Technique

The patient is connected to a valve, shutter apparatus, or the PF testing system with a mouthpiece (a flanged mouthpiece may facilitate testing in subjects with excessive muscle weakness) and noseclip in place. The mouthpiece can be placed in the mouth or the lips pressed against the mouthpiece opening, as would be done with a bugle, thus the early term for the procedure “bugles” (Figure 10-1). Regardless of the mouth-device interfaced used, there should be a tight fit so that the patient can exert maximal pressure. The airway is occluded by blocking a port in the valve or by closing a shutter. In either system, a small, fixed leak is introduced between the occlusion and the patient’s mouth. The leak may be a small opening such as a large-bore needle or created by the PFT system in their hardware. The leak eliminates pressures generated by the cheek muscles during the MEP maneuver by allowing a small amount of gas to escape the oral cavity. Likewise, the leak prevents glottic closure during the MIP maneuver. The incorporation of this small leak does not significantly change lung volume or the pressure measurement.

Pressure may be measured using a manometer, an aneroid-type gauge, or a pressure transducer. The pressure-monitoring device should be linear over its range. It should be able to record pressures from −200 to approximately +200 cm H₂O. Pressure transducers are typically used in PF testing systems with the output incorporated into a data acquisition screen and algorithms used to calculate the sustained pressure. If a manometer or aneroid gauge is used, the technologist directly observes the pressure and records it. This type of monitoring is common in the hospital where measuring vital capacity and respiratory pressures are used to assess ventilatory adequacy (Figure 10-2). The technologist should record the plateau pressure that the patient can maintain for 1–2 seconds.

For the MIP test, the patient is instructed to expire maximally. Monitoring expiratory flow or having the patient signal helps determine when maximal expiration has been achieved. Then the airway is occluded as described. The patient inspires maximally and maintains the inspiration for 1–2 seconds. The first portion of each maneuver is disregarded because it may include transient pressure changes that occur initially (Figure 10-3). The most negative value from at least three efforts that vary less than 20% is recorded.

MEP is recorded similarly. The patient inhales as much as possible, then exhales maximally against the occluded airway for 1–2 seconds. Longer efforts should be avoided as cardiac output can be reduced by the high thoracic pressures (e.g., Valsalva maneuvers) that are sometimes developed. MEP is usually larger than MIP in healthy patients. The pressure-monitoring device should be able to withstand the higher pressure without damage. The most positive value from at least three efforts that vary less than 20% is recorded. As for MIP, initial pressure transients during the MEP are disregarded. Both MIP and MEP require patient cooperation and effort. Low values may reflect a lack of understanding or insufficient effort. (Box 10-1)

Significance and Pathophysiology

MIP primarily measures inspiratory muscle strength. Healthy adults can generate inspiratory pressures greater than -50 cm H₂O in women, and -75 cm H₂O in men. Decreased MIP is seen in patients with neuromuscular disease or diseases involving the diaphragm, intercostals, or accessory muscles. MIP may also be decreased in patients with hyperinflation, as in emphysema where the diaphragm is flattened by the increased volume of trapped gas in the lungs. The intercostals and accessory muscles may also be compromised by injury to or diseases of the chest wall. Patients with chest wall or spinal deformities (e.g., kyphoscoliosis) may also have reduced inspiratory pressures. MIP is sometimes used to assess patient response to strength training of respiratory muscles. MIP is often used in the assessment of respiratory muscle function in patients who need ventilatory support.

MEP measures the pressure generated during maximal expiration. It depends on the function of the abdominal muscles and accessory muscles of respiration and the elastic recoil of the lungs and thorax. Healthy adults can generate MEP values greater than 80 cm H₂O in women and greater than 100 cm H₂O in men. MEP may be decreased in neuromuscular disorders, particularly those resulting in generalized muscle weakness. Another common disorder that results in the reduction of MEP is high cervical spine fracture. Damage to nerves controlling abdominal and accessory muscles of expiration can dramatically reduce MEP. However, MIP may be preserved in these patients.

Reduced MEP often accompanies increased RV, as seen in emphysema. A low MEP is associated with the inability to cough effectively. Inability to generate an adequate cough may complicate chronic bronchitis, cystic fibrosis, or other diseases that result in excessive mucus secretion.

Accurate measurement of MIP and MEP depends largely on patient effort. The technologist should carefully instruct the patient on how to do the maneuver. Low values may result if the patient fails to inhale or exhale completely before the airway is occluded. Some patients may show increased MIP or MEP with repeated efforts (training effect). Others may demonstrate decreasing pressures with repeated efforts (muscle fatigue). The best efforts should be reproducible within 20% or 10 cm H₂O, whichever is greater. Widely varying pressures for either MIP or MEP should be assessed carefully before interpretation.

Sniff nasal inspiratory pressure (SNIP) has been proposed as an alternative or complementary test to MIP. The measurement is performed by occluding a nostril during a maximal sniff maneuver performed through the contralateral nostril from functional residual capacity or residual volume. In the contralateral nostril, a nasal olive with a central catheter is connected to a pressure transducer. Instrumentation can be sophisticated with computer incentive screens to simple hand-held devices (Figure 10-4). Measurement limitations include nasal obstruction or collapse during the maneuver. Several papers have compared the test method to sniff pressures measured using an esophageal catheter with good correlation in subjects with neuromuscular disease. A sniff nasal-inspiratory force less than 40 cm H₂O has been shown to predict mortality in patients with amyotrophic lateral sclerosis (sensitivity 97%, specificity 79%).

Techniques

Fe_NO can be measured either on-line or off-line. The methods for each type of collection differ slightly in adults and children. On-line measurements sample exhaled gas continuously at the mouth; off-line measurements collect exhaled air in a sampling device for later analysis.

On-Line Fe_NO in Adults

Before measuring Fe_NO, patients should refrain from smoking, eating, or drinking (except water) for at least 1 hour before testing. Measurement of eNO should be performed before other tests such as spirometry, methacholine challenge, or exercise testing. Any recent infections, as well as the current medication regimen, should be recorded at the time of testing.

Because NO is produced in the airways (and in the alveoli), it is important that the patient inhale NO-free gas. This is accomplished by having the subject inspire through an NO scrubber. The ambient NO level should be recorded as well. The patient should be instructed to exhale to RV, then insert the mouthpiece and inspire over a 2- to 3-second interval to TLC. A noseclip is not used; this lessens the possibility that the much higher nasal NO will accumulate and contaminate the lower airway sample.

Without breath holding, the patient then exhales slowly and evenly while exhaled gas is sampled continuously. To prevent contamination of the exhalate with nasal NO, the patient exhales against an expiratory resistance while receiving feedback to maintain a positive pressure at the mouth. This positive pressure (usually about +5 cm H₂O) causes the velum in the posterior pharynx to close, preventing nasal NO from entering the air stream. The fractional concentration of NO in the exhaled gas varies inversely with the flow. To standardize on-line measurements, an exhaled flow of 0.05 L/sec (i.e., 50 mL/sec) ±10% is recommended. This flow allows dead space gas to be exhaled and a plateau in NO to be observed in about 10 seconds in adults (Figure 10-5). The correct flow can be maintained by using a pressure-sensitive flow controller and providing visual feedback to the subject. Current commercially available instrumentation (Chapter 11 uses visual incentives to assure standardized flow/pressure and will mark a maneuver as not meeting acceptability criteria if flow/pressure is not maintained).

Fe_NO is measured from the plateau of the single-breath exhalation profile (see Figure 10-5). The plateau phase may slope up or down slightly. The exhalation should last long enough to establish this plateau (>6 seconds for adults and children older than 12 years, >4 seconds for children ages 12 years and younger). Two points should be chosen on the plateau that represent a 3-second interval (about 0.15 L) in which the Fe_NO varies less than 10%. The Fe_NO is the mean concentration over this 3-second interval. For Fe_NO values of 10 ppb or less, variability of 1 ppb NO may be used in place of the 10% criteria. A minimum of 30 seconds should elapse between repeated measurements with the subject breathing air (off the NO sampling circuit).

At least two acceptable measurements of Fe_NO that agree within 10% of each other should be averaged for the final report value. Three acceptable measurements should be averaged if Fe_NO is measured at multiple flow rates.

Nasal Nitric Oxide

Although various methods of sampling nasal NO have been described, the recommended method uses transnasal airflow in series. In this technique, air is aspirated into one naris and out the opposite side, where NO is sampled. The subject exhales against a resistance of approximately 10 cm H₂O, while air is aspirated at a constant flow rate. As for measurement of Fe_NO from the lower airways, exhalation against resistance closes the velum in the posterior pharynx to prevent contamination of the sample. Airflow of 0.25–3.0 L/min is used for nasal NO measurements. Flows in this range allow a plateau in the NO signal within 20–30 seconds in most adults. The flow used for NO analysis, along with the transnasal flow, should be recorded (Figure 10-6).

Significance and Pathophysiology

Normal values for Fe_NO depend largely on the flow at which gas is sampled during analysis. At a standardized flow of 0.05 L/sec (50 mL/sec), healthy adults show Fe_NO values of 10–30 ppb, whereas in children the values are slightly lower (5–15 ppb). Fe_NO actually increases with increasing age in children. The upper limit of normal in adults isapproximately 35 ppb (25 ppb in children) when Fe_NO is measured using standardized methods and flows (50 mL/sec). Fe_NO appears to be related to airway size; thus, it tends to be slightly higher in males than in females.

Exhaled NO appears to correlate most closely with eosinophilic inflammation in the airways. Because this type of inflammation is characteristic of bronchial asthma, measurement of Fe_NO can be viewed as a surrogate for measuring eosinophils in induced sputum samples, bronchoalveolar lavage, or bronchial biopsy in patients who have asthma. These correlations persist when inflammation is treated, making Fe_NO an excellent tool for monitoring therapy.

Some studies have indicated a correlation between Fe_NO and bronchial hyperresponsiveness, as measured by the PC₂₀ from methacholine or histamine challenge. However, many studies show little or no correlation between eNO and hyperresponsiveness. These conflicting findings may result because eosinophilic inflammation is characteristic mainly in atopic individuals. Responsiveness to methacholine appears to correlate with FEV₁, whereas increased Fe_NO correlates with other markers of inflammation.

Although pulmonary function tests (including bronchial challenge) are considered a standard method for diagnosing and assessing asthma, there appears to be little correlation between these measures and airway inflammation. In general, most tests of lung function do not correlate with levels of eNO. Changes in NO during periods of exacerbation tend to occur more rapidly than changes in pulmonary function indices (e.g., FEV₁). Spirometry and bronchial challenge tests can reduce the level of eNO, so that if both procedures are to be performed on a patient, Fe_NO should be measured first.

Fe_NO is reduced by corticosteroids’ effects on airway inflammation. Numerous well-designed studies have demonstrated that steroid therapy, including inhaled corticosteroids, can be monitored and evaluated using Fe_NO as a marker of inflammation. Fe_NO does not appear to be reduced by either short-acting or long-acting β-agonists, either alone or in combination with inhaled corticosteroids. Fe_NO may also be reduced in some patients treated with leukotriene modifiers.

Because of the correlation between Fe_NO and airway inflammation and the known anti-inflammatory effects of inhaled corticosteroids, eNO has several potential uses in asthma diagnosis and management. Fe_NO can be used as a simple diagnostic screening tool to differentiate asthma from other conditions (such as chronic cough). Exhaled NO compares favorably with bronchial challenge tests (methacholine, exercise) in terms of sensitivity and specificity in detecting asthma. Patients who have an elevated NO level typically respond to corticosteroid therapy. Fe_NO is therefore a good tool to evaluate response to anti-inflammatory therapy. Failure of Fe_NO to decrease with steroid treatment suggests that the patient may be unresponsive to standard therapy or that the patient may be noncompliant with the recommended treatment. Some studies have suggested that the dosage of inhaled corticosteroids can be optimized with Fe_NO to guide therapy.

Patients who have COPD often show normal levels of Fe_NO. However, some studies have shown increased NO in patients with COPD. These differences may be related to the presence or absence of eosinophilic inflammation in COPD patients. Many COPD patients respond poorly to inhaled corticosteroids; measurement of Fe_NO may provide an indicator as to whether eosinophilic inflammation is present and whether the patient may respond to steroid therapy. Fe_NO may also be increased in pulmonary diseases that are characterized by inflammatory changes such as chronic bronchitis, chronic cough, sarcoidosis, pneumonia, alveolitis, bronchiolitis obliterans syndrome (BOS), and bronchiectasis.

Fe_NO is typically decreased in smokers, even though smoking causes airway inflammation. The physiologic explanation for the reduction in NO levels in smokers is unclear. Cigarette smoking may decrease the production of NO by epithelial cells lining the airways. Exhaled NO levels are also usually lower than normal in patients who have cystic fibrosis (CF). As in the case of smokers, it is not clear whether the reduced levels in CF are a result of decreased production or increased metabolism of NO in the lungs.

Nasal NO levels are typically much higher than eNO. Values from 100 ppb up to more than 1000 ppb have been reported. Most of the nasal NO appears to be produced by the epithelial cells in the paranasal sinuses. Patients with allergic rhinitis show elevated levels of NO that appear to be responsive to nasal corticosteroids. One disease in which nasal NO measurements may be particularly useful is primary ciliary dyskinesia (PCD). Patients who have PCD have much lower levels of nasal NO (Interpretive Strategies Box 10-1).

Spirometry

FVC, FEV₁, MVV. Obstructive disease can be easily identified with simple spirometry. A significant percentage of patients who may develop postoperative problems can be detected with minimal screening. Patients who have reduced FVC, with or without airway obstruction, typically have an impaired ability to cough effectively when VC decreases further during the immediate postoperative period. The FEV₁ is also used to predict postoperative pulmonary function in lung resection or pneumonectomy.

Bronchodilator Studies

Operative candidates with airway obstruction should also be tested with bronchodilators. Post-bronchodilator values for FVC, FEV₁, and MVV may be used in estimating surgical risk. There may be significantly less risk if the patient’s airway obstruction is reversible. Bronchodilator studies are similarly helpful in planning perioperative care. Bronchodilator therapy or inhaled corticosteroids may improve the patient’s bronchial hygiene both before and after surgery.

Blood Gas Analysis

Arterial blood gas analysis is helpful in assessing patients with documented lung disease to determine the response to pulmonary changes that occur postoperatively. Pao₂ is generally not a good predictor of postoperative problems. Individuals with hypoxemia at rest usually also have abnormal spirometry results, and therefore are at risk. Pao₂ may improve postoperatively in patients undergoing thoracotomy for lung resection if the resected portion contributed to /abnormalities. Paco₂ appears to be the most useful blood gas indicator of surgical risk. Some studies have shown that a Paco₂ above 45 mm Hg, in combination with airway obstruction and pulmonary symptoms (e.g., wheezing, cough), presents an increased risk of postoperative morbidity and mortality.

Exercise Testing

Exercise studies can accurately predict patients at risk. Individuals who cannot tolerate moderate workloads often have airway obstruction or similar ventilatory limitations. Patients who have an O₂ uptake (o₂) greater than 20 mL/min/kg typically have a low incidence of cardiopulmonary complications. Those unable to attain a o₂ of 15 mL/min/kg have an increased risk of postoperative complications.

Diffusing Capacity (Dlco)

A few studies have indicated that a low percent predicted postoperative diffusing capacity is an independent indicator of increased morbidity and mortality in patients undergoing lung resection. An accurate assessment of diffusing capacity is important in selecting patients who may be candidates for lung volume reduction surgery (LVRS).

In addition to routine pulmonary function studies, several other tests are used in predicting postoperative lung function in candidates for pneumonectomy or lobectomy. These procedures are normally used in combination with spirometry and blood gas analysis.

Perfusion and /Scans

Lung scans are particularly useful in estimating the remaining lung function in patients who are likely to require removal of all or part of a lung. Split-function scans are performed. These allow partitioning of lungs into right and left halves, or into multiple lung regions. Although ventilation-perfusion scans give the best estimate of overall function, simple perfusion scans yield similar information. Lung scan data, in the form of regional function percentages, are used in combination with simple spirometric indices to calculate the patient’s postoperative capacity. An example follows:

Postoperative FEV1=Preoperative FEV1× %Perfusion to unaffected regions

This calculation is termed the predicted postoperative FEV₁, or ppo-FEV₁.

Patients whose postoperative FEV₁ is less than 800 mL are typically not considered surgical candidates. Resection of any lung parenchyma resulting in an FEV₁ less than 800 mL would leave the patient more severely impaired. One exception to this general guideline occurs in patients referred for lung volume reduction surgery (LVRS). These candidates are usually end-stage COPD patients, often with FEV₁ values less than 800 mL and significant air trapping. Removal of poorly ventilated lung tissue often results in an improvement in spirometry, with significant increases in both FVC and FEV₁.

Pulmonary Artery Occlusion Pressure

In some candidates for pneumonectomy, the development of postoperative pulmonary hypertension may be a limiting factor. To estimate the effect of redirecting the entire right ventricular output to the remaining lung, a catheter is inserted into the pulmonary artery of the affected lung and blood flow occluded by means of a balloon. The resulting pulmonary artery pressure increase in the remaining lung is then measured. A pressure increasing to less than 35 mm Hg is usually considered consistent with acceptable postoperative pressures. The effect of redirected blood flow on oxygenation may also be a consideration. This can also be examined during occlusion to estimate postoperative Pao₂.

Tests that predict the effects of resection on the remaining lung are normally done in series, with spirometry done first, followed by split-function lung scans (if spirometry results are acceptable), and then pulmonary artery occlusion pressure (if cor pulmonale is a concern). Table 10-1 summarizes general value ranges used for preoperative pulmonary function testing.

Table 10-1

Preoperative Pulmonary Function

Test	Increased Postoperative Risk	High Postoperative Risk	Candidate for Pneumonectomy*
FVC	< 50% of predicted	< 1.5 L
FEV1	< 2.0 L or 50% of predicted	< 1.0 L	> 2.0 L
MVV		< 50 L/min or 50% of predicted	> 50 L/min or 50% of predicted
Paco2		> 45 mm Hg
o2max	15–20 mL/min/kg	< 15 L/min/kg
Predicted postoperative FEV1			> 0.8 L/min
Pulmonary artery occlusion			> 35 mm Hg

^*Values in this column determine whether the patient is to be considered a candidate for lung resection (see text).

Forced Vital Capacity and Forced Expiratory Volume

Spirometry is the most useful index for the assessment of impairment caused by airway obstruction. The test should not be performed unless the patient is stable. The reported FVC and FEV₁ should be the largest values obtained from at least three acceptable maneuvers. The two largest FVC values and FEV₁ values should be repeatable within 5% or 0.1 L, whichever is greater. Peak flow should be achieved early in the expiration, and the spirogram should show gradually decreasing flow throughout the breath. Spirometry should be repeated after inhaled bronchodilator if the patient’s FEV₁ is less than 70% of the predicted value. Spirometric efforts, before and after bronchodilators, should meet these repeatability criteria. Standing height, without shoes, should be used for comparison of measured values with limits for disability (Table 10-2). In case of marked spinal deformity, arm-span measurement should be used (see Chapter 1).

Computation of the FEV₁ should be done with back-extrapolated volumes (see Chapter 2). The spirogram is acceptable if the back-extrapolated volume is less than 5% of the FVC, or 0.1 L, whichever is greater. Each maneuver should be continued for 6 seconds or until there is no detectable change in volume for the last 2 seconds of the maneuver. It is unacceptable to report FEV₁ when only an F-V curve is recorded. A volume-time tracing from which FEV₁ can be measured is required. All lung volumes and flows must be reported at body temperature, pressure, and saturation (BTPS).

Volume calibration of the spirometer should agree to within 1% of a 3-L syringe. If spirometer accuracy is less than 99% but within 3% of the calibration syringe, a calibration correction factor should be used (see Chapter 12). If a flow-sensing spirometer is used, linearity should be documented by performing calibration at three different flows (3 L/6 sec, 3 L/3 sec, and 3 L/1 sec). The volume-time tracing should have the time sensitivity marked on the horizontal axis and the volume sensitivity marked on the vertical axis. The paper speed should be at least 20 mm/sec and the volume excursion at least 10 mm/L to allow manual calculation of the FEV₁ and FVC. The manufacturer and model of the spirometer should be stated in the report (see Criteria for Acceptability Box 10-2).

Diffusing Capacity

The Dlco is useful in determining impairment because of chronic impairment of gas exchange in both obstructive and restrictive disorders. The single-breath method should be used. The standard criteria for acceptability and repeatability for the Dlco maneuver may be applied (see Chapter 3). However, the IVC should be at least 90% of the patient’s best VC and the breath-hold time between 9 and 11 seconds. The reported value should be uncorrected for hemoglobin (Hb), but abnormal Hb or carboxyhemoglobin (COHb) values should be reported. Correction for altitude should be made if the P_IO₂ is significantly different from 150 mm Hg. If the Dlco is greater than 40% of predicted but less than 60%, resting blood gas analysis is indicated.

Arterial Blood Gases

Although blood gas results are objective, they are largely nonspecific in determining impairment. Blood gases should be obtained while the subject is breathing air, either sitting or standing. The A-aO₂ gradient may not be reliable because it can be affected by hyperventilation (Table 10-3). Blood gas analysis may be required in diffuse pulmonary fibrosis and should include Pao₂ and Paco₂. Blood gases (and A-a gradient) may also be assessed during exercise. The requirement for supplemental O₂ may also be quantified by exercise blood gas analysis. Pulse oximetry or capillary blood gas analysis is not an acceptable substitute for arterial blood gas analysis. Blood gas analysis should be performed by a laboratory certified by a state or federal agency.

Exercise Testing

Patients considered for exercise evaluation should first have resting blood gas evaluation, either sitting or standing. A steady-state exercise test (see Chapter 7) is then performed, preferably with a treadmill. The patient should exercise for 4–6 minutes at an O₂ consumption rate (o₂) of approximately 17.5 mL/min/kg (approximately 5 METs) breathing room air. An equivalent workload should be used for cycle ergometry (e.g., 75 W for a 175-lb patient). Blood gas samples should be drawn at this workload to determine whether significant hypoxemia is present (see Table 10-3). If the patient does not desaturate at this level, a higher workload can be used to determine exercise capacity. If the patient cannot achieve a workload of 5 METs, a lower workload can be selected to determine exercise capacity.

ECG should be monitored continuously throughout the exercise evaluation and blood gases drawn during the final 2 minutes of the test. It may be helpful to measure o₂, co₂, and _E. The altitude of the test site and barometric pressure should be included in the report to assist with interpretation of blood gas values.

In reporting impairment for the purpose of determining disability, the remaining functional capacity is as important in determining the patient’s ability to perform a certain task as the percentage of lost function. Some statement of the patient’s ability to understand and cooperate during pulmonary function measurements should accompany the tabular and graphic data.

Limits for determining disability based on respiratory impairment have been set for the United States by the Social Security Administration. Criteria are set according to the disease category (see Interpretive Strategies 10-1). COPD is evaluated by comparing FEV₁ with the values in Table 10-2. Restrictive ventilatory disorders are evaluated by comparing FVC with the values in Table 10-2. Impaired gas exchange is evaluated by comparing Pao₂ with the values in Table 10-3. Disability caused by asthma is also evaluated with FEV₁. Episodes of asthma (requiring emergency treatment or hospitalization) occurring at least every 2 months or at least six times per year may also be evidence of disability (Criteria for Acceptability 10-3 and Interpretive Strategies 10-2).

Techniques

Indirect calorimetry may be performed with either an open-circuit or a closed-circuit system to measure O₂ consumption, CO₂ production, and RER. The open-circuit method is more commonly used in clinical practice.

Open-Circuit Calorimetry

Exchange of O₂ and CO₂ may be measured by recording the fractional differences of O₂ and CO₂ between inspired and expired gas. These measurements are accomplished with a mixing chamber, a dilution system, or a breath-by-breath system similar to those used for expired gas analysis during exercise (see Chapter 7). o₂ and co₂ are measured as described for exercise testing with mixing chamber and breath-by-breath systems. _E, V_T, and f_b (respiratory rate) may be measured simultaneously. In systems that use the dilution principle, a constant flow of gas is mixed with expired air. The dilution of CO₂ is then used to calculate ventilation. Connection to the patient may be made by a standard directional breathing valve with a mouthpiece and noseclips. A ventilated hood or canopy (Figure 10-11) may also be used. Almost all metabolic measurement systems provide for connection to a mechanical ventilator circuit.

A hood or canopy allows long-term measurements without direct connection to the patient’s airway. The hood is ventilated by drawing a flow of gas through it that exceeds the patient’s peak inspiratory demand (40 L/min is usually adequate). Ventilation can be calculated by measuring the change in flow into and out of the hood during breathing (“bias” flow).

Connection to a ventilator requires a means of measuring exhaled volume along with fractional concentrations of both inspired and expired gas. Breath-by-breath metabolic measurement systems usually sample gas at the patient-ventilator connection.

Performing Metabolic Measurements

The primary purpose of indirect calorimetry is to estimate REE over an extended period, usually 24 hours. To extrapolate the values obtained during the sampling period, the patient’s condition during the measurement is critical (Criteria for Acceptability 10-4). The calorimeter or metabolic cart should be calibrated at least daily, preferably before each test. Gas analyzers should be calibrated using gas concentrations appropriate for the clinical situation. Sample lines and gas-conditioning devices (absorbers)

Criteria for acceptability 10-4   Indirect Calorimetry

1. Appropriate calibration of gas analyzers and volume transducers should be documented before each test.

2. RQ should be within the normal physiologic range of 0.67–1.30.

3. Measured o₂ and co₂ values should vary by no more than 5% or less for a 5-minute data collection; longer data collection intervals may be necessary if the variability is greater than 5%.

4. Data should be collected for a minimum of 5 minutes with minimal variability.

5. RQ values should be consistent with the patient’s current nutritional intake.

6. Documentation should include the patient’s medications, nutritional support, body temperature at time of test, and ventilatory support setting (if applicable).

7. The patient should be resting; no bolus feedings or pharmacologic stimulants or depressants. There should be no physical therapy, airway care, or major ventilator changes immediately before the assessment.

8. If a stable F_IO₂ cannot be achieved, REE may be estimated from the co₂ with an assumed RQ of 0.85.

9. If a 24-hour urinary urea nitrogen (UUN) is collected for substrate use, it should be concurrent with the metabolic study.

Adapted from American Association for Respiratory Care: Clinical practice guideline: Metabolic measurements using indirect calorimetry during mechanical ventilation–2004 revision & update. Respir Care. 2004; 49:1073–1079.

10-2   How To…

Perform REE Study (Open Circuit)

1. Tasks common to all procedures

a. Calibrate and prepare equipment

b. Review order

c. Introduce yourself and identify patient according to institutional policies

d. Describe and demonstrate procedure

2. Verify compliance with pre-test instructions.

a. Post-absorptive state, for example, 12 hours after the last meal

b. Effect of eating a meal increases the metabolic rate by 46%, which does not disappear for 12 hours

3. Preliminary rest period of 20 minutes

4. Place the device on the subject or in-line (ventilator) with the subject.

5. Remind the subject to breathe quietly/normally during the test (if spontaneously breathing)

a. Hyperventilation during the test will increase the RQ

6. Subject should be recumbent.

7. Observations:

a. Record the time the rest period begins.

b. Record heart rate and respiratory rate at least twice.

c. Note respiratory rate characteristics.

d. Shallow, deep, forced, regular, or irregular

e. Temperature and BP measured 10 minutes into rest period

f. Muscular activity should be recorded.

8. Post-Test Data Assessment

a. RQ <0.71 or >1.0 indicates a nervous patient or error in the measurement.

b. Ideally average 10 minutes of steady-state data.

9. Report results and note comments related to test quality.

should be checked before each test. If calibration or testing produces questionable values, the device should be checked against a known standard. Burning ethanol or other material with a fixed RQ can be used. A large-volume syringe can be used to simulate a patient with o₂ and co₂ values near zero. Alternately, biologic controls can be used to check the precision of the calorimeter.

Pre-test instruction should include fasting after midnight in the outpatient subject or for 2–4 hours before the test starts in a hospitalized patient. If the inpatient is receiving either enteral or parenteral feedings, the feedings should be continuous rather than in bolus form. Information about the type and amount of nutritional support in the previous 24 hours may be helpful in interpreting test results. Drugs or substances that alter metabolism should be avoided. Substances such as caffeine and nicotine are particularly common stimulants. Theophylline-based drugs may also increase metabolic rate. The subject should refrain from exercise. Typically these tests are performed in the morning hours to try to reduce the amount of activity performed before testing. The patient should be recumbent or supine for 20–30 minutes before beginning measurements and should stay quiet during the test. Ideally, the patient should be awake and alert during testing. The testing apparatus should not cause discomfort or exertion for the patient, which is the reason canopy testing is ideal for this procedure because breathing valves, mouthpieces, and noseclips may alter the patient’s breathing pattern. The patient should be in a neutral thermal environment. Special corrections may be required for patients who are febrile or hypothermic. The patient’s temperature at the time of the test should be recorded along with a temperature history of the previous 24 hours. Temperature changes of 1 °C can result in a 13% change in REE. Data collection should continue long enough to establish a stable baseline and verify steady-state conditions (Figure 10-12). Ten to 15 minutes of stable readings for o₂ and co₂ may be required, but an adequate measurement can be obtained in as short an interval as 5 minutes. Common indicators of steady-state conditions are the parameters assessed as part of the metabolic study. o₂ and co₂ should not vary more than 5% from the mean value measured during the te st (at least 5 minutes). Respiratory quotient (RQ) values should be within the normal physiologic range (0.67–1.30). If the patient does not achieve steady-state conditions, a longer test interval may be required to average representative periods of metabolic activity. Patients on ventilators should be in a stable condition. Leaks in the ventilator circuit, around cuffed endotracheal tubes, or from chest tubes or bronchopleural fistulas may invalidate measurements of RQ and REE. No ventilator adjustments should be made 1–2 hours before the test period. Modifications in minute ventilation or F_IO₂ settings can cause gross changes in the patterns of gas exchange, particularly in patients with pulmonary disease. The ventilator must have a stable delivered O₂ concentration; F_IO₂ settings greater than 0.60 may result in erroneous o₂ measurements. Appropriate valves may need to be used for ventilator modes that involve continuous gas flow.

Metabolic Calculations

The Harris-Benedict equations are commonly used to estimate REE:

Men:

REE(kcal/24hr)=66.47+13.75W+5 H−6.76A

Women:

REE(kcal/24 hr)=655.1+9.56W+1.85H−4.68A

where:

W= weight, kilograms

H= height, centimeters

A= age, years

The REE by these formulas was originally described as the basal metabolic rate (BMR). These equations may be used to estimate the caloric expenditure in normal individuals under conditions of minimal activity. BMR in these circumstances is related to lean body mass. To determine the optimum level of caloric intake, BMR must be adjusted upward because trauma, surgery, infections, and burns all cause the REE to increase.

The Weir equation is used to calculate REE from respiratory gas exchange and urinary nitrogen:

REE(kcal/24  hr)=5.68V·O2+1.59V·CO2−2.17  UN

where:

o₂ is expressed in mL/min (STPD)

co₂ is expressed in mL/min (STPD)

UN = urinary nitrogen (g/24 hr)

If UN is unknown, REE may be calculated

Indirect calorimetry by the open-circuit method provides measures of both O₂ consumption and CO₂ production. As previously mentioned, RER is the ratio co₂/o₂. Under steady-state conditions, RER approximates the mean respiratory quotient (RQ) at the cell level. RQ normally varies from 0.71–1.00, depending on the substrates being metabolized. Carbohydrate oxidation produces an RQ near 1.0, fat oxidation produces an RQ near 0.71, and protein oxidation produces an RQ of 0.82. RQ attributable to carbohydrates and fats may be determined by subtracting o₂ and co₂ derived from protein. This form of the RQ is termed the nonprotein RQ or RQnp and is calculated as follows:

RQnp  =  1.44V·CO2−4.754UN1.44V·O2−5.923UN

where:

co₂ is expressed in mL/min

o₂ is expressed in mL/min

UN= urinary nitrogen (g/24 hr)

1.44= factor to convert mL/min to L/24 hr

Because CO₂ production varies with O₂ uptake, deviations of the RQ from the average value of 0.85 result in differences of less than 5% in the calculation of REE if only o₂ and RQ are used. Indirect calorimetry by the closed-circuit (volumetric) method takes advantage of this small difference by assuming a fixed RQ (usually 0.85) and measuring only o₂. Open-circuit calorimetry is usually limited to measurements on patients whose F_IO₂ is 0.6 or less. However, co₂ can be measured on these patients and o₂ estimated, again by assuming an RQ of 0.85. This method provides a means of estimating caloric needs, even though o₂ cannot be measured accurately.

UN is obtained from a 24-hour urine collection. Because protein metabolism accounts for only a small portion of total calories per day (approximately 12%), omission of the UN in the Weir equation changes the calculated REE by only 2%.

The Consolazio equations can be used to determine energy expenditure from gas exchange (o₂, co₂), UN, and the caloric equivalents of carbohydrates, fats, and proteins:

CHO=5.926V·CO2−4.189V·O2−1.539UNFAT=2.432V·O2−2.432V·O2−1.943UNPRO=6.250UN

where:

CHO= Carbohydrates oxidized in grams/24 hours

FAT= Fat oxidized in grams/24 hours

PRO= Protein oxidized in grams/24 hours

From the grams of each substrate used, the kcal derived from that source can be computed:

Carbohydrates (in kcal) = 4.18 carbohydrates (in grams)

Fat (in kcal) = 9.46 fat (in grams)

Protein (in kcal) = 4.32 protein (in grams)

Total (in kcal) = carbohydrate + fat + protein

The percentage of calories from each substrate may also be calculated by dividing the kcal derived from that substrate by the total kcal. Because the Consolazio equations are intended for analysis of normal substrate partitioning, RQ values outside of the range of 0.71–1.00 will result in negative values for either carbohydrates or lipids (fat). These negative values are erroneous if RER does not equal RQ (i.e., the patient is not in a metabolic steady state).

Significance and Pathophysiology

See Interpretive Strategies 10-3. Indirect calorimetry assesses nutritional status in patients whose daily energy needs are altered by disease, injury, or therapeutic interventions. REE accounts for approximately two thirds of the daily energy requirements in healthy patients. The Harris-Benedict equations, or similar predictive equations, are commonly used to estimate REE. Various factors can be used to adjust estimated REE to account for additional caloric needs imposed by the patient’s clinical status. This approach works well in many patients. However, metabolic requirements of critically ill patients vary widely. Indirect calorimetry is indicated for patients who do not respond favorably to traditional methods of nutritional assessment and support. Indirect calorimetry can be used to detect undernourishment, overnourishment, or use of inappropriate substrates (Box 10-2).

Undernourishment or starvation can occur during acute or chronic illness. It may be detected by caloric expenditure in excess of caloric intake (negative energy balance). Both fat stores and protein from muscle breakdown may contribute to metabolism during periods of undernourishment. Indirect calorimetry is often used along with measurement of body weight, triceps skinfold measurements, and other approximations of energy reserves. These measurements allow planning of nutritional therapy to replenish diminished reserves.

Overnourishment occurs when any substrate is supplied in excess of the energy requirements. Overfeeding is most deleterious when the patient’s nutritional status is already adequate. Excess lipid or carbohydrate calories are stored as fat, which may place stress on one or more organ systems (e.g., liver).

Patients who have pulmonary disease present a special dilemma. Excessive carbohydrate intake results in increased CO₂ production because the RQ of carbohydrates is 1. For patients in respiratory failure, excess CO₂ production increases the ventilatory load on the respiratory system. Adjustments in substrate use can be made after the nonprotein RQ is determined by indirect calorimetry. Lipids (i.e., fats) are typically substituted for glucose so that the RQ can be reduced while the caloric intake is maintained. Patients in respiratory failure may also experience atrophy of ventilatory muscles. Substrate analysis can be used to assess N₂ balance related to the breakdown of muscle protein. Substrate analysis permits measurement of nutritional requirements necessary to maintain N₂ balance.

Technical considerations involved in indirect calorimetry include the accuracy of gas analysis and measurement of expired volume during the test (open-circuit methods). The most common problem during metabolic measurements is attainment of a true steady state. Only if the measurements are made under steady-state conditions is the metabolic rate representative of caloric expenditure over 24 hours. Hyperventilation resulting from connection to a mask or mouthpiece, or from ventilator manipulation, occurs frequently. Head hoods or continuous-flow canopies can eliminate much of the stimulation associated with connection to the metabolic measurement system (see Figure 10-10, A) but cannot be used for patients on mechanical ventilators. Hoods or canopies may also cause hyperventilation in awake, alert patients. An RER greater than 1.0 should always be evaluated in relation to _E and end-tidal CO₂. Abnormally high _E and low end-tidal CO₂ values may indicate hyperventilation. RER values in excess of 1 that cannot be explained as hyperventilation may be caused by storage of excess calories as fat (lipogenesis). RER values between 0.67 and 0.70 may occur in ketosis caused by extreme fasting or diabetic ketoacidosis. However, more commonly, low RER values (<0.67) signal improper calibration of the CO₂ or O₂ analyzers. Inaccurate calibration or improper performance of gas analyzers can result in RER values outside of the usual metabolic range of 0.70–1.

Special problems may be encountered in performing metabolic measurements on patients requiring mechanical ventilatory support. A common difficulty relates to measurements of O₂ consumption in patients receiving supplemental O₂. Measurement of o₂ by respiratory gas exchange requires analysis of the difference between inspired and expired O₂ along with _E. In patients who are breathing air, inspired F_IO₂ is constant. Many O₂-blending systems, such as those used on ventilators, may not provide a constant fraction of inspired O₂. Large differences in calculated o₂ may result from small fluctuations in F_IO₂, even if F_EO₂ remains relatively constant. Small differences in inspired and expired volumes (resulting from the RER) are corrected by adjusting the inspired fraction of O₂, according to the following equation:

(1−FEO2−FECO2)1−FIO2  ×  FIO2

This correction of inspired F_IO₂ for gas balance in the lung (i.e., the Haldane transformation) limits the accuracy of the open-circuit method of determining o₂. As F_IO₂ increases, the value in the denominator of the equation becomes smaller. Even with very accurate gas analyzers, measurement of differences between F_IO₂ and F_Eo₂ (when F_IO₂ is above 0.60) is variable. Breath-by-breath analysis of exhaled gas can reduce the problem of variable F_IO₂ by measuring the fractional gas concentrations at the patient’s airway and computing o₂ and co₂ for individual breaths. Indirect calorimetry by the volumetric method (i.e., a closed system) avoids this problem by measuring the actual volume of O₂ removed during rebreathing. Allowing the patient to breathe from a reservoir bag containing an elevated F_IO₂ (typically 0.60) can usually accommodate measurement of o₂ and co₂ in spontaneously breathing patients who require supplemental O₂.

If a stable F_IO₂ cannot be achieved (as is often the case when it is 0.60), REE can be estimated from the co₂. If an RQ of 0.85 is assumed, o₂ can be estimated by dividing the co₂ by the RQ and then solving the Weir equation (see pg 342). This method will underestimate the REE when the RQ is greater than 0.85, with a maximal error of about 25% if the RQ is really 1.20. Similarly, the REE will be overestimated for RQ values less than 0.85, with a maximal error of approximately 19% if the RQ is 0.67.

Other considerations involved in metabolic measurements of ventilated patients include the effects of positive pressure on gas analysis and on volume determination. Analysis of O₂ and CO₂ in the ventilator circuit must take into account the effect of positive pressure breaths on the gas analyzers. Depending on the sampling method used, positive pressure swings during each breath may generate falsely high partial pressure readings. Closed-circuit calorimetry places a volumetric device in the breathing circuit between the ventilator and the patient (Figure 10-10, B). The volume delivered by the ventilator must be increased to accommodate the higher compressible gas volume in the circuit, approximately 1 mL/cm H₂O for each liter of added volume.