Technique

V_T can be measured directly by simple spirometry (see Figure 2-1). The patient breathes into a volume-displacement or flow-sensing spirometer (see Chapter 11). Volume change may be measured directly from the excursions of a volume spirometer. V_T may also be measured from an integrated flow signal (see Chapter 11). A graphic representation of tidal breathing can be displayed on a computer screen. Because no two breaths are the same, inhaled or exhaled tidal breaths should be measured for at least 1 minute and then divided by the rate to determine an average volume:

< ?xml:namespace prefix = "mml" />VT=V·fb

where:

   = volume expired or inspired per minute (usually the _E )

f_b = number of breaths for the same interval (i.e., the respiratory rate)

The inspired minute volume (_I ) and V_T are normally slightly greater than the _E because at rest the body produces a slightly lower volume of CO₂ than the volume of O₂ consumed. This exchange difference is termed the respiratory exchange ratio (RER). It is calculated as the co₂/o₂, where co₂ is the volume of CO₂ produced and o₂ is the volume of O₂ consumed per minute. It is assumed that RER is approximately 0.8 in resting patients. For most clinical purposes, expired volume is measured to calculate V_T.

V_T may also be estimated by means of a respiratory inductive plethysmography (RIP). The RIP uses coils of wire as transducers that respond to changes in the cross-sectional area of the rib cage and abdominal compartments. With appropriate calibration, inductive plethysmography can be used to measure V_T. This method allows the measurement of V_T and minute ventilation without a direct connection to the patient’s airway.

Respiratory frequency (f_b) may be determined by counting chest movements, noting the excursions of a volume displacement spirometer (Criteria for Acceptability 5-1), or most commonly by measuring flow changes while the subject breathes through a flow-sensing spirometer. Counting the rate for several minutes and taking an average produces a more accurate value than shorter measurements. Prolonged measurement of V_T and rate with a volume-displacement spirometer requires a means of removing CO₂. This is called a rebreathing system and uses a chemical CO₂ absorber (see Figure 4-1, B). Sodium hydroxide crystals (Sodasorb) or barium hydroxide crystals (Baralyme) are commonly used to scrub CO₂ from rebreathing systems. Flow-sensing spirometers usually do not require a chemical absorber.

The _E may be measured by allowing the patient to breathe into or out of a volume-displacement or flow-sensing spirometer for at least 1 minute. A shorter breathing interval can be used with minute volume extrapolated but may give a misleading estimate of ventilation if the patient’s breathing rate is irregular. If a rebreathing system is used, a CO₂ absorber must be included, as well as a means of replenishing O₂. Measuring expired gas volume for several minutes and dividing by the time gives an average _E. _E, measured from expired gas, is usually slightly smaller than _I because of the RER, as described previously. For most clinical purposes, this difference is negligible. BTPS corrections should be made.

Significance and Pathophysiology

See Interpretive Strategies 5-1. Average V_T for healthy adults at rest ranges between 400 and 700 mL, but there is considerable variation. Decreased V_T occurs in many types of pulmonary disorders, particularly those that cause severe restrictive patterns. Pulmonary fibrosis and neuromuscular diseases (e.g., myasthenia gravis) often cause reduced V_T. Decreased tidal breathing usually accompanies changes in the mechanical properties of the lungs or chest wall (i.e., compliance and resistance). These changes usually produce an increased respiratory rate (f_b) required to maintain an adequate _A. Decreases in both V_T and respiratory rate are often associated with respiratory center depression because of drugs or pathologic conditions affecting the brain stem. Low V_T and rate usually result in alveolar hypoventilation.

Some patients who have pulmonary disease may exhibit increased V_T, particularly at rest. The V_T alone is not a good indicator of the adequacy of alveolar ventilation ( _A). Tidal volume should always be considered in conjunction with respiratory rate and _E. Many healthy patients display increased V_T simply because of breathing into the pulmonary function apparatus with the nose occluded. Estimates of resting ventilation may be artifactually increased when measured during pulmonary function testing. Some subjects adopt unusual breathing strategies (e.g., large tidal volumes with slow respiratory rate or small tidal volumes with rapid breathing rates) during exercise or stress for nonphysiologic reasons.

The normal respiratory rate (f_b) ranges from 10–20 breaths/min in adults. Increased demand for ventilation, such as during exercise, usually results in increases in both the rate and depth of breathing (i.e., the tidal volume). Increases or decreases in the respiratory rate are indications of a change in the ventilatory status. Breathing frequency, when evaluated with the V_T, may be used as an index of ventilation. Hypoxia, hypercapnia, metabolic acidosis, decreased lung compliance, and exercise can all result in increased respiratory rate. Rapid breathing rates and small tidal volumes may suggest increased V_D or hypoventilation but must be correlated with arterial pH and Pco₂ values to confirm those conditions. Decreased breathing frequency is common in central nervous system depression and in CO₂ narcosis. Respiratory rate may be falsely elevated in patients connected to unfamiliar breathing circuits, with or without a noseclip.

Normal _E ranges from 5–10 L/min in healthy adults with wide variations in normal patients. The _E, when used in conjunction with blood gas values, indicates the adequacy of ventilation. _E is the sum of the _D (dead space ventilation per minute) and _A. Because the relative proportions of these components can change, absolute values for _E do not necessarily indicate either hypoventilation or hyperventilation. In other words, low minute ventilation does not necessarily indicate hypoventilation. Similarly, elevated _E does not indicate hyperventilation. To make these diagnoses, arterial pH and Pco₂ must be measured.

A large _E at rest (greater than 20 L/min) may result from an enlarged V_D because an increase in total ventilation is required to maintain adequate _A. _E increases in response to hypoxia, hypercapnia, metabolic acidosis, anxiety, and exercise. Hyperventilation is ventilation in excess of that needed to adequately remove CO₂, resulting in respiratory alkalosis.

Decreased ventilation may result from hypocapnia, metabolic alkalosis, respiratory center depression, or neuromuscular disorders that involve the ventilatory muscles. Hypoventilation is defined as inadequate ventilation to maintain a normal arterial Pco₂, with respiratory acidosis as the result. The diagnosis of either hyperventilation or hypoventilation requires blood gas analysis (see Chapter 6).

Anatomic dead space is sometimes estimated from an individual’s body size as 1 mL/lb of ideal body weight. The actual respiratory dead space, however, is of greater clinical importance. V_D can be calculated in two ways. The first uses the Enghoff modification of the Bohr equation defining V_D:

VD=FACO2−F E¯CO2FACO2×VT

where:

V_T   = tidal volume

F_Aco₂  = fraction of CO₂ in alveolar gas

Fco₂ = fraction of CO₂ in mixed expired gas

Because the fractional concentration of alveolar CO₂ is difficult to measure, partial pressure of CO₂ may be substituted and the equation written as follows:

VD=(PaCO2−P E¯CO2)PaCO2×VT

where:

Paco₂ = arterial Pco₂

PE¯co₂ = Pco₂ of mixed expired gas sample

Note that the Paco₂ is substituted for the alveolar Pco₂. This substitution presumes perfect equilibration between alveoli and pulmonary capillaries. This may not be true in certain diseases. The test also assumes that little CO₂ is in the atmosphere. Therefore, the Pco₂ in expired gas is inversely proportional to the V_D. Exhaled gas is collected over a short interval, and arterial blood is obtained simultaneously to measure Paco₂. V_D is calculated by applying the previous equation. The estimate usually becomes more representative as more expired gas is collected. Accuracy depends on measurement of V_T (usually derived from _E and f_b) and on the precision of the partial pressures of CO₂ measured in expired gas and arterial blood. The mixed expired gas sample is usually collected in a bag or balloon after filling and emptying it several times with expired gas to wash out room air from the valves, tubing, and bag itself. The volume of gas in the bag can be measured during collection by including a flow-sensing spirometer in the circuit. If _E and respiratory rate are recorded, the volumes of V_D and V_T can be determined. If expired volume is not measured, only a dilution ratio can be determined; this is called the V_D/V_T ratio.

The V_D/V_T ratio can be calculated if arterial and mixed-expired Pco₂ values are known. It can also be estimated noninvasively. End-tidal Pco₂ (see the section on capnography in Chapter 6) can be used to estimate Paco₂. The main advantage of this method is that it is not necessary to obtain an arterial blood sample. This technique is often used in systems that monitor expired CO₂ continuously and in breath-by-breath metabolic measurement devices. V_D/V_T may be calculated as follows:

VDVT=PETCO2−PE¯CO2PETCO2

where:

Petco₂ = end-tidal Pco₂

Pco₂= Pco₂ of mixed-expired gas sample

In some patients, particularly those with severe obstruction, Petco₂ may not accurately reflect Paco₂. Consequently, the V_D/V_T ratio may be estimated incorrectly. Paco₂ should be used in the V_D calculation whenever possible.

Alveolar Ventilation

_A can be calculated in two ways:

V·A=fb(VT−VD)

where:

V_T = tidal volume

V_D = respiratory dead space

f_b = respiratory rate

For convenience, V_D is often estimated as equal to anatomic dead space. This method is valid only when there is little or no alveolar dead space, as in individuals who do not have pulmonary disease.

Because atmospheric gas contains almost no CO₂, _A can be calculated on the basis of CO₂ elimination from the lungs. A volume of expired gas may be collected in a bag, balloon, or spirometer and analyzed to determine the volume of CO₂ (see Chapter 7). The following equation can then be used:

V·A=V·CO2FACO2

where:

co₂= volume of CO₂ produced in liters per minute (STPD)

F_Aco₂= fractional concentration of CO₂ in alveola

If an end-tidal CO₂ monitor (i.e., a capnograph) is used, a close approximation of the concentration of alveolar CO₂ is easily obtained, and the equation is simplified as follows:

V·A=V·CO2% alveolar CO2×100

End-tidal CO₂ may not equal alveolar CO₂ in patients with grossly abnormal patterns of ventilation-perfusion (see Chapter 6).

The same equation can be used substituting Paco₂ for the alveolar Pco₂ (i.e., P_Aco₂), again presuming that arterial blood and alveolar gas are in equilibrium. The equation is then as follows:

V·A=V·CO2PaCO2×0.863

where:

co₂= CO₂ production in mL/min (STPD)

Paco₂= partial pressure of arterial CO₂

0.863= conversion factor (concentration to partial pressure, correcting co₂ to BTPS)

Significance and Pathophysiology

See Interpretive Strategies 5-2. Measurement of V_D yields important information regarding the ventilation-perfusion characteristics of the lungs. Anatomic dead space is larger in men than in women because of differences in body size. It increases along with the V_T during exercise, as well as in certain forms of pulmonary disease (e.g., bronchiectasis). It may be decreased in asthma or in diseases characterized by bronchial obstruction or mucus plugging. Because of the difficulty in measuring the anatomic dead space, estimates based on age, sex, functional residual capacity, or body size may be used. For clinical purposes, anatomic dead space in milliliters is sometimes considered equal to the patient’s ideal body weight in pounds or twice their weight in kilograms.

Of greater clinical significance is the measurement of respiratory dead space, which is accomplished reasonably well by applying the Bohr equation. The portion of ventilation wasted on the conducting airways and poorly perfused alveoli is usually expressed as the V_D/V_T ratio. The normal value for V_D/V_T in spontaneously breathing adults is about 0.3 (with a range of 0.2–0.4). V_D/V_T is also commonly expressed as a percentage (e.g., 30%). Expressing dead space in this way eliminates the need to measure the volume of expired gas in the Bohr equation. However, if V_T or _E is known, dead space volume can be easily calculated. Physiologic dead space measurements are a good index of ventilation-blood flow ratios because all CO₂ in expired gas comes from perfused alveoli (see Chapter 6). If there were no dead space in the lung, arterial and mixed-expired CO₂ would be equal. As the difference between arterial and mixed-expired CO₂ increases, the volume of “wasted” ventilation rises.

The V_D/V_T ratio decreases in healthy subjects during exercise. As cardiac output increases, perfusion of alveoli at the lung apices also increases. This increased perfusion is referred to as recruitment. Alveoli at the apices are poorly perfused at rest, accounting for some of the normal resting dead space. Both V_D and V_T increase with exercise. In healthy individuals, the V_T increases more than V_D; thus, the ratio decreases.

Increased dead space and V_D/V_T ratio may be observed in pulmonary embolism and in pulmonary hypertension. In pulmonary embolism, large numbers of arterioles may be blocked, resulting in little or no CO₂ removal in the associated alveoli. In pulmonary hypertension, increased pulmonary arterial pressure causes most alveoli to be perfused, so there is little or no recruitment of underperfused gas exchange units. This is most notable during exercise when the V_D/V_T ratio normally decreases. In both pulmonary embolism and hypertension, the patient may be very short of breath (i.e., dyspneic) because of the increased dead space.

The _A at rest is approximately 4–5 L/min with wide variations in healthy adults. The adequacy of _A can be determined by arterial blood gas studies only. Low _A associated with acute respiratory acidosis (Paco₂ greater than 45 and pH less than 7.35 in healthy patients) defines hypoventilation. Excessive _A (Paco₂ less than 35 and pH greater than 7.45 in healthy patients) defines hyperventilation. Chronic hypoventilation and hyperventilation are associated with abnormal Paco₂ values but near-normal pH values (see Chapter 6). Decreased _A can result from absolute increases in dead space and decreases in _E.

Technique

The response to increasing levels of CO₂ (hypercapnia) can be measured in two ways:

Response to decreasing levels of O₂ (hypoxemia) can also be measured by either open-circuit or closed-circuit techniques:

1. Open-circuit technique. The patient breathes gas mixtures containing O₂ concentrations from 20%–12%, to which CO₂ is added to maintain alveolar Pco₂ (Paco₂) at a constant level. When a steady state is reached, Pao₂, _E, and P₁₀₀ can be measured. This procedure, often called a step test, is repeated with decreasing O₂ concentrations to produce the response curve. Continuous monitoring of Petco₂ is necessary to titrate the addition of CO₂ to the system to maintain isocapnia (Figure 5-1). Pulse oximetry may be used to monitor changes in saturation. CO₂ response curves are sometimes measured at widely varying Pao₂ levels, and the subsequent difference in ventilation or P₁₀₀ at any particular Pco₂ is attributed to the response to hypoxemia.

2. Closed-circuit technique (progressive hypoxemia). The patient rebreathes from a system similar to that used for the closed-circuit CO₂ response, but the system contains a CO₂ scrubber. CO₂ can be added to the inspired gas to maintain isocapnia, or an adjustable blower may be used to direct a portion of the rebreathed gas through the scrubber to maintain isocapnia (see Figure 5-1). Response to decreasing inspired Po₂ is monitored by recording _E or P₁₀₀, and the Pao₂ or saturation is measured either directly by indwelling catheter or by pulse oximetry.

PF Tip 5-3

To measure response to hypoxemia, it is necessary to maintain a constant level of CO₂ (isocapnia). To measure response to hypercapnia, it is necessary to maintain normoxia (Pao₂ of 80–100 mm Hg).

P₁₀₀ is measured with a system similar to that in Figure 5-1. A port at the mouth records pressure changes versus time, by means of a computer or high-speed recorder. A large-bore stopcock or electronic shutter mechanism is included in the inspiratory line so that inspiratory flow can be randomly occluded. The stopcock or shutter can be closed so that inspiration occurs against a complete occlusion near functional residual capacity. The entire apparatus is usually hidden so that the patient is unaware of the impending airway occlusion. A pressure-time curve is recorded. P₁₀₀ is usually measured at varying Petco₂ values or levels of desaturation to assess the effect of changing stimuli to ventilation. P₁₀₀ and _E are usually graphed against Petco₂ (Figure 5-2) or versus O₂ saturation (for O₂ response tests). See Criteria for Acceptability 5-2 for ventilatory response measurements.

Significance and Pathophysiology

See Interpretive Strategies 5-3. The response to an increase in Paco₂ in a normal individual is a linear increase in _E of approximately 3 L/min/mm Hg (Pco₂). The normal range of response varies from 1–6 L/min/mm Hg Pco₂. Some variation is present in repeated testing of the same individual. The response to CO₂ in patients who have obstructive disease may be reduced. This is partially attributable to increased airway resistance, which has been shown to reduce ventilatory drive in healthy individuals. It is unclear why some patients who have obstructive disease increase ventilation to maintain a normal Paco₂, whereas others tolerate an increased Paco₂. Genetic variation in drive may explain some of the differences in blood gas tensions in patients with chronic obstructive pulmonary disease (COPD). Lesions in the central nervous system may also cause a decreased sensitivity to CO₂ (Figures 5-3, A and B). Some individuals who have no respiratory muscle weakness, mechanical ventilatory problems, or neurologic disease have a decreased sensitivity to CO₂. This condition is described as primary alveolar hypoventilation. These patients can lower their Pco₂ by voluntary hyperventilation (Figure 5-4).

Technique

To replicate the in-flight P_IO₂ at sea-level pressure (760 mm Hg), the F_IO₂ would need to be 0.15 in a nitrogen balance. To estimate the target F_IO₂ at an

altitude other than sea level, a factor is calculated to use in the alveolar air equation:

Factor=(1−6.873E−6×Alt[Feet])5.256

BagFIO2=([760×factor]/localPBaro)×0.21

The desired F_IO₂ can be delivered via a specialized tank mixture administered with a demand valve, a mixed gas (100% nitrogen and room air added to a Douglas bag, analyzed to desired F_IO₂ and delivered via directional valve), a blender attached to 100% nitrogen supply and compressed air tanks, or a Ventimask driven by a 100 nitrogen source (40% setting = 14%-15% F_IO₂; 35% setting = 15%-16% F_IO₂). Patient interface has been evaluated with mask and canopy being the preferred methods by the subject (Figure 5-5). Once the desired F_IO₂ is established and the mode of delivery determined, the subject can be tested. It is typical to monitor the patient’s electrocardiogram (5 leads at a minimum) during the procedure. The Borg scale may also be used to assess dyspnea or breathlessness during the study. The patient oxygen level is monitored with pulse oximetry. Some laboratories assess end of test oxygen status using arterial blood gas, whereas others rely on the oximetry readings if the signal quality is acceptable. The subject breathes the hypoxic gas mixture for 20 minutes. The test is terminated early if the patient’s SpO₂ is less than 80%, there is a change in the ECG rhythm, ST-T wave depression/elevation is greater than 1.0 mm, or the patient develops symptoms suggesting intolerance.

Supplemental oxygen is recommended if the test results yield a SaO₂ or SpO₂ of less than 84%. In most cases, an oxygen flow of 2 L/min via nasal cannula is adequate to correct for the altitude effect.

Significance and Pathophysiology

Air travel causes significant hypobaric hypoxemia in patients at risk. The British Thoracic Society recommends an evaluation before airline travel in subjects with severe COPD or asthma, severe restrictive disease, cystic fibrosis, and comorbidity conditions worsened by hypoxemia (CAD, CHF, etc.). A HAST should be performed if the screening process yields a resting SpO₂ between 92%-95% with additional risk factors (Table 5-1).

Equations are available to predict in-flight hypoxemia; however, several authors have concluded that equations do not accurately predict altitude Pa_o2 and favor a hypoxia altitude test (see Criteria for Acceptability 5-2 and Interpretive Strategies 5-3).

The normal response to a decrease in Pao₂ varies, depending on the level of Pco₂ at which the measurement is made. There is little change in ventilation until the Pao₂ falls to less than 60 mm Hg. The response appears to be exponential once the Pao₂ has fallen to the range of 40–60 mm Hg, and it varies widely between individuals on a genetically determined basis. The hypoxic response is increased in the presence of hypercapnia and decreased in hypocapnia. Patients who have severe COPD with CO₂ retention receive their primary respiratory stimulus from the hypoxemic response. This group of patients may experience severe or even fatal respiratory depression if that response is obliterated by uncontrolled O₂ therapy.

Some patients with minimal intrinsic lung disease show a markedly decreased response to hypoxemia or hypercapnia. These include patients with myxedema, obesity-hypoventilation syndrome, obstructive sleep apnea, central apnea, and idiopathic hypoventilation. CO₂ and O₂ response measurements, along with tests of pulmonary mechanics, may be particularly valuable in the evaluation and treatment of these types of patients.

The P₁₀₀ (P_0.1) has been suggested as a measurement of ventilatory drive independent of the mechanical properties of the lungs. Because no airflow occurs during occlusion of the airway, significant interference from mechanical abnormalities (e.g., increased resistance or decreased compliance) is omitted. Reflexes from the airways and chest wall are also of little influence during the first 100 msec of the occluded breath. Therefore, the pressure generated can be viewed as proportional to the neural output of the medullary centers that drive the rate and depth of breathing. This proportionality may be influenced by other factors, however, such as body position and the contractile properties of the respiratory muscles.

Individuals with normal Paco₂ values have P₁₀₀ values in the range of 1.5–5 cm H₂O. P₁₀₀ has been shown to increase in hypercapnia and hypoxia and appears to correlate well with the observed ventilatory responses. Increasing Pco₂, and thereby inducing hypercapnia, in healthy patients typically results in an increase in the occlusion pressure of 0.5–0.6 cm H₂O/mm Hg Pco₂, with as much as 20% variability. Healthy subjects increase their P₁₀₀ when breathing through artificial resistance on challenge with high Pco₂ or low Po₂. Some patients who have chronic airway obstruction demonstrate no increase in P₁₀₀ in response to increasing Pco₂, even with increased airway resistance. This failure to respond to increased resistance in the airways may predispose individuals with COPD to respiratory failure when lung infections occur. Similarly, patients supported by mechanical ventilation may be difficult to wean if their ventilatory drive is compromised, as demonstrated by the failure to increase P₁₀₀ when challenged with increased Pco₂. Determination of P₁₀₀ may prove helpful in determining the effects of treatment in patients who have abnormal ventilatory responses.