Elsevier

The Lancet

Volume 376, Issue 9743, 4–10 September 2010, Pages 784-793
The Lancet

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

https://doi.org/10.1016/S0140-6736(10)61115-4Get rights and content

Summary

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 (PaO2) 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 PaO2 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.

Introduction

Dyspnoea has been defined as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations varying in intensity. The experience derives from interactions among multiple physiological, psychological, social, and environmental factors”.1 Prevalence of severe dyspnoea has been reported as 65%, 70%, and 90% in terminally ill patients with heart failure, lung cancer, and chronic obstructive pulmonary disease (COPD), respectively.2 Dyspnoea often presents as a chronic disorder that intensifies during the dying process;3 it can erode quality of life, psychological wellbeing, and social functioning.4

The exact nature and cause, and therefore appropriate treatment, of dyspnoea remain elusive. Objective measures, such as desaturation with exercise, hint at underlying pathology, but do not reliably indicate subjective experience. Current pharmacological treatments for dyspnoea include opioids, psychotropic drugs, inhaled furosemide, helium-oxygen mixture (heliox 28; 72% helium, 28% oxygen), and oxygen; opioids remain the mainstay of treatment.5, 6 Palliative interventions seek to alleviate the sensation of breathlessness; they are generally applied in palliative care irrespective of underlying pathology and respiratory functioning.7

Long-term oxygen therapy is indicated for COPD patients with severe hypoxaemia (partial pressure of oxygen in arterial blood [PaO2] ≤7·3 kPa at rest); such treatment improves survival, dyspnoea, and functional status.8, 9, 10 Palliative oxygen is frequently prescribed to manage dyspnoea in people with advanced life-limiting illness, irrespective of PaO2, and is generally considered standard of care.11, 12 More than 70% of physicians caring for patients with dyspnoea in palliative care prescribe palliative oxygen, usually for refractory symptoms (65%) or at the patient's request (30%).13 There is not, however, clear evidence showing symptomatic benefit of palliative oxygen,14, 15, 16 although the intervention entails cost and logistical burden. Hospices worldwide commonly prescribe oxygen on the basis of symptomatic criteria, rather than on the basis of pulse oximetry readings. In Canada, compassionate use of oxygen that does not meet criteria for long-term oxygen therapy represents 30% of the budget for oxygen therapy.9 Lack of evidence to support use of palliative oxygen and absence of available clinical practice guidelines have led to inconsistent access and variable use.17

This study assessed the symptomatic effectiveness of palliative oxygen for patients with life-limiting illness, refractory breathlessness, and PaO2 more than 7·3 kPa. The comparator was room air provided via a modified concentrator (altered according to a standard protocol); the null hypothesis was that oxygen therapy is not superior to room air in this setting.

Section snippets

Participants

This international, multicentre, double-blind, randomised controlled trial was undertaken from April, 2006, to March, 2008. The study protocol was approved by the Duke University Health System Institutional Review Board, and local research and ethics committees or institutional review boards of all participating sites. The full protocol for the trial is available from the corresponding author.

Participants were recruited from outpatient pulmonary, palliative care, oncology, and primary care

Results

Figure 1 shows the trial profile. Table 1 shows baseline characteristics of study participants. 13 (5%) participants withdrew before the study started and completed no assessments. Additionally, 15 (6%) patients withdrew before completing the final (day 6) assessment.

The primary outcome, breathlessness, did not differ between groups at any time during the study period (figure 2). For morning dyspnoea, 58 (52%) of 112 patients assigned to oxygen and 40 (40%) of 101 patients assigned to room air

Discussion

This study shows that compared with room air delivered by a nasal cannula, oxygen provides no additional symptomatic benefit for relief of refractory breathlessness in patients with PaO2 more than 7·3 kPa. Intensity of dyspnoea decreased during the study in both groups, temporally related to the provision of the concentrator; improvement in quality of life scores and exertional capacity mirrored changes in breathlessness. Breathlessness scores of patients with moderate to severe baseline

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