OXYGEN THERAPY AND OXYGEN TOXICITY
Introduction - Causes of low oxygen delivery - Oxygen dissociation curve - Hypoxia and oxygen delivery -Types of hypoxia - Oxygen cascade - Oxygen administration - Oxygen toxicity
Oxygen is essential to life due to its function as the final electron and H+ acceptor in the mitochondrial cytochrome chain whereby ATP is produced as the cellular energy source. Without 'aerobic' metabolism, ATP production is not only reduced 20-fold but lactic acid is produced in excess, causing intracellular acidosis and eventually death. The reserves of ATP are small, so a constant supply of oxygen is necessary for living cells. Many disease states lead to failure to deliver oxygen to tissues, which often is the ultimate cause of death. Following anaesthesia and surgery, oxygen delivery is often compromised by the following factors:
Causes of compromised oxygen delivery in the postoperative period
Reduced oxygen delivery to the alveoli
- The patient's respiratory drive is depressed as a result of opioid analgesics and residual quantities of other central nervous system (CNS) depressants.
- When controlled ventilation is instituted during balanced anaesthesia there is often a tendency to reduce the patient's arterial carbon dioxide tension (PaCO2). This, together with the effect of residual CNS depressants, leads to hypoventilation in the immediate post-operative period until PaCO2 has been restored to normality. As a result, oxygen delivery to the alveoli may be insufficient to maintain oxygenation unless its concentration in the inspired gas is increased.
- The capacity to ventilate the lungs and to cough may also be impaired due to residual effects of long-acting neuromuscular blockers and to pain.
Reduced oxygen delivery from the alveoli to the tissues
- Inadequate fluid administration may lead to occult hypovolaemia and lowered cardiac output and thus oxygen delivery. In addition, the oxygen-carrying capacity of blood may be decreased due to red cell loss
- The cardiac output may also be significantly reduced due to heart disease or to depressant drugs, regional perfusion is impaired as well.
Increased tissue demand for oxygen
- Wound healing following tissue injury (due to trauma or surgery) increases the metabolic demand for oxygen.
- A pyrexial patient has an increased metabolic rate and demand for oxygen
- A cold operating theatre, administration of inadequately warmed fluids and blood, lack of warming and humidification of inspired gases, loss of the patient's normal mechanisms of heat conservation under anaesthesia , exposure of large areas of bowel and so on all contribute to loss of heat and reduction of body temperature during major surgery. As soon as the operation is complete, the patient restores body temperature to normal by shivering, resulting in big increases in oxygen demand.
These are some of the important reasons why oxygen therapy is indicated post-operatively.
Blood Oxygen Content and Dissociation Curve
Haemoglobin is employed as a specialised oxygen carrying system. Simple solution of oxygen in plasma, at ambient pressure and concentration, is insufficient for cellular oxygen demand. (Since only 3 ml of O2 is carried per litre of plasma, thus for a normal O2 demand of 250 ml. per minute to be met from plasma dissolved oxygen would require a cardiac output of 80 lpm!). The relation between the partial pressure of oxygen in blood and haemoglobin saturation is a sigmoid curve, with the steepest portion occurring in the range 2.6-9.3 kPa (20-70 mmHg) as seen in Fig 12.1.
One gram of haemoglobin can carry 1.34 ml of oxygen when fully saturated. Thus with a Hb of 15 g dl-1, an arterial oxygen tension (PaO2) of 13.3 kPa (100 mmHg) and a saturation (SaO2) of 98%:
Arterial oxygen content:
= 15 x 1.34 x 0.98
= 20 ml 100 ml-1 of blood (ignoring that dissolved in plasma)
or = 200 ml l-1
NB Each litre of air also contains about 200 mls of oxygen … thus the close matching of ventilation to perfusion (V/Q).
Hypoxia and Oxygen delivery to tissues
Oxygen delivery
Oxygen carried in blood leaving the lungs has to reach the cells to allow aerobic metabolism to take place. The concept of tissue 'oxygen delivery' or 'availability' is an important one because it gives a good idea of the factors determining tissue oxygenation.
Overall oxygen delivery = arterial oxygen content x cardiac output
Normally, cardiac output (Q) is about 5 l min-1 and oxygen content 200 ml.l-1
Thus:
Oxygen delivery = 5 * 200
= 1000 ml min-1
Note the three variables which affect oxygen availability; Hb, SaO2 and Q. At an oxygen consumption of 250 ml min-1, this leaves 750 ml of oxygen returning to the lung in the venous blood. If each one of the variables is halved, oxygen delivery is reduced to 1/8 of normal, i.e. to 125 ml min-1. This results in anaerobic metabolism, lactic acid production and cellular acidosis.
Anoxic or hypoxic
This is due to a fall in the partial pressure of the inspired gas (PIO2) such as at altitude, or if inspired oxygen is reduced in accidental misconnection of pipes under anaesthesia. This results in a fall in PAO2. An increase in PaCO2 or in the alveolar to arterial gradient for oxygen ((A-a)dO2) lowers PaO2 directly.
Anaemic
This is due to failure of oxygen carriage, as a result of low Hb, with normal cardiac output and saturation, or to alteration in the oxygen carrying capacity of Hb as a result of combination with carbon monoxide. The latter binds more strongly with Hb than does oxygen with the result that the tissues receive an inadequate oxygen supply.
Ischaemic or Stagnant
This results from inadequate blood perfusion to tissues due to myocardial failure, sepsis, raised systemic vascular resistance, or arterial embolism.
Histotoxic
Here the oxygen delivery to the tissue is normal, but mitochondrial oxygen utilisation is defective, such as in cyanide poisoning
Oxygen cascade from environment to cell
Oxygen therapy is ultimately designed to ensure adequate mitochondrial oxygen tensions. The points at which failure to achieve this may occur are outlined in Table 12.1.
TABLE 12.1 Causes and classification of hypoxia
|
System
level
|
Defect
|
Classification
|
|
Inspired gas
|
Low Inspired oxygen tension (PIO2) Low barometric pressure (pB) |
Hypoxic
|
|
Inspired gas to alveolar gas |
Low alveolar ventilation Raised oxygen consumption |
Hypoxic
|
|
Alveolar gas
to arterial blood
|
Venous admixture or shunt V/Q inequality (>1) Impaired diffusion |
Hypoxic
|
|
Arterial blood
to cell
|
Low or inadequate blood flow |
Ischaemic
|
|
Arterial blood
to cell
|
Low haemoglobin Carbon monoxide poisoning |
Anaemic
|
|
Cell
|
Metabolic poisons |
Histotoxic
|
| Increased metabolism |
Ischaemic
|
Matching of ventilation to whole body oxygen consumption
As oxygen is taken up from alveolus to capillary the partial pressure in the alveolus (PAO2) declines unless oxygen is constantly added by ventilation. At a normal oxygen consumption of 250 ml min-1 with alveolar ventilation of 5 l min-1, the PAO2 is 13.3 kPa (100 mmHg). If oxygen consumption doubles, as a result of raised temperature, excessive muscular activity or shivering, then the same alveolar ventilation only results in a PAO2 of 8 kPa (60 mmHg). Although the healthy patient may be able to double or treble alveolar ventilation to compensate for the increased demand, post-operative or sick patients may not. Increasing the inspired oxygen fraction (FIO2) to 0.4 partially compensates.
Matching of ventilation and perfusion in the lung
Ventilation (V) and perfusion (Q) must be closely matched so that oxygen delivery by ventilation to the lungs (1000 ml min-1) matches oxygen uptake and transport from the lungs to the tissues (1000 ml min-1). Although we can look at the lung as a whole, it is obviously important that each alveolus and its perfusing blood supply are also closely matched for V and Q in a ratio of 1 : 1. In health, due to the effect of gravity, the alveoli at the base of the lung tend to be relatively overperfused (V/Q 0.8 : 1) whilst those at the apex which do not receive such a good blood supply are relatively over ventilated (V/Q 2 : 1). Overall, the figure is close to 0.9 : 1.
If ventilation to an alveolus is restricted (due to secretions, oedema or bronchospasm leading to atelectasis) and its perfusion is maintained, then the V/Q ratio would fall from around 1 : 1 to say 0.2 : 1. Oxygen uptake exceeds supply so that blood leaving the alveolus is not properly oxygenated. This hypoxic blood meets arterialised blood from normal alveoli and results in an overall reduction of PaO2. This is called 'venous admixture' and is correctable by increasing the FIO2. This has the effect of increasing the actual amount of oxygen reaching the alveolus by increasing the concentration.
If ventilation to an alveolus is obstructed completely, no amount of additional oxygen will help and the patient has a true 'shunt'. This may be due to complete atelectasis or an extra-pulmonary shunt as in congenital heart disease.
Therapeutic implications
Although simply increasing the FIO2 counteracts the deleterious effects of atelectasis in the short term, no effort should be spared in assisting the patient to re-expand the collapsed alveoli. atelectasis predisposes to infection and effectively reduces lung volume and respiratory reserve. Thus, especially following upper abdominal surgery, and particularly if the patient is a heavy smoker or has chronic obstructive pulmonary disease, breathing exercises and physiotherapy are encouraged to prevent this serious complication.
.
The alveolar air equation
From the above, it can be seen that raising the FIO2 is a primary form of treatment for many of the conditions causing hypoxia. It is symptomatic and not curative.
The effect that increased FIO2 has on PAO2 can be determined from the 'alveolar air equation', i.e.
PAO2 = PIO2 - PaCO2/R
PIO2 refers to the inspired O2 tension (FIO2 x barometric pressure, BP). Thus, working in mm Hg., at an FIO2 of 0.4, and a BP of 713 (760 mmHg - water vapour pressure in the lungs of 47 mmHg), PIO2 is equal to about 280. R refers to the respiratory exchange ratio, i.e. the amount of CO2 produced divided by the amount of O2 consumed (in ml min-1). This ratio is normally 0.8. Thus if the PIO2 is 280 and PaCO2 is 40,
PAO2 = 280 - 40/0.8
= 230
The difference between the calculated PAO2 and the actual PaO2 gives the 'A-a' gradient, (A-a)dO2. This is a useful estimate of the amount of venous admixture or shunted blood passing through the lungs without coming into contact with alveolar air. An increase in the gradient suggests an increased admixture. The alveolar air equation also emphasises the deleterious effect on PaO2 of a rise in PaCO2, and why an increase in FIO2 goes some way in compensation.
Devices for oxygen therapy
Devices for delivering oxygen (raising the FIO2) include masks, nasal prongs, tents and hyperbaric chambers.
Two types are in common use (see Figure 12.2):
Low flow devices: these are simple, cheap devices such as the Mary Catterall (MC), Hudson mask and nasal prongs. A fixed flow of oxygen (2-4 l min-1) enters the mask (or nasopharynx) so that the patient inspires an oxygen-air mixture. The flow of oxygen is less than the air flow during inspiration so the final oxygen concentration is determined, not only by the oxygen flow rate into the mask but also by the patient's minute volume. If the latter declines, the fractional concentration of inspired oxygen (FIO2) increases. In those patients dependent on hypoxic drive with chronic CO2 retention, too high an initial FIO2 may be achieved, leading to hyperoxia, hypoventilation and a further rise in FIO2 as the minute volume falls. The ensuing increase in PaCO2 may be sufficient to render the patient unconscious.
For this reason, low flow devices are reserved for those patients in whom a precise knowledge of inspired oxygen concentration is unnecessary e.g. postoperative recovery. In the average adult, a flow of 4 l min into the mask results in an FIO2 of approximately 0.4.
Air entrainment devices: in patients dependent on hypoxic drive to ventilation a more precise concentration of oxygen is needed to prevent hyperoxia and respiratory depression. This mask (e.g. Vickers Ventimask) using a 'constant pressure jet mixing' mechanism which ensures entrainment of a large flow (30-40 lpm) of room air through side holes by a small but constant flow of oxygen (3 to 8 lpm). Low flows of oxygen entrain air to a concentration of about 24% whilst higher flows allow the oxygen concentration to reach over 50% (Figure 12.2 c). However, as the oxygen 'enriched' air always exceeds the patients maximum inspiratory flow and minute volume a known, fixed FIO2 can be delivered (usually 0.24, 0.28 or 0.35).
Figure 12.2 Types of oxygen mask (a) Mary Catterall or Hudson (b) Vickers Ventimask
Although essential to life, prolonged increases in PIO2 above normal may result in toxicity. This is particularly seen in the premature neonate as retinopathy of prematurity and in the older patient as pulmonary oxygen toxicity.
Pulmonary oxygen toxicity
Oxygen radicals are utilised by the body's defence systems, particularly the polymorphs, for killing harmful microorganisms. This involves the production of free superoxide radicals (O2 + electron) which are then broken down to hydrogen peroxide by superoxide dismutases, and thence by catalases to oxygen and water. There is evidence that excess oxygen pressures increase superoxide formation and decrease its breakdown by inhibition of superoxide dismutase.
Excess free radicals are normally rendered harmless by scavenging compounds which contain -SH groups. The latter are also affected by high oxygen concentrations which leave the free radicals able to attack cell membrane phospholipids producing lipid peroxidation. This occurs primarily in the lung, presumably as it faces the highest partial pressures. Capillary endothelial damage results, and this leads to interstitial fluid accumulation and reduced compliance with consequent pulmonary failure. PIO2 should always be kept below about 40 kPa (300 mmHg, FIO2 0.4) to reduce the likelihood of this occurring.