In Chapters 1 and 2, I reviewed the essential aspects of pulmonary physiology and discussed how the respiratory system uses the interrelated processes of ventilation and gas exchange to maintain a normal partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) in the arterial blood. Recall that the essential components of normal ventilation and gas exchange are:
• Delivery of oxygen
• Excretion of carbon dioxide
• Matching of ventilation and perfusion
• Gas diffusion
As I discussed in Chapter 7, disease-induced abnormalities of one or more of these components cause respiratory failure, which can be divided into oxygenation, ventilation, and oxygenation-ventilation failure, based on the PaO2 and PaCO2 and the difference between the calculated mean alveolar and measured arterial PO2 (the A–a gradient). This chapter reviews the tests that can be used to determine the type and severity of respiratory failure and the extent to which one or more of the components of normal ventilation and gas exchange have been compromised by disease.
PaO2 and SaO2
The simplest way to determine how much lung disease has interfered with normal gas exchange is to measure the PaO2 and arterial hemoglobin saturation (SaO2). The arterial hemoglobin saturation is the ratio of O2-carrying hemoglobin (oxyhemoglobin; O2Hb) to total hemoglobin (THb) and is usually expressed as a percentage.(9.1)
Total hemoglobin consists of oxyhemoglobin, deoxygenated hemoglobin (HHb), and abnormal hemoglobins, including methemoglobin (MetHb) and carboxyhemoglobin (COHb), which are normally present in very small quantities.
Arterial hemoglobin saturation is measured from an arterial blood sample using a technique called co-oximetry, which takes advantage of the fact that each form of hemoglobin has its own light-absorption profile or spectrum (Figure 9.1). Co-oximetry generates a minimum of four different wavelengths of light, which allows it to distinguish between the various forms of hemoglobin based on their absorbance patterns. By measuring the fraction of each wavelength that is absorbed by and transmitted through a hemolyzed blood sample, the concentration of each form of hemoglobin can be accurately measured, and SaO2 can be calculated as:(9.2)
The relationship between PaO2 and SaO2 is shown by the oxygen–hemoglobin dissociation curve (Figure 9.2). Because of its well-known sigmoidal shape, SaO2 changes relatively little once the PaO2 exceeds 60–70 mmHg, but below this level, even small changes in the PaO2 have large effects on the SaO2. As shown in Figure 9.2, the curve shifts to the right as body temperature increases and blood pH falls, and SaO2 decreases at a given PaO2. Hypothermia and alkalemia cause the curve to shift in the opposite direction.
Be careful! Co-oximetry is not used by all blood gas laboratories. Sometimes SaO2 is calculated from the measured PaO2 by using the predicted oxygen–hemoglobin dissociation curve. This technique is subject to a number of errors, the most important being the assumption that there are negligible amounts of MetHb and COHb.
Like co-oximetry, pulse oximetry calculates arterial hemoglobin saturation by measuring the amount of light absorbed and transmitted by the arterial blood. There are two important technical differences, though. First, pulse oximeters use only two wavelengths of light, which correspond to the maximum absorption of oxyhemoglobin (940 nM) and deoxygenated hemoglobin (660 nM) (Figure 9.1). Second, light is transmitted through tissue (usually a fingertip) rather than a hemolyzed blood sample. This requires software to determine the amount of each wavelength absorbed by the pulsatile arterial blood while factoring out absorption by tissue and venous blood. The hemoglobin saturation, which is referred to as the SpO2, is determined by comparing the absorption ratio of these two wavelengths with a stored set of reference values.
The advantage of pulse oximetry, of course, is that it can noninvasively and continuously measure and display the arterial hemoglobin saturation. When everything goes right, the SpO2 is usually within ±2% of the SaO2 measured by co-oximetry. Unfortunately, several patient-related factors may lead to significant errors.
First, pulse oximetry is often inaccurate in patients with hypotension or poor peripheral perfusion because of its inability to detect and isolate absorption by pulsatile blood. Although most oximeters generate a plethysmographic pulse tracing, a normal-appearing waveform, while helpful, does not guarantee an accurate SpO2 under these conditions. Since pulse oximeters only measure oxyhemoglobin and deoxygenated hemoglobin, a second problem is that significant errors occur when abnormal amounts of MetHb or COHb are present. Methemoglobin absorbs light at both 940 nm and 660 nm (Figure 9.1). The net result is that SpO2 falls with increasing MetHb concentration but then plateaus at about 85–88%. This causes pulse oximetry to overestimate the true hemoglobin saturation at high MetHb concentrations. Since carboxyhemoglobin and oxyhemoglobin have very similar absorption at 660 nm, SpO2 usually remains normal even at high COHb concentrations. Finally, it’s not uncommon to see significant and totally unexplained differences between SpO2 and SaO2. Because of these problems, I recommend that you routinely confirm the accuracy of SpO2 readings by measuring SaO2 every day or two. More frequent measurements are appropriate for patients with hypotension, poor perfusion, abnormal plethysmographic tracings, or markedly impaired oxygenation.
The Alveolar to Arterial PO2 Gradient
Also referred to as the A–a gradient, this is the difference between the mean alveolar and the measured PaO2. As discussed in Chapter 2, is calculated using the alveolar gas equation:(9.3)
In this equation, PB is barometric pressure, PH2O is the partial pressure of water in the lungs (47 mmHg), FIO2 is the fractional concentration of O2 entering the lungs, is the mean alveolar PCO2 (assumed to equal the PaCO2), and R is the respiratory quotient (assumed to be 0.8). Since the FIO2 must be known, the A–a gradient can be calculated only if the patient is breathing room air (FIO2 = 0.21) or receiving a known FIO2 through a closed system (i.e., an endotracheal tube).
Remember that if the lungs were “perfect,” every alveolus would have the same ventilation–perfusion ratio, and PaO2 would be equal, and the A–a gradient would be zero. In the presence of ventilation–perfusion mismatching, low alveoli and shunt cause the PaO2 to fall without altering the calculated , and the A–a gradient rises. Since even normal lungs have mismatching of ventilation and perfusion as well as a small amount of intrapulmonary shunting, the normal A–a gradient is about 6–10 mmHg. In the presence of lung disease, the A–a gradient increases with the number of low and unventilated alveoli.
Although there’s a general correlation between the A–a gradient and the extent of lung disease, its usefulness as a measure of disease severity is limited by its dependence on FIO2 and the underlying gas exchange abnormality. Recall from Chapter 8 that mismatching causes a curvilinear relationship between FIO2 and PaO2 that varies with the severity and extent of disease (Figure 9.3A). Since increases linearly with FIO2 (Equation 9.3), you can see that the A–a gradient must first rise and then fall as the FIO2 is increased from 0.21 to 1.0 (Figure 9.4A). On the other hand, when intrapulmonary shunting predominates (Figure 9.3B), the PaO2–FIO2 relationship is linear, and its slope decreases as the proportion of the cardiac output that passes through unventilated alveoli (the shunt fraction) increases. It follows that the A–a gradient must increase with FIO2 and the shunt fraction (Figure 9.4B).
The PaO2:FIO2 Ratio
An alternative method of assessing disease severity, and in particular the extent and severity of low and unventilated alveoli, is to divide the PaO2 by the FIO2. If, for example, a patient has a PaO2 of 80 mmHg while receiving an FIO2 of 0.8, the PaO2:FIO2 (or P:F) ratio is 80/0.8 or 100. The lower the P:F ratio, the more severe the disturbance in gas exchange. The P:F ratio is sometimes used in place of the A–a gradient as a measure of low regions and shunt because it is thought (with little justification) to be less affected by changes in FIO2. It’s also used to classify ARDS patients into those with mild, moderate, and severe disease (Chapter 12).
Venous Admixture and Shunt Fraction
The magnitude and severity of low regions and shunt and their effect on gas exchange can also be assessed by calculating the venous admixture . This calculation assumes that the lungs contain only ideal and non-ventilated alveoli (Figure 9.5). Recall from Chapter 2 that ideal alveoli have a of approximately 1.0. The venous admixture is then the fraction of the mixed venous blood that would have to pass through non-ventilated alveoli to produce the calculated O2 content (discussed later) of arterial blood. The venous admixture is equal to the difference between the O2 content of ideal (CiO2) and arterial (CaO2) blood divided by the difference between the O2 content of ideal and mixed venous blood. This is expressed mathematically as:(9.4)
Alternatively, hemoglobin saturation can be substituted for oxygen content. If the saturation of ideal blood is assumed to be 100%, Equation 9.4 can be written as:(9.5)
Here, is the hemoglobin saturation of mixed venous blood.
When FIO2 is 1.0, the blood leaving even very poorly ventilated alveoli has a hemoglobin saturation of 100%, so low regions no longer contribute to the venous admixture. Equations 9.4 and 9.5 then allow us to calculate the fraction of the cardiac output that flows through intra-pulmonary and intra-cardiac right-to-left shunts, and this is referred to as the shunt fraction
Physiologic Dead Space to Tidal Volume Ratio
From a conceptual standpoint, there are several parallels between the venous admixture and the dead space to tidal volume ratio. The venous admixture quantifies the effect of shunt and low alveoli by assuming that the oxygen content or hemoglobin saturation of arterial blood is due to the mixing of blood from ideal alveoli with a fraction of the mixed venous blood. The ratio of physiologic dead space to tidal volume (VD/VT) quantifies the effect of high and non-perfused alveoli plus the volume of the conducting airways by assuming that the PCO2 of expired gas results from the mixing of gas leaving ideal alveoli with gas from non-perfused alveoli; i.e., inspired air (Figure 9.6). Figure 9.7 illustrates these similarities by modifying Figure 2.2 in Chapter 2 to show VD/VT and as shunts that allow a portion of total ventilation and total perfusion to bypass the alveolar–capillary interface.
Analogous to , VD/VT is the difference between the PCO2 of ideal alveolar gas (PiCO2) and expired gas divided by the difference between the PCO2 of ideal alveolar gas and inspired gas. Since inspired gas can be assumed to have no CO2, this can be expressed as:(9.6)
The problem with Equation 9.6 is that PiCO2 is a theoretical construct and cannot be measured. The Bohr-Enghoff equation, which substitutes PaCO2 for PiCO2, is most commonly used to overcome this problem.(9.7)
Recall from Chapter 2 that when VD/VT is low, alveolar volume is a large component of each breath, and ventilation is very effective at excreting CO2 from the lungs. When VD/VT is high, most of each breath is dead space, and ventilation becomes very inefficient at removing CO2.
Oxygen Content and Delivery
Recall from Chapter 2 that the oxygen content of arterial blood (CaO2) is expressed as the volume of O2 (in ml) carried by one deciliter (dl) of blood. If the very small volume of dissolved O2 is neglected, arterial O2 content is calculated as the product of the volume of O2 carried by one gram (g) of fully saturated hemoglobin (1.34 ml/g), the hemoglobin concentration (Hb; g/dl), and the fractional arterial hemoglobin saturation (SaO2/100).(9.8)
The volume of O2 delivered by the arterial circulation (O2 delivery; ) is calculated by multiplying CaO2 by the cardiac output (CO).(9.9)
Oxygen delivery is expressed as ml of oxygen/min, CO is in L/min, and multiplying by 10 converts CaO2 from ml/dl to ml/L.
Also recall from Chapter 2 that PaCO2 is determined by the balance between the rates at which CO2 is produced by the body and excreted by the lungs .(9.10)
CO2 excretion is directly proportional to alveolar ventilation , which is the volume of gas that moves into and out of optimally perfused alveoli each minute.
Since is the difference between total (minute) ventilation and dead space ventilation , Equation 9.11 can be rewritten as:(9.11)
This equation shows that measuring the PaCO2 is a simple but very effective way to assess the adequacy of ventilation. An elevated PaCO2 (hypercapnia) means that the respiratory system is unable to maintain the ventilation needed to excrete the CO2 produced by the body, and this can be caused by a fall in , an increase in , or a rise in CO2 production.
Hypocapnia (low PaCO2) is caused by excessive alveolar ventilation. It often results from physical or psychological distress, but other common causes include metabolic acidosis, sepsis, and hepatic failure. As discussed in Chapter 8, hypocapnia in mechanically ventilated patients may also be iatrogenic and can be corrected by lowering the set mandatory rate.
Capnography is the graphical display of the CO2 content of respiratory gas. The partial pressure or fractional concentration (FCO2) of carbon dioxide is measured using the same principle as co-oximetry and pulse oximetry. Gas between the endotracheal tube and the ventilator circuit is continuously exposed to infrared light at wavelengths absorbed by CO2, and FCO2 and PCO2 are calculated by measuring the amount of absorbed and transmitted light. FCO2, or more commonly, PCO2 is displayed on the Y-axis and plotted against either time (time capnography) or exhaled volume (volume capnography). As shown in Figure 9.8, time-capnograms provide a continuous display throughout the entire respiratory cycle, whereas volume-capnograms show only expiration.
The exhaled portion of a time or volume-capnogram is conventionally divided into three phases (Figure 9.9). Phase I is due to emptying of the conducting airways. Since this gas didn’t reach the alveoli during inspiration and didn’t participate in gas exchange, it contains no CO2, and PCO2 is zero. During Phase II, PCO2 increases rapidly as the remaining gas from the conducting airways mixes with an increasing volume of alveolar gas. Phase III reflects the PCO2 of pure alveolar gas; the normal, positive slope reflects the successive emptying of alveoli with worsening ventilation, falling , and increasing PCO2. The PCO2 at the end of expiration is called the end-tidal PCO2 (PETCO2).
Time capnography is most often used to measure PETCO2 as a noninvasive estimate of PaCO2. Continuous monitoring of PETCO2 has long been the standard of care in the operating room and is also commonly used to assure the adequacy of ventilation in patients receiving procedural sedation. The substitution of PETCO2 for PaCO2 is based on the assumption that the difference between these two measurements is small and fairly constant. In the absence of lung disease, this is generally true, and on average, PaCO2 exceeds PETCO2 by 3–6 mmHg.
In theory, PETCO2 could also serve as a surrogate for PaCO2 in mechanically ventilated ICU patients. This would be an attractive alternative to frequent blood gas measurements and could be used to adjust and monitor the effect of changes in ventilator settings. Unfortunately, studies have shown that the difference between PETCO2 and PaCO2 can vary widely and unpredictably in mechanically ventilated, critically ill patients. Even worse, PaCO2 and PETCO2 often move in opposite directions!
There are several reasons for this. First, alveolar dead space generated by high and unperfused alveoli dilutes the expired PCO2 and reduces PETCO2 without changing PaCO2. Second, intra-pulmonary shunting increases PaCO2 without affecting PETCO2.1 Third, because Phase III has a positive slope, PETCO2 decreases when patients (especially those with obstructive lung disease) have insufficient time for complete exhalation. Finally, when cardiac output is reduced, the venous blood delivers less CO2 to the lungs, less is excreted with each breath, and PETCO2 falls. The bottom line is that PETCO2 should not be used to estimate PaCO2, or even to assess which direction it’s moving in critically ill patients.
Volume capnography can also provide a continuous display of PETCO2, but because it measures FCO2 and PCO2 relative to exhaled volume, it can also be used to perform a number of other measurements and calculations. This makes it much more useful than time capnography in the assessment and management of mechanically ventilated ICU patients.
The volume of CO2 exhaled during a single breath is equal to the area under the FCO2–volume curve (Figure 9.10). Multiplying by the respiratory rate yields the volume of CO2 excreted each minute .
Physiological Dead Space, Dead Space to Tidal Volume Ratio, Dead Space Ventilation, and Alveolar Ventilation
As previously discussed, VD/VT is calculated using the Bohr-Enghoff equation (Equation 9.7). PaCO2 is measured from an arterial blood sample, and volume capnography is used to calculate the mean expired PCO2 . This requires two steps. First, the mean expired fractional concentration of is determined by dividing the volume of expired CO2 by the expired tidal volume.(9.12) (9.13)
Figure 9.11 shows the relationship between PaCO2, PETCO2, and . Physiologic dead space (VD) is calculated by multiplying VD/VT by the exhaled tidal volume, and multiplying by the respiratory rate gives dead space ventilation . Alveolar ventilation is the difference between minute ventilation and dead space ventilation.
Airway and Alveolar Dead Space
Airway dead space (VD-AW) is determined graphically by bisecting Phase II of the volume capnogram with a perpendicular line (Figure 9.12). This transforms Phase II from a gradual to an abrupt transition between airway and alveolar gas, and the volume to the left of the line is assumed to equal the airway dead space. Once physiologic and airway dead space have been determined, alveolar dead space (VD-ALV) is calculated as the difference between them.
Fortunately, most modern volume capnographs perform all these measurements and calculations for you. All you have to do is measure and input the PaCO2. The problem is figuring out practical and clinically relevant uses for all of this information. One promising application of volume capnography is to assist in identifying the appropriate level of PEEP in patients with the acute respiratory distress syndrome, and this will be discussed in Chapter 12.
Ventilation is possible only when the respiratory muscles or a mechanical ventilator provides enough pressure to overcome the elastic recoil and viscous forces of the respiratory system. Respiratory mechanics is the interaction of these applied and opposing forces and was discussed in detail in Chapter 1. Here, I focus on several clinically important measurements during a mechanical breath.
Airway and Alveolar Pressures
The peak airway pressure (PPEAK) is the maximum airway pressure (PAW) reached during a mechanical breath and can be read from the PAW–time curve or the digital display on the ventilator user interface. During a passive, volume control (VC) breath with constant inspiratory flow, PAW increases linearly with the delivered volume, and PPEAK is reached at end-inspiration (Figure 9.13). During pressure control (PC), adaptive pressure control (aPC), pressure support (PS), and adaptive pressure support (aPS) breaths, PPEAK equals the constant PAW maintained throughout inspiration.
The plateau pressure (PPLAT) is measured during an end-inspiratory pause, which holds the tidal volume in the lungs for a short time before expiration is allowed to proceed. Figure 9.13 shows the effect of an end-inspiratory pause during a passive VC breath. Since there are no viscous forces in the absence of flow, PPLAT is the end-inspiratory alveolar pressure (PALV). It is also the sum of the pressure needed to balance the increase in elastic recoil during inspiration (PER) and total PEEP (PEEPT). Like PPEAK, PPLAT can be read from either the graphical or the digital display on the user interface.
Total PEEP (PEEPT) is the sum of set or extrinsic PEEP (PEEPE) and intrinsic PEEP (PEEPI) due to dynamic hyperinflation. Total PEEP equals end-expiratory PALV, which is the total elastic recoil pressure of the respiratory system just before the next mechanical breath. As shown in Figure 9.13, PALV and flow decrease exponentially during expiration, and flow stops only when PALV has returned to zero (atmospheric pressure) or to the level of PEEPE.
Notice that PAW reaches this pressure well before PALV does. You can understand why by looking at Figure 9.14. Mechanical ventilators measure PAWproximal to the expiratory valve. Throughout inspiration, the expiratory valve is closed, so PAW equals the pressure in the ventilator circuit and the large airways of the lungs. During expiration, though, the expiratory valve opens and the pressure sensor is exposed to PEEPE. That’s why PAW falls so quickly and why it doesn’t reflect PALV during expiration.
PEEPT can be measured during an end-expiratory pause, which closes the expiratory valve and stops any remaining expiratory flow. As shown in Figure 9.15, this allows pressure to equilibrate between the lungs and the ventilator circuit, and PAW becomes equal to PALV. If expiratory flow has already stopped and the respiratory system has reached its equilibrium position, PEEPT will equal PEEPE. When expiratory time is insufficient to allow complete exhalation, PEEPT will equal the sum of PEEPE and PEEPI (Figure 9.16). Chapter 10 is devoted to dynamic hyperinflation and PEEPI.
Before performing an end-expiratory pause, you can “screen” for PEEPI simply by looking at the expiratory flow–time curve. As shown in Figure 9.17, if expiratory flow stops before the onset of the next mechanical breath, PEEPT must equal PEEPE. If end-expiratory flow is greater than zero, PEEPI must be present, and PEEPT will exceed PEEPE.
Compliance and Resistance
Remember from Chapter 1 that elastic recoil is most often expressed in terms of compliance (C), which is the ratio of the volume change (∆V) produced by a change in transmural pressure (∆PTM).(9.14)
Viscous forces are quantified by resistance (R), which is the intramural pressure gradient between two points of a tube or circuit (∆PIM) divided by the flow that it produces .(9.15)
Both the compliance and resistance of the respiratory system can be calculated from measurements obtained during a passive, VC breath (Figure 9.13). Respiratory system compliance (CRS) over the tidal volume range is equal to the set tidal volume (VT) divided by the pressure needed to overcome elastic recoil (PER), which is the difference between PALV at the end of inspiration (PPLAT) and the end of expiration (PEEPT).(9.16)
Respiratory system resistance (RRS) is equal to the pressure needed to overcome viscous forces (PV) divided by the end-inspiratory flow rate . Since viscous forces disappear during an end-inspiratory pause, PV is the difference between PPEAK and PPLAT.(9.17)
Although compliance and resistance calculations are fairly straightforward, there are several things to keep in mind. First, VT and end-inspiratory flow must be known. That’s why you must use a volume-control breath with a set, constant inspiratory flow rate. Second, the measured PPEAK, PPLAT, and PEEPT will be accurate only if ventilation is passive. Patient effort can usually be minimized by providing sufficient sedation. Alternatively, you can induce hypocapnia by briefly increasing the set respiratory rate. This will reduce the patient’s respiratory drive, and when the rate is decreased, a brief period of apnea will usually allow accurate pressure measurements to be obtained.
Bekos V, Marini JJ. Monitoring the mechanically-ventilated patient. Crit Care Clin. 2007;23:575–611.Find this resource:
Hess DR. Respiratory mechanics in mechanically ventilated patients. Respir Care. 2014;59:1773–1794.Find this resource:
Truwitt JD, Marini JJ. Evaluation of thoracic mechanics in the ventilated patient. Part 1: primary measurements. J Crit Care. 1988;3:133–150.Find this resource:
Truwitt JD, Marini JJ. Evaluation of thoracic mechanics in the ventilated patient. Part 2: applied mechanics. J Crit Care. 1988;3:199–213.Find this resource:
1 The increase in respiratory drive and alveolar ventilation triggered by hypercapnia restores PaCO2 to normal, but the accompanying dilution of the expired PCO2 maintains the abnormal PaCO2–PETCO2 gradient.