Basic science

Oxygen delivery and demandJane Ward

AbstractThe most important function of the cardiovascular and respiratory sys-

tems is to transport a continuous supply of oxygen to the tissues. Oxy-

gen is needed for the efficient generation of adenosine triphosphate

(aTP) from substrates such as glucose. Tissues vary in their tolerance of

hypoxia. The brain is most susceptible; cerebral function is lost within

seconds of losing its oxygen supply and irreparable damage occurs after

about five minutes, but all tissues are eventually damaged by prolonged

hypoxia. Tissue hypoxia occurs if oxygen delivery is too low relative to

the oxygen needs of the tissue. For any given metabolic rate, there is

a critical oxygen delivery below which oxygen consumption and aTP

production fall, and anaerobic metabolism gives rise to increasingly

severe lactic acidosis. Oxygen delivery depends on blood flow and arte-

rial oxygen content, which in turn depends on arterial partial pressure

of oxygen, the affinity of haemoglobin for oxygen, and the haemoglobin

concentration. aTP production can also fall if the ability of the tissue

to extract oxygen or mitochondrial utilization of oxygen is impaired.

Tissue damage may result if one or more of these factors are abnormal.

improving the match between oxygen supply and oxygen need is an

important goal in many seriously ill patients and can be achieved by

lowering oxygen requirements and/or increasing the oxygen supply. The

inter-relationships between the factors that contribute to oxygen supply

must be considered because improving one of these factors may impair

another.

Keywords oxygen; carbon dioxide; aTP; lactic acid; alveolus; tissue;

haemoglobin; hypoxaemia; anaemia; ischaemia; cyanosis; anaerobic;

hypoxia

Oxygen requirements: whole body and tissues

The most important function of the cardiovascular and respira-tory systems is to transport a continuous supply of oxygen to the tissues. A resting adult of weight 70 kg uses about 250 ml of oxy-gen per minute. Consumption of oxygen can increase by >20 fold in an athlete during exercise.

Production of adenosine triphosphate (ATP)ATP is produced by oxidation of substrates such as glucose (see Maughan, CROSS REFERENCES). It is the most important short-term store of energy for muscle contraction and ion pumping.

Jane Ward MB ChB PhD is a Senior Lecturer in Physiology at King’s

College, London, UK.

sURGeRY 24:10 354

ATP must be continuously resynthesized and the most efficient pathway requires oxygen. Aerobic metabolism produces carbon dioxide, water and 38 moles of ATP for each mole of glucose used. Mitochondria are essential for this oxidative phosphory-lation and they cease to function when the partial pressure of oxygen (PO2) within them falls below about 0.13 kPa (1 mmHg). Anaerobic metabolism becomes important when oxygen demand outstrips supply. It generates lactic acid and just 2 moles of ATP from each mole of glucose. In rapidly metabolizing tissues, it is not be possible to provide glucose fast enough to produce an adequate supply of ATP by this pathway and, in the brain, lactic acid accumulates because it cannot readily cross the blood–brain barrier. Such factors underlie the variable tolerance to hypoxia found in different tissues. Without its oxygen supply, loss of function occurs: • in the brain within 5–15 seconds • in the heart after about four minutes • in skeletal muscle after about two hours.Irreversible damage occurs in the brain after about five minutes and in other tissues by about four times the loss of function time.

Factors affecting oxygen consumptionThere are big differences in the oxygen consumption of different tissues and at different levels of activity (Table 1).

In health, core temperature is controlled at 36–37.5°C, but changes in core temperature can affect metabolic rate in dis-ease. Most chemical reactions speed up by about 2.5 times for every 10°C rise in temperature. This ‘Q10 effect’ contributes to the increased consumption of oxygen in fever until, at very high temperatures, it falls because proteins denature and metabolism is impaired. The direct effect of temperature is complicated by the metabolic cost of thermoregulation, and oxygen consumption also rises as core temperature falls when shivering is initiated (see Wilkins, CROSS REFERENCES).

Other factors that can raise metabolic rate include increased circulating concentrations of thyroxine, adrenaline, and drugs such as isoprenaline. Pain and anxiety increase oxygen con-sumption by a combination of restlessness and increased con-centration of catecholamines in plasma. The work of breathing is usually responsible for <5% of resting consumption of oxygen, but it can rise to 30% in respiratory disease, in which case oxy-gen consumption is significantly reduced by mechanical ventila-tion (see Ward, CROSS REFERENCES).

Oxygen consumption in tissues

Organ Oxygen consumption

(ml/minute per 100 g tissue)

Brain 3

Kidney 5

skin 0.2

skeletal muscle (resting) 1

Heart (resting) 8

Heart in maximal exercise 70

skeletal muscle (heavy exercise) 50

Table 1

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Basic science

Overview of oxygen carriage

In the alveolus and bloodAlveolar PO2 (PAO2) is determined by alveolar ventilation and the PO2 of the moistened inspired gas, which is 19.9 kPa (149 mmHg, at 37°C saturated with water) at sea level. In health, pulmonary capillary blood equilibrates with alveolar gas so that pulmonary end-capillary PO2 equals PAO2. Arterial PO2 (PaO2) is slightly lower because some right-to-left shunting occurs from the bron-chial circulation and Thebesian veins. The ‘A–a PO2 gradient’ (PAO2–PaO2) is normally <2 kPa in young adults.

Oxygen is carried in blood in solution and combined with hae-moglobin in the red blood cell. The solubility of oxygen is low (0.225 ml O2 per l blood per kPa or 0.03 ml/l/mmHg); at a nor-mal PaO2 of 13 kPa (97 mmHg), there is only 3 ml dissolved oxy-gen per litre compared to 200 ml per litre bound to haemoglobin. The percentage of the haem sites that are combined with oxygen (oxygen saturation, SO2) is determined by the PO2 to which the haemoglobin is exposed, as described by the oxyhaemoglobin dissociation curve (Figure 1a). The affinity of haem sites for oxy-gen is also affected by other factors in the blood. For example, increased partial pressure of carbon dioxide (PCO2), increased temperature and reduced pH (as found in metabolically active tissue), reduce the affinity of haem groups for oxygen, aiding its release from haemoglobin. This is reflected by a rightward shift of the oxyhaemoglobin dissociation curve (Figure 1a). The effects of anaemia and poisoning by carbon monoxide (CO) on the dissociation curve are shown in Figure 1b and their effects on oxygen delivery are discussed below.

Haemoglobin is nearly fully saturated (>97%) with oxygen at a normal PaO2 of about 13 kPa (97 mmHg). Each gram of haemo-globin can combine with 1.36 ml of oxygen, so that with a normal

sURGeRY 24:10 35

haemoglobin concentration ([Hb]) of 150 g/l, the arterial oxygen content is about 200 ml/l ((150 × 1.36 × 0.97) + 3). The dissoci-ation curve plateaus above 8 kPa (60 mmHg, SO2 = 91%). Conse-quently, in health at sea level, oxygen content is little affected by a small fall in PaO2 (e.g. mild hypoventilation) or a rise in PaO2 (e.g. hyperventilation or breathing oxygen). In contrast, in a hypoxic patient with a PO2 of <8 kPa (60 mmHg), arterial O2 content can be markedly affected by small increases or decreases in arterial PaO2 (steep part of the curve, Figure 1a) e.g. by small changes in ventilation or concentration of inspired oxygen.

In the tissuesOxygen is consumed and as tissue capillary PO2 falls, oxygen is released from the haemoglobin store to replenish the dissolved oxygen as it diffuses to the tissues. The higher the [Hb], the larger the oxygen store and the slower will be the fall in PO2 along the capillary. PO2 falls rapidly at first and then more slowly, so that mean capillary PO2 is closer to venous than arterial PO2. Venous PO2 and SO2 vary from tissue to tissue, depending on the oxygen consumption of the tissue relative to its blood flow. Despite the high consumption of oxygen in the kidney, the renal venous SO2 is high (90%) because of the very high renal blood flow. Coro-nary blood flow is much less generous relative to myocardial oxygen consumption, so the coronary venous SO2 is much lower (40%).

Mixed venous and central venous oxygenMixed venous blood (sampled in the pulmonary artery), has an SO2 that reflects the average venous values for the whole body. Superior vena cava SO2 (sampled via a central venous catheter) is usually lower than mixed venous SO2. At rest, normal mixed venous PO2 is about 5.3 kPa (40 mmHg), SO2 is about 70–75%

The red line shows the relationship between PO2 and saturation when pH = 7.4, PCO2 = 5.3 kPa and temperature = 37° C. The blue line shows the dissociation curve shifted to the right (Bohr shift) by the increased PCO2 and reduced pH of venous blood. Point a represents the normal values for arterial blood and point v those for mixed venous blood at rest. Thevalues for oxygen content assume a normal haemoglobin concentration of 150 g/l. Anincreased concentration of the red cell metabolite 2,3-diphosphoglycerate (2,3-DPG), asoccurs at altitude, also shifts the dissociation curve to the right. The position of thedissociation curve is defined by its P50, the PO2 at which the haemoglobin is 50% saturated.

a

a = Normal arterial bloodPO2 = 13.3 kPa (100 mmHg)O2 content = 200 ml/lO2 saturation = 97%

v = Resting mixed venous bloodPO2 = 5.3 kPa (40 mmHg)O2 content = 150 ml/lO2 saturation = 75%

Oxyhaemoglobin dissociation curve

0

200

↑pH, ↓PCO2,↓Temperature↓2,3-DPG

↓pH, ↑PCO2,↑Temperature↑2,3-DPG(Bohr shift)

Dissolved oxygen

150v

100

50

642 8 12 1610 14 kPa

Oxy

ge

n c

on

ten

t (m

l/l)

0

25

50

75

100

Oxy

ge

n s

atu

rati

on

(%

)

18 20

0 50 100PO2

mmHg150

a

The red line represents the dissociation curve for an anaemic patientwith a haemoglobin concentration of 75 g/l and the dashed green linethe curve for a patient with a normal haemoglobin concentration of 150 g/l with 50% of binding sites bound to CO. The black line is a normaldissociation curve for a haemoglobin concentration of 150 g/l. Points A,B and C represent resting mixed venous PO2 in the normal subject, theanaemic subject and the subject poisoned by CO, respectively. Forsimplicity, the effect of the Bohr shift has been ignored.

b

Oxyhaemoglobin dissociation curve in anaemiaand poisoning by carbon monoxide

0

200

150

100

50

6

A

42 8 1210 14 kPa

Tissues remove50 ml/l (Bohrshift ignored)

O2 c

on

ten

t (m

l/l)

16

0 20 40 60PO2

80 100 mmHg120

BC

Tissues remove50 ml/l

Normal, [Hb] = 150 g/l

Anaemia, [Hb] = 75 g/l

CO poisoning, [Hb] =150 g/l, 50% COHb

Figure 1

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Basic science

and oxygen content about 140–150 ml/l. Hence, resting oxygen extraction, EO2 ((arterial SO2−mixed venous SO2)/arterial SO2) is about 25%. The maximum possible EO2 is usually about 75%. The limit of oxygen extraction is reached when capillary PO2 has fallen too low to drive diffusion fast enough to keep up with oxygen consumption. Small improvements in maximum EO2 can occur with athletic training and acclimatization to chronic hypoxia in tissues (at altitude or in chronic lung or cardiac dis-ease) and this permits a slightly lower tissue capillary PO2 to be tolerated. The mechanisms include increased capillary density (which reduces diffusion distances), increased numbers of mito-chondria and increased aerobic enzymes.

Oxygen storesThe total oxygen stored in the body is about 1.5 l. Most of this (450 ml) is in the lungs or attached to haemoglobin (800 ml), with only small amounts dissolved in the fluids of the body (50 ml) or attached to myoglobin (200 ml). Haemoglobin and myoglobin are normally nearly fully saturated and oxygen solubility is low, so the only way to increase these stores significantly is by increasing the volume of oxygen in the lungs by: • taking a deep breath • increasing concentration of alveolar oxygen by hyperventilation • breathing air enriched with oxygen. Not all of the stored oxygen can be used because the bound oxygen cannot be fully removed while maintaining a sufficiently high tissue capillary PO2 for diffusion. The stores are usually suf-ficient for 3–4 minutes if breathing stops. Breathing 100% oxygen

sURGeRY 24:10 35

increases stored oxygen to about 4200 ml, largely by replacing nitrogen with oxygen in the lungs, and this increases the apnoeic survival time to about 10 minutes.

Causes of tissue hypoxia and depletion of ATP

Normal production of ATP and cellular wellbeing requires adequate delivery and utilization of oxygen (Figure 2). The causes of impaired delivery of oxygen and tissue hypoxia were identified by Joseph Barcroft (Cambridge, UK) in the 1920s: arterial hypoxaemia, anaemia and ischaemia. These causes of impaired oxygen delivery, as well as the fourth cause of ATP depletion, inadequate utilization of oxygen (histotoxic), are dis-cussed below. Unqualified, the term ‘hypoxia’ has come to mean ‘arterial hypoxia’. Consequently terms like ‘anaemic hypoxia’, as shorthand for anaemic tissue hypoxia, are confusing and should be avoided. Anaemia is not a cause of a low PaO2.

Arterial hypoxaemiaThe five main causes of low PaO2 are illustrated in Figure 3. Increasing the concentration of inspired oxygen can be expected to significantly raise the PaO2 and oxygen content in most of these conditions (1, 2, 3 and 5). It is least effective in a pure right-to-left shunt (4) because the shunted blood is not exposed to the increased oxygen and the O2 content of blood passing through normally functioning alveolar regions can improve little. Of these five causes of arterial hypoxaemia, only hypoventilation (2) is inevitably accompanied by a raised arterial PCO2 and this

Arterial PO2, PaO2

Arterialoxygen

saturation

Arterialoxygencontent

Oxygendelivery(DO2)

O2extraction

(EO2)

Factors involved in oxygen delivery and usage in the tissues

Gas exchange• Inspired PO2 • Hypoventilation• Alveolar–capillary diffusion block• Right-to-left shunt• Ventilation– perfusion mismatch

Affinity of Hbfor O2• PaCO2• pHa• Temperature• 2,3-DPG• Hb variant• CO poisoning

Number of availableHb binding sites e.g.• [Hb] anaemia/ polycythaemia• CO poisoning• MetHb

Ability ofmitochondriato use O2 e.g.• Cyanide• Sepsis

Global and localblood flow e.g.• Cardiac output• Reflex vasoconstriction• Thrombosis• Embolus• Blood viscosity

O2 release and diffusionin the tissues e.g.• Capillary density• Oedema• Regional distribution of blood flow• Hb affinity for O2

• Oxygen consumption (VO2 = DO2 × EO2)• ATP production• Cellular health• Tissue PO2 and PvO2 (both low if delivery, diffusion or release of O2 is the problem; may be normal or high if ability of mitochondria to use O2 is primary problem)

(Hypoxic)

(Anaemic)

(Histotoxic)

.

(Ischaemic)

Figure 2

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Basic science

1 Breathing gas with a low PO2 (e.g. high altitude,

reduced concentration of inspired oxygen).

2 Inadequate alveolar ventilation (e.g. head injury, respiratory depressant drugs, severe chronic obstructive pulmonary disease, respiratory muscle weakness).

3 Diffusion impairment may be caused by a thickened alveolar capillary membrane (e.g. pulmonary oedema, lung fibrosis) and prevent equilibration of the pulmonary capillary blood with alveolar gas.

4 A right-to-left shunt (e.g. consolidation or atelectasis of a lung region, some congenital heart disease (e.g. tetralogy of Fallot) means some deoxygenated blood returning from the tissues fails to undergo gas exchange. This blood depresses oxygen content and arterial PO2 when it mixes with the blood that has undergone normal gas exchange in the remaining lung.

5 Ventilation–perfusion mismatch (e.g. asthma, obstructive pulmonary disease) produces some regions that are over- ventilated and others that are under-ventilated in relation to their perfusion. The under-ventilated regions (low V

A/Q)

behave qualitatively like true right-to-left shunts (VA/Q = 0).

1 and 2 cause a low PO2 by lowering alveolar PO2. 3, 4 and 5are associated with an increased A–a PO2 gradient.

Air or alveolar gas with normal PO2

Air or alveolar gas with reduced PO2

Deoxygenated blood (‘mixed venous’ or right-sided)

Normal, fully oxygenated

Incompletely oxygenated blood

1 Low inspired PO2

High Va/Q

Low Va/Q

2 Hypoventilation

3 Diffusion impairment

5 Ventilation– perfusion mismatch

4 Right-to-left shunt

Normal inspired PO2

Normal alveolarventilation

Normal alveolar–capillary membrane

Matching of ventilation and perfusion throughout the lungs

>98% cardiac outputpassing through gas-exchanging alveoli

Normal

Mechanisms of arterial hypoxia (low PaO2)

. .

. .

. .. .

Figure 3

will not be improved by breathing gas mixtures rich in oxygen. Hypoxaemia stimulates the carotid body chemoreceptors and the reflex increase in ventilation usually corrects (or over-corrects) any increase in PaCO2 caused by the primary problem. Conse-quently, when arterial hypoxia is caused by anything other than hypoventilation, PaCO2 is usually normal or low unless some-thing (e.g. exhaustion in a severe asthma attack) is interfering with the normal ventilatory response to hypoxia.

Anaemia and CO poisoningAnaemia reduces arterial oxygen content and results in reduced mean tissue capillary PO2 (B on Figure 1b). Unless anaemia is very severe ([Hb] of <50 g/l), the capillary to tissue PO2 gradi-ent remains sufficiently high for adequate diffusion at rest, but becomes inadequate as oxygen consumption increases, limiting exercise tolerance. The oxygen store is also reduced when some of the haemoglobin binding sites are occupied by CO, but tissue hypoxia is much worse than in anaemia with the same arterial PO2 and O2 content. Binding of CO to some haem groups increases the affinity of the remaining haem groups for oxygen, as reflected by the leftward shift and altered shape of the dissociation curve

sURGeRY 24:10 3

(green dashed line, Figure 1b). To release the required amount of oxygen as blood passes through the tissue capillaries, PO2 must fall to a level (C, Figure 1b) that excessively slows diffusion.

Polycythaemia (produced by transfusion, erythropoietin, or alti-tude acclimatization) has sometimes been exploited by athletes to improve their aerobic performance, and it may seem a con-venient way to improve oxygen delivery in critically ill patients. However, the disadvantages of increased viscosity (increased total peripheral resistance, increased cardiac work and impaired microcirculatory flow) often more than offset the benefits of increased carriage of oxygen. An optimum [Hb] is considered to be ≤ 100 g/l in many seriously ill patients.

IschaemiaLocal ischaemia underlies the focal tissue death that occurs in many common conditions (e.g. myocardial infarction, stroke). A generalized inadequacy of blood flow throughout the body is present in circulatory shock. Causes include: • haemorrhage (hypovolaemia) • myocardial infarction (pump failure)

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Basic science

• pulmonary embolus (circulatory obstruction) • sepsis and anaphylaxis (vasodilation and increased capillary

permeability). Blood pressure may be well preserved in the early stages of shock because the rise in total peripheral resistance offsets the fall in cardiac output (see Ackermann, CROSS REFERENCES). Reflex vasoconstriction in response to a reduced cardiac out-put and/or reduced blood pressure is strong in the splanchnic, renal and skeletal muscle circulations, whereas the coronary and cerebral circulations are relatively spared. The splanchnic and renal circulations can tolerate much longer periods of ischaemia than the brain or heart, but they will be damaged if the ischaemia is sustained; this is an important factor in the ‘golden hour’ when treating trauma patients and those in circulatory shock (see Hassan, CROSS REFERENCES).

Inadequate utilization of oxygenATP depletion and tissue damage can also result from an inability of cells to utilize delivered oxygen because of mitochondrial dysfunction (e.g. after cyanide poisoning). Thus, the fourth major type of tissue ‘hypoxia’ is histotoxic (or cytopathic) although PO2 in the tissue, capillary and venous blood may be high in this form. There is increasing evidence that impaired utilization contributes to the tissue problems occurring in severe sepsis (see Kumar; Hargunani, CROSS REFERENCES).

Relationship between the delivery and consumption of oxygen

If mean capillary PO2 falls below a critical pressure, the PO2 in the mitochondria of some cells (usually those farthest from a capillary) will fall below that at which aerobic respiration can continue (Figure 4). This critical capillary PO2 is increased if tis-sue metabolism is increased or if diffusion distances are increased due to oedema.

sURGeRY 24:10 35

Oxygen delivery to a tissue is the product of blood flow (l/ minute) and arterial oxygen content (ml/l). The normal value for oxygen delivery in the whole body (DO2) in a resting adult is about 1000–1200 ml/minute (cardiac output 5–6 l/minute; arterial oxygen content 200 ml/l). This is equivalent to about 550–650 ml/minute/m2. Moderate reductions in DO2 relative to metabolism are well tolerated, with oxygen consumption initially maintained by increased extraction of oxygen (Figure 5). A criti-cal DO2 is reached (C in Figure 5) below which oxygen extrac-tion fails to increase, or increase sufficiently, to compensate for reduced delivery, and oxygen consumption falls. Increasingly intense tissue hypoxia and anaerobic metabolism occur as oxy-gen delivery falls below this critical point.

With increased metabolic rate, the oxygen consumption– oxygen delivery curve shifts upwards and to the right, and the critical DO2 below which oxygen consumption would fall is increased (dashed green line, Figure 5).

Cardiac output and oxygen delivery normally increase in exer-cise (e.g. 4 times) but they do so proportionately less than the increased oxygen consumption (e.g. 10 times), so increased oxy-gen extraction is required (2.5 times in this example). Maximum consumption of oxygen (VO2 max) is reached when neither cardiac output nor oxygen extraction can increase further.

Detecting and monitoring mismatch between oxygen need and oxygen delivery

A single measurement that reliably indicates a mismatch between oxygen requirement and oxygen delivery does not exist, but there are many useful signs, symptoms and measurements which, when taken together, indicate a problem.

In circulatory shock, many of the signs and symptoms relate to the dysfunction of organs with an inadequate supply of oxygen for their needs (nausea, faintness, reduced urine output) and/or

This is a schematic diagram showing how tissue PO2 mayvary between two adjacent capillaries. Cells furthest fromthe capillaries have a lower PO2 than cells adjacent to thembut, provided capillary PO2 is kept above a critical value,cells have a sufficiently high PO2 (light grey) in theirmitochondria to permit aerobic respiration. If capillary PO2falls, some cells in the critical zone furthest from a capillarybecome hypoxic (dark grey). The dark grey area around themitochondria on the edge of the critical zone indicatesthat PO2 may vary in different regions of a cell, with ‘lowspots’ around areas of high usage of O2.

Maximum

0

8

6

4

2

Tiss

ue

PO

2 (

kP

a)

0

60

45

30

15Tiss

ue

PO

2 (

mm

Hg

)

0 0

PcO2 = 6.5 kPa or 3.0 kPa

PcO2 = 1.5 kPa (or athigher PcO2 withincreased metabolism)

Distance from capillary

PcO

2 = 6.5 kPa (48.8 mmHg)

Effect of mean capillary PO2 (PcO2) on tissue oxygenation

PcO2 = 3.0 kPa (22.5 mmHg)

PcO2 = 1.5 kPa (11.3 mmHg)

Figure 4

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Basic science

Over quite a wide range of oxygen delivery (pink region),

oxygen consumption (green line) stays relatively constant

in healthy people and most disease situations. The red

dashed line shows how O2 extraction, EO2, must change

to maintain a constant oxygen consumption as DO2 falls.

As O2 delivery falls in the pink region, EO2 increases (red

solid line = red dashed line) to meet the O2 needs of the

tissue. Below a certain critical delivery of O2 (blue zone),

O2 consumption cannot be maintained because the EO2

cannot increase further, or not enough to compensate

for the reduced delivery of O2 (red solid line < red dashed

line). There is a progressive increase in anaerobic

metabolism and a progressive increase of lactate in plasma

as O2 delivery falls in this region. When metabolism is

increased (green dashed line), the critical oxygen delivery

required to maintain the increased consumption of oxygen

is increased.

Oxygen consumption VO2 ml/minute/m2

(dashed line: with increased metabolism)

Percentage oxygen extraction EO2(solid line: actual; dashed: needed tokeep VO2 constant)

Concentration of lactate in plasma(mmol/l)

C = Critical DO2

Oxygen delivery (DO2; ml/minute/m2)

VO2 = Oxygen needVO2 O2

need

..

Effect of oxygen delivery on oxygen consumption

.

Figure 5

to the reflex responses attempting to maintain blood pressure (tachycardia, pallor, cold extremities).

CyanosisCyanosis, a greyish blue hue, is caused by a high concentration of deoxygenated haemoglobin in the tissue being viewed. In the lips and buccal mucosa (central cyanosis), it indicates arterial hypoxaemia. Peripheral cyanosis in the absence of central cya-nosis indicates poor perfusion. It suggests inadequate cardiac output when present in both hands and feet not exposed to the cold. For a tissue to appear cyanosed, about 40–50 g/l of deoxy-genated haemoglobin are needed in the microcirculation (not in the arterial blood, a common misquote of the original papers!). This occurs when arterial deoxygenated [Hb] is about 15 g/l. For an adult with [Hb] = 150 g/l, this occurs when arterial SO2 falls to about 90% at a PaO2 of about 7.7 kPa (58 mmHg). In anaemia, PaO2 must be lower to achieve the required deoxygenated [Hb] and cyanosis appears more readily in polycythaemia. Central cyanosis is not a very sensitive sign of arterial hypoxaemia and may not be possible in severe anaemia.

Anaerobic metabolismAnaerobic metabolism gives rise to metabolic acidosis with increased concentration of lactate in plasma and increas-ingly negative base excess. These can be useful clues to tissue hypoxia, but blood lactate is also affected by hepatic clearance and there are other causes of a metabolic acidosis (e.g. renal failure).

Mixed venous SO2

Mixed venous SO2 is about 75% in a healthy resting adult. Val-ues between 50% and 75% indicate an oxygen delivery system under stress (e.g. exercise or in disease because of reduced deliv-ery and/or increased demand). Values <50% are associated with tissue hypoxia and lactic acidosis, which are severe at 30%.

sURGeRY 24:10 3

Venous oxygen saturation will be high despite a failure of aerobic metabolism, if impaired extraction or usage of oxygen is impor-tant (e.g. arteriovenous shunting, sepsis, cyanide poisoning) or if tissue death has occurred.

Avoiding and relieving tissue hypoxia

Studies on acutely ill ICU patients revealed a correlation between high delivery of oxygen (>600 ml/minute/m2) and ultimate sur-vival.1 In critically ill patients, it was thought that raising oxygen delivery to this level and keeping central or mixed venous oxy-gen saturation high (>70% and >65%, respectively) may avoid hypoxic tissue damage and improve outcome. Results of trials of this ‘goal-directed’ therapy have been variable, probably because of differences in patient populations and the timing of applying measures that raise oxygen delivery.2 Oxygen delivery can be raised by adjusting the factors shown in Figure 2. This usually involves increasing arterial PO2, [Hb] and/or cardiac output. The risk–benefit balance differs considerably between patients and with the technique used to raise oxygen delivery. Cardiac output can be increased using volume expansion, vasodilators and ino-tropic drugs, all of which have potential for deleterious effects. Vigorous volume expansion is helpful in the volume-depleted patient in early shock, but may cause oedema and impair oxygen diffusion in late shock where vascular permeability and myocar-dial function are abnormal. Many cardiovascular and respiratory factors affect oxygen delivery and they have complex inter- relationships. For example, it is usually desirable to use oxy-gen supplementation and/or ventilatory strategies to raise PaO2 to >10 kPa, thereby increasing arterial oxygen content. The appli-cation of positive end-expiratory pressure may help to achieve this by raising functional residual capacity and recruiting previ-ously inadequately ventilated alveoli. However, in a patient with severely compromized circulation, the increased intrathoracic pressure caused by positive end-expiratory pressure may lower

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cardiac output. Oxygen delivery may fall despite an improve-ment in PaO2. Disadvantages of sympathomimetic, inotropic and chronotropic drugs include increased consumption of oxygen.

Lowering consumption of oxygen in tissues is often the best initial approach to matching supply and demand in the critically ill. Fever can be reduced using antipyretic drugs and mechani-cal ventilation can reduce or eliminate the work of breathing. Painkillers and sedatives can reduce restlessness, anxiety and catecholamine secretion. In certain circumstances, reducing tem-perature to below normal (locally or using whole body cooling) may protect against hypoxic damage when delivery or utiliza-tion of oxygen is impaired. The metabolic cost of the various methods (vasodilators, inotropes, volume expansion) should be considered and minimized when an increase in oxygen delivery is required. ◆

ReFeRenCeS

1 shoemaker Wc, appel PL, Waxman K, schwartz s, chang P. clinical

trial of survivors’ cardiorespiratory patterns as therapeutic goals

in critically ill postoperative patients. Crit Care Med 1982; 10:

398–403.

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2 Vincent JL, De Backer D. Oxygen transport—the oxygen delivery

controversy. Intensive Care Med 2004; 30: 1990–6.

CROSS ReFeRenCeS

ackermann U. Regulation of arterial blood pressure. Surgery 2004;

22(5): 120a–f.

Hargunani R, stotz M. sepsis, siRs and MODs. Surgery 2005;

23(8): 299–301.

Hassan a, Tesfayohannes B. clinical assessment of major injuries.

Surgery 2006; 24(6): 185–9.

Kumar s, Leaper DJ. Basic science of sepsis. Surgery 2005; 23(8):

272–7.

Maughan R. Basic metabolism i: fat. Surgery 2005; 23(3): 83–8.

Ward J. Physiology of breathing ii. Surgery 2005; 23(12): 430–5.

Wilkins ia, Wheeler DW. Regulation of temperature. Surgery 2004;

22(7): 168a–e.

FuRTheR ReADIng

Leach RM. critical care medicine at a glance. Oxford: Blackwell, 2004.

Lumb aB, ed. nunn’s applied respiratory physiology, 5th edn. Oxford:

Butterworth-Heinemann, 2000.

Ward JPT, Ward J, Wiener cM, Leach RM. The respiratory system at a

glance, 2nd edn. Oxford: Blackwell, 2006.

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