, Julie Burkin1, Catherine Moffat1 and Anna Spathis1
(1)
Department of Palliative Care, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
Abstract
Despite its widespread use, there is little evidence that oxygen palliates breathlessness. This chapter outlines the evidence base and provides a practical clinical guideline for oxygen therapy. Fan therapy is then described, a key strategy in the management of breathlessness in advanced disease.
Introduction
Breathless patients seem to have an intuitive sense that they need ‘more air’. Patients typically seek fresh, moving air, for example by keeping hospital bed curtains open, opening windows and using a fan. As oxygen is the vital constituent of inhaled air, it is not surprising that people equally expect supplemental oxygen to be helpful. The majority of patients and healthcare professionals, including respiratory and palliative care staff, believe that breathless patients benefit from oxygen therapy. Administration of oxygen is an automatic treatment for breathless patients admitted to hospital, and a significant proportion of those with incurable underlying respiratory disease are then prescribed oxygen for use at home.
Some of the dangers of oxygen therapy have long been understood, including the risks of hypercapnic respiratory failure and oxygen toxicity. However, only in recent years has there been an understanding of the need to reduce emergency oxygen administration, with an emerging body of evidence revealing worse outcomes in many patients receiving oxygen. Non-hypoxaemic stroke patients, for example, randomised to oxygen therapy have a higher mortality, and neonates resuscitated with room air appear to do better than those given oxygen. Recent guidance for emergency oxygen use recommends prescribing according to a target saturation range, rather than a flow rate or concentration.
The target saturation range is 94–98 % for most acutely ill patients and 88–92 % for those at risk of hypercapnic respiratory failure.
Homeostasis is a complex and effective process. Hypoxia leads to a reflex constriction of pulmonary vessels, to reduce ventilation perfusion (VQ) mismatch, and reflex dilatation of cardiac, cerebral and systemic vessels increases oxygen delivery to the tissues. Patients acclimatise to chronic hypoxaemia, and patients with chronic cardiorespiratory disease can, like mountaineers, tolerate low oxygen saturations, often well below 70 %. It is, therefore, unsurprising that hindering normal homeostatic mechanisms with supplemental oxygen can be harmful. Oxygen therapy can worsen VQ mismatch, as well as causing cerebral and cardiac vasoconstriction, reduction in cardiac output, absorption atelectasis and an increase in toxic free radicals.
In this context, one would expect the widespread use of oxygen for palliation of breathlessness to be supported by evidence of benefits outweighing harms. Does this evidence exist? This chapter seeks to outline research evidence both for the use of oxygen and of air, and gives detailed guidance to inform clinical practice.
Oxygen Therapy
Evidence Base
Booth et al. published a seminal paper in 1996, which showed that inhalation of both cylinder oxygen and cylinder air significantly improved breathlessness in hospice cancer patients (Booth et al. 1996). Importantly, there was no difference between the two gases; both oxygen and air led to symptom palliation. A large number of single assessment and pragmatic longer-term studies have since attempted to evaluate the role of oxygen in breathlessness management, and the evidence is summarised in the box below.
Research Evidence
Oxygen can be delivered as long-term oxygen therapy (LTOT) where oxygen is inhaled for 15 or more hours out of every 24 h; as short-burst oxygen therapy (SBOT) with intermittent use before or after exertion; and as ambulatory oxygen therapy given using small cylinders during exertion.
LTOT
In COPD patients with severe hypoxaemia (PaO2 < 7.3), there is clear evidence that LTOT increases survival, improves quality of life and relieves breathlessness. In non-hypoxaemic patients, a recent systematic review has revealed a small reduction in breathlessness (equating to 0.9 points in a 0–10 numerical rating scale) of borderline clinical significance (Uronis et al. 2011). Subgroup analysis showed the benefit occurred in LTOT and not SBOT trials. However, this review did not include data from a subsequent RCT which revealed no difference between oxygen and air received for >15 h/day over a 7 day period in a mixed group of predominantly COPD patients (Abernethy et al. 2010). There have been no trials evaluating the use of LTOT in cancer patients.
SBOT and ambulatory oxygen therapy
In non-hypoxaemic COPD patients, as described above, a systematic review has shown no benefit from SBOT. A subsequent RCT in the same patient group also failed to demonstrate benefit from ambulatory oxygen (Moore et al. 2011). In a systematic review of non- or mildly hypoxaemic cancer patients receiving either SBOT or ambulatory oxygen therapy oxygen did not palliate breathlessness (Uronis et al. 2008). In this review, the single positive trial out of the five included studies was the one with the most hypoxaemic patients (all participants SaO2 < 90 %).
Although there is little evidence for oxygen improving breathlessness across study populations, within each trial a number of patients did benefit from oxygen.
The response to oxygen, importantly, does not appear to correlate with the degree of hypoxaemia, degree of desaturation on exercise, or any test of lung function.
The response is extremely variable between individuals, although more reproducible at an individual level. (Spathis and Booth 2008)
Potential Mechanisms
A number of possible mechanisms of action for oxygen have been proposed of which the most important are as follows:
Reversal of hypoxaemia. Hypoxaemia is a potent stimulus of respiratory drive, which is believed to result in breathlessness by increasing the mismatch between demand for ventilation and feedback on actual ventilation (see page 18) Oxygen therapy prevents this process from occurring.
Reduction in blood lactate levels. Reduction in oxygenation of muscle leads to lactic acid production. This increases ventilatory demand, in an attempt to compensate for the metabolic acidosis. Supplemental oxygen will reduce lactic acid formation. This mechanism could increase the ability to recondition by exercise training, although this may be limited by the fact that there is some evidence that lactic acid production can enhance the training effects on muscle.
Reduction in dynamic hyperinflation. Lung hyperinflation occurs when there is incomplete lung emptying in obstructive airways disease (see page 94). The functional restriction in inhalation puts greater reliance on tachypnoea to increase ventilation. However, tachypnoea gives less time for full exhalation, leading to a vicious cycle. It is believed oxygen breaks this cycle by reducing the demand for ventilation and therefore the respiratory rate.
Stimulation of facial and nasopharyngeal receptors. Receptors stimulated by a cool flow of gas project afferent information that reduces the perception of dyspnoea; local anaesthesia in this region has been shown to increase breathlessness (Liss and Grant 1988). Oxygen may work simply by providing a flow of a cool gas, and this may explain why studies have shown benefit from both cylinder oxygen and cylinder air.
Placebo effect. The widely held view that oxygen should reduce breathlessness may in itself alter central processing of the sensation through a placebo effect.
The range of potential mechanisms both involved in the genesis of breathlessness (see page 17) and explaining the effect of oxygen (above) may explain why, for individual patients, benefit from oxygen does not appear to correlate with the degree of hypoxaemia. Oxygen in a non-hypoxaemic patient, for example, may help breathlessness by reducing dynamic hyperinflation. Conversely, the breathlessness of a hypoxaemic patient may relate to afferent information from lung or chest wall receptors that is not influenced by reversal of hypoxaemia.
Clinical Guideline for Use of Non-emergency Supplemental Oxygen
This guidance provides a pragmatic approach, based on a combination of current evidence and expert opinion. Although the evidence points to a lack of benefit for oxygen (other than LTOT in hypoxaemic COPD patients), palliation of breathlessness does occur in a few patients. The only way to decide whether or not to prescribe oxygen for a particular patient is to undertake an individual clinical assessment.
An individual clinical assessment involves measuring breathlessness severity both with and without supplemental oxygen. This can range in rigour from a formal ‘N = 1 randomised controlled trial’ to a simple explanation about the lack of evidence for oxygen therapy and asking patients to assess critically whether or not they feel oxygen is helping them. In practice, a pragmatic compromise involves selecting a specific activity within a patient’s home (such as climbing the stairs), and asking the patient to keep a diary quantifying breathlessness on a 0–10 numerical rating scale after undertaking this activity, both with and without oxygen.
Oxygen therapy is not appropriate in patients with SpO2 > 92 %.
LTOT should be provided only to severely hypoxaemic COPD patients with a PaO2 < 7.3 kPa. This is a lifetime commitment to use oxygen for over 15 h per day. In severely hypoxaemic cancer patients, LTOT can be considered, although the use is not evidence based. LTOT is best supplied by an oxygen concentrator and delivered via nasal cannulae, with access to ambulatory oxygen.
Ambulatory oxygen alone can be considered in less hypoxaemic patients with exercise desaturation, specifically when the SpO2 falls by >4 % to below 90 % during exercise. Its effectiveness must still be checked by recording the distance a patient can walk and the dyspnoea severity (with 0–10 numerical rating scale) both with and without oxygen. Lightweight portable cylinders are available.
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