Respiratory Monitoring

American Society of Anesthesiologists Standards

The word monitoring is often associated with electronic instrumentation, and it is noteworthy that the current American Society of Anesthesiologists’ (ASA) Standards for Basic Anesthetic Monitoring states in Standard I that “Qualified anesthesia personnel shall be present in the room throughout the conduct of all general anesthetics, regional anesthetics, and monitored anesthesia care” ( Box 41.1 ). This precedes reliance on any instrumentation (as implied in Standard II), and clearly indicates that the anesthesia provider brings essential expertise and interpretation to monitoring beyond information provided by equipment. Increased safety in our specialty lies primarily in high-quality training and environments that encourage continuing education, and not exclusively on new technology. The ASA Standards for Basic Anesthetic Monitoring reflect monitoring principles during anesthesia established in the 1980s ³ and should be systematically followed. The standards represent a foundation to additional monitoring according to clinical requirements.

Physiologic Fundamentals

The primary role of the cardiorespiratory system is the transport of O ₂ and CO ₂ throughout the body. O ₂ delivery is quantified as the product of arterial O ₂ content and cardiac output (see Chapter 13 , “Respiratory Physiology and Pathophysiology”). Arterial O ₂ content (C _a O ₂ , in mL of O ₂ per 100 mL of blood [hemoglobin—Hb], mL/100 mL) is calculated as

where 1.34 mL/g is the O ₂ binding capacity of Hb (i.e., Hüfner constant, theoretically equal to 1.39 mL/g but experimental range between 1.31 and 1.37 mL/g because of the presence of small amounts of other Hb species ); S _a O ₂ is the O ₂ saturation of Hb in the arterial blood (percent saturation/100); Hb is the concentration of Hb in the arterial blood (g/dL); 0.0031 is the solubility of O ₂ in blood (mL/100 mL/mm Hg); and P _a O ₂ is the arterial partial pressure of O ₂ (mm Hg). As can be inferred from Eq. (41.1) , S _a O ₂ and Hb are the major determinants of O ₂ content in the blood and consequently O ₂ delivery to the tissues.

Five species of Hb are found in adult blood: oxygenated Hb (O ₂ Hb), deoxygenated Hb (deO ₂ Hb); carboxyhemoglobin (COHb); methemoglobin (MetHb); and sulfhemoglobin (SHb). Under normal circumstances, the concentrations of COHb, MetHb, and SHb are small (1%-3% for COHb and less than 1% for MetHb and SHb). Functional O ₂ saturation (S _a O ₂ ) refers to the amount of O ₂ Hb as a fraction of the total amount of O ₂ Hb and deO ₂ Hb and is expressed as

The O ₂ Hb fraction or fractional saturation is defined as the amount of O ₂ Hb as a fraction of the total amount of Hb :

S _a O ₂ is a function of the P _a O ₂ . The relationship between the two is described by the O ₂ Hb dissociation curve ( Fig. 41.2 ). As can be appreciated by inspection of the curve, the relationship is not linear. This has important consequences. First, a high S _a O ₂ cannot discriminate between normoxic and hyperoxic conditions; this can be relevant when attempting to limit O ₂ exposure in neonates or patients at risk for O ₂ toxicity. Second, a large numeric change in P _a O ₂ at the flat portion of the curve (P _a O ₂ approximately above 70 mm Hg) has relatively small consequences in terms of blood O ₂ content. Furthermore, changes in temperature, pH, P _a CO ₂ , and erythrocyte 2,3-diphosphoglycerate concentration can shift the curve such that the same S _a O ₂ can be present under a range of different oxygen partial pressures (PO ₂ ). This may be relevant, given that diffusion from the microcirculation to tissue depends on PO ₂ gradients.

Measurement Principles

Oximetry

Oximetry is the measurement of the O ₂ saturation of Hb. It is an application of the Beer-Lambert law ( Eq. 41.4 ), which relates the transmission of light through a solution to the concentration of the solute in the solution. For each solute in a solution,

${\text{I}}_{\text{trans}}={\text{I}}_{\text{in}}{\text{e}}^{-\text{DC}\epsilon }$

where I _trans is the intensity of transmitted light, I _in is the intensity of the incident light, e is the base of the natural logarithm, D is the distance the light is transmitted through the solution, C is the concentration of the solute, and ε is the extinction coefficient of the solute.

The concentration of a single solute in solution can be calculated by measuring the amount of light transmitted through the solution as long as the other variables are known. For a solution containing multiple solutes, the calculation of the concentrations of the different solutes requires that light absorption be measured at a number of different wavelengths at least equal to the number of solutes. In a sample of blood in a cuvette, the absorption of a given wavelength of light passing through the blood will depend on the concentrations of the different species of Hb. Fig. 41.3 A illustrates the absorption spectra of the five species of Hb for wavelengths of light along the visible spectrum. To measure the concentrations of all five species of Hb in a sample of blood, light absorption of at least five different wavelengths must be measured. This measurement is typically conducted using a co-oximeter. A co-oximeter uses the principle of oximetry to measure the S _a O ₂ as well as the concentrations of other Hb species in a blood sample. Co-oximetry is considered the gold standard for S _a O ₂ measurements and is relied on in circumstances when pulse oximetry readings are inaccurate or unobtainable.

Pulse Oximetry

Standard pulse oximetry aims to provide a noninvasive, in vivo, and continuous assessment of functional S _a O ₂ . Estimates of S _a O ₂ based on pulse oximetry are denoted as S _p O ₂ . The history of the development of the pulse oximetry has been reviewed in detail elsewhere.

Pulse oximetry takes advantage of the pulsatility of arterial blood flow to provide an estimate of S _a O ₂ by differentiating light absorption by arterial blood from light absorption by other components. When compared with in vitro oximetry of an arterial blood sample, the challenge of obtaining arterial O ₂ saturation in vivo is to ensure that the light is sampling arterial blood and to account for its absorption by other tissues. As illustrated in Fig. 41.4 , light absorption by tissue can be divided into a time-varying (pulsatile) component, historically referred to as “AC” (from “alternating current”), and a steady (nonpulsatile) component, referred to as “DC” (“direct current”). In conventional pulse oximetry, the ratio (R) of AC and DC light absorption at two different wavelengths is calculated. The wavelengths of light are selected to maximize the difference between the ratios of the absorbances of O ₂ Hb and deO ₂ Hb (see Fig. 41.3 B ). The most commonly used wavelengths of light are 660 nm and 940 nm. At 660 nm, there is greater light absorption by deO ₂ Hb than by O ₂ Hb. At 940 nm, there is greater light absorption by O ₂ Hb than by deO ₂ Hb,

$\text{R}=\frac{{\text{AC}}_{660}/{\text{DC}}_{660}}{{\text{AC}}_{940}/{\text{DC}}_{940}}$

where AC ₆₆₀ , AC ₉₄₀ , DC ₆₆₀ , and DC ₉₄₀ denote the corresponding AC and DC components of the 640-nm and 940-nm wavelengths.

The ratio R is then empirically related to O ₂ saturation based on a calibration curve internal to each pulse oximeter ( Fig. 41.5 ). Each manufacturer develops its own calibration curve by having volunteers breathe hypoxic gas mixtures to create a range of S _a O ₂ values between 70% and 100%. The FDA recommends root mean square differences between measured values (S _p O ₂ ) and reference values (S _a O ₂ ) under normal conditions ranging from 70% to 100% S _p O ₂ of ≤3.0% for transmittance, wrap and clip pulse oximeter sensors and of ≤3.5% for ear clip and reflectance sensors. Most manufacturing literature reports an accuracy of ± 2% to 3% S _p O ₂ over this range. The dependence of S _p O ₂ on pulsatility may result in inaccurate estimates of S _a O ₂ when pulsatility is reduced or absent.

A pulse oximeter probe is composed of a light emitter and a photodetector. Transmission pulse oximetry involves the placement of the emitter and detector on opposite sides of the tissue being measured, usually of a finger. Reflectance pulse oximetry probes have the emitters and detector arranged on the same side. They are typically placed on the forehead. In a typical pulse oximeter, two light-emitting diodes (LEDs) are used to emit light at the two wavelengths. During operation, each LED is turned on and off in sequence. The photodetector measures transmission of light from each LED. When both LEDs are turned off, the photodetector measures ambient light and subtracts it from the signals obtained throughout the remainder of the cycle.

Pulse oximetry has been an integral component of intraoperative anesthetic management since the first anesthetic monitoring standards were introduced in 1986. It was adopted as a minimum monitoring standard by the ASA the same year and has subsequently been defined as a minimum standard for intraoperative monitoring by the World Federation of Societies of Anaesthesiologists and the World Health Organization (WHO). The use of pulse oximetry is a part of the WHO safe surgery checklist.

Multiwavelength pulse oximeters—that is, pulse oximeters with additional wavelengths of light to allow for the continuous noninvasive measurement of total hemoglobin concentration (S _p Hb) —as well as concentrations of MetHb and COHb utilizing up to 12 wavelengths have been developed. S _p Hb in the surgical and intensive care unit (ICU) settings has shown reasonable bias and precision when compared with laboratory measurements. However, few of the measurements were obtained in patients with Hb concentrations within the clinically relevant range of 6 to 10 mg/dL. Another limitation of S _p Hb may be its absent or unreliable signal under conditions of low peripheral perfusion. To date, noninvasive COHb measurements have not shown enough precision to replace laboratory measurements. Accuracy has improved at hypoxic O ₂ levels, but detecting COHb for S _a O ₂ less than 87% is still unreliable. Pulse oximetry-based MetHb measurements with a newer device are accurate, even under conditions of hypoxia.

Universal pulse oximetry has been recommended by the US Secretary of Health and Human Services to screen newborns for critical congenital heart disease. Use of a clinical algorithm based on detection of S _p O ₂ lower than 95% in either right upper or lower limbs, or more than a 2% difference led to a sensitivity of 75% in suspected cases and 58% in cases that were not suspected. When this modality is combined with a routine anomaly scan and newborn physical examination screening, 92% of critical congenital heart disease lesions can be identified.

Photoplethysmography . Along with measuring O ₂ saturation, the pulse oximeter can also be used as a photoplethysmograph. Because the absorption of light is proportional to the amount of blood between the transmitter and photodetector, changes in the blood volume are reflected in the pulse oximeter trace ( Fig. 41.6 ). During anesthesia, the plethysmographic trace is affected by changes in blood volume pulsations, which depends on the distensibility of the vessel wall, as well as on the intravascular pulse pressure. Variations in the amplitude of the pulse oximetry plethysmographic waveform (ΔPOP) have been shown to predict fluid responsiveness in mechanically ventilated patients. An index derived from the percent difference between the maximum and minimum amplitudes of the plethysmographic waveform during a respiratory cycle (PVI, Pleth Variability Index) has been incorporated into a commercially available pulse oximeter and used to quantify ΔPOP and predict fluid responsiveness. A number of studies have shown it to be a reasonably reliable indicator of fluid responsiveness perioperatively and in critically ill patients. The technique does have greater reliability in mechanically ventilated patients compared with spontaneously breathing patients, but its accuracy may be compromised by the presence of cardiac arrhythmias. Its accuracy has also been shown to be better for 500 mL fluid challenges compared with 250 mL. Goal-directed fluid management based on PVI has been shown to improve outcomes in major abdominal surgery.

Limitations and Sources of Error

S _p O ₂ is an estimate of S _a O ₂ of circulating hemoglobin. As a consequence, it does not provide information about tissue oxygenation. Because S _p O ₂ is a measurement of functional and not fractional S _a O ₂ , the presence of other Hb variants can significantly affect its accuracy. The nonlinearity of the Hb dissociation curve prevents the detection of hyperoxia with S _p O ₂ for high S _a O ₂ , whereas for low saturations such as at altitude, small changes in P _a O ₂ can produce large changes in S _p O ₂ . There is significant variability in the actual in vivo Hb dissociation curve. Thus changes in S _p O ₂ are not necessarily well correlated with changes in S _a O _2. These measurements illustrate that knowledge of the individual Hb dissociation curve is important for correct interpretation of S _a O ₂ and P _a O ₂ . More importantly, pulse oximetry does not provide information about ventilation or acid-base status.

A number of conditions can lead to inaccuracies in pulse oximeter readings ( Table 41.1 ). These conditions include decreased perfusion, motion artifact, venous pulsation, low S _a O ₂ , variant Hb species, the presence of intravascular dyes, and the presence of nail polish.

Despite the recommendations of numerous boards and guidelines, there is no evidence that the use of pulse oximetry improves patient outcomes, not during transfers to ICUs nor in terms of improving patient mortality. There is evidence that pulse oximetry reduces the incidence of hypoxemia, and the duration and cost of ICU stay, suggesting it allows for early intervention.

The calibration of pulse oximeters is based on curves obtained in normal individuals under experimental conditions with S _a O ₂ as low as 70%. As such, pulse oximeters have limited accuracy for S _a O ₂ values less than 70%. Moreover, systematic errors in S _p O ₂ tend to increase as S _a O ₂ falls below 90%. At S _a O ₂ levels under 70%, a positive or negative bias of the S _p O ₂ value can be observed, depending on the manufacturer of the pulse oximeter. Manufacturers have developed pulse oximeters with increased accuracy at saturations as low as 60%. Preliminary data suggest that these probes may be useful in neonates with cyanotic congenital heart disease.

Hypoperfusion leads to a reduction in the amplitude of the pulsatile component of the light absorbance waveform, the essential signal for pulse oximetry, consequently giving rise to absent or inaccurate readings. Significantly erroneous reductions in S _p O ₂ may be observed for systolic blood pressures lower than 80 mm Hg. Motion artifact can produce considerable error in the pulse oximeter reading. Manufacturers have developed advanced proprietary signal processing algorithms that effectively filter out noise caused by motion.

With continued clinical use, the performance of the LEDs in the probe may be degraded, leading to inaccuracy in the S _p O ₂ value outside of the range specified by the manufacturer. These inaccuracies are expected to be more pronounced at lower saturations (i.e., <90%).

Venous pulsations may result in the detection of venous O ₂ Hb saturation by the pulse oximeter, resulting in artifactual reduction of the presumed arterial S _p O ₂ being measured. Venous pulsations can be due to excessively tight placement of adhesive finger probes, severe tricuspid regurgitation, probe placement in dependent positions (e.g., forehead during Trendelenburg position), and possibly in distributive shock when vasodilation may result in physiologic arteriovenous shunting.

The presence of additional species of Hb can also generate erroneous pulse oximeter readings. As outlined earlier, the function of the pulse oximeter is predicated on the assumption that the only components present in the blood capable of absorbing light at the two wavelengths used are O ₂ Hb and deO ₂ Hb. Under normal circumstances, this assumption is valid, and the S _p O ₂ readings accurately reflect the S _a O ₂ . However, the presence of significant concentrations of other Hb species or substances absorbing light at the used wavelengths will lead to erroneous S _p O ₂ readings. As illustrated in Fig. 41.3 , both COHb and MetHb absorb light at one or both of the wavelengths used by the pulse oximeter. Accordingly, the presence of these Hb species will produce errors in S _p O ₂ . The absorption of light at 660 nm by COHb is similar to that of O ₂ Hb. At 940 nm, COHb absorbs virtually no light. Thus, in a patient with carbon monoxide poisoning, the S _p O ₂ will be falsely elevated. MetHb absorbs a significant amount of light at both 660 nm and 940 nm. As a result, in its presence, the ratio of light absorption R ( Eq. 41.5 ) approaches unity. An R-value of 1 represents the presence of equal concentrations of O ₂ Hb and deO ₂ Hb and corresponds to an S _p O ₂ of 85%. Thus, in a patient with methemoglobinemia, the S _p O ₂ will be 80% to 85%, irrespective of the S _a O ₂ . SHb absorbs red light (660 nm) more than deoxyhemoglobin (HHb) or MetHb, and likely as much near the infrared spectrum. This results in S _p O ₂ values close to 85% in severe cases of sulfhemoglobinemia. Although newer generations of co-oximeters can detect SHb, most existing co-oximeters cannot; consequently, additional clinical laboratory testing may be required if sulfhemoglobinemia is suspected.

With normal S _a O ₂ , anemia has little effect on S _p O ₂ . However, in the presence of hypoxia, S _p O ₂ readings underestimate S _a O ₂ in anemic patients with true hypoxemia. Pulse oximeters are sufficiently accurate in adult patients with sickle cell disease, as well as in the presence of fetal Hb. However caution is warranted when using pulse oximetry in patients with sickle cell disease, because heme metabolism may result in elevated COHb. Some studies also suggest that S _p O ₂ may overestimate S _a O ₂ during vaso-occlusive crises. Another relevant point is that in patients with sickle cell disease, the affinity of O ₂ for Hb is normal under normoxic conditions but becomes low during hypoxia.

A relatively uncommon cause for reduced S _p O ₂ readings is the presence of congenital variants of Hb. Some variants, such as Hb Bassett, Hb Rothschild, and Hb Canabiere, have a reduced affinity for O ₂ , and changes in S _p O ₂ appropriately reflect changes in S _a O ₂ . Other variants, such as Hb Lansing, Hb Bonn, Hb Koln, Hb Cheverly, and Hb Hammersmith, have altered absorption spectra (closer to HHb) that result in low S _p O ₂ readings in the setting of normal S _a O ₂ .

The administration of intravenous dyes can result in inaccurate S _p O ₂ readings. Methylene blue leads to a transient, marked decrease in S _p O ₂ down to 65% due to its peak light absorption at 668 nm, which is very close to that of HHb. Indigo carmine and indocyanine green also artificially decrease S _p O ₂ measurements, although to a lesser extent than methylene blue, because they do not substantially absorb red light. Isosulfan blue can produce a prolonged reduction at higher doses.

Although all colors of nail polish can reduce the calculated value of S _p O ₂ , black, purple, and dark blue colors have the greatest effect. Nonetheless, the error generally remains within 2%. Depending on the brand of pulse oximeter, artificial acrylic nails may impair S _p O ₂ readings, although generally not to a clinically significant extent. Under conditions of normal S _a O ₂ , skin pigmentation has no effect on S _p O ₂ estimates. However, increased skin pigmentation is associated with S _p O ₂ values that overestimate S _a O ₂ by as much as 8% for S _a O ₂ less than 80%.

In the presence of severe hyperbilirubinemia (30 mg/dL or greater) caused by increased hemolysis or liver disease, the fraction of oxygenated hemoglobin (FO ₂ Hb) may be falsely low by artifactual increase in MetHb and COHb, resulting in more accurate S _p O ₂ than FO ₂ Hb measurements. Although earlier case reports and small studies have suggested that ambient light may interfere with the accuracy of S _p O ₂ readings, a large prospective study found no significant effect on S _p O ₂ accuracy with exposure to five types of light sources: quartz-halogen, incandescent, fluorescent, infant bilirubin lamp, and infrared. Infrared light pulses from image guidance systems used for navigational neurosurgery can interfere with pulse oximetry readings by causing decreased readings or disruptions in S _p O ₂ waveform detection. Different pulse oximeters show variable susceptibility to such interference. Shielding the probe with a single layer of aluminum foil can protect from this effect. Misplacement of the probe can allow for direct detection of LED light by the photodetector. This optical shunt gives rise to an S _p O ₂ reading of 85%.

In patients with intraaortic balloon pump support, S _p O ₂ accuracy depends on the brand of pulse oximeter used as well as the support ratio. Accuracy is generally reduced in the setting of higher support ratios. In patients with continuous flow ventricular assist devices, pulse oximetry may not be possible because of the absence of pulsatile flow. In these cases, the use of cerebral oximetry as an adjunct is advocated.

Physiologic Fundamentals

Mixed venous oxygen saturation ( ${\text{S}\overline{\text{v}}\text{O}}_2$ ) is the O ₂ saturation of blood at the proximal pulmonary artery. It has been a frequently monitored variable in critically ill patients, since it reflects the average O ₂ saturation of the blood returning from the body to the right heart, weighted by the respective regional blood flows. As such, it is a measure of the balance between global oxygen delivery (DO ₂ ) and global oxygen uptake ( ${\dot{\text{V}}}_{{\text{O}}_2}$ ), and a useful resuscitation target. Factors that influence the ${\text{S}\overline{\text{v}}\text{O}}_2$ can be illustrated through a derivation of the mixed venous O ₂ content equation.

${\dot{\text{V}}}_{{\text{O}}_2}$ (mL/min) is defined as

where ${\dot{\text{Q}}}_{\text{T}}$ is the cardiac output (L/min), and ${\text{C}\overline{\text{v}}\text{O}}_2$ is the O ₂ content of the mixed venous blood (mL/100 mL).

Rearranging Eq. (41.6) to solve for ${\text{C}\overline{\text{v}}\text{O}}_2$ yields

The contribution of dissolved O ₂ to the blood O ₂ content is small. By expanding the definition of O ₂ content ( Eq. 41.1 ) and ignoring the term for dissolved O ₂ , Eq. (41.7) can be rewritten as

Normal values of ${\text{S}\overline{\text{v}}\text{O}}_2$ range between 65% and 80%. Values close to 40% are associated with tissue hypoxia, anaerobic metabolism, and lactate production. ${\text{P}\overline{\text{v}}\text{O}}_2$ can be derived from ${\text{S}\overline{\text{v}}\text{O}}_2$ values by utilizing the O ₂ Hb dissociation curve adjusted to mixed-venous pH, PCO ₂ , and temperature (see Fig. 41.2 ). The normal value of ${\text{P}\overline{\text{v}}\text{O}}_2$ is 40 mm Hg.

DO ₂ is defined as

As is evident from Eq. (41.8) , a low ${\text{S}\overline{\text{v}}\text{O}}_2$ indicates either a reduction in DO ₂ secondary to low S _a O ₂ , low Hb, or low ${\dot{\text{Q}}}_{\text{T}}$ , or an increase in ${\dot{\text{V}}}_{{\text{O}}_2}$ . The association among ${\text{S}\overline{\text{v}}\text{O}}_2$ , DO ₂ , and ${\dot{\text{V}}}_{{\text{O}}_2}$ can be illustrated by expressing ${\text{S}\overline{\text{v}}\text{O}}_2$ as a function of the O ₂ extraction ratio, ERO ₂ .

Expanding the terms yields

Assuming that the O ₂ dissolved in plasma is a negligible component to total O ₂ content dissolved in the arterial or mixed venous blood, Eq. (41.11) can be rewritten as

For conditions in which the arterial blood is fully saturated, Eq. (41.12) may be further simplified:

Solving for ${\text{S}\overline{\text{v}}\text{O}}_2$ yields

Thus a reduction in ${\text{S}\overline{\text{v}}\text{O}}_2$ results from an increase in ERO ₂ , from either an increased ${\dot{\text{V}}}_{{\text{O}}_2}$ or a decreased DO ₂ ( Fig. 41.7 ). A decrease in DO ₂ occurs in conditions such as hemorrhagic or hypovolemic shock. An increase in ${\dot{\text{V}}}_{{\text{O}}_2}$ may occur in conditions such as stress, pain, shivering, sepsis, and thyrotoxicosis. Conversely, an increase in ${\text{S}\overline{\text{v}}\text{O}}_2$ indicates either an increase in O ₂ supply (elevated S _a O ₂ , Hb, or ${\dot{\text{Q}}}_{\text{T}}$ ) or a reduction in ${\dot{\text{V}}}_{{\text{O}}_2}$ , as occurs during hypothermia.

There are some subtle considerations in the interpretation of changes in ${\text{S}\overline{\text{v}}\text{O}}_2$ . At PO ₂ values typical of venous blood, small increases in the fraction of inspired oxygen (F _I O ₂ ) can cause significant increases in ${\text{S}\overline{\text{v}}\text{O}}_2$ because of the shape of the O ₂ Hb dissociation curve ( Fig. 41.2 ). Therefore, when ${\text{S}\overline{\text{v}}\text{O}}_2$ is tracked as a measure of cardiac function, changes in F _I O ₂ must be taken into account during its interpretation. In the setting of septic shock, impairment in O ₂ extraction may yield normal ${\text{S}\overline{\text{v}}\text{O}}_2$ values, despite the presence of tissue hypoxia.

Direct measurement of ${\text{S}\overline{\text{v}}\text{O}}_2$ requires the insertion of a pulmonary artery catheter, a procedure associated with some morbidity. However, in most clinical situations, the O ₂ saturation of a blood sample drawn from a central venous catheter will suffice. Thus the use of central venous saturation can be a surrogate for ${\text{S}\overline{\text{v}}\text{O}}_2$ . The saturation of blood at the level of a central venous catheter placed in the superior vena cava (S _cv O ₂ ) reflects the balance between O ₂ supply and demand in the brain and upper extremities. Under normal physiologic conditions, S _CV O ₂ is typically 2% to 5% less than ${\text{S}\overline{\text{v}}\text{O}}_2$ , primarily because of the higher O ₂ content of splanchnic and renal venous blood. However, during hemodynamic instability, as circulation is redistributed to the upper body, the relationship between ${\text{S}\overline{\text{v}}\text{O}}_2$ and S _CV O ₂ may reverse, and the difference between the two may increase significantly. Although trends in S _CV O ₂ may reflect those in ${\text{S}\overline{\text{v}}\text{O}}_2$ , the two measures cannot be used interchangeably.

Mixed venous CO ₂ has been used to compute the arteriovenous CO ₂ difference (ΔPCO ₂ = P ${\overline{\text{v}}\text{C}\text{O}}_2$ −P _a CO ₂ ). In conditions of steady-state CO ₂ production, ΔPCO ₂ changes inversely and nonlinearly with cardiac output as a result of the Fick equation. Accordingly, ΔPCO ₂ is an indicator of the adequacy of cardiac output to provide adequate clearance of tissue CO ₂ . However, because of several limitations, the parameter has not yet found widespread clinical use.