Oxygen delivery (DO2) is arguably the most critical requirement for the maintenance of normal organ function and can be illustrated by Equation 1:
where CaO2 is total oxygen content, made up largely of oxygen bound to haemoglobin and, to a much smaller degree, oxygen dissolved in plasma. DO2 therefore depends not only on the degree of oxygenation of the blood but also on cardiovascular function and haemoglobin concentration. Despite its importance, it is not the most tightly regulated physiological parameter for metabolism and gas exchange. This is well illustrated by a study of repeated venesection resulting in isovolaemic anaemia (5 g/dl) in healthy humans.1 While cardiac output rose, it was insufficient to maintain DO2 but because of the steep slope of the oxyhaemoglobin dissociation curve at the tissue level, the fall in DO2 was offset by increased oxygen extraction, indicated by a reduction in mixed venous oxygen (SvO2).
SvO2 is therefore a much better indicator of oxygen delivery than arterial saturation (SaO2), and is one of the targets in resuscitation in sepsis. SaO2 is readily measurable and helpful in resuscitation, although attention should be paid to integrated physiological function.2
The normal ranges of arterial oxygen tension (PaO2) and SaO2 are 10–13 kPa and 94–98%, respectively. It is apparent that DO2 cannot be significantly enhanced by increasing PaO2 above 16 kPa, where haemoglobin is 100% saturated and the amount of oxygen dissolved in the plasma is small. This manoeuvre will maximise CaO2 but may not always optimise DO2.
Oxygen ‘toxicity’
There are many reasons why maximising SaO2 may firstly not optimise DO2 and secondly may impact adversely on other aspects of a patient's physiology. The best-known example of this occurs during acute exacerbations of chronic obstructive pulmonary disease (COPD). Here PaO2 above 10 kPa is associated with respiratory acidosis and worse outcomes.3,4 Decreased hypoxic drive, absorption atelectasis and the Haldane effect (decreased CO2 buffering by oxyhaemoglobin) all contribute to hypercapnia, but the greatest effect is likely to relate to worsened ventilation-perfusion mismatch. Deoxygenated pulmonary arterial blood is diverted away from areas of diseased lung because alveolar hypoxia due to poor ventilation causes vasoconstriction and thus decreased local perfusion (ie hypoxic pulmonary vasoconstriction). If high-flow oxygen is applied, these alveoli re-oxygenate and reperfuse, but remain poorly ventilated and fail to clear CO2. In reasonably healthy lungs, regional failure to clear CO2 can be compensated by an overall increase in ventilation, but impaired respiratory mechanics prohibit this in COPD.
Other adverse effects of hyperoxia relate to effects on the cardiovascular system and the production of reactive oxygen species (discussed in detail elsewhere5). Table 1 summarises some of the concepts, with selected references. Hyperbaric oxygen therapy for stroke and intracoronary hyperoxaemic reperfusion for myocardial infarction (MI) are currently being explored. It is possible that the significant rise in oxygen tension in infarcted tissue may outweigh the physiological changes and oxidative stress, but these data are awaited. Studies of supraphysiological DO2 in critical illness have so far failed to show benefit.10
The adverse effects of hyperoxia achieved with normobaric oxygen.
Emergency oxygen use in adults
Guidelines
Recent guidelines for emergency oxygen in adults have been developed under the auspices of the British Thoracic Society (BTS) in association with 21 UK societies.5 In determining emergency oxygen policy, the committee felt two diametrically opposed philosophical positions could be assumed due to the paucity of evidence:
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1. Plentiful oxygen. Maximising SaO2 with high-concentration oxygen (HCO) is advisable in many situations, particularly in critical illness when monitoring is unavailable (eg at the roadside). Even when saturations are being monitored, it may be appropriate as other contributors to DO2 (Equation 1) may not yet be known. Furthermore, it can provide a margin of safety in the event of worsening gas exchange. However, this margin of safety may also mask deterioration11 since saturations will fall only when the alveolar-arterial gradient is large or the PaO2/fractional concentration of oxygen in inspired gas (FiO2) ratio falls below 100. Other clinical features may flag deterioration, but patients who need increasing oxygen to maintain saturations may trigger warning systems earlier.
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2. Oxygen only when needed to achieve normal oxygen saturations, given the absence of proven benefit of aiming higher and of concerns over the physiological and potentially toxic effects of hyperoxia.
The latter is the position taken by the committee. Notably, in the areas reviewed in Table 1, guidelines from other societies recommend administering oxygen to patients with stroke12 and MI13,14 only in the event of hypoxaemia.
Consequently, the guidelines (Fig 1) recognise the necessity for HCO in critical illness, but in other situations recommend that oxygen is given only if saturations fall below the normal range (94–98%).5 Aligned with the Surviving Sepsis Campaign,15 the guidelines emphasise that maximised SaO2 is not synonymous with optimised DO2 and that vascular filling, haematocrit and cardiac output also need appropriate adjustment.
Initial algorithm for inhospital prescription of oxygen. ABG = arterial blood gas; SpO2 = peripheral oxygen saturation.5
Exception is made, however, for patients at risk of hypercapnic respiratory failure, typically patients with COPD, but also with neuromuscular and chest wall disorders. The recommended SaO2 is 88–92%, based on observations that PaO2 of 7.3–10 kPa is associated with the lowest incidence of acidosis.3 Patients known to be at risk of hypercapnic respiratory failure should be given an alert card with a prespecified saturation target range, usually 88–92%, although for some this may be lower. Arterial blood gases should guide further management as soon as they are available.
Key Points
Optimisation of oxygen delivery requires more than oxygen therapy and attention should be paid to vascular filling, haematocrit and cardiac output
High-concentration oxygen may cause worse outcomes through physiological effects and reactive oxygen species
Emergency oxygen should be prescribed to a target saturation (88–92% in those at risk of hypercapnic respiratory failure, 94–98% in those not at risk), except in critical illness
Oxygen therapy at home should be assessed, prescribed and followed up by a specialised oxygen service, usually led by a respiratory physician in secondary care
In active patients, ambulatory oxygen should be prescribed to maintain saturations above 90%
Overzealous withdrawal of HCO may do more harm than good through rebound hypoxaemia. This can be best understood through use of the alveolar gas equation (Equation 2):
where RER is the respiratory exchange ratio of O2 consumption to CO2 production. When the partial pressure of inspired oxygen (PIO2) is increased with HCO, alveolar CO2 (PACO2) will rise. When PIO2 is reduced to baseline, alveolar PO2 (PAO2) will therefore be lower than previously (until the CO2 body stores are blown off). Consequently, arterial PaO2 will be lower than prior to HCO. It can be considered conceptually as CO2 occupying more ‘space’ in the alveolus. Thus, if an at-risk patient has been given HCO, oxygen should be withdrawn gradually, stepping down through fixed-concentration Venturi masks.
Criticisms of the guidelines
Following these guidelines, there is likely to be further argument about the risk of giving high or low levels of oxygen to patients with COPD. Critics of the lower saturation policy often quote a randomised pilot study of COPD exacerbations in which PaO2 was titrated to 6.6 kPa in one group and 9 kPa in the other.16 There was a non-significant trend to worse outcomes in the former group. It is beyond the scope of this article to enumerate all the reasons why this trial cannot be used to justify HCO in COPD exacerbations. One compelling factor, though, is that in neither group was PaO2 allowed to rise significantly. It was therefore a trial comparing two levels of controlled oxygen. Furthermore, with regard to the effect of the degree of hypercapnic acidosis present in their population on the oxygen dissociation curve (the Bohr effect), target PaO2 values of 6.6 kPa and 9 kPa theoretically translate to saturations of 74% and 89%, respectively. While, on average, the PaO2 levels were higher than this, the higher target PaO2 was actually much closer to the BTS recommendations.
A criticism often levelled at the controlled oxygen protagonist is that the sickest patients require higher concentration oxygen and for this reason there is an association with worse respiratory failure. Against this a study from Norwich showed that when a policy of giving 28% oxygen from the outset is instituted, there is no clear increase in complications or significant hypoxaemia.17 In addition, far fewer patients present with respiratory acidosis.
Oxygen at home
In 2006, a new policy for the prescription of home oxygen, to include long-term, ambulatory and short-burst treatments, was introduced by the Department of Health based on a report by the Royal College of Physicians in 1999.18 The two key components of the policy were to:
rationalise oxygen providers, with groups of primary care trusts assigning contracts to one of four companies, and
move the responsibility of oxygen assessment, prescription and follow up largely to secondary care, with patients assessed by a service directed by a respiratory physician. There is a requirement for a detailed prescription, consent form and record form by the service.
Long-term oxygen therapy
The criteria for long-term oxygen therapy (LTOT) for COPD have been extended to other long-term conditions (Fig 2). If nocturnal hypoventilation is suspected, formal assessment by a respiratory physician is necessary as non-invasive ventilation will be more appropriate in conditions such as neuromuscular and chest wall diseases, rather than oxygen. There is now greater access to ambulatory oxygen, but evidence suggests that, when it is prescribed, many patients use it rarely. A diary card should be provided with the first two-month supply to determine need for continuation.
Algorithm for prescription of long-term oxygen therapy (LTOT) and ambulatory oxygen. COPD = chronic obstructive pulmonary disease; PaO2 = arterial oxygen tension; SpO2 = peripheral oxygen saturation.
Patients being assessed for ambulatory oxygen are subdivided into two groups:
low activity: those who are usually immobile and need oxygen for leaving the home. They will need the same oxygen flow rate as their LTOT
active: those likely to benefit from increased exercise capacity. Within this group there will be patients on LTOT and some not, but who desaturate on exercise. Both subgroups should be assessed by six-minute or shuttle-walk testing to titrate the optimal flow rate and to assess the objective improvement in exercise capacity.
Ambulatory therapy is not indicated in chronic heart failure, but desaturation identifies coexistent pulmonary vascular disease and patients may benefit in this instance.
Short-burst therapy provided by cylinders kept in the home and used as required for the relief of breathlessness, may also be prescribed. A recent review, however, suggested little gain to patients with COPD and there is little clear guidance on who will benefit.19 It remains largely a clinical decision for the relief of breathlessness, but other palliative care approaches should also be considered.
- © 2009 Royal College of Physicians
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