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