Arterial Gases

The variables that determine alveolar gas tension have been described. The following additional factors also determine the gas tensions in arterial blood:

1. Ventilation-perfusion (V̇A/) mismatching
2. Right-to-left shunt
3. Diffusion nonequilibrium

To understand fully the role of V̇A/ in determining arterial gas tensions, it is necessary to discard the homogeneous lung model and consider a model with multiple parallel units of gas exchange and blood flow in which the resulting arterial gas tension is determined by the mixing of different proportions of blood from each gas exchange unit. The gas tensions in each unit depend on the regional ventilation, perfusion, and diffusion.

Gas exchange units with low or zero V̇A/ ratios have low end-capillary PO₂ . The O₂ -blood dissociation curve has a plateau at the point at which hemoglobin is fully saturated (see Fig. 36-9 ), and there is a maximum to which gas exchange units with normal ventilation and perfusion can raise the end-capillary O₂ content. Arterial O₂ content (and therefore PO₂ ) is a flow weighted average of all gas exchange units. Under usual conditions, V̇A/ mismatching always results in arterial hypoxemia. The only circumstance in which V̇A/ mismatch results in increased arterial PO₂ is during the uptake of nitrous oxide.

The effect of V̇A/ mismatching on PaCO₂ is often erroneously assumed to be negligible because PaCO₂ can usually be maintained within the normal range, even in the face of severe pulmonary pathology. This is true because the CO₂ -blood dissociation curve ( Fig. 36-2 ) is a monotonically increasing one. Moreover, the degree to which end-capillary PCO₂ (Pc'CO₂ ) can be increased by gas exchange units with abnormal V̇A/ is relatively small. The venoarterial PCO₂ difference is usually only 5 mm Hg under resting conditions and rarely exceeds 10 mm Hg. It is therefore usually possible for lung units with low PACO₂ (and therefore

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Figure 36-2 Carbon dioxide (CO₂ ) content of arterial blood as a function of PCO₂ . For a given PCO₂ deoxygenated blood has a higher CO₂ content than oxygenated blood (i.e., Haldane effect). Unlike the HbO₂ saturation curve, the CO₂ content curve has no plateau and can be approximated by a straight line in the clinically useful range. (Data from Christiansen J, Douglas CG, Haldane JS: The absorption and dissociation of carbon dioxide by human blood. J Physiol [Lond] 48:244, 1914.)

Figure 36-3 Arterial PO₂ as a function of FIO₂ and shunt fraction (S/T). Assumptions are shown on the upper left of the graph. The presence of a shunt decreases arterial PO₂ for a given FIO₂ . As S/T increases, supplemental O₂ has progressively less effect on arterial PO₂ . (Adapted from Benumof JL: Anesthesia for Thoracic Surgery, 2nd ed. Philadelphia, WB Saunders, 1995, and Lawler PGP, Nunn JF: A reassessment of the validity of the iso-shunt graph. Br J Anaesth 56:1325, 1984.)

Right-to-left shunting is a special case of V̇A/ mismatch, with a V̇A/ ratio of zero. Blood flowing through a right-to-left shunt, whether intrapulmonary or intracardiac, has gas tensions equal to mixed venous values. The net effect on arterial PO₂ and PCO₂ depends on the magnitude of the shunt ( Fig. 36-3 ) and the mixed venous and pulmonary capillary gas tensions. Because major determinant of mixed venous PO₂ (and to a lesser extent mixed venous PCO₂ ) is cardiac output (), changes in may modify the degree to which arterial PO₂ is determined by pulmonary gas exchange ( Fig. 36-4 ).

Diffusion nonequilibrium can exist when the gas tensions in the pulmonary capillary erythrocyte (Pc'O₂ , Pc'CO₂ ) are not equal to the alveolar gas tensions. This can occur under two physiologic conditions: increased pulmonary blood flow such that the erythrocyte does not have sufficient time in the alveoli to enable gas tensions to reach equilibrium or a thickening of the alveolar-capillary membrane such that the rate of diffusion of gas from alveolus to capillary (O₂ ) or vice versa (CO₂ ) is slowed. For CO₂ diffusion, nonequilibrium would result in an arterial PCO₂ (PaCO₂ ) value higher than that of PACO₂ . For O₂ , nonequilibrium means that PaO₂ is less than PAO₂ . In practice, there has never been any evidence for failure of diffusion equilibrium of CO₂ . Despite much discussion of O₂ diffusion nonequilibrium, it probably rarely exists in clinical medicine. There is evidence for its existence during moderate exercise in patients with interstitial fibrosis and during severe exercise in normal individuals, particularly at higher altitudes.^[7] In anesthesia or critical care, O₂ diffusion nonequilibrium would probably occur only under very unusual circumstances, such as a septic patient with high cardiac output breathing air at the top of Pike's Peak (i.e., altitude of 4301m and barometric pressure of 444 mm Hg).

The following are the most likely causes of low PaO₂ :

1. Low PIO₂
2. Hypoventilation
3. V̇A/ mismatching, including right-to-left shunt (effect modified by mixed venous PO₂ )

A common measurement used to assess the adequacy of pulmonary gas exchange is the alveolar-arterial (A-a) gradient:

A-a gradient = PAO₂ − PaO₂ (7)

Calculation of the A-a gradient takes into account any degree of hypoventilation or low inspired PO₂ such that an abnormally high A-a gradient reflects a V̇A/ mismatch (more specifically, low V̇A/ in gas exchange units) or shunt. The normal value of A-a gradient for a child or young adult is less than 10 mm Hg, with an increase due to aging^[14] according to the following formula:

A-a gradient = 0.21 × (age in years + 2.5) (8)

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Figure 36-4 Effect of cardiac output on PO₂ . A, Arterial and mixed venous O₂ tension and content are shown at a cardiac output of 5 L/min. B, Assuming a constant V̇O₂ , an increase in cardiac output to 8 L/min increases the PaO₂ from 78 to 85 mm Hg. This occurs because Sv̄O₂ increases at higher cardiac output. The resulting increase in O₂ content of the shunted blood (here assumed to be 10% of cardiac output) then raises arterial O₂ content and PaO₂ . PO₂ values are in mm Hg, and O₂ content is in mL/dL.

There is considerable scatter of the data around the mean values predicted by the relationship in Equation 8, with individual values for the A-a gradient exceeding 30 mm Hg. The A-a gradient also increases with abnormalities of pulmonary gas exchange. The usefulness of the A-a gradient may be demonstrated by an example. Interpretation of the following arterial blood gases in an unconscious individual in an emergency room (breathing room air) may be aided by calculating the A-a gradient: PaO₂ = 50 mm Hg, PaCO₂ = 76 mm Hg, and pH = 7.17. Assuming that barometric pressure = 760 mm Hg, body temperature = 37°C (therefore PH₂ O = 47 mm Hg), and R = 0.8 (in this case using Equation 2), PAO₂ = 59 mm Hg. The A-a gradient therefore equals 59 − 50 = 9 mm Hg, a normal value. Because the impairment of arterial oxygenation is associated with a normal A-a gradient, there is no intrinsic abnormality of pulmonary gas exchange. The diagnosis is most likely central respiratory depression.

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A problem with the clinical use of the A-a gradient is that its normal value is highly dependent on inspired O₂ concentration. As FIO₂ increases, the A-a gradient becomes larger. In a normal individual breathing 100% O₂ , the A-a gradient can exceed 70 mm Hg. A more useful parameter that obviates this problem is the a/A ratio (i.e., PaO₂ /PAO₂ ). Empirically, the a/A ratio has been shown to be relatively constant with varying FIO₂ , ^[15] even in a hyperbaric chamber up to an ambient pressure of 3 atm absolute (see Chapter 70 ). The normal a/A ratio is 0.85; lower values indicate impaired pulmonary gas exchange.

If mixed venous blood is available for analysis, a solution can be found for a simplified but clinically useful compartmental model of the lung. This three-compartment model assumes the following division of gas exchange units within the lung:

A compartment with V̇A/ = 1 (optimal matching of ventilation and perfusion)

A compartment with V̇A/ = 0 (shunt compartment)

A compartment with V̇A/ = ∞ (dead space compartment)

Shunt fraction (venous admixture) is the proportion of total blood flow perfusing the shunt compartment and can be calculated from the following equation:





In Equation 9, S is shunt blood flow, and T is cardiac output. Cc'o₂ , Cao₂ , and Cv̄o₂ are the O₂ contents of end-capillary, arterial, and mixed venous blood, respectively. Cao₂ and Cv̄o₂ can be calculated directly. Cc'o₂ must be calculated from PAo₂ and the Hb-O₂ dissociation curve.





In Equation 10, the O₂ content is given in mL/dL; PO₂ is in mm Hg; and the hemoglobin concentration is in g/dL.

If PAO₂ is high enough that end-capillary blood has a hemoglobin O₂ saturation close to 100%, by dividing numerator and denominator by the O₂ capacity (i.e. O₂ content at 100% saturation) Equation 8 can be rewritten as the following approximation:





S/T calculated using either equation (i.e., using O₂ as the "marker gas") includes gas exchange units of low V̇A/ in addition to pure shunt. Breathing 100% O₂ , however, eliminates the contribution of low V̇A/ gas exchange units to S/T because any lung unit with nonzero V̇A/ fully saturates with O₂ the capillary blood perfusing it. Use of this technique to assess shunt is complicated by the fact that breathing 100% O₂ results in the progressive development of resorption atelectasis and a parallel increase in shunt.^[16]

Whereas pathology that affects pulmonary O₂ exchange (typically low V̇A/ or shunt) can be detected by inspection of the arterial blood gases and FIO₂ (or formal calculation of the a/A ratio), lung abnormalities that affect pulmonary CO₂ exchange (typically high V̇A/ gas exchange units or dead space) require additional information. To measure physiologic dead space (VDS), the Bohr equation can be used:





In Equation 12, PECO₂ is the mixed expired PCO₂ and VT is the tidal volume. PACO₂ can be assumed equal to PaCO₂ (i.e., Enghoff modification). To measure PECO₂ , expired gas must be analyzed in a mixing box, or a bag must be used to collect several expired breaths. Alternatively, PECO₂ can be measured by placing a CO₂ sensor in a bypass flow-mixing chamber (i.e., bymixer) in the expiration limb of an anesthesia or ventilator circuit ( Fig. 36-5 ).^[17] The dead space calculated using this equation includes anatomic and physiologic dead space, as well as external dead space such as in the breathing circuit. Dead space can also be measured on a breath-by-breath basis if a volume capnogram is used (see Fig. 36-17 ). Dead space measured using this formula (i.e., total physiologic dead space) includes airway dead space (i.e., anatomic or series dead space) and alveolar dead space (i.e., intrapulmonary or parallel dead space). Dead space is usually expressed as a fraction of the tidal volume (VD/VT ratio).

Mixed expired gas analysis is often not clinically available, but an assessment of dead space ventilation may be made by examining the relationship between minute ventilation (V̇E) and PaCO₂ . V̇E is continuously displayed by modern ventilators, including anesthesia ventilators, and can be measured in spontaneously breathing individuals by using a spirometer. Assuming normal V̇CO₂ , the following equation^[18] describes an empirical relationship:

V̇E × PaCO₂ ≤ 8 W (13)

In Equation 13, W is the body weight. If V̇E (L/min) times PaCO₂ (mm Hg) exceeds eight times the body weight (kg), an increase in dead space exists, indicating that to maintain a normal PaCO₂ , higher than usual ventilation is required. V̇E × PaCO₂ can also be elevated by increased CO₂ production (e.g., shivering, fever, metabolic acidosis).

Figure 36-5 Bymixer. This compartment, placed in the expiratory limb of a circle system, provides a mixing chamber through which a portion of the exhaled gas flows. Mixing of gas within this chamber provides constant mixed expired O₂ and CO₂ concentrations, from which V̇O₂ , V̇CO₂ , and dead space can be calculated. (Adapted from Breen PH, Serina ER: Bymixer provides on-line calibration of measurement of CO₂ volume exhaled per breath. Ann Biomed Eng 25:164, 1997.)

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Using the respiratory gases to assess pulmonary gas exchange has some drawbacks. First, the relationship between partial pressure and gas content is nonlinear for both O₂ and CO₂ . Alterations in cardiac output, hemoglobin concentration (resulting in altered venous blood gas tensions), or inspired gas composition may lead to different calculated values of S/T or VD/VT even if actual V̇A/ ratios in the lung are unchanged. ^[19] Second, changes in O₂ or CO₂ exchange can provide information only on a limited portion of the spectrum of V̇A/ ratios. An increase in calculated S/T (Equation 9) cannot distinguish between a shift to lower V̇A/ ratios and an increase in true shunt.

In a more sophisticated technique described by Wagner and coworkers, ^{[16] [20]} a dilute mixture of several inert (i.e., not metabolically active) tracer gases is infused intravenously. The ratio of partial pressures Pc'/Pv̄ or PA/Pv̄ at a gas exchange unit is described by the following equation:

Figure 36-6 Effect of anesthesia on pulmonary atelectasis and gas exchange. A, Computed tomography of the chest of an awake patient. Adjacent to the scan is the distribution of ventilation (open circles) and perfusion (solid circles) in a 50-compartment lung model, determined by using the multiple inert gas method. A unimodal distribution is shown for the awake individual with a shunt fraction (S/T) of 0.8%. B, After a period of general anesthesia with positive-pressure ventilation, crescent-shaped areas of increased tissue density (arrows) appear in posterior lung regions. Corresponding to these changes are a widening of both V̇A and distributions and an increase in S/T to 7.4%. C, The scan and data are shown for the same individual after application of 10 cm H₂ O of PEEP. Very little change is observed in the areas of atelectasis, and V̇A/ matching is further worsened, with the development of a bimodal ventilation distribution and a further increase in S/T to 11.1%. These changes are accompanied by a drop in PaO₂ from 162 to 137 mm Hg. (Adapted from Tokics L, Hedenstierna G, Strandberg A, et al: Lung collapse and gas exchange during general anesthesia: Effects of spontaneous breathing, muscle paralysis and positive end-expiratory pressure. Anesthesiology 66:157, 1987.)

In this technique of multiple inert gas (MIG) elimination, the six gases typically used are sulfur hexafluoride, ethane, cyclopropane, enflurane, diethyl ether, and acetone, spanning a partition coefficient of about 70,000. Each gas provides information about a particular region in the spectrum of V̇A/, permitting a multiple-compartment model to be calculated. The MIG method has been used to demonstrate the development of V̇A/ mismatching and shunt during general anesthesia.^[21] Figure 36-6 demonstrates the use of MIG to calculate a 50-compartment model of V̇A/. Using this model, shunt fraction assessed by using the MIG method has been correlated with atelectatic areas in dependent lung regions visible on chest computed tomography (CT) (see Fig. 36-5 ).^{[22] [23]} The MIG method has been used to demonstrate improved V̇A/ matching

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Figure 36-7 Hemoglobin-oxygen (OXYHb) saturation versus inspired partial pressure of oxygen (PO₂ ). The curves are plotted by changing inspired PO₂ in a stepwise fashion. A, A series of theoretical curves obtained by calculating the effect of different degrees of right-to-left shunt. Increasing shunt displaces the curves downward. B, The curve on the left of the graph (0%) is from a normal subject. The middle curve (30%) represented a 30% right-to-left shunt from the 30% curve seen in A. The curve on the right of this graph is from a patient undergoing thoracotomy for esophageal surgery. The points cannot be fitted by any of the shunt curve, but the fit is quite good when the 30% curve is shifted to the right. This implies a combination of shunt and V̇A/ mismatch. (Adapted from Jones JG, Jones SE: Discriminating between the effect of shunt and reduced VA/Q on arterial oxygen saturation is particularly useful in clinical practice. J Clin Monit Comput 16:337, 2000.)

A noninvasive method of assessing the independent effects of shunt and V̇A/ mismatching on arterial PO₂ is to plot simultaneously arterial O₂ saturation versus inspired PO₂ ( Fig. 36-7 ).^[30]