What is the Oxygen Cascade?

The oxygen cascade describes the process of declining oxygen tension from atmosphere to mitochondria.

The purpose of the cardio-respiratory system is to extract oxygen from the atmosphere and deliver it to the mitochondria of cells. Oxygen, being a gas, exerts a partial pressure, which is determined by the prevailing environmental pressure. At sea level, the atmospheric pressure is 760mmHg, and oxygen makes up 21% (20.094% to be exact) of inspired air: so oxygen exerts a partial pressure of 760 x 0.21 = 159mmHg. This is the starting point of the oxygen cascade, as one moves down through the body to the cell, oxygen is diluted down, extracted or otherwise lost, so that at cellular level the PO2 may only be 3 or 4mmHg.

The first obstacle that oxygen encounters is water vapor, which humifies inspired air, and dilutes the amount of oxygen, by reducing the partial pressure by the saturated vapor pressure (47mmHg). This will, obviously, affect the PIO2 (the partial pressure of inspired oxygen), which is recalculated as: (760 - 47) x 0.2094 = 149mmHg.

Air consists of oxygen and nitrogen, but as gas moves into the alveoli, a third gas, carbon dioxide, is present. The alveolar carbon dioxide level, the PACO2, is usually the same as the PaCO2, which can be measured by a blood gas analyzer. The alveolar partial pressure of oxygen PAO2 can be calculated from the following equation: PAO2 = PIO2 – PaCO2/R. R is the respiratory quotient, which represents the amount of carbon dioxide excreted for the amount of oxygen utilized, and this in turn depends on the carbon content of food (carbohydrates high, fat low). For now let us assume that the respiratory quotient is 0.8, the PAO2 will then be 149 – (40/0.8) = 100mmHg (approx).

The next step is the movement of oxygen from alveolus to artery, and as you would expect, there is a significant gradient, usually 5 –10 mmHg, explained by small ventilation perfusion abnormalities, the diffusion gradient and physiologic shunt (from the bronchial arteries).

Oxygen is progressively extracted thru the capillary network, such that the partial pressure of oxygen in mixed venous blood, PVO2, is approx 47mmHg.

What is essential to understand about the oxygen cascade is that if there is any interference to the delivery of oxygen at any point in the cascade, significant injury can occur downstream. The most graphic example of this is ascension to altitude. At 19,000 feet (just above base camp at Mount Everest, the barometric pressure is half that at sea level, and thus, even though the FiO2 is 21%, the PIO2 is only 70mmHg, half that at sea level. Conversely, if the barometric pressure is increased, such as in hyperbaric chambers, the PIO2 will actually be higher.

Four factors influence transmission of oxygen from the alveoli to the capillaries 1. Ventilation perfusion mismatch, 2. Right to left shunt, 3. Diffusion defects, 4. Cardiac output.

The amount of oxygen in the bloodstream is determined by the oxygen carrying capacity, the serum hemoglobin level, the percentage of this hemoglobin saturated with oxygen, the cardiac output and the amount of oxygen dissolved (see below).

The PVO2 is determined by whole body oxygen demand, and the capacity of the tissues to extract oxygen. In sepsis there appears to be a fundamental abnormality of

tissue oxygen extraction. How much oxygen is in the blood?

The amount of oxygen in the blood is calculated using the formula: [1.34 x Hb x (SaO2/100)] + 0.003 x PO2 = 20.8ml

Oxygen is carried in the blood in two forms: dissolved and bound to hemoglobin. Dissolved oxygen obeys Henry’s law – the amount of oxygen dissolved is proportional to the partial pressure. For each mmHg of PO2 there is 0.003 ml O2/dl (100ml of blood). If this was the only source of oxygen, then with a normal cardiac output of 5L/min, oxygen delivery would only be 15 ml/min. Tissue O2 requirements at rest are somewhere in the region of 250ml/min, so this source, at normal atmospheric pressure, is inadequate.

Hemoglobin is the main carrier of oxygen. Each gram of hemoglobin can carry 1.34ml of oxygen. This means that with a hemoglobin concentration of 15g/dl, the O2 content is approximately 20ml/100ml. With a normal cardiac output of 5l/min, the delivery of oxygen to the tissues at rest is approximately 1000 ml/min: a huge physiologic reserve.

Hemoglobin has 4 binding sites for oxygen, and if all of these in each hemoglobin molecule were to be occupied, then the oxygen capacity would be filled or saturated. This is rarely the case: under normal conditions, the hemoglobin is 97% to 98% saturated. The amount of oxygen in the blood is thus related to the oxygen saturation of hemoglobin.

Taking all of these factors into account, we can calculate the oxygen content of blood where the PO2 is 100mmHg, and the hemoglobin concentration is 15g/L:

[1.34 x Hb x (saturation/100)] + 0.003 x PO2 = 20.8ml

As one would expect, this figure changes mostly with the hemoglobin concentration: when the patient is anemic the oxygen content falls, when polycytemic, it rises. In either case the O2 saturation of hemoglobin may be 97 – 100%, but there may be a large

discrepancy in content.             

How much oxygen is delivered to the tissues per minute?

The delivery of oxygen to the tissues per minute is calculated from: DO2 = [1.39 x Hb x SaO2 + (0.003 x PaO2)] x Q

The following is the single most commonly quoted equation in critical care, and it’s worth remembering:

DO2 = [1.39 x Hb x SaO2 + (0.003 x PaO2)] x Q

The Delivery of oxygen (DO2) to the tissues is determined by:

The amount of oxygen in the blood: the oxygen binding capacity of haemoglobin x the concentration of haemoglobin x the saturation of haemoglobin + the amount of dissolved oxygen all Multiplied by the Cardiac Output (Q).

The cardiac output is determined by preload, afterload and contractility.

The hemoglobin concentration  is determined by production, destruction and loss.

The SaO2 (the saturation of haemoglobin at arterial level with oxygen - as opposed to the SpO2

which is measured by pulse oximetery) is determined by:

The oxygen saturation curve: which equates PaO2 (arterial oxygen tension) against SaO2.

So if a patient has a hemoglobin of 15g/l, a cardiac output of 5L, a PaO2 of 100 and a SaO2 of 100%, what is his oxygen delivery?

DO2 = [1.39 x 15 x 100 + (0.003 x PaO2)] x Q = 1000 ml

           

How much oxygen is extracted per minute?

Tissue oxygen extraction is calculated by subtracting mixed venous oxygen content from arterial oxygen content.

The Fick equation is used to calculate the VO2, the oxygen consumption. This is computed by figuring out how much oxygen has been lost between the arterial side and the venous side of the circulation and multiplying the result by the cardiac output. In the following equation, VO2 is the oxygen consumption per minute, CaO2 is the content of oxygen in arterial blood, and CvO2 is the content of oxygen in venous blood:

VO2 = Q x (CaO2-CvO2) mlO2/min

The CnO2 is (1.34 x Hb x SnO2/100) + 0.003 x PnO2, where n = a or v

The major difference between the two is obviously the hemoglobin saturation, which is roughly 100% on the arterial side and 75% on the venous side.

Substituting inwards, where hemoglobin is 15g/dl: CaO2 is approx 20ml/100ml, CvO2 is 15ml/100ml: the difference is 5ml/100ml = 50 ml/l multiplied by a cardiac output of 5L = O2 consumption per minute is 250ml.

So the mixed venous O2 saturation can be used to calculate the oxygen consumption: if SvO2 is decreasing, the O2 consumption is increasing.

What is the oxyhemoglobin dissociation curve and why is it important?

The Oxyhemoglobin dissociation curve describes the non-linear tendency for oxygen to bind to hemoglobin: below a SaO2 of 90%, small differences in hemoglobin saturation reflect large changes in PaO2

The oxyhemoglobin dissociation curve mathematically equates the percentage saturation of hemoglobin to the partial pressure of oxygen in the blood. The strange sigmoid shape of the curve relates to peculiar properties of the hemoglobin molecule itself:

Hemoglobin and oxygen act a little like parents and children. When all are living at home (i.e. hemoglobin is fully saturated) then the parents don’t want any to leave: but once one has flown the nest (i.e. dissociated from hemoglobin) – parents find it progressively easier to let go. What this means that the conformation of the hemoglobin molecule depends on the number of molecules bound: as one molecule of oxygen becomes unbound, the affinity for the others falls [and vice-versa]. This is represented by the oxyhemoglobin dissociation curve.

The lack of linearity of the curve makes interpretation of the oxygen content of blood difficult. At higher saturation levels, above 90%, the curve is flat, but below this level the PaO2 declines sharply, such that at 75% saturation the PaO2 is about 47mmHg (mixed venous blood), at 50% saturation the PaO2 is 26.6mmHg, and at 25% saturation the PaO2 is a miserable 15mmHg.

 

The oxyhemoglobin dissociation curveCLICK ON THUMBNAIL TO VIEW IMAGE

The position of this curve may shift rightwards (lower saturation for given PaO2) or leftwards (higher saturation for a given PaO2). Certain circumstances make the blood more likely to dump oxygen into the tissues, and others make it more likely to cling on to oxygen. Active muscle needs more oxygen, so heat, exercise, acidosis, hypercarbia and increased 2,3-DPG all cause a shift in the curve rightwards – releasing oxygen. Conversely, when activity is minimal – such as in cold weather or during rest, when the tissues are cold, alkalotic, hypocarbic and low 2,3-DPG, then hemoglobin holds onto oxygen. The curve also shifts leftwards in carbon monoxide poisoning.

The oxygen dissociation curve is an essential component in understanding critical care medicine. Everything we do is about optimizing the delivery of blood to the tissues as a means of maintaining homeostasis and promoting healing, and in the end it is the oxygen content of blood that is more important than the partial pressure of oxygen (which we commonly measure). The oxygen content relates specifically to the amount of hemoglobin present and how saturated it is. A reduction in the hemoglobin concentration from 15 to 10g/dl reduces the arterial oxygen content (CaO2) by as much as a reduction in PaO2 from 100mmHg to 40mmHg. Moreover a small drop in SaO2 may represent a large drop in PaO2, due to the shape of the oxyhemoglobin dissociation curve: when hemoglobin is 50% saturated the PaO2 is 28mmHg, at 75% the PaO2 is about 40mmHg (mixed venous blood).

Although many pages of critical care textbooks are often devoted to discussions about oxygen delivery, there is no clear indication what the optimal hemoglobin actually is. We know from the TRICC (transfusion requirements in critical care) study (1) that transfusing patients with blood above a hemoglobin of 7.0g is probably harmful. This probably relates to problems associated with the actual process of storing and transfusing products, than the effect of a “normal” hemoglobin itself. The availability of therapeutic erythropoietin has allowed intensivists induce red cell production, and replace blood mass without external transfusion.

In any case, there is a large physiologic reserve between oxygen delivery and oxygen consumption.  The cardiac output is probably a bigger player in the delivery of O2 to the tissues that the O2 content. This is because the cardiac output can almost instantaneously respond to a fall in PaO2 saturation of Hb. Moderate hypoxemia leads to an increase in the cardiac output and a reduction in peripheral vascular resistance. On the other hand, compensation for a fall in cardiac output is slow and weak – that is because it takes time to increase Hb production and the oxyhemoglobin dissociation curve is flat – it can’t become anymore saturated. Nevertheless, in the clinical setting, it is often easier to increase the Hb or the FiO2 than to increase the cardiac output

Reference

   (1)    Hebert PC. Transfusion requirements in critical care (TRICC): a multicentre, randomized, controlled clinical study. Transfusion Requirements in Critical Care Investigators and the Canadian Critical care Trials Group. Br J Anaesth 1998; 81

Suppl 1:25-33. What problems are associated with right to left shunting?

Right to left shunting causes hypoxemia resistant to oxygen therapy.

When blood passes through the lungs without coming in contact with air, a right to left shunt exists. This deoxygenated blood mixes with well oxygenated blood on the far side of the lung, and reduces the percentage saturation of hemoglobin. In all individuals a small physiologic shunt is present, principally arising from blood in the bronchial circulation. This has little effect on blood oxygen content. Larger shunts may cause significant problems, however. The reason for this is the curious shape of the oxyhemoglobin dissociation curve, as you can see from the diagram below:

The effect of shunt on the oxyhemoglobin dissociation curveCLICK ON THUMBNAIL TO VIEW IMAGE

The addition of mixed venous blood, slides the patient down the curve to the steep slope, where severe hypoxemia may result. Shunt classically does not respond to oxygen, although the administration of 100% oxygen may increase the dissolved oxygen content and increase the mixed venous oxygen saturation. The higher the SVO2, the less damaging a shunt is. The PaCO2 is usually normal, as the patient increases minute ventilation to blow off CO2 derived from the shunt, due to activation of chemoreceptors.

The shunt equation is used to calculate the magnitude of a shunt:

Qs/Qt  =  CcO2 – CaO2/CcO2 – CvO2 where CcO2 is the capillary oxygen content in the ideal capillary, CaO2 is the arterial oxygen content, and CvO2 is the mixed venous oxygen content. The content is calculated by using the equation discussed above: CnO2

is (1.34 x Hb x SnO2/100) + 0.003 x PnO2, where n = a or v or c. The PO2 is derived from the alveolar gas equation.

As one would expect, the greater the magnitude of the shunt, the larger the PAO2 – PaO2 difference.

A 17 year old male presents to the emergency room after being stabbed in the chest, on chest x-ray his right lung was fully collapsed, and yet his SpO2 was 94% on room air - why?

A 17 year old male presents to the emergency room after being stabbed in the chest, on chest x-ray his right lung was fully collapsed, and yet his SpO2 was

94% on room air - why?

What is hypoxic pulmonary vasoconstriction?

Hypoxic Pulmonary Vasoconstriction is a physiologic protective mechanism which prevents right to left shunting of blood.

Right to left shunt causes hypoxemia unresponsive to oxygen therapy

One would expect that this patient would have a 50% shunt due to perfusion but no ventilation of the right lung; this does not happen. Hypoxic pulmonary vasoconstriction (HPV) takes place. Many of the tissues in the body are capable of regulating their own blood flow – the heart, the kidney, the brain and the gut all autoregulate blood flow. It appears that HVP is a similar mechanism within the lung, to prevent right to left intrapulmonary shunting, and thus the presence of deoxygenated blood in the peripheral circulation. This process is most florid in utero, when blood is diverted away from the lungs through the ductus arteriosis, due to high pulmonary arterial pressures. We know that pulmonary smooth muscle cells are extremely sensitive to alveolar oxygen tensions, but the mechanism of vasoconstriction is unknown. HPV is probably multifactorial in origin and modulated by a variety of endothelium dependent factors (nitric oxide, endothelin, prostacyclin etc).

Certain pharmacological interventions and disease processes interfere with HPV: general anesthesia with volatile agents such as isoflurane, and the use of systemic vasodilators such as sodium nitroprusside and prostacyclin, reverse HPV and may cause ventilation-perfusion mismatch. Acute lung injuries and, in particular, lung contusions, may have a similar effect. The result is ventilation-perfusion mismatch and possible right to left shunting of deoxygenated blood. The treatment is recruitment of collapsed alveoli using continuous positive airway pressure (CPAP), and positioning the patient away from the injury side (good side down, always).

What are the effects of diffusion defects and ventilation-perfusion mismatches on arterial oxygenation?

Diffusion defects and ventilation perfusion mismatches cause hypoxemia, responsive to exogenous oxygen and positive pressure ventilation.

Oxygen diffuses from the alveoli to the pulmonary capillaries along a partial pressure gradient – there is less oxygen in the blood, the higher the inspired concentration of oxygen, the more rapidly the gases diffuse. For most individuals, an equilibrium position occurs early in inspiration, when the arterial blood becomes fully saturated with oxygen, and the rate of uptake of oxygen depends on capillary blood flow.

The diffusion capacity depends on the thickness of the alveolar wall, the area available for gas exchange and the partial pressure difference between the two sides. If the thickness of the wall increases – such as in pulmonary fibrosis, chronically, or pulmonary edema, acutely, the diffusion capacity is lower. Moreover, with increasing heart rate, the time for equilibration may be shorted, and the patient may become hypoxemic. The treatment is to increase the partial pressure gradient for oxygen by administering exogenous oxygen to the patient. If the patient has pulmonary edema, the surface area may be increased by increasing the transalveolar pressure (and

marginalizing fluid), through administration of continuous positive airway pressure (CPAP).

Ventilation perfusion mismatch occurs along a spectrum: on one end alveoli are ventilated but not perfused (pure dead space ventilation), and on the other end alveoli are perfused but not ventilated (pure shunt). The best ventilation perfusion (V/Q) ratios occur in dependent regions of the lung, due to the preferential effect of gravity on both ventilation and perfusion. The non dependent regions are relatively better ventilated than perfused (alveolar dead space). Extensive ventilation perfusion mismatch occurs due to lung injuries, whether due to consolidation (filling alveoli with exudates), perioperative atelectasis, or “acute lung injury” where there is alveolar edema and capillary microthrombosis. Hypoxemia due to ventilation-perfusion mismatch can usually be reversed with application of supplemental oxygen. Where there is extensive atelectasis due to gas absorption (see below) or mucus plugging, the treatment is oxygen, bronchial toilet and perhaps CPAP, to recruit collapsed airways. Stiff lungs (low compliance) may induce an overwhelming workload to breathing, and additional inspiratory support may be required to reduce workload and improve V/Q matching.

           

What is “absorption atelectasis”?

Absorption atelectasis refers to the tendency for airways to collapse if proximally obstructed. Alveolar gases are reabsorbed; this process is accelerated by nitrogen washout techniques.

Oxygen shares alveolar space with other gases, principally Nitrogen. Nitrogen is poorly soluble in plasma, and thus remains in high concentration in alveolar gas. If the proximal airways are obstructed, for example by mucus plugs, the gases in the alveoli gradually empty into the blood along the concentration gradient, and are not replenished: the alveoli collapse, a process known as atelectasis. This is limited by the sluggish diffusion of Nitrogen. If nitrogen is replaced by another gas, that is if it is actively “washed out” of the lung by either breathing high concentrations of oxygen, or combining oxygen with more soluble nitrous oxide in anesthesia, the process of absorption atelectasis is accelerated. It is important to realize that alveoli in dependent regions, with low V/Q ratios, are particularly vulnerable to collapse.

           

What is pathological supply dependence on oxygen?

The mixed venous oxygen saturation is a measurement of oxygen consumption, made using a pulmonary artery catheter (the measurements are made from the pulmonary artery, and are thus accurate). The SvO2 (mixed venous oxygen saturation) is proportional to SaO2 – VO2/Q x Hb (VO2 is the venous oxygen content).

 

This diagram describes oxygen delivery (DO2) and consumption (VO2) in normal and pathological states.

We know that we can go from being completely sedentary to taking high impact exercise without developing tissue hypoxia. This is because we have a physiologic reserve. Under normal conditions, during exercise, if oxygen demand is increased, supply is increased also – by increasing minute ventilation and cardiac output. But what happens if, for example, oxygen delivery starts to fall off (e.g. in a patient who has progressively worsening respiratory or cardiovascular function)? What actually happens, in normal people, is that we compensate for this lower O2 delivery by making use of our physiologic reserve, we redistribute blood preferentially to the tissues that need them and the amount of oxygen extracted (extraction ratio) increases. Eventually reserve runs out and a critical point (point A on the diagram above) is reached: there just isn’t enough O2 to match supply, and anaerobic glycolysis takes place.

This is known as “physiological dependence of VO2 on DO2”, and can be measured by an increase in arterial lactate concentration.

This plateau in VO2 is maintained by increasing the extraction ratio for oxygen (O2ER). Blood flow is redistributed to match local demand for oxygen. The meditors for this process are multiple, the most important of which are the autonomic nervous system and nitric oxide. The critical O2ER is the point where anaerobic glycolysis takes place. The critical DO2 in health is about 7 to 10ml/kg/min.

In pathological circumstances, such as systemic sepsis, this whole protective system falls apart: in diseases that affect the microcirculation, there is a loss of O2 extraction capacity. There is a school of thought that believes that DO2 needs to be maintained at a higher level that in health, as the tissues are less able to efficiently extract O2 (1;2) . There is a higher critical DO2 (to 12ml/kg/min) and pathological dependence of VO2 on DO2. A hypothesis was formed that by increasing the DO2 (supernormalization) by increasing cardiac output and oxygen carriage in sepsis, then oxygen extraction would improve. Randomized controlled trials have been disappointing. We now believe that the inability to extract oxygen occurs on the demand side, due to microcirculatory abnormalities, rather that overall oxygen delivery.

References

   (1)    Appel PL, Shoemaker WC. Relationship of oxygen consumption and oxygen delivery in surgical patients with ARDS. Chest 1992; 102(3):906-911.

   (2)    Shoemaker WC, Appel PL, Kram HB. Role of oxygen debt in the development of organ failure sepsis, and death in high-risk surgical patients. Chest 1992; 102(1):208-215.

 How much oxygen do I give?

The objective of oxygen therapy is to give the patient as much oxygen as is required to return the PaO2 to what is normal for the particular patient.

There is no secret to this – you give as much oxygen as is required to return the PaO2 to what is normal for the particular patient. You perform a therapeutic maneuver – giving Oxygen, and you measure the result, by performing serial blood gases. There is nothing to be gained by giving too much oxygen, and a huge amount to be lost by not giving enough.

The initial inspired concentration of oxygen depends on the clinical circumstances – if the patient is only mildly hypoxemic, saturating in the late 80s, then small amounts of supplemental oxygen given by nasal cannulae are all that is necessary. However, if the patient is in-extremis, then always start with 100% (or thereabouts) and work downwards.

 Shouldn’t I be careful about the amount of oxygen that I give COPD patients?

There is a universal misnomer that if you give too much oxygen to patients with COPD that they stop breathing, and hence medical and nursing students are often taught that COPD patients should not be given more than 28% oxygen because their respiratory drive is oxygen dependent (due to chronic CO2 retention) and they will lose their stimulus to breath. Physicians will cite rising CO2 levels in patients treated with oxygen as evidence of this.

There is a fundamental flaw in this theory: throughout this tutorial we have discussed the mechanisms by which oxygen is prevented from entering the blood. It is the blood oxygen content that is important, not the inspired fraction. Patients, depending on the extent of disease, will have differing extents of ventilation-perfusion mismatch and diffusion defects: the patient needs enough inspired oxygen to return the PaO2 to what is normal for them, and the way to establish this is by starting high and working downwards with serial blood gases.

We know that high CO2 levels are well tolerated by the body, but hypoxia is not: withholding oxygen therapy for fear of hypercarbia is negligent. It is not clear that such hypercarbia results, in any case, from hypoventilation: a number of studies (1;2)  have demonstrated that the increase in PaCO2 after administration of oxygen is due mainly to an increase in the ratio of dead space to tidal volume (Vd/Vt). This is probably due to reversal of hypoxic pulmonary vasoconstriction. Moreover, the increase in oxygenated hemoglobin leads to an increase in CO2 release by way of the Haldane effect.

References

   (1)    Crossley DJ, McGuire GP, Barrow PM, Houston PL. Influence of inspired oxygen concentration on deadspace, respiratory drive, and PaCO2 in intubated patients with chronic obstructive pulmonary disease. Crit Care Med 1997; 25(9):1522-1526.

   (2)    Sassoon CS, Hassell KT, Mahutte CK. Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1987; 135(4):907-911.

How do I administer Oxygen? Oxygen is given thru fixed and variable performance devices. Fixed performance devices deliver a flow of oxygen equal to or in excess of

peak inspiratory flow Variable performance devices use the deadspace of the nasopharynx or

face masks as a reservoir of oxygen. They cannot deliver high inspired concentrations of oxygen.

Oxygen can be delivered to the upper airway by a variety of devices, in this section we will address only the non invasive methods. There are two types of devices – variable performance devices and fixed perfomance devices. The differentiation is based on the difference between the delivered concentration of oxygen FDO2 and the actual inspired concentration FiO2. Performance is based on matching the flow rate of gas leaving the device with the inspiratory flow rate entering the patient.

Take a deep breath in: you have probably just inspired 1 liter of air in about 1 second. Your inspiratory flow rate is thus approximately 60 liters per minute during this deep breath. Every breath you take varies in depth and volume, but if you were in respiratory failure you may well require flow rates of this magnitude (or more). To be guaranteed a FiO2 appropriate to your flow demand, a fixed performance flow-generating device must be placed at your airway with a flow rate of 60 or so liters of oxygen-air (mixed as required) to satisfy demand. To be a fixed performance device, the gas flow must exceed the patient’s peak inspiratory flow. Machines with this type of performance are expensive, and are usually only located in intensive care or high dependency units. Moreover, not all patients requiring supplemental oxygen require facemasks, which are unpleasant to wear.

Variable performance devices fit into two categories, nasal cannula and facemasks. The premise behind nasal cannula is to use the dead space of the nasopharynx as a reservoir for oxygen. When the patient inspires, entrained air mixes with the reservoir air and the inspired gas is enriched. Obviously, the FIO2 depends on the magnitude of flow of oxygen, the patient’s minute ventilation and peak flow. For most patients, each addition 1litre per minute of O2 flow with nasal cannula represents an increase in the FIO2 by 4%. So 1 liter is 24%, 2 liters is 28% and so on. At 6 liters (44%), it is not possible to raise the FIO2 further, due to turbulence, in the tubing and in the airway.

There are a couple of problems with nasal cannula: if they are not positioned at the nares, they are useless. Disorientated patients appear to be remarkably successful at dislodging cannula. Secondly, the effectiveness may be disrupted by the pattern of breathing: there appears to be little difference whether the patient is a mouth or a nose breather, but it is preferable if the patient exhales through his/her mouth rather than nose, so the reservoir is maintained.

The big advantage of nasal cannula is comfort for the patient – they can eat and speak easily while receiving oxygen.

Standard oxygen masks provide a reservoir for oxygen, but the FIO2 is difficult to calculate unless calibrated Venturi devices are attached. With Venturis, there are slits in the oxygen delivery system which become smaller or larger depending whether a high or low FIO2 is required. The rate of delivery of oxygen is calibrated for the size of the Venturi and amount of mixing therein. For example, a 60% oxygen Venturi requires 15L/min fresh gas flow. Standard masks struggle to provide an FIO2 of greater than 60%. A non rebreather reservoir bag can be attached to the facemask, to provide a larger reservoir (the bag fills when the patient is not actively inspiring), the two liter capacity should, in theory at least, allow the patient to inspire 100% oxygen.

What is Hyperbaric Oxygen therapy? Hyperbaric oxygen therapy is used to increase the amount of oxygen

dissolved in the plasma, by increasing the ambient pressure.

At normal atmospheric pressure, the amount of oxygen dissolved in the blood is so low, that we don’t even bother to quantify it. However, increasing the environmental pressure, using a hyperbaric chamber, increases the solubility of oxygen in the blood. If 100% oxygen is inspired at 3 atmospheres, the inspired PO2 is over 2000mmHg, and this should increase the volume of oxygen in solution in the blood to approximately 6ml/100ml of blood. The normal A-V oxygen difference is 5ml/100ml. Increases in tissue oxygen tensions, however, vary widely – depending on local perfusion and metabolic conditions. The high pressure increases the solubility of other gases, principally nitrogen, which can come out of solution in rapid diving ascents (the bends) and embolize to tissues; a similar problem can occur with air embolism. Hyperbaric treatment reduces bubble size and improves oxygen delivery to tissues. In addition, anerobic bacteria which infect poorly perfused tissue should be terminally sensitive to increased tissue oxygen concentration, and hyperbaric oxygen (HBO) treatment is thus potentially bactericidal to clostridial and other anerobic species.

Diseases for which hyperbaric oxygen therapy is indicated (1):

Arterial gas embolism Decompression sickness (the bends) Severe carbon monoxide poisoning

Osteoradionecrosis Clostridial myonecrosis

References

   (1)    Moon RE, Camporesi EM. Hyperbaric oxygen therapy: from the nineteenth to the twenty-first century. Respir Care Clin N Am 1999; 5(1):1-5.

What is Carbon Monoxide Poisoning? Carbon monoxide causes tissue ischemia by avidly binding to hemoglobin

and displacing oxygen. The treatment is 100% oxygen, and possibly HBO therapy.

Carbon monoxide (CO) binds to hemoglobin approximately 200 times more avidly than oxygen. This results in impaired oxygen transport and utilization (the oxyhemogloblin dissociation curve shifts leftwards). Conventional pulse oximetery overestimates the true saturation of hemoglobin with oxygen, and, in addition to reduced oxygen delivery to tissues, CO binds to cellular proteins and causes tissue hypoxemia.

Carbon monoxide poisoning causes cell and tissue ischemia, and can prove fatal. It has been established that breathing 100% oxygen considerably reduces the half time of COHb (carboxyhemoglobin) binding. If oxygen is delivered in a hyperbaric environment, this half time is reduced further (1). In patients with moderate to severe CO poisoning, hyperbaric oxygen may reduce late neurological sequelae as compared to normobaric oxygen (2). Although there is no compelling data to support the use of HBO in this group of patients, if facilities are available HBO should be strongly considered if the COHb is greater than 25%, there is a history of neurological impairment or the patient has evidence of cardiac abnormalities (ischemia, arrhythmias etc) (3).

References

   (1)    Moon RE, DeLong E. Hyperbaric oxygen for carbon monoxide poisoning. Med J Aust 1999; 170(5):197-199.

   (2)    Thom SR, Taber RL, Mendiguren II, Clark JM, Hardy KR, Fisher AB. Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995; 25(4):474-480.

   (3)    Piantadosi CA. The role of hyperbaric oxygen in carbon monoxide, cyanide and sulfide intoxication. Probl Respir Care 1991; 4:215-231.

Why is Oxygen considered toxic?

High inspired oxygen concentrations cause toxicity by causing formation of oxygen free radicals (which damage tissues), and by causing absorption atelectasis and V/Q mismatch.

The issue of oxygen toxicity has been topical for a generation, following the discovery that therapeutic oxygen causes blindness in premature babies (retrolental fibroplasias) with respiratory distress syndrome. In addition, it has been established that high inspired concentrations of oxygen may cause acute lung injury, probably due to oxygen free radical production – superoxide, hydroxyl, hydrogen peroxide and singlet O2 molecules. These agents damage biomolecules such as membrane lipids, enzymes and nucleic acids. The extent of injury appears to depend on 1. The FiO2, 2. The duration of exposure, 3. The barometric pressure under which exposure occurred. It appears that the critical FiO2 for toxicity is around 50% (1), above which lung recruitment maneuvers should be condidered (CPAP).

High concentrations of inspired oxygen may cause absorption atelectasis. In addition high FiO2 may cause increased peripheral vascular resistance in congestive heart failure leading to reduced cardiac output.

How much oxygen is safe is a moot point. It is more important that you do not withhold life saving oxygen therapy than to be concerned about oxygen toxicity. It is, nonetheless, important that FiO2 is minimized to normalization of blood gas in intensive care patients: i.e. there is little to be gained in having a PaO2 of greater than 100mmHg. Often elevated oxygen requirements can be compensated for by appropriate patient positioning and increasing mean airway pressures to improve matching of ventilation and perfusion.

References

   (1)    Register SD, Downs JB, Stock MC, Kirby RR. Is 50% oxygen harmful? Crit Care Med 1987; 15(6):598-601.

How do Pulse Oximeters work?

Pulse oximeters measure the absorption of red and infrared light by pulsatile blood. They are inexpensive, continuous and portable. Accuracy declines below a SpO2 of 90%.

Oxygenated blood absorbs light at 660nm (red light), whereas deoxygenated blood absorbs light preferentially at 940nm (infra-red). Pulse oximeters consist of two light emitting diodes, at 600nm and 940nm, and two light collecting sensors, which measure the amount of red and infra-red light emerging from tissues traversed by the light rays. The relative absorption of light by oxyhemoglobin (HbO) and deoxyhemoglobin is processed by the device and an oxygen saturation level is reported. The device directs its attention at pulsatile arterial blood and ignores local noise from the tissues. The result is a continuous qualitative measurement of the patients oxyhemoglobin status.

Oximeters deliver data about pulse rate, oxygen saturation (SpO2) and even cardiac output. They are, however, far from perfect monitors.

The use of pulse oximeters is limited by a number of factors: they are set up to measure oxygenated and deoxygenated haemoglobin, but no provision is made for measurement error in the presence of dyshemoglobin moieties – such as carboxyhemoglobin (COHb) and methemoglobinemia. COHb absorbs red light as well as HbO, and saturation levels are grossly over-represented. Arterial gas analysis or use of co-oximetery is essential in this situation. Co-oximeters measure reduced haemoglobin, HbO, COHb and methemoglobin. Abnormal movement, such as occurs with agitated patients, will cause interference with SpO2 measurement. Low blood flow, hypotension, vasoconstriction and hypothermia will reduce the pulsatility of capillary blood, and the pulse-oximeter will under-read or not read at all. Conversely, increased venous pulsation, such as occurs with tricuspid regurgitation, may be misread by the pulse-oximeter as arterial blood, with a low resultant reading. Finally, it is generally accepted that the percentage saturation is unreliably reported on the steep part of the oxyhemoglobin dissociation curve. While the trend between the SaO2 (arterial saturation) and SpO2 appears accurate, the correlation between the two numbers is not. Thus a drop in the SpO2 below 90% must be considered a significant clinical event.

In spite of these limitations, the pulse oximeter has emerged as the de-facto monitoring device in the operating room, patient transport and intensive care.

Clinical Scenario 1 Solution 

An 18 year old male is brought to the recovery room following an appendectomy. He has just been extubated. He is awake and breathing normally, but his SpO2 is 88%. You administer 60% oxygen, and after a few moments his SpO2 increases to 99%.

What has just happened?

This is a process known as diffusion hypoxia, which is not uncommon after anesthesia with nitrous oxide. This agent is floods back into the alveoli from the blood at termination of anesthesia, along the concentration gradient, and displaces oxygen. As the partial pressure of oxygen in the alveoli has fallen, so too has the tension of oxygen in the blood. The treatment is to increase the FiO2, which, according to the alveolar gas equation, will increase the PAO2. Patients who hypoventilate, such as those given opioids, have increased alveolar levels of CO2 and may require supplemental oxygen.

Scenario 2 Solution

A 59 year old female undergoes abdominal surgery. She is extubated and returned from the recovery room to the floor. She becomes moderately short of breath three hours later. The nurse

applies a pulse-oximeter. Her SpO2 is 89%. She treats the patient with 40% oxygen and calls you. When you arrive, the patient’s SpO2 is 94%.

What is the cause of this patient’s hypoxemia and what is your plan of management?

This patient has atelectasis, presumably in the dependent regions of her lungs, as a result of anesthesia and surgery. This is manifesting itself as ventilation-perfusion abnormalities. The treatment is supplemental oxygen, chest physical therapy, and mobilization.

CLICK HERE FOR MORE INFORMATION ABOUT VENTILATION PERFUSION RELATIONS

Scenario 3 Solution

You are called to the emergency room (ER). A 62 year old male with a history of chronic bronchitis has been admitted with a lower respiratory tract infection. The ER resident is requesting admission to intensive care for mechanical ventilation. On examination, the patient is tachypneic and cyanosed. His blood gas is pH 7.34 PCO2 54 PO2 45 HCO3 30 BE-2.

You request a piece of information, perform a therapeutic maneuver and 30 minutes later the patient’s blood gas is: pH 7.32 pCO2 60 PO2 55 HCO3 31 BE 0. The nurse wishes to reduce the FiO2.

What information did you look for? What therapeutic maneuver did you perform, and what do you plan to do about the last blood gas?

What you were interested in was the patient’s baseline blood gas (from a previous admission): it was pH 7.38 PCO2 55 PO2 55 HCO3 32. The patient is hypoxemic at baseline, and retains CO2.

You increased the FiO2 to 40%, and have returned the PaO2 to baseline for this patient.

The nurses concern about the blood gas is inappropriate: this relates to the widely held misconception that inspired oxygen tension should be minimized in COPD patients to prevent loss of respiratory drive. This is incorrect, even if there is some truth in the basic science (questionable), chemoreceptors respond to arterial oxygen tension, not what is given at the mouth. In this case, the patients PaO2 is normal for him, and he is receiving the appropriate amount of oxygen. The raised CO2 relates to ventilation-perfusion mismatch, resulting from the underlying acute injury, and release of hypoxic pulmonary vasoconstriction. The administration of oxygen may have increased the amount of dead space ventilation. In addition, raised PACO2 displaces O2 at alveolar level, requiring a higher FiO2.

Scenario 4 Solution

A 78 year old male is admitted with a six month history of shortness of breath, ankle edema, orthopnea, a productive cough, hoarseness and 30-40lb weight loss. He has a palpable mass in

his abdomen, which turns out to be colonic cancer. As part of his preoperative work up, a blood gas is performed: pH 7.42 PaCO2 36 PaO2 41 SaO2 78%. He is put on 100% oxygen, has a chest x-ray performed, which is normal, and a spiral CT of his thorax, which also appears normal. His blood gas on 100% oxygen is: pH 7.46, PaCO2 36, PaO2 42, SaO2 78%.

What do you think is wrong with this patient?

Hypoxemia refractory to oxygen therapy is a right to left shunt until otherwise proven. This patient underwent echocardiography which showed a markedly enlarged right ventricle with reduced right ventricular function; there was reduced global left ventricular function. On cardiac catheterization this patient had a patent foramen ovale, a right to left shunt (with Eisenmenger physiology), and equalization of pulmonary and systemic blood pressures. Of his 8 liter cardiac output, 6 litres were shunting right to left. He was unsuitable for surgery.

Key Points

1. The oxygen cascade describes the process of declining oxygen tension from atmosphere to mitochondria. 

2. The amount of oxygen in the blood is calculated using the formula: [1.34 x Hb x (SaO2/100)] + 0.003 x PO2 = 20.8ml 

3. The delivery of oxygen to the tissues per minute is calculated from: DO2 = [1.39 x Hb x SaO2 + (0.003 x PaO2)] x Q 

4. Tissue  oxygen extraction is calculated by subtracting mixed venous oxygen content from arterial oxygen content. 

5. The Oxyhemoglobin dissociation curve describes the non-linear tendency for oxygen to bind to hemoglobin: below a SaO2 of 90%, small differences in hemoglobin saturation reflect large changes in PaO2 Right to left shunting causes hypoxemia resistant to oxygen therapy. 

6. Hypoxic Pulmonary Vasoconstriction is a physiologic protective mechanism which prevents right to left shunting of blood. 

7. Right to left shunt causes hypoxemia unresponsive to oxygen therapy Diffusion defects and ventilation perfusion mismatches cause hypoxemia, responsive to exogenous oxygen and positive pressure ventilation. Absorption atelectasis refers to the tendency for airways to collapse if proximally obstructed, gases are reabsorbed, this process is accelerated by nitrogen washout techniques. 

8. The objective of oxygen therapy is to give the patient as much oxygen as is required to return the PaO2 to what is normal for the particular patient. 

9. Oxygen is given thru fixed and variable performance devices. 

10.Fixed performance devices deliver a flow of oxygen equal to or in excess of peak inspiratory flow 

11.Variable performance devices use the deadspace of the nasopharynx or face masks as a reservoir of oxygen. They cannot deliver high inspired concentrations of oxygen. 

12.Hyperbaric oxygen therapy is used to increase the amount of oxygen dissolved in the plasma, by increasing the ambient pressure Carbon monoxide causes tissue ischemia by avidly binding to hemoglobin and displacing oxygen. The treatment is 100% oxygen, and possibly HBO therapy. 

13.High inspired oxygen concentrations cause toxicity by causing formation of oxygen free radicals (which damage tissues), and by causing absorption atelectasis and V/Q mismatch. 

14. Pulse oximeters measure the absorption of red and infrared light by pulsatile

blood. They are inexpensive, continuous and portable. Accuracy declines below

a SpO2 of 90%.

Further Reading and Source Material 

1. Lumb, A.B. Nunn’s Applied Respiratory Physiology 5th ed, Butterworths, Oxford 2000

2. West, J.B. Pulmonary Physiology, the essentials 5th ed, Lippincott Williams and Wilkins, 1998

3. West, J.B. Pulmonary Pathophysiology, the essentials 6th ed, Lippincott Williams and Wilkins, 2000

References

(1)   Hebert PC. Transfusion requirements in critical care (TRICC): a multicentre, randomized, controlled clinical study. Transfusion Requirements in Critical Care Investigators and the Canadian Critical care Trials Group. Br J Anaesth 1998; 81 Suppl 1:25-33.

(2)   Appel PL, Shoemaker WC. Relationship of oxygen consumption and oxygen delivery in surgical patients with ARDS. Chest 1992; 102(3):906-911.

(3)   Shoemaker WC, Appel PL, Kram HB. Role of oxygen debt in the development of organ failure sepsis, and death in high-risk surgical patients. Chest 1992; 102(1):208-215.

(4)   Crossley DJ, McGuire GP, Barrow PM, Houston PL. Influence of inspired oxygen concentration on deadspace, respiratory drive, and PaCO2 in intubated patients with chronic obstructive pulmonary disease. Crit Care Med 1997; 25(9):1522-1526.

(5)   Sassoon CS, Hassell KT, Mahutte CK. Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1987; 135(4):907-911.

(6)   Moon RE, Camporesi EM. Hyperbaric oxygen therapy: from the nineteenth to the twenty-first century. Respir Care Clin N Am 1999; 5(1):1-5.

(7)   Moon RE, DeLong E. Hyperbaric oxygen for carbon monoxide poisoning. Med J Aust 1999; 170(5):197-199.

(8)   Thom SR, Taber RL, Mendiguren II, Clark JM, Hardy KR, Fisher AB. Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995; 25(4):474-480.

(9)   Piantadosi CA. The role of hyperbaric oxygen in carbon monoxide, cyanide and sulfide intoxication. Probl Respir Care 1991; 4:215-231.

(10) Register SD, Downs JB, Stock MC, Kirby RR. Is 50% oxygen harmful? Crit Care Med 1987; 15(6):598-601.

Introduction

In order to survive humans have to be able to extract oxygen from the atmosphere and transport it to their cells where it is utilised for essential metabolic processes. Some cells can produce energy without oxygen (anaerobic metabolism) for a short time, although it is inefficient. Other organs (e.g.brain) are made up of cells that can only make the energy necessary for survival in the presence of a continual supply of oxygen (aerobic metabolism). Tissues differ in their ability to withstand anoxia (lack of oxygen). The brain and the heart are the most sensitive. Initially a lack of oxygen affects organ function but with time irreversible damage is done (within minutes in the case of the brain) and revival is impossible.   

OXYGEN TRANSPORT FROM AIR TO TISSUES

Oxygen is transported from the air that we breathe to each cell in the body. In general, gases move from an area of high concentration (pressure) to areas of low concentration (pressure). If there are a mixture of gases in a container, the pressure of each gas (partial pressure) is equal to the pressure that each gas would produce if it occupied the container alone.    

Atmosphere to alveolus

The air (atmosphere) around us has a total pressure of 760 mmHg (1 atmosphere of pressure = 760mmHg = 101kPa = 15lbs/sq. in). Air is made up of 21% oxygen, 78% nitrogen and small quantities of CO2, argon and helium. The pressure exerted by the main two gases individually, when added together, equals the total surrounding pressure or atmospheric pressure. The pressure of oxygen (PO2) of dry air at sea level is therefore 159 mmHg (21/100 x 760=159). However by the time the inspired air reaches the trachea it has been warmed and humidified by the upper respiratory tract. The humidity is formed by water vapour which as a gas exerts a pressure. At 37oC the water vapour pressure in the trachea is 47 mmHg. Taking the water vapour pressure into account, the PO2 in the trachea when breathing air is (760-47) x 21/100 = 150 mmHg. By the time the oxygen has reached the alveoli the PO2 has fallen to about 100 mmHg. This is because the PO2 of the gas in the alveoli (PAO2) is a balance between two processes: the removal of oxygen by the pulmonary capillaries and its continual supply by alveolar ventilation (breathing).    

Alveolus to blood

Blood returning to the heart from the tissues has a low PO2 (40 mmHg) and travels to the lungs via the pulmonary arteries. The pulmonary arteries form pulmonary capillaries, which surround alveoli. Oxygen diffuses (moves through the membrane separating the air and the blood) from the high pressure in the alveoli (100 mmHg) to the area of lower pressure of the blood in the pulmonary capillaries (40 mmHg). After oxygenation blood moves into the pulmonary veins which return to the left side of the heart to be pumped to the systemic tissues. In a 'perfect lung' the PO2 of pulmonary venous blood would be equal to the PO2 in the alveolus. Three factors may cause the PO2 in the pulmonary veins to be less than the PAO2: ventilation/perfusion mismatch, shunt and slow diffusion.    

Ventilation/perfusion mismatch

In a 'perfect lung' all alveoli would receive an equal share of alveolar ventilation and the pulmonary capillaries that surround different alveoli would receive an equal share of cardiac output ie.ventilation and perfusion would be perfectly matched. Diseased lungs may have marked mismatch between ventilation and perfusion. Some alveoli are relatively overventilated while others are relatively overperfused (the most extreme form of this is shunt where blood flows past alveoli with no gas exchange taking place (figure 1). Well ventilated alveoli (high PO2 in capillary blood) cannot make up for the oxygen not transferred in the underventilated alveoli with a low PO2 in the capillary blood. This is because there is a maximum amount of oxygen which can combine with haemoglobin (see haemoglobin-oxygen dissociation curve figure 2a). The pulmonary venous blood (mixture of pulmonary capillary blood from all alveoli) will therefore have a lower PO2 than the PO2 in the alveoli (PAO2). Even normal lungs have some degree of ventilation/perfusion mismatch; the upper zones are relatively overventilated while the lower zones are relatively overperfused and underventilated.

Shunt occurs when deoxygenated venous blood from the body passes unventilated alveoli to enter the pulmonary veins and the systemic arterial system with an unchanged PO2 (40 mmHg). (Figure 1.) Atelectasis (collapsed alveoli), consolidation of the lung, pulmonary oedema or small airway closure (see later) will cause shunt.  

 

 

Diffusion

Oxygen diffuses from the alveolus to the capillary until the PO2 in the capillary is equal to that in the alveolus. This process is normally complete by the time the blood has passed about one third of the way along the pulmonary capillary. In the normal lung, the diffusion of oxygen into the blood is vary rapid and is complete, even if the cardiac output is increased (exercise) and the blood spends less time in contact with the alveolus. This may not happen when the alveolar capillary network is abnormal (pulmonary disease). However, the ability of the lung to compensate is great and problems caused by poor gas diffusion are a rare cause for hypoxia, except with diseases such as alveolar fibrosis. In order to decrease the detrimental effect that shunt and ventilation/perfusion mismatch have on oxygenation, the blood vessels in the lung are adapted to vasoconstrict and therefore reduce blood flow to areas which are underventilated. This is termed hypoxic pulmonary vasoconstriction and reduces the effect of shunt.    

Oxygen carriage by the blood

Oxygen is carried in the blood in two forms. Most is carried combined with haemoglobin (figure 2b) but there is a very small amount dissolved in the plasma. Each gram of haemoglobin can carry 1.31 ml of oxygen when it is fully saturated. Therefore every litre of blood with a Hb concentration of 15g/dl can carry about 200 mls of oxygen when fully saturated (occupied) with oxygen (PO2 >100 mmHg). At this PO2 only 3 ml of oxygen will dissolve in every litre of plasma.

 

If the PO2 of oxygen in arterial blood (PAO2) is increased significantly (by breathing 100% oxygen) then a small amount of extra oxygen will dissolve in the plasma (at a rate of 0.003 ml O2/100ml of blood /mmHg PO2) but there will normally be no significant increase in the amount carried by haemoglobin, which is already >95% saturated with oxygen. When considering the adequacy of oxygen delivery to the tissues, three factors need to be taken into account, haemoglobin concentration, cardiac output and oxygenation.  

  Oxygen cascade

Oxygen moves down the pressure or concentration gradient from a relatively high level in air, to the levels in the respiratory tract and then alveolar gas, the arterial blood, capillaries and finally the cell. The PO2 reaches the lowest level (4-20 mmHg) in the mitochondria (structures in cells responsible for energy production). This decrease in PO2 from air to the mitochondrion is known as the oxygen cascade and the size of any one step in the cascade may be increased under pathological circumstances and may result in hypoxia (figure 3).  

 

 

Oxygen delivery

The quantity of oxygen made available to the body in one minute is known as the oxygen delivery and is equal to the cardiac output x the arterial oxygen content (see previously) ie. 5000ml blood/min x 200 mlO2/1000 ml blood = 1000ml O2/min.

Oxygen delivery (mls O2/min) = Cardiac output (litres/min) x Hb concentration (g/litre) x 1.31 (mls O2/g Hb) x % saturation    

Oxygen consumption

Approximately 250 ml of oxygen are used every minute by a conscious resting person (oxygen consumption) and therefore about 25% of the arterial oxygen is used every minute. The haemoglobin in mixed venous blood is about 70% saturated (95% less 25%).

In general there is more oxygen delivered to the cells of the body than they actually use. When oxygen consumption is high (eg. during exercise) the increased oxygen requirement is usually provided by an increased cardiac output - see formula above for how this works. However, a low cardiac output, a low haemoglobin concentration (anaemia) or a low haemoglobin O2 saturation will result in an inadequate delivery of oxygen, unless a compensatory change occurs in one of the other factors. Alternatively, if oxygen delivery falls relative to oxygen consumption the tissues extract more oxygen from the haemoglobin (the saturation of mixed venous blood falls below 70%)(a-b in figure 4). A reduction below point 'c' in figure 4 cannot be compensated for by an increased oxygen extraction and results in anaerobic metabolism and lactic acidosis.  

 

OXYGEN STORES

In spite of the great importance of oxygen, the stores of oxygen in the body are small and would be unable to sustain life for more than a few minutes. If breathing ceases, oxygen stores are limited to the oxygen in the lung and in the blood. The amount of oxygen in the blood depends on the blood volume and haemoglobin concentration. The amount of oxygen in the lung is dependent on the lung volume at functional residual capacity (FRC) and the alveolar concentration of oxygen. The FRC is the volume of air (about 3 litres in an adult) that is present in the lungs at the end of a normal expiration ie when the elastic recoil of the lung is balanced by the relaxed chest wall and diaphragm. While breathing air the total stores (oxygen in blood and lung) are small and because the major component of this store is the oxygen bound to haemoglobin (see Table 1) only a small part of these stores can be released without an unacceptable reduction in PaO2 (when haemoglobin is 50% saturated with oxygen the PaO2 will have fallen to 26 mmHg). Breathing 100% oxygen causes a large increase in the total stores as the FRC fills with oxygen. The major component of the store is now in the lung and 80% of this oxygen can be used without any reduction in haemoglobin saturation (PAO2 still about 100mmHg). This is the reason why pre-oxygenation is so effective. (see later)  

Table 1. Principle stores of oxygen in the body

 While breathingAIR

While breathing100% O2

In the lungs (FRC) 450ml 3000ml

In the blood 850ml 950ml

Dissolved or bound in tissues(FRC) 250ml 300ml

Total 1550ml 4250ml 

OXYGEN TRANSPORT - THE EFFECTS OF ANAESTHESIA

Hypoventilation may occur during anaesthesia due to airway obstruction, the effects of volatile anaesthetic agents, opioids and other sedatives. In contrast, ketamine and ether anaesthesia (less than 1 MAC) cause less respiratory depression than other anaesthetic agents. Alveolar PO2 is a balance between the oxygen supplied by breathing and that used by metabolic processes in the body. Hypoventilation and a decreased inspired oxygen concentration will therefore cause a reduction in alveolar PO2(PAO2). The increased utilisation of oxygen when metabolic rate is raised such as with postoperative shivering or malignant hyperpyrexia also causes a reduction in alveolar PO2.

If the PaO2 falls to less than 60mmHg the aortic and carotid body chemoreceptors respond by causing hyperventilation and increasing cardiac output through sympathetic nervous system stimulation. This normal protective response to hypoxia is reduced by anaesthetic drugs and this effect extends into the post-operative period.

Following induction of anaesthesia there is a rapid reduction in FRC that results in airway closure - small airways, particularl in dependant parts of the lung, collapse and remain closed throughout the respiratory cycle. This results in some alveoli not being ventilated at all (true shunt). Ventilation/perfusion (V/Q) mismatch is also increased.

Atelectasis (collapsed alveoli) also develops rapidly in the dependant lung regions and results in true shunt. As explained earlier, airway closure, V/Q mismatch and shunt will cause the oxygen saturation in the pulmonary veins to be less than in the pulmonary capillaries of ventilated alveoli. This 'venous admixture' increases from 1% to around 10% following induction of anaesthesia. With the possible exception of patients spontaneously breathing while anaesthetised with ketamine, this increase in venous admixture occurs irrespective of the anaesthetic agent used and whether muscle relaxants are used or not. It should be viewed as an unavoidable adverse effect of anaesthesia. Volatile anaesthetic agents suppress hypoxic pulmonary vasoconstriction, and blood flow to underventilated or collapsed alveoli is not reduced. Many anaesthetic agents depress cardiac output and therefore decrease oxygen delivery.

Anaesthesia causes a 15% reduction in metabolic rate and therefore a reduction in oxygen requirements. Artificial ventilation causes a further 6% reduction in oxygen requirements as the work of breathing is removed. Anaesthetic agents do not affect the carriage of oxygen by haemoglobin.    

THE PRACTICAL USE OF OXYGEN

Inspired oxygen concentration

The efficiency of oxygenation during anaesthesia is reduced due to hypoventilation and venous admixture. An inspired oxygen in the range of 25%-30% is usually effective in restoring the PaO2 to normal when hypoxaemia is due to hypoventilation. (figure 6)

 

When hypoxaemia is due to venous admixture it is only possible to restore the PaO2 by increasing the inspired oxygen concentration if the venous admixture does not exceed the equivalent of a 30% shunt. (figure 7) The inspired oxygen concentration during maintenance of anaesthesia should routinely be increased to 30% whenever possible to compensate for hypoventilation and shunt which normally accompany anaesthesia. Additional oxygen may need to be administered to patients at risk of decreased oxygen delivery (anaemia or decreased cardiac output) or increased oxygen consumption (fever).

 

Pre-oxygenation

The small volume of the oxygen stores in the FRC of a patient breathing air means that there will be a rapid fall in oxygen saturation during apnoea (e.g. following induction of anaesthesia, during laryngospasm or during upper airway obstruction). Pre-oxygenation involves the breathing of 100% oxygen for three minutes through an anaesthetic circuit with a face mask firmly applied to the face. This is the time taken to replace the nitrogen in the FRC with oxygen using normal tidal ventilation. Although FRC falls on induction of anaesthesia the extra oxygen contained within the FRC provides an essential store of oxygen for periods of apnoea, such as may occur during rapid sequence induction or difficult intubation. Patients with a small FRC (infants, pregnancy, obesity) or a low haemoglobin concentration and therefore smaller oxygen stores desaturate more rapidly and pre-oxygenation is especially indicated in these patients.

Anoxic gas mixtures

If, during the course of an anaesthetic 100% nitrous oxide is given to the patient in error, the fall in alveolar PO2 will be much more rapid than during apnoea. The alveolar PO2 can fall to dangerously low levels in as little as 10 seconds. This is because the oxygen in the patient's lungs and blood (oxygen stores) is being actively washed out with each breath that contains no oxygen. The fall in PO2 is therefore more rapid than would occur if it was only being used up by the metabolic needs of the body (250ml/min).

Crisis management

When managing emergencies during anaesthesia consideration should always be given to the immediate administration of 100% oxygen while the cause is found and rectified. It is the most appropriate treatment for acute deterioration in cardiorespiratory function.

Diffusion hypoxia

Nitrous oxide is forty times more soluble in blood than nitrogen. When nitrous oxide is discontinued at the end of anaesthesia, nitrous oxide diffuses out of the blood into the alveoli in large volumes during the next 2 - 3 minutes. If the patient is allowed to breathe air at this time the combination of nitrous oxide and nitrogen in the alveoli reduces the alveolar PO2. This is called diffusion hypoxia and is avoided by increasing the inspired concentration of oxygen by the administration of 100% oxygen for 2 - 3 minutes after discontinuing nitrous oxide.

Postoperative oxygen

The causes of increased venous admixture (ventilation/perfusion mismatch, shunt and airway closure) and the abnormal response to hypoxia continue into the postoperative period for a number of days following major surgery. Postoperative hypoventilation is common and may be due to the residual effect of anaesthesia, the use of opioid analgesia, pain or airway obstruction. Shivering in the immediate postoperative period causes an increase in oxygen consumption. Additional oxygen should therefore be given to all unconscious patients in recovery and to those awake patients who either shiver, hypoventilate, desaturate or who are considered to be at special risk (eg. ishaemic heart disease).

Postoperatively, on the ward, episodes of airway obstruction during sleep are common and may aggravate borderline oxygenation due to the above factors. This is due to the use of opioid analgesia and a change in sleep pattern that occurs on the second and third postoperative nights. It is clear that after major surgery the risk of hypoxaemia extends well into the postoperative period. Small degrees of cyanosis are not easy to detect clinically, especially in anaemic patients, and therefore oxygen should be given to these patients wherever possible. It is especially important to give it overnight to patients at special risk (ischaemic heart disease). Postoperative pain should be effectively treated (see Update 7) as patients in pain following abdominal or thoracic surgery will be reluctant to breathe deeply. If opioid analgesics are indicated, hypoventilation should be anticipated, and oxygen given.    

PROBLEMS ASSOCIATED WITH OXYGEN ADMINISTRATION

It is has been suggested that high concentrations of oxygen (90-100%) administered to patients for a prolonged period (several days) may cause pulmonary damage. There is little evidence to support this and should never prevent its use in treating severe hypoxia.

High concentrations of oxygen will encourage collapse of alveoli with low ventilation/perfusion ratios. Oxygen is rapidly and completely absorbed from these alveoli, and when it is the only gas being given, these underventilated alveoli collapse. When air and oxygen is used, the nitrogen present is absorbed more slowly and prevents the alveolus from collapsing.

Oxygen therapy may rarely depress ventilation in patients suffering from severe chronic obstructive airways disease. Some of these patients lose their sensitivity to carbon dioxide and rely on hypoxia to stimulate breathing. In these patients, when high concentrations of oxygen are given, serious hypoventilation and hypercapnia can result due to the fact that their hypoxia is reversed. This is extremely rare.

In the second part of this article we plan to discuss the more practical aspects of oxygen production and storage and the equipment needed to safely administer oxygen to patients.  

References

1. Nunn JF. Applied Respiratory Physiology (3rd Edition). Butterworths 1987 2. West JB. Respiratory Physiology (4th Edition). Williams and Wilkins 1990