and those who received oxygen (table 1; see appendix for baseline characteristics by PaCO

Discussion

Our findings suggest that NIV is well accepted by patients, is more effective in reducing dyspnoea compared with oxygen therapy, and requires less morphine than does oxygen therapy. We know of no other randomised trial assessing the feasibility of NIV as a palliative measure in comparison with oxygen in terminally ill patients with solid tumours and acute respiratory failure and distress. Our recruitment and consent rate was good, with 85% of eligible patients participating in the trial

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