Monitoring oxygenation

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Chapter 14 Monitoring oxygenation

ALVEOLAR GAS

In a patient receiving 100% oxygen, alveolar PO2 in individual lung units can range from < 40 mmHg to > 600 mmHg. Consequently, end-tidal PO2 monitoring is of no value.

DISTRIBUTION OF ALVEOLAR VENTILATION

Clinicians routinely track chest movement, auscultate air entry and examine plain chest radiographs. Although computed tomography scanning can reveal occult overdistension,7 it has logistical disadvantages and is a significant radiation hazard. Electrical impedance tomography is under development as an alternative, and shows promise.8 Simple and non-invasive, it tracks lung volume changes in real time, with potential to optimise alveolar ventilation distribution while limiting overdistension.9

TRANSFER FROM ALVEOLI TO ARTERIAL BLOOD (PULMONARY OXYGEN TRANSFER)

The MIGET technique has identified V/Q mismatch and intrapulmonary right-to-left shunt as the two main causes of reduced pulmonary oxygen transfer in critical illness.15 Intrapulmonary shunt predominates in the acute respiratory distress syndrome (ARDS), in lobar pneumonia and after cardiopulmonary bypass, whereas V/Q mismatch without shunt is more prominent in chronic lung disease.16

BEDSIDE INDICES OF PULMONARY OXYGEN TRANSFER

These are either tension-based or content-based.

TENSION-BASED INDICES

A-a gradient

The A-a gradient is calculated as PAO2PaO2, where PAO2 is the ‘ideal’ compartment alveolar PO2 determined from the alveolar gas equation (Equation 14.2). Hypoxaemia can then be classified under two headings:

CONTENT-BASED INDICES

Venous admixture (Qs/Qt)

Venous admixture, another construct based on the three-compartment lung model (see above), represents the proportion of mixed venous blood flowing through the shunt (V/Q = 0) compartment. It is determined according to the formula:

Equation 14.3 image

Cc’O2, CaO2 and CvO2 are the oxygen contents of pulmonary end-capillary, arterial and mixed venous blood respectively. CaO2 and CvO2 are calculated using data from arterial and mixed venous blood gas analysis and CO oximetry (see Table 14.4, below). Cc’O2 is derived differently, since pulmonary end-capillary blood cannot be sampled. image is assumed to equal PAO2 as derived from the alveolar gas equation (Equation 14.2). image (normally close to 1) can then be computed from an algorithm for the HbO2 dissociation curve.22

ARTERIAL BLOOD

Indices of arterial oxygenation are PaO2 and SaO2. They are linked by the HbO2 dissociation curve (Figure 14.4).

Clinically significant hypoxaemia is defined as PaO2 < 60 mmHg or SaO2 < 0.9. These values normally lie near the descending portion of the HbO2 dissociation curve, so that a further drop in PaO2 leads to a marked fall in SaO2 and thus CaO2.

BLOOD GAS ANALYSIS AND CO-OXIMETRY

Arterial blood is collected in a purpose-designed syringe containing lyophilised heparin to a final concentration of 20–50 U/mL. PaO2 measurements are made by a Clark electrode, and SaO2 by CO-oximetry. The Clark electrode works on polarographic principles, and CO-oximeters compute the concentrations of each of the four main haemoglobin species (HbO2, Hb, COHb, MetHb) from light absorbances of haemolysed blood over several wavelengths. SaO2 is functional saturation, determined from concentrations of HbO2 and Hb (see Table 14.4, below). Interference to CO-oximetry arises from substances with competing absorbance spectra, such as bilirubin, HbF, lipid emulsions and intravenous dyes. Newer multi-wavelength techniques reduce or eliminate this interference. SaO2 should always be measured rather than calculated.

ERRORS (Table 14.1)

Temperature correction

All measurements are made at 37°C. Temperature-corrected values can be calculated if the core temperature of the patient is entered into the device software. Most clinicians interpret blood gas data at 37°C, except when evaluating the A-a gradient.

Table 14.1 Preanalytic and analytic errors in PO2 measurement

Preanalytic Analytic
Oxygen diffusing into or out of air bubbles, according to the tension gradient Interanalyser variability. There is 7–8% measurement variation on the same sample
Contamination with flush solution. Discard volume should be 2–3 times the internal volume of cannula and tubing Inadequate anticoagulation, allowing protein deposition on the electrodes
Pseudohypoxaemia. Oxygen consumption in vitro from extreme leukocytosis Non-linearity at high PO2 (> 150 mmHg)
Artifactual PaO2 elevations. With polypropylene syringes stored on ice, the semipermeable plastic allows oxygen ingress, facilitated by the cold-induced increase in oxygen solubility Maintenance of electrode temperature within narrow limits (37 ± 0.1°C) is critical. PO2 changes by 7% for every degree Celsius temperature change
Interference by nitrous oxide and halothane is minimal, provided the polarizing voltage of the electrode does not exceed 600 mV
Quality control materials such as aqueous, perfluorocarbon and bovine haemoglobin solutions are used for convenience, but tonometry is the primary reference method
Arterial blood gas tensions fluctuate breath to breath Intermittent analysis is a snapshot

CONTINUOUS INTRA-ARTERIAL BLOOD GAS MONITORING (Table 14.2)24

Multiparameter fibreoptic sensors can be placed in the arterial stream. Fibreoptic sensors are called ‘optodes’, and those measuring PO2 normally operate by fluorescence quenching. They require calibration with precision gases or solutions before use. Typical sensors are 0.5 mm in diameter, and can be inserted through 20-G arterial cannulae. The 90% in vitro response time to a change in PO2 is 78 seconds. PO2 drift in vivo is 0.03 mmHg/hour. Recalibration in vivo can be performed against conventional blood gas analysis. Accuracy on in vitro and animal testing is good.

Table 14.2 Continuous intra-arterial PaO2 monitoring – advantages and disadvantages

Advantages Disadvantages
Eliminates preanalytic errors of intermittent blood gas analysis The ‘wall’ effect – a sudden decrease in measured Pao2 due to contact with the arterial wall, with averaging of arterial and wall oxygen tensions. The problem is reduced in larger arteries such as the femoral artery
More sensitive than pulse oximetry to changes in arterial oxygenation when PaO2 > 70 mmHg (the flat part of the HbO2 dissociation curve). The ‘flush’ effect. Unless the sensor is inserted a sufficient distance beyond the cannula tip, measured PaO2 can be altered by contamination with the continuous flush solution
Free from the sources of error of pulse oximetry (see Table 14.3) Damping of the arterial waveform
Near real-time PaO2 allows prompt tracking of responses to changed ventilator settings Large footprint of the free-standing monitor
Reduced exposure of personnel to potentially infected blood  
Reduced blood loss for diagnostic purposes  

Clinical trials evaluating the accuracy of these monitoring systems have revealed varying degrees of bias and imprecision. Trials demonstrating an improved outcome when therapeutic decisions are based on data from these devices are lacking. These factors, combined with the costs of these devices, have limited their bedside application.

Some problems encountered with intra-arterial sensors, particularly artefact due to flow and position, have prompted the development of extracorporeal monitors placed in line but ex vivo. These devices do not provide continuous real-time data. When a measurement is desired, a sample is drawn into the externally located cassette, and then returned. Results are available in 2 minutes. In preterm neonates this method has allowed significant reductions in red cell transfusions.25

PULSE OXIMETRY27,28

Pulse oximetry determines SpO2 from the absorbance of light at wavelengths 660 nm (red) and 940 nm (infrared) by tissue capillary beds such as fingers, earlobes and the nasal septum. Two light-emitting diodes cycle on and off at multiples of the mains frequency. A single photodiode detects the transmitted light, and a third interval allows correction for background ambient light. The emergent signal is pulsatile due to arterial volume fluctuations. Subtraction of the background signal (tissue, capillary blood and venous blood) isolates the arterial component.

For both wavelengths, absorbance (A) is determined as follows:

image

where I0 = incident light intensity, and I = emergent light intensity. For a given chromophore, A is proportional to its concentration (Beer’s law) and to the path length (Lambert’s law). From the pulsatile (AC) and background (DC) absorbance signals at both wavelengths, a ratio (R) is derived:

image

SpO2 is then computed from R, using software ‘look-up’ tables of empirically derived relationships between R-values and either SaO2 or fractional saturation (FHbO2) measured in the arterial blood of volunteers breathing hypoxic gas mixtures.

SpO2 is usually displayed as a percentage. Only two wavelengths are used, forcing the assumption that HbO2 and Hb are the only haemoglobin species in the light path. This is always incorrect, but the error is trivial with normal dyshaemoglobin concentrations. Some manufacturers calibrate R against FHbO2 rather than SaO2 (functional saturation). Because volunteers generating the data have normal dyshaemoglobin concentrations, differences between the two calibrations are small.

ERROR

Causes of error are set out in Table 14.3. A falsely high SpO2 is of greatest concern.

Table 14.3 Causes of error in SpO2 readings

Factor Comment
Carboxyhaemoglobin Measured as HbO2SpO2 may be falsely high – see text
Methaemoglobin Absorbs both wavelengths – see text
Low saturations Progressive inaccuracy below 70–80%, usually falsely low SpO2
Prominent venous signal Dependent limb, tricuspid regurgitation (venous pulsations) – falsely low SpO2
Non-pulsatile flow Cardiopulmonary bypass – poor signal
Vasoconstriction, limb ischaemia, shock states Low pulsatile signal
Motion artefact Tremor, voluntary movement – falsely low SpO2
Ambient light Strong sunlight, fluorescent and xenon lamps, flickering light– falsely low SpO2
Anaemia No effect
Dyes Methylene blue, indocyanine green, indigo carmine – falsely low SpO2
Black skin pigmentation Variable precision and bias. May require separate calibration
Nail polish Especially blue. Falsely low SpO2. Acrylic nails do not interfere
Optical shunting Due to inadequate probe contact – falsely low SpO2
Radiofrequency interference Reported with magnetic resonance imaging scanners – falsely high SpO2

Unlike CO-oximetry, pulse oximetry is not subject to interference from bilirubin, lipid emulsions and HbF.

MONITORING HAEMOGLOBIN–OXYGEN AFFINITY

Haemoglobin–oxygen affinity is the relationship between the oxygen tension of blood and its oxygen content, described by the sigmoid-shaped HbO2 dissociation curve (see Figure 14.4). The P50 is the oxygen tension at SO2 = 0.5. The normal value in humans is 26.7 mmHg. Factors which decrease haemoglobin–oxygen affinity increase the P50. They include acidaemia (the Bohr effect), hypercapnia, high levels of erythrocytic 2,3-diphosphoglycerate (2,3-DPG) and fever, whereas P50 is decreased (increased affinity) by alkalaemia, hypocapnia, low 2,3-DPG levels, hypothermia, COHb, MetHb and FHb.

In the intensive care unit, it is possible to calculate accurate P50 values from a single measurement of blood gases and SaO2 up to SaO2 = 0.97.29 However the impact of haemoglobin–oxygen affinity on tissue oxygenation in critical illness appears to be small,30 making routine monitoring unnecessary.

OXYGEN DYNAMICS

Common indices of oxygen dynamics are set out in Table 14.4.

DO2/VO2 RELATIONSHIPS

More than 30 years ago an association was reported between hyperdynamic oxygen flow patterns and survival after high-risk non-cardiac surgery.31 This led to the hypothesis that an induced perioperative hyperdynamic state is protective, subsequently supported by single-unit studies,3235 but not by larger multicentre studies.36,37 Much of any benefit may be due to fluid loading, or even increased care and attention. Typical therapeutic goals have been cardiac index (CI) > 4.5 l/min per m2, DO2I > 600 ml/min per m2, VO2I > 170 ml/min per m2. More recently more emphasis has been placed on the DO2I target, since supranormal VO2I values are much harder to achieve. It is now also clear that in sepsis, aggressive pursuit of hyperdynamic goals is counterproductive.38

MEASURING DO2I

Although DO2I determinations require accurate measurements of CI and CaO2, a PA catheter is not essential (see Chapter 12). Normal ranges can be quoted (Table 14.4), but oxygen demand in critical illness is so variable that isolated DO2I measurements are difficult to interpret.

MIXED VENOUS BLOOD

Mixed venous sampling is by gentle aspiration of blood from the distal port of an unwedged PA catheter. This ensures complete admixture of blood from superior and inferior venae cavae and coronary sinus. Mixed venous O2 and CO2 tensions and content are flow-weighted averages of the venous effluents of multiple tissues. The integrating process can conceal pockets of hypoxia and hypercapnia.

MIXED VENOUS PO2 (PvO2)

Venous gas tensions reflect postcapillary and tissue gas tensions. At a PvO2 of 26 mmHg, the average intracellular PO2 has fallen from 11 to 0.8 mmHg.40 A PvO2 below this value is highly suggestive of intracellular hypoxia. However, a normal or high PvO2 does not exclude regional tissue hypoxia, whether cytopathic hypoxia5 or hypoxia due to tissue shunting.41

MIXED VENOUS OXYGEN SATURATION (Svo2)

SvO2 is measured either intermittently by CO-oximetry on mixed venous samples or continuously by fibreoptic reflectance oximetry using a modified PA catheter. SvO2 measurements have a number of potential uses:

1 To calculate CvO2 (Table 14.4). CvO2 can then be used to determine Qs/Qt, VO2I by the reverse Fick method, the oxygen extraction ratio (Table 14.4) and cardiac output by the Fick method.
2 As an indirect index of tissue hypoxia. A SvO2 value of 0.5 corresponds to the theoretical critical PvO2 of 26 mmHg. Values between 0.7 and 0.8 represent a desirable balance between global oxygen supply and demand (Table 14.4), with lactic acidosis appearing between 0.3 and 0.5.42 Values exceeding 0.8 can be seen in high-flow states such as sepsis, hyperthyroidism and severe liver disease.

SvO2 as a therapeutic target (> 0.7) failed to improve survival in a multicentre trial.43 Only two-thirds of the treatment group achieved the SvO2 target. Like PvO2, SvO2 is insensitive to cytopathic hypoxia and tissue shunting. In chronic heart failure, low values can be surprisingly well tolerated.

REGIONAL OXYGENATION INDICES

REGIONAL PCO248

Regional PCO2 reflects the balance between arterial blood CO2 content, tissue blood flow and tissue CO2 production. The CO2 gap, which is regional PCO2PaCO2, was devised to correct regional PCO2 for varying arterial CO2 content. As tissue blood flow falls, reduced CO2 clearance causes the CO2 gap to increase. With the onset of anaerobic metabolism, tissue CO2 production steadily decreases, although worsening regional metabolic acidosis generates some CO2 by proton titration of tissue and capillary image. A rising CO2 gap merely signals falling tissue blood flow. It cannot identify the onset of anaerobic metabolism.

GASTRIC TONOMETRY49

The impetus to develop regional gastric capnometry was the knowledge that splanchnic hypoperfusion occurs early in circulatory shock, tends to persist as ‘covert shock’, and is manifested by intramucosal hypercapnia and acidosis. A gastric tonometer was therefore developed as a modified nasogastric tube with a silicone balloon 11.4 cm from the tip. Gastric mucosal CO2 equilibrates with luminal CO2, which equilibrates with (and is measured in) fluid filling the balloon. Early on, this fluid was saline. Subsequently air was found to have more rapid equilibration characteristics, and automated cycling of air through an infrared CO2 analyser was far more efficient than measuring saline PCO2 intermittently and applying time-based correction factors.

The original concept involved calculation of intramucosal pH (pHi) via the Henderson–Hasselbalch equation, using gastric luminal PCO2 and arterial image. Intramucosal acidosis was defined as pHi < 7.3, and taken to indicate inadequate splanchnic perfusion. Changing the monitoring end-point from pHi to the mucosal–arterial CO2 gap (normally 8–10 mmHg) removed the most fundamental flaw – the use of arterial image as a surrogate for mucosal image. Automated air tonometry combined with simultaneous end-tidal CO2 measurement allows the regular calculation of a gastric to end-tidal CO2 gap, a parameter linked to outcome in high-risk surgery.50

Even with these improvements, the technique has not found widespread application, and is unlikely to do so for several reasons:

OTHER REGIONAL TECHNIQUES

Orthogonal polarisation spectroscopy (OPS) allows real-time in vivo imaging of microcirculatory blood flow.42 Tissue beds visualised in intensive care have included the sublingual, rectal, oral and ileal (via stoma) microcirculations. OPS can be combined with near-infrared spectroscopy to monitor deeper regional mitochondrial redox status, and with reflectance spectrophotometry for measurement of superficial microcirculatory oxygen saturation. Combinations of this type provide uniquely integrated information on oxygen transport distribution during sepsis and septic shock.

Other techniques showing promise include in vivo magnetic resonance imaging53 and optical spectroscopy.54

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