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Oxygen must be transported effectively from Table 1 The relative influence of anaemia on oxygen delivery
the atmosphere to the tissues in order to sustain
Parameter Normal Anaemic Anaemic þ Key points
normal metabolism. An understanding of oxygen
oxygen delivery is therefore central to the man- therapy Oxygen is carried in arterial
agement of patients during anaesthesia, resus- blood dissolved in solution
Inspired oxygen (%) 21 21 100
citation and during critical illness. This review PaO2 (kPa) 12 12 85
(<2% when breathing air) and
SaO2 (%) 98 98 98 combined with haemoglobin
deals specifically with the transport of oxygen
Hb concentration 150 75 75 (>98% in air).
from the lungs to non-pulmonary tissues. (g litre1)
Dissolved oxygen 3 3 19 Tissue hypoxia is a deficiency
(ml litre1) of oxygen at the tissue level; it
Hb-bound oxygen 197 98 98 may be caused by increased
Definitions (ml litre1) demand, decreased supply or
Total CaO2 (ml litre1) 200 101 117
Oxygen delivery D_ O2 (ml min1), 1000 505 585
abnormal cellular utilization.
assuming a cardiac The main physiological
Global oxygen delivery (D_ O2) is the amount of output of 5 litre min1
responses to acute
oxygen delivered to the whole body from the
PaO2, arterial partial pressure of oxygen; SaO2, arterial oxygen normovolaemic anaemia are
lungs. It is the product of total blood flow or increased cardiac output and
saturation; Hb, haemoglobin; CaO2, oxygen content of
cardiac output (CO) and the oxygen content of arterial blood; D_ O2, oxygen delivery. increased oxygen extraction
arterial blood (CaO2) and is usually expressed In practice the cardiac output increases during anaemia ratio.
because blood viscosity and cardiac afterload decrease.
in ml min1:
The ‘critical’ haemoglobin
_ O ¼ CO CaO
D 2 2
At present, it is only practical to routinely concentration is that below
measure global D_ O2. If regional blood flow is which tissue hypoxia occurs; it
The oxygen content of arterial blood (CaO2) is available, the same principles can be used to is 50 g litre1 in healthy
described using the equation: measure regional oxygen delivery. humans.
CaO ¼ ðk1 HbSaO Þ þ ðk2 PaO Þ
2 2 2
Most stable perioperative and
Oxygen consumption critically ill patients can be
Where Hb is the haemoglobin concentration managed with a haemoglobin
(g litre1), SaO2 is the arterial Hb oxygen Global oxygen consumption (V̇O2) is the
transfusion threshold of 70 g
saturation and PaO2 is arterial oxygen partial volume of oxygen consumed by the tissues per litre1.
pressure. Arterial oxygen content is the sum minute. Under aerobic conditions, oxygen is
of the two forms in which oxygen is carried. consumed to generate energy so that V̇O2 cor-
In health >98% of oxygen is bound to Hb responds to the metabolic rate. Measure-
S. A. McLellan MB ChB BSc MRCP FRCA
(Table 1). The oxygen combining capacity of ments of V̇O2 are sometimes used to assess the
University Department of Anaesthetics
Hb is represented by the constant k1 above adequacy of D_ O on the assumption that if D_ O
2 2 Critical Care and Pain Medicine
and is sometimes termed Hüfner’s constant. is inadequate V̇O2 becomes supply-dependent Royal Infirmary of Edinburgh
(see below). V̇O2 can be measured directly by Little France
The exact value for this constant is contro- Edinburgh
versial and differs between authors. In theory, analysis of respiratory gases or derived from
cardiac output and arterial and venous oxygen T. S. Walsh MB ChB BSc MRCP FRCA
each gram of Hb binds 1.39 ml of oxygen. MD
However, in practice, the presence of abnormal contents. Gas analysis techniques require spe-
University Department of Anaesthetics
forms of Hb, such as carboxyhaemoglobin cialized equipment that accurately measures Critical Care and Pain Medicine
and methaemoglobin, reduces the oxygen gas volumes and concentrations adjusting for Royal Infirmary of Edinburgh
temperature and pressure changes and other Little France
combining capacity of Hb to 1.31 ml g1. Edinburgh
Most modern co-oximeters measure the pro- sources of inaccuracy. Calculation from car- Tel: 01312 423136
portion of these Hb types. Dissolved oxygen diac output and arterial-mixed venous oxygen Fax: 01312 423138
content difference is simpler and can be done E-mail: tim@walsh.sol.co.uk
in plasma is determined by the solubility (for correspondence)
coefficient of oxygen at body temperature using a pulmonary artery catheter. The reverse/
(k2 above; 0.23 ml litre1 kPa1) and the PaO2. inverse Fick principle is used: Declaration of interest:
British Journal of Anaesthesia/Royal
Even at high FIO2, this oxygen is insignificant College of Anaesthetists Research
V̇O2 ¼ COðCaO CvO Þ
(Table 1) at normal atmospheric pressure. 2 2
Fellowship (Stuart McLellan).
DOI 10.1093/bjaceaccp/mkh033 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 4 Number 4 2004
ª The Board of Management and Trustees of the British Journal of Anaesthesia 2004 123
Oxygen delivery and haemoglobin
VO2 supply
Shivering dependent
Seizures
Agitation/anxiety/pain 100
Adrenergic drugs
Weaning from ventilation
Factors decreasing V̇O2 50
Sedation/analgesics
Muscle paralysis
Shock/hypovolaemia
0
Hypothermia/cooling 0 200 400 600
Mechanical ventilation
Oxygen delivery (ml min-1)
Antipyretics
Starvation/hyponutrition
Fig. 1 The oxygen supply and demand relationship in health.
124 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 4 Number 4 2004
Oxygen delivery and haemoglobin
VO2 (mL/min)
(NIRS), are indirect methods of measuring tissue oxygenation,
which are still being evaluated. The value for critical D_ O2 has
been estimated to be 4 ml kg1 min1 in humans.
.
In critical illness
Tissue hypoxia is common during critical illness. As a result,
understanding the relationship between D_ O2 and V̇O2 during critical
illness is central to intensive care. Early studies suggested that
many critically ill patients had inadequate D_ O2 because when
D_ O2 was increased by blood transfusions, fluids or inotropic
Fig. 2 The variability of oxygen consumption (V_ O2) in a critically ill patients.
drugs the V̇O2 also increased. This implied that V̇O2 was dependent
on D_ O2 over a much wider range than normal and that there was a with established critical illness and organ failures do not seem to
persistent oxygen debt caused by ischaemic hypoxia. This was benefit and in some cases may be harmed by aggressive D_ O2-
termed ‘pathological oxygen supply dependency’. However, directed protocols. It is not clear if the benefit from this approach
many of these studies were complicated by methodological prob- comes from the specific goals and protocols used or if it relates to
lems and many were detecting physiological, rather than patho- the improved overall care that may be associated with them.
logical, supply dependency.
A linear ‘dependent’ relationship between D_ O2 and V̇O2 can What is an adequate haemoglobin
occur when there is a primary change in metabolic rate and concentration?
D_ O2 changes proportionately to match the newly created oxygen
requirements. This is normal physiological coupling, as would The normal physiological response to anaemia
occur during exercise. Minute to minute changes in metabolic When patients become anaemic a number of physiological
rate occur commonly in patients in the intensive care unit. In responses occur that maintain D_ O2 until the critical Hb concentra-
particular, therapeutic interventions such as physiotherapy can tion is reached (Table 3). The main responses are increased cardiac
result in large increases in metabolic rate (Fig. 2). Recent work output and increased oxygen extraction ratio.
shows that pathological oxygen supply dependency is much less Cardiac output increases during normovolaemic anaemia; the
common and much less severe than previously thought in most magnitude of this increase is closely related to the reduction in
clinically resuscitated critically ill patients. Abnormal oxygen blood viscosity. A reduction in blood viscosity decreases the res-
extraction capabilities do exist in critically ill patients, particularly istance to blood flow, which consequently increases venous return
in organs such as the gut that has a circulation that is prone to and facilitates left ventricular emptying by decreasing afterload.
hypoxia. At present, there are no reliable monitors that detect The net effect is an increase in cardiac output. Sympathetic activa-
pathological supply dependency in individual organs. tion also occurs, which may increase heart rate and/or myocardial
contractility, but these play a minor role in increasing the cardiac
Goal-directed therapy
output of a normal heart in anaemia as long as normovolaemia is
This is the use of therapeutic goals to guide the management of maintained. This is advantageous because of the increase in myo-
oxygen delivery in patients. The idea came from the observation cardial oxygen consumption associated with these two factors.
that patients with higher D_ O2 are more likely to survive than those Increased oxygen extraction by the tissues occurs during
with lower D_ O2 and the belief that they had pathological oxygen anaemia by improved matching of oxygen delivery to oxygen
supply dependency. Various therapeutic goals have been proposed demand. There is a redistribution of blood flow to areas of
for cardiac output, D_ O2, V̇O2, mixed venous oxygen saturation, high demand, such as the myocardium and the brain. In the micro-
central venous oxygen saturation and other physiological circulation a number of mechanisms help to maintain tissue oxy-
measures. The goals are often ‘supra-normal’ levels. Many of genation. Red blood cells normally lose oxygen as they travel
these have been tested in randomized trials using goal-directed pro- through the arterial tree. However, in the anaemic state, blood
tocols. Interpreting these trials is difficult and controversial. The flow is increased and the pre-capillary oxygen loss is reduced. The
results seem to indicate that, for patients who do not yet have organ net effect of all of these changes is a more efficient utilization of the
failures but are at high risk of developing them, a goal-directed remaining red cell mass. In addition, normovolaemic anaemia has
approach to managing D_ O2 is beneficial. Patients with sepsis who little effect on the capillary haematocrit because the latter is norm-
are treated early in the clinical course before organ failures are well ally very low because of an effect called ‘plasma skimming’. The
established also benefit from this approach. However, patients ‘normal’ capillary haematocrit has been estimated to be 8.5%.
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 4 Number 4 2004 125
Oxygen delivery and haemoglobin
Acidotic or
Consider
The haemoglobin transfusion threshold Normal
acid-base status &
increased lactate
lactate
Assuming that patients are normovolaemic, it is important to .
Continue Consider further augmenting DO2.
appreciate what level of Hb is safe to achieve an adequate D_ O2 current In "early" cases consider
that avoids tissue hypoxia. This is of increasing interest because management a goal-directed approach. aiming
and reassess for "supra-normal" DO2.
blood transfusions carry risks and blood is an increasingly scarce regularly
126 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 4 Number 4 2004