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TECHNOLOGY, COMPUTING, AND SIMULATION

Novel Portable Device Measures Preoperative Patient Metabolic Gas Exchange

From the Department of Anesthesiology, University of California, Irvine, California.

Address correspondence and reprint requests to Peter H. Breen, MD, FRCPC, Department of Anesthesiology, UCI Medical Center, Building 53, Room 227, 101 The City Drive South, Orange, CA 92868. Address e-mail to pbreen{at}uci.edu.

	Abstract

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BACKGROUND: Indirect calorimetry (IC), the measurement of airway CO₂ elimination (co₂), o₂ uptake (o₂), and respiratory exchange ratio (RER = co₂/o₂), is a noninvasive modality for the assessment of body metabolism. In anesthesia, IC can signal critical events and onset of acute metabolic derangements. We have previously demonstrated the accuracy and precision of a new IC measurement system designed for mechanically ventilated patients, comprised of a new clinical bymixer, fast response humidity and temperature sensor, and a flowmeter. However, measurement of IC during spontaneous breathing is challenging because of unstable tidal volume, frequency, and functional residual capacity (FRC).

METHODS: A new device for IC measurements, designed specifically for spontaneous breathing, was validated against a metabolic lung simulator bench setup. In a second study, the same device was used to conduct preoperative measurements of co₂ and o₂ in 15 patients.

RESULTS: Our measurements showed excellent correlation and agreement with metabolic lung simulator values: The average (±sd) percent error for airway co₂ was –4.7% ± 3.31%; the average (±sd) percent error for airway o₂ was –0.30% ± 5.25%. Average values of co₂ and o₂ in the patient study (3.01 ± 0.56 and 3.44 ± 0.69 mL · kg^–1 · min^–1, respectively) were in agreement with previously reported values.

CONCLUSION: We have shown that the new, portable bymixer-flow device, using a bymixer and a fast response humidity sensor, provided accurate and convenient bedside measurement of co₂ and o₂. We believe that it can contribute in the future to preoperative assessment and baseline reference value for perioperative management.

	Introduction

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Preoperative determination of oxygen uptake (o₂) and CO₂ elimination (co₂) can serve several purposes. First, it can estimate perioperative risk by identifying the anaerobic threshold (AT) during exercise, as described by Older et al.1 Second, the determination of preoperative co₂ and o₂ provides baseline values that can be compared with intraoperative and postoperative measurements whereby changes may herald critical events. For example, an abrupt decrease in co₂ and o₂ may indicate critical reduction in cardiac output (t).2 Third, determination of the respiratory exchange ratio (RER = co₂/o₂) may help to detect anaerobic metabolic acidosis and define nutritional status (e.g., hypoglycemia, ketoacidosis).3

Currently, there are several commercial metabolic monitors that can measure co₂ and o₂ in spontaneously breathing patients.4–6 The Deltatrac (Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland) requires both a ventilated hood system and about 40 min to complete measurements during spontaneous ventilation.7 Another metabolic monitor, the MMC Horizon (SensorMedics, Yorba Linda, CA)8, is specifically used for exercise testing and is not designed for bedside assessment of co₂ and o₂.

A common method to noninvasively measure airway metabolic gas exchange is indirect calorimetry (IC) where co₂ and o₂ are determined by measuring gas flow and fractions at the airway opening. Hence, in the usual condition when the inspired CO₂ fraction is zero, co₂ can be calculated by9:

where e is the expired volume and Fco₂ is the mixed expired CO₂ fraction. Measurement of mixed gas fractions is a challenging problem, which we solve with the new bymixer (see below). o₂ is given by subtracting the expired O₂ flow from the inspired O₂ flow:

where i denotes inspiration. Standard IC methodology invokes the principle of conservation of the inert gas nitrogen during the steady-state condition (Haldane transformation), where SYMBOL. Substitution into Eq. 2 yields10

View larger version (8K): [in this window] [in a new window]   Symbol. No caption available.

Accordingly, co₂ and o₂ can be determined from measurements of e and mixed inspired and expired gas fractions. Hence, the Haldane transformation8,11 compensates for flow measurement inaccuracies between inspiration and expiration.

IC is commonly used in intensive care medicine. However, anesthesia presents unique challenges to this measurement; first, collection of expired gas for the measurement of mixed gas fraction is impossible in the anesthesia circle circuit, since most of the expired gas is reused for the following inspiration. Furthermore, the expired gas in the circle circuit is humidified and heated, which requires standard temperature and pressure dry (STPD) correction. Third, anesthesia is a dynamic period of patient care, which requires a rapid update rate and continuous measurement of co₂ and o₂. Current metabolic monitors do not provide an adequate solution for challenges to obtaining IC measurements in the anesthetized patient. Accordingly, we have designed two devices specifically for anesthesia: First, the bymixer12 is a new inline mixing chamber for the measurement of inspired and expired mixed gas fractions. It is specially designed for the anesthesia circle circuit and affects neither the circuit resistance nor dead-space. Second, the new fast response humidity and temperature airway sensor13 corrects gas flow to STPD conditions. Without this correction, o₂ measurement error can reach 50% in a breath-by-breath measurement system.10 We have extensively validated our system in a metabolic lung simulator bench setup14 during mechanical ventilation, and have demonstrated excellent correlation and agreement between the bymixer flow measurement and alcohol combustion, for both o₂ and co₂.9

The bymixer-flow measurement of co₂ and o₂ requires special apparatus during spontaneous breathing, where tidal volume (Vt), respiratory frequency (f), and functional residual capacity (FRC) are unstable. Hence, we have designed a special portable bymixer-flow breathing device, using the bymixer, flowmeter, humidity sensor, nonrebreathing valve, and special computation algorithms, and validated the device against the metabolic lung simulator. In a second experimental stage with the new measurement system, we preoperatively collected co₂ and o₂ in 15 awake, spontaneously breathing patients.

	METHODS

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The portable bymixer-flow breathing device (Fig. 1) was composed of an inspiratory inlet arm and an expiratory arm, connected by a Y-shaped two-way nonrebreathing valve (Hans Rudolph, KS City, MO). The bymixer was incorporated into the expiratory arm. The filter, temperature and humidity sensor, and the pneumotachometer cuvette were placed at the airway opening. The apparatus is compact, light weight and inexpensive. A common anesthesia monitor (Datex-Engstrom Division, Instrumentarium Corp., Helsinki, Finland) provided measurements of airway flow and gas fractions (side-stream sampling).

View larger version (13K): [in this window] [in a new window]   Figure 1. Specially-designed indirect calorimetry apparatus to measure airway CO2 elimination (co2) and O2 uptake (o2) in spontaneously breathing awake patients. The patient breathed through the filter (to prevent contamination), fast response temperature and humidity sensor (for standard temperature and pressure dry [STPD] correction), pneumotachometer cuvette (to measure gas flow), and the non-rebreathing valve. This valve connected the inspiratory arm inlet and the expiratory arm outlet (incorporating the bymixer). The non-rebreathing valve is depicted during the expiratory phase. During the clinical studies, the patient inspired room air. During the metabolic lung simulator studies, a reservoir supplied inspired O2 fraction of 35%.

Bymixer Design (Patent Pending)
The bymixer (Fig. 1) was constructed from conventional anesthesia tubing and was composed of a main flow arm placed in parallel with a mixing arm. The mixing arm was a 121-cm pediatric circuit corrugated tube (15 mm ID, Expandoflex; Cleveland Tubing, Cleveland, TN) with a total volume of 200 mL. A fixed orifice resistor was placed downstream. The resistor forced most of the gas flow to be directed through the main flow arm (approximately 1:9 ratio) and also slowed down the flow inside the mixing arm, allowing for better homogenous mixing. The corrugated tubing design of the mixing arm enhanced the turbulent flow of the respiratory gas, which also improved gas mixing. Because a constant proportion of total gas flow was directed through the mixing arm, gas sampled at the port yielded accurate mixed gas fractions. In a previous publication we showed excellent accuracy and precision of this device.12

Fast Response Temperature and Humidity Sensor (US Patent Number 6,014,890)13
Two thermometers (copper and constantan type T thermocouples, Omega Engineering, Stamford, CT) were incorporated into a standard anesthesia adapter (T adapter; Datex-Ohmeda, Milwaukee, WI). One of the thermometers was kept constantly wet with a specialized wicking system. As respiratory gas relative humidity decreased, evaporation caused the "wet" temperature reading to measure lower than the ‘dry’ thermometer reading. Psychrometry equations allowed relative humidity to be calculated from the wet and dry thermometer readings.

The portable bymixer-flow breathing device to measure airway co₂ and o₂ was validated (Fig. 2) in a metabolic lung simulator bench setup, described previously.14 In brief, a precise flow of ethanol was infused into a custom-made, wickless burner inside an airtight metabolic chamber. The screw-type syringe pump (Syringe Pump A-99, Razel Scientific Instruments, Stamford, CT) accuracy was 2% for flow rates of 0.025 to 430 mL/h. From the known flow of ethanol, stoichiometric calculations15 provided the reference values of co₂ and o₂. Upstream and downstream roller pumps circulated the gas flow between the metabolic chamber and the mechanical lung. The anatomical dead-space, as calculated by the Bohr principle, was 150 mL.14 The portable bymixer-flow breathing device was connected at the airway opening of the mechanical lung. A 15-L reservoir bag supplied 35% O₂ to the inspiratory arm. Spontaneous breathing patterns were achieved by a second (driving) lung (dual lung mechanical lung, Dual Adult TTL, Model 1600, MI instruments, Grand Rapids, MI) connected to an open-circuit ventilator (Servo Ventilator 900C, Siemens, Sweden). The driving lung actuated the test lung via a coupling clip. Hence, in contrast to standard mechanical ventilation, the pressure in the test lung was negative during inspiration, mimicking spontaneous breathing.

View larger version (16K): [in this window] [in a new window]   Figure 2. Metabolic lung simulator bench setup was used to validate airway CO2 elimination (co2) and O2 uptake (o2) measured by the portable bymixer-flow breathing device. The precision syringe pump supplied ethanol to a custom wickless burner enclosed in an airtight chamber. Two occlusion pumps directed gas flow in a circular manner between the mechanical lung and the metabolic chamber. The portable bymixer-flow breathing device was connected at the airway opening of the mechanical lung. Another ventilator drove the second mechanical lung which actuated the test lung through the coupling clips. Spontaneous breathing characteristics were achieved by changing respiratory rate, tidal volume (Vt), and positive end-expiratory pressure (PEEP) of the driving ventilator and lung every 3 breaths. Measurements were repeated 3 times over the range of 66.70 to 333.50 mL/min for co2 and 100.10–500.25 mL/min for o2 (respiratory quotient, RQ = 0.67).

Table 1 summarizes the measurement protocol. Over the range of co₂ (66.7–334 mL/min) and o₂ (100–500 mL/min) (respiratory quotient, RQ = 0.67), minute ventilation (Vt · f) was adjusted so that end-tidal Pco₂ (Pet_co2) remained near 40 mm Hg. We perturbed f (8–16 breaths/min) and Vt (195 ± 43 mL to 626 ± 120) every 3 breaths to generate variations in f, Vt, and inspiratory pressure and mimic the spontaneous breathing pattern. Positive end-expiratory pressure (PEEP, 0–12 cm H₂O) was adjusted every 3 breaths to generate variable FRC.

All data were collected by computer using an analog-to-digital converter as described previously.9,14 We developed a custom computer program for complex calculations, including an automated system to recognize the start and end of each respiratory cycle, integration of flow to volume, calculation of inspired and expired relative humidity using the psychrometry principle,16 correction of gas flow to STPD conditions,10 and the calculation of co₂ and o₂ by processing gas flows and mixed gas fractions (Eqs. 1 and 3).

In a second experimental stage, we tested the device preoperatively in 15 patients and measured airway co₂ and o₂ during awake spontaneous breathing. After IRB approval, each patient was called the night before surgery for verbal approval to participate in the study. On the day of surgery, after informed written consent and before administration of sedation, the patient was asked to breathe in a normal pattern through the mouthpiece of the apparatus. A nose clip was used to ensure mouth breathing only. The patients were breathing room air (Fig. 1). We began data capture after stabilization of the expiratory bymixer value (usually 30s after the patients started breathing through the apparatus). Each measurement was conducted over 60 s. For the first 30 s, gas was sampled from the inspiratory arm and for the second 30 s, gas was sampled from the expiratory bymixer. These 30s intervals permitted adequate measurements of airway gas flow. This entire measurement sequence was repeated twice in each patient, separated by a 60s time interval.

	RESULTS

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Stage 1: Use of Metabolic Lung Simulator to Validate Measurements of co₂ and o₂ by the New Portable Bymixer-Flow Device During Spontaneous Breathing
Figure 3 presents a typical spontaneous breathing pattern of airway flow and pressure for the metabolic lung simulator (upper panel) and for a patient (lower panel). Key elements of spontaneous breathing are demonstrated, including negative pressure inspiration, variable airway flow, and variable f. (FRC was changed by varying PEEP of the driving ventilator). For both the metabolic lung simulator and patients, airway flow was between 50 to –50 L/min and airway pressure was between 5 to –5 cm H₂O.

View larger version (23K): [in this window] [in a new window]   Figure 3. Typical airway flow and pressure waveforms during spontaneous breathing for 60 s with the metabolic lung simulator (upper panel) and by a patient (lower panel). Inspiration is negative flow and pressure; expiration is positive flow and pressure. Note the negative airway pressure during inspiration, variable airway flow, and variable airway P. Changing functional residual capacity (FRC) was achieved by differential positive end-expiratory pressure (PEEP), applied to the driving ventilator.

Figure 4 displays the linear regression of the bymixer-flow airway measurements of co₂ (upper panel, open circles) and o₂ (lower panel, solid circles) versus the stoichiometric values generated by metered ethanol combustion. Each point was the average of three consecutive replicate measurements conducted 3 min apart. When all data points were analyzed together by linear regression, for co₂, slope (m) was 0.97, Y-intercept (b) was –2.63, and the coefficient of determination (R²) was 0.997. For o₂, m was 0.95, b was 11.8, and R² was 0.988. Thus, the correlation between the bymixer-flow and stoichiometric values for both co₂ and o₂ were good in all experiments.

View larger version (12K): [in this window] [in a new window]   Figure 4. Linear regression of CO2 elimination (co2) (upper panel) and oxygen uptake (o2) (lower panel) demonstrates good correlation between the bymixer-flow values during simulated spontaneous breathing and the stoichiometric reference values generated by the metabolic lung simulator. Each point was the average of three consecutive replicate measurements conducted 3 min apart.

Figure 5 depicts the limits of agreement (LOA)17 analysis between the bymixer-flow measured values of co₂ and o₂ and the stoichiometric values generated by ethanol combustion. LOA (mean ± 1.96 sd) for co₂ were –8.83 ± 11.96 mL/min, where 95% of the points were bounded by those limits (upper panel, open symbols, Fig. 5). However, as average co₂ increased along the x axis, LOA were greater (i.e., scatter of the differences around the mean increased along the y axis). Thus, LOA poorly reflected the overall accuracy of co₂. In a similar analysis for o₂ (lower panel, closed symbols), LOA were –4.36 ± 33.89 mL/min. As the average value of o₂ increased along the x axis, there was an increase in the scatter of differences around the mean along the y axis. Again, LOA poorly reflected the overall accuracy of o₂.

View larger version (12K): [in this window] [in a new window]   Figure 5. Limits of Agreement (LOA) differences plot as described by Bland and Altman.17 For CO2 elimination (co2, upper panel. open symbols), the difference between the bymixer-flow co2 and the stoichiometric value (generated by the metabolic lung simulator) were plotted against the mean of both values. The LOA (mean ± 1.96 sd) for co2 were –8.83 ± 11.96 mL/min, where 95% of the points were bounded by those limits. For o2 (lower panel, closed symbols), LOA were –4.36 ± 33.89 mL/min. As the average values of co2 and o2 increased along the x axis, there was an increase in the scatter of differences above and below the mean along the y axis.

To account for these increases in LOA differences as the average value increased along the x axis, we plotted the ratio of the bymixer-flow airway measurement-to-stoichiometric value against the average of both values (Fig. 6) (Bland–Altman ratio plot).18 For co₂ (upper panel), the ratio LOA (mean ± 1.96 sd) were 0.953 ± 0.065 or, expressed as a percentage, –4.7% ± 6.5%, where 95% of all points lay within these limits. In a similar analysis for o₂ (lower panel), ratio LOA were 0.997 ± 0.103 or, expressed as a percentage, –0.30% ± 10.3%.

View larger version (14K): [in this window] [in a new window]   Figure 6. Limits of Agreement (LOA) ratio plot, as described by Bland and Altman,18 compensate for the increased scattering of data as the mean value increased along the x axis (Fig. 5). The ratio of the measured-to-stoichiometric value was plotted against the average of the two values. For co2, ratio LOA (mean ± 1.96 sd) were 0.953 ± 0.065 (upper panel) or, expressed as a percentage, –4.7% ± 6.5%, where 95% of all points lay within these limits. In a similar analysis for o2 (lower panel), ratio LOA were 0.997 ± 0.103 or, expressed as a percentage, –0.30% ± 10.3%.

The average (±sd) percent error for bymixer-flow airway co₂ (compared with the stoichiometric value) was –4.7% ± 3.31%. The average (±sd) percent error for airway o₂ was –0.30% ± 5.25%. Average RER was 0.638 ± 0.033. If inspired and expired gas flows were not converted to STPD conditions, the average percent error (mean ± sd) in airway measurements of co₂ and o₂ increased significantly (6.65% ± 3.85% and 10.23% ± 6.72%, respectively). The coefficient of variation between the consecutive measurements was 3.3% for the measurement of o₂, and 3.2% for the measurement of co₂. The range of inspired relative humidity was 3%–8% and inspired temperature was 22.7°C–23.4°C. The range of expired relative humidity was 39% to 64% (inversely proportional to minute ventilation) and expired temperature was 23.0°C–23.5°C.

Stage 2: Preoperative Measurement of co₂ and o₂ in Spontaneously Breathing Awake Patients Using the New Bymixer-Flow Apparatus
The average age of the patient population was 62.2-yr-old (range of 37 to 72 yr of age). Twelve patients were ASA Class I and II and three patients were ASA III. For the 15 spontaneously breathing awake patients, average co₂ and o₂ were 232.9 ± 69.2 mL/min and 275.9 ± 65.1 mL/min, respectively. When indexed by body weight, average co₂and o₂ were 3.01 ± 0.56 and 3.44 ± 0.69 mL · kg^–1 · min^–1, respectively. Average RER was 0.88 ± 0.043. There was no statistically significant difference between the 2 consecutive measurements conducted for each patient (for co₂, P = 0.594 and for o₂, P = 0.982).

	DISCUSSION

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
IC, the measurement of airway co₂ and o₂, has evolved from a research tool to a clinical measurement in critical care medicine and exercise physiology.19 Current anesthesia monitoring provides clinical data describing O₂ delivery,20 adequate ventilation, and hemodynamic performance.21,22 However, monitoring of cellular metabolism and well-being are the missing links in anesthesia, because IC measurement instrumentation (specific for anesthesia) and understanding of co₂, o₂, and respiratory quotient are not currently present. We have previously described how the airway bymixer, temperature and humidity airway sensor, and flowmeter, in conjunction with a sophisticated computer program (bymixer-flow measurement), can provide rapid and accurate metabolic gas exchange measurement during mechanical ventilation.9 However, this measurement is difficult during spontaneous awake breathing because the respiration pattern is irregular and the FRC fluctuates.

Consequently, we have developed and validated a new portable bymixer-flow breathing device, composed of the new clinical bymixer, the fast-response airway temperature and humidity sensor, standard airway flowmeter, and a non-rebreathing valve (Fig. 1). The portable bymixer-flow breathing device is compact, portable, and inexpensive. The measurement methodology is noninvasive and confers minimal discomfort to the patient. The bymixer does not increase dead-space nor airway resistance.12 The fast response temperature and humidity sensor is inexpensive, stable, light-weight, and also does not significantly increase dead-space nor airway resistance.23 In comparison to commercial monitors (e.g., GE-Datex Deltatrac, Sensormedics Vmax), our bymixer-flow device does not require a breathing hood, is portable, is comfortable for the patient, and acquires measurements quickly. We also plan to use the portable bymixer-flow device in exercise studies.

Validation of the measurement is impossible in patients because a wide range of reference values of co₂ and o₂ are required. Accordingly, we have developed a metabolic lung simulator (Fig. 2), which was modified to provide a spontaneous ventilation waveform. Compared to reference values generated by ethanol combustion in the metabolic lung simulator, the spontaneous breathing bymixer-flow apparatus measured accurate values of co₂ and o₂ (average ± sd percent error of –4.7% ± 3.31% and –0.30% ± 5.25%, respectively) (Figs. 4–6). The coefficient of variation between consecutive measurements demonstrated good precision of the measurement.

The average expired relative humidity and temperature values in the metabolic lung simulator were lower than values found during clinical breathing. We have previously tested the bymixer-flow system in the metabolic lung simulator with added expired moisture (relative humidity = 100%) and heat (expired temperature approximately 36°C),24 and demonstrated excellent accuracy and precision of measured co₂ and o₂.

With the metabolic lung simulator, inspired O₂ fraction was 35% in order that the burner flame would not extinguish during low Vt. However, since the Haldane transformation relies on N₂ conservation, we can expect the precision of the bymixer-flow measurements of co₂ and o₂ to be even higher during room air breathing (higher N₂ gas fractions, see Eq. 3).

Figure 3 displays the spontaneous breathing waveforms generated by the metabolic simulator and by the awake breathing patient. Compared with the metabolic lung simulator, there are several features of patient breathing. Patients do not pause between inspiration and expiration. Positive airway pressure in expiration is due to the small but finite resistance of the bymixer-flow circuit. The patients’ expiratory waveforms were blunted in magnitude and expanded in duration, compared with the metabolic lung simulator. However, the high, thin expiratory waveform of the metabolic lung simulator stressed the response of the bymixer-flow system and further supports the accuracy and precision of the measurement. PEEP is not present on the pressure waveform because the bymixer-flow breathing apparatus is open to atmosphere.

In the second stage of the study, we were able to successfully measure, in preoperative, awake, spontaneously breathing patients, co₂ and o₂ values (3.06 ± 0.98 and 3.52 ± 0.74 mL · kg^–1 · min^–1, respectively), which are similar to reports in the literature.25 There was close agreement between consecutive duplicate measurements in each patient. We used the fast response temperature and humidity sensor10,13,23 for STPD correction in the portable bymixer-flow device. However, during spontaneous breathing of room air, inspired gas temperature and humidity are relatively constant and, alternatively, could be measured by other slow-response thermometers and hygrometers. We chose to measure temperature and humidity with our fast response sensor because it is inexpensive, easy-to-use, and incorporated into our bymixer-flow measurement system9 used during mechanical ventilation under anesthesia. Since we want to compare measurements in the preoperative and intraoperative periods, we need to maintain a constant measurement methodology. The temperature and humidity sensor in the bymixer-flow device contributes to the accuracy of the IC measurements. For example, during mechanical ventilation, without the temperature and humidity sensor, errors increase in the measurements of co₂ (0.1% ± 2.4% to 6.1% ± 5.1%) and o₂ (1.1% ± 2.9% to 6.5% ± 6.9%).9 Expired gas contributes less variability to the measurements of co₂ and o₂ because body temperature is constant and gas is saturated.

An interesting clinical challenge is the portable bymixer-flow measurement of o₂ in patients who are receiving supplemental inspired O₂. Currently, the device does not just assume room air breathing (Fi_o2 = 0.21) but measures inspired O₂ fraction. We are planning future experiments that will deal with supplemental inspired O₂ breathing employing two strategies: First, the inspiratory arm of the portable bymixer-flow device could be connected to an O₂ reservoir system that is continuously supplied with a known fraction of O₂. Second, another bymixer could be attached to the inspired limb of the portable bymixer device and provide online measurements of inspired O₂ fraction.

IC depends on a steady-state condition, where ventilation and circulation are constant, so that airway co₂ and o₂ represent the tissue values. In our bench studies with the metabolic lung simulator, we have shown that the portable bymixer-flow device can measure co₂ and o₂ accurately in 60 s. (In contrast the Datex Deltatrac and Sensormedics Vmax can require longer periods for measurement). During the clinical studies, we conducted two consecutive 1-min measurements, separated by 1 min. Over this 3-min period, there was no statistically significant difference between the two measurements. Thus, this 3-min period of measurement may be surprisingly representative of the patient’s preoperative metabolic state. We plan future studies in which we will conduct sequential measurements of airway co₂ and o₂ over a longer period to address how non-steady-state conditions can affect airway IC in the preoperative setting. For example, the 1-min portable bymixer-flow measurements can be repeated over longer intervals (e.g., 15 min) to ascertain steady-state, while not upsetting the patient with a long continuous measurement.

In summary, we have developed a simple, inexpensive, portable bymixer-flow device capable of accurate and fast measurements of airway co₂ and o₂ in awake spontaneously breathing patients. We have demonstrated the ease of collecting precise preoperative baseline IC data at the bedside. In future studies, the ability to measure baseline awake values will allow us to compare metabolic changes that occur after induction of anesthesia. Moreover, this bymixer-flow device can be used for preoperative exercise testing26,27 for the determination of anaerobic threshold (AT).1 AT is the threshold of exercise requiring the addition of anaerobic lactate metabolism which increases co₂ relative to o₂.

	ACKNOWLEDGMENTS

 
The authors thank David Chien, BSc, Computer Support Specialist, for assistance in the development of the metabolic lung simulator and the digital data acquisition program, and Jeffrey C. Milliken, MD and Lane W. Parker, CCP, Division of Cardio-Thoracic Surgery, for providing and supporting the precision occlusion roller pump. We also thank Jody Cimbalo, MS, UCI medical student, for her help conducting the bench studies.

	Footnotes

 
Accepted for publication September 13, 2007.

Full support by National Heart Lung and Blood grant R01 HL-42637 (P.I.: PH Breen). Additional partial support from the Committee on Research and Graduate Academic Programs (P.I.: A Rosenbaum), the Department of Anesthesiology, University of California-Irvine, and the National Center for Research Resources grant M01 RR00827.

	REFERENCES

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 

1. Older P, Hall A, Hader R. Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest 1999;2:355–62
2. Isserles SA, Breen PH. Can changes in end-tidal Pco₂ measure changes in cardiac output? Anesth Analg 1991;73:808–14[Abstract/Free Full Text]
3. Breen PH, Isserles, SA, Taitelman UZ. Non-steady state monitoring by respiratory gas exchange. J Clin Monit 2000;16:351–60[Web of Science]
4. McLellan S, Walsh T, Burdess A, Lee A. Comparison between the Datex-Ohmeda M-COVX metabolic monitor and the Deltatrac II in mechanically ventilated patients. Intensive Care Med 2002;28:870–6[Web of Science][Medline]
5. Matarese LE. Indirect calorimetry: technical aspects. J Am Diet Assoc 1997;97(suppl 2):S154–S160[Web of Science][Medline]
6. Davies G, Hess D, Jebson P. Continuous Fick cardiac output compared to continuous pulmonary artery electromagnetic flow measurement in pigs. Anesthesiology 1987;66:805–9[Web of Science][Medline]
7. Tissot S, Delafosse B, Bertrand O, Bouffard Y, Viale JP, Annat G. Clinical validation of the Deltatrac monitoring system in mechanically ventilated patients. Intensive Care Med 1995;21: 149–53[Web of Science][Medline]
8. Makita K, Nunn JF, Royston B. Evaluation of metabolic measuring instruments for use in critically ill patients. Crit Care Med 1990;18:638–44[Web of Science][Medline]
9. Rosenbaum A, Kirby C, Breen PH. Measurement of oxygen uptake and carbon dioxide elimination using the bymixer: validation in a metabolic lung simulator. Anesthesiology 2004;100:1427–37[Web of Science][Medline]
10. Breen PH. Importance of temperature and humidity in the measurement of pulmonary oxygen uptake per breath during anesthesia. Ann Biomed Engl 2000;28:1159–64
11. Burzstein S, Elwyn DH, Askanazi J, Kinney JM. Energy metabolism, indirect calorimetry, and nutrition. 1st ed. Baltimore: William & Wilkins, 1989:119–72
12. Rosenbaum A, Breen PH. Novel, adjustable, clinical bymixer measures mixed expired gas in anesthesia circle circuit. Anesth Analg 2003;97:1414–20[Abstract/Free Full Text]
13. Breen PH. Fast response humidity and temperature sensor device. United States Patent No. 6,014,890, January 18, 2000
14. Rosenbaum A, Kirby C, Breen PH. New metabolic lung simulator: development, description, and validation. J Clin Monit Comput 2007;21:71–82[Medline]
15. Ebbing DD. General chemistry. 5th ed. Boston: Houghton Mifflin, 1996:148–57
16. Morris E. Humidity measurement, temperature and humidity measurement. 1st ed. Bentley RE, ed. Signapore: Springer-Verlag, 1988:133–223
17. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;8476:307–10
18. Bland M. An introduction to Medical Statistics. 2nd ed. United Kingdom: Oxford Medical Publications, 1995:195–9, 269–73, 338–40
19. Reid CL, Carlson GL. Indirect calorimetry: a review of recent clinical implications. Curr Opin Clin Nutr Metab Care 1998;1: 281–6[Medline]
20. Murphy GS, Vender JS. Monitoring the anesthetized patient. In: Barash PG, Cullen BF, Stoelting RK, eds. Clinical anesthesia. 4th ed. Lipincott Williams & Wilkins, 2000:667–88
21. Cahalan MK, Litt L, Botvinick EH, Schiller NB. Advances in noninvasive cardiovascular imaging: implications for the anesthesiologist. Anesthesiology 1987;66:356–72[Web of Science][Medline]
22. Shippy CR, Appel PL, Shoemaker WC. Reliability of clinical monitoring to assess blood volume in critically ill patients. Crit Care Med 1984;107–12
23. Rosenbaum A, Breen PH. Importance and interpretation of fast-response airway hygrometry during ventilation of anesthetized patients. J Clin Monit Comput 2007;21:137–146[Medline]
24. Rosenbaum A, Howard HC, Harako M, Breen PH. Can the bymixer-flow system measure accurate airway Vco₂ and Vo₂, when expired gas is heated and humidified in the metabolic lung simulator? Anesthesiology (abstract) 2004;101:A574
25. Sheeren TL, Schwarte LA, Arndt JO. Metabolic regulation of cardiac output during inhalation anesthesia in dogs. Acta Anaesthesiol Scand 1999;43:421–30[Web of Science][Medline]
26. Sue DY, Wasserman K. Impact of integrative cardiopulmonary exercise testing on clinical decision making. Chest 1991;99: 981–92[Web of Science][Medline]
27. Gilbreth EM, Weisman IM. Role of exercise stress testing in preoperative evaluation of patients for lung resection. Clin Chest Med 1994;15:389–403[Web of Science][Medline]

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