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(Chest. 2005;128:3576-3584.)
© 2005 American College of Chest Physicians

Estimation of PaCO2 During Exercise in Children and Postoperative Pediatric Patients With Congenital Heart Disease*

Hideo Ohuchi, MD, PhD; Tamaki Hayashi, MD; Osamu Yamada, MD and Shigeyuki Echigo, MD

* From the Department of Pediatrics, National Cardiovascular Center, Osaka, Japan.

Correspondence to: Hideo Ohuchi, MD, Department of Pediatrics, National Cardiovascular Center, 5–7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan; e-mail: hohuchi{at}hsp.ncvc.go.jp


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results of Study 1...
 Results of Study 2...
 Discussion
 Conclusions
 References
 
We evaluated how PaCO2 and respiratory variables relate during and after exercise and derived a new noninvasive estimation of PaCO2 in children and postoperative patients with congenital heart disease. We randomly selected 8 subjects from each of three categorized groups from our previous studies: 15 control subjects (8 to 21 years old), 16 Fontan procedure patients (9 to 22 years old), and 13 patients after right ventricular outflow tract reconstruction (RVOTR) [7 to 21 years old], and used their respiratory variables during exercise testing to estimate PaCO2 (study 1). In a stepwise multiple regression analysis, end-tidal carbon dioxide tension (PETCO2), age, ventilatory equivalent for carbon dioxide (minute ventilation [VE]/carbon dioxide production [VCO2]), and gas exchange ratio (R) were major determinants of PaCO2 in control subjects: PaCO2 = 12.0 + 0.54 PETCO2 + 0.15 VE/VCO2 – 3.6 R + 0.22 age (r = 0.86). In addition to PETCO2 and VE/VCO2, arterial oxygen saturation and tidal volume were additional major determinants for Fontan procedure and RVOTR patients, respectively. We derived equations to predict the PaCO2 (r = 0.92 for Fontan procedure and r = 0.74 for RVOTR). These equations were applied to the remaining study subjects to estimate PaCO2 (study 2). Estimated values correlated with the measured PaCO2 (r = 0.71 to 0.86), and the mean differences for the control subjects, Fontan procedure, and RVOTR patients were – 0.1, – 0.1, and – 1.0, with limits of agreement of ± 3.3, ± 4.4, and ± 3.1, respectively. Although estimated PaCO2 based on the Jones equation correlated with the measured PaCO2 in all groups, their slopes were significantly flatter than ours. PaCO2 throughout exercise testing may be estimated in control children and postoperative pediatric patients. The Jones equation should be applied with great care in pediatric subjects.

Key Words: children • congenital heart disease • end-tidal carbon dioxide tension • exercise • PaCO2


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results of Study 1...
 Results of Study 2...
 Discussion
 Conclusions
 References
 
Evaluation of abnormal ventilatory regulation at rest and during exercise is important and helps understand the postoperative pathophysiology in patients with congenital heart disease. Control mechanisms for ventilation in children differ from those in adults and mature during growth.123456 Knowledge of the PaCO2 is crucial in evaluating normal and abnormal ventilatory responses. However, an invasive procedure is necessary to measure the actual PaCO2 and is not ethically acceptable for repeated evaluations, especially in children.7 Most studies689101112 of ventilatory pathophysiology have relied on an invasive technique in pediatric cardiac patients as well as adult patients. However, some investigators have used the Jones equation to predict PaCO2 during exercise:

where PETCO2 is end-tidal carbon dioxide tension and VT is tidal volume, and have included pediatric subjects.513 Although the validity of the estimation of PaCO2 during exercise is established in normal adult subjects,14 its validity in children remains uncertain. Therefore, it is necessary to validate a feasible noninvasive estimation of PaCO2 during exercise in children that would be helpful in studies of ventilation-related issues. We hypothesized that the maturation process and the abnormal hemodynamics significantly impact PaCO2 during exercise and some modification of traditional estimations based on the Jones equation12 would be necessary to estimate the PaCO2 of children and pediatric cardiac patients. The purposes of the present study were to investigate relationships between measured PaCO2 and ventilatory variables in randomly selected subjects from our previous studies, and to determine a feasible method of estimating PaCO2 during exercise in normal children and some pediatric patients with congenital heart disease.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results of Study 1...
 Results of Study 2...
 Discussion
 Conclusions
 References
 
Subjects
We retrospectively analyzed 45 subjects from our previous studies in whom invasive measurement of PaCO2 during exercise was performed. The subjects consisted of three disease-based subgroups: 15 patients with a history of Kawasaki disease without significant coronary artery stenosis served as control subjects, 16 patients after the Fontan procedure, and 13 patients after right ventricular outflow tract reconstruction (RVOTR), mostly for tetralogy of Fallot.6911 None of the control subjects had abnormal findings on physical examination, chest radiography, ECG, two-dimensional echocardiography, pulmonary function testing, or treadmill exercise testing. Postoperative patients with significant residual intracardiac shunts were excluded from the present study. Informed consent was obtained from each subject and his or her parents. The protocol was in agreement with the guidelines of the Ethics Committee of the National Cardiovascular Center.

Allocation of Study Subjects
Prediction Study: Subjects were classified into two groups: one for evaluation of the relationship between the measured PaCO2 and ventilatory variables (study 1), and the other for validation of equations derived from study 1 to estimate PaCO2 during exercise (study 2). For the selection of study 1 subjects, the subjects in each disease-based group were first classified into two subgroups, ie, younger subjects (< 14 years old) and older subjects (≥ 14 years old), so that the age in each study 1 group could vary widely. The numbers of younger subjects for the control, Fontan procedure, and RVOTR groups were 8, 12, and 9, respectively, and for the older groups were 7, 4, and 4. Next, from each disease-based group, eight subjects were randomly selected from the age-based subgroups. Specifically, four of eight younger subjects and four of seven older subjects for the control group, six younger and two older subjects for the Fontan procedure group, and five of nine younger and three of four older subjects for the RVOTR group were randomly selected for the study 1 (Table 1 ).


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  		Table 1.. Subject Characteristics*

 
Validation Study: The remainder of the subjects (seven, eight, and five subjects for the control, Fontan procedure, and RVOTR groups, respectively) were allocated to study 2. There were no differences in age or body size between the study 1 and study 2 groups or among the three disease-based subgroups in the two groups.

Exercise Protocol
The subjects performed a ramp-like progressive exercise test on a treadmill (Q-5000 System; Quinton; Seattle, WA). After a 4-min rest, the patients completed a 3-min warm-up walk at a speed of 1.5 kilometers per hour (grade of 0%) and then exercised with progressive intensity until exhausted.15 After a 30-s walk-down period, the patients sat on a chair, and cardiorespiratory variables were obtained during the next 10 min. The exercise intensity was increased by 0.7 metabolic units every 30 s, and the incremental part of the test was completed in approximately 10 min. Twelve standard ECG leads were placed to monitor the heart rate during testing.

Gas Exchange Measurements
Ventilation and gas exchange were measured breath by breath. The subject breathed through a mask connected to an anemometer (Riko AS500; Minato Medical Science; Osaka, Japan). This system consists of a hot-wire flowmeter and oxygen and carbon dioxide analyzer (zirconium element-based oxygen analyzer and infrared carbon dioxide analyzer). Gas was sampled at a rate of 220 mL/min with a suction pump and passed through a filter and gas analyzers. Before each exercise test, the delay times and response characteristics of the oxygen and carbon dioxide analyzers due to the transit time for the gases in the capillary and the response speeds of the instrument were measured (700 to 800 ms) by the area-midpoint method.16 The 0 to 95% rise time of the infrared analyzer for partial carbon dioxide pressure was < 100 ms. These conditions enabled our study to cope with the faster respiration in children.12 Two sizes of full face masks were used: one with a dead space of 80 mL for children from 120 to 150 cm in height, and another with a dead space of 100 mL for subjects > 150 cm in height. In the breath-by-breath protocol, derived respiratory parameters, including the respiratory rate, VT, minute ventilation (VE), ventilatory equivalents for oxygen uptake (VO2) and carbon dioxide production (VCO2) [VE/VO2, VE/VCO2], and the respiratory gas exchange ratio (R), were computed in real-time and displayed with heart rate and VO2 on a monitor. A personal computer (PC-9801; NEC; Tokyo, Japan) was used for data acquisition and storage. Breath-by-breath data were averaged to provide 1 data point for each 30-s period. Anaerobic threshold was determined by the V-slope method.17

Arterial Blood Gas Analysis
Eight arterial blood samples were obtained from an indwelling 22-G angiocatheter placed in a radial or brachial artery in each subject; samples were obtained at rest, 3 min after starting warm-up walking, at anaerobic threshold, at peak exercise, and 1, 2, 4, and 10 min after exercise. Samples were stored on ice (< 20 min) until analyzed for pH, bicarbonate, PaO2, and PaCO2 (ABL3 blood gas analyzer; Radiometer; Copenhagen, Denmark).

Calculations
The difference between PETCO2 and PaCO2 (P[ET-a]CO2), and the physiologic dead space/tidal volume ratio (VD/VT) were calculated using a modified Bohr equation with PaCO2.18

Pulmonary Function Tests

In all patients and control subjects, we measured vital capacity (VC) and the percentage of FEV1 (Spirosift, SP-600; Fukuda Denshi; Tokyo, Japan). VC was also calculated as the percentage of the body height-predicted normal value for our 44 control subjects.

Statistical Analysis
Differences in clinical variables, including cardiorespiratory variables, between the two main groups and the three subgroups were assessed by paired or unpaired t test and one-way analysis of variance, respectively, where appropriate. Relationships between continuous variables were assessed by simple linear regression analysis. Major determinants of the dependent variables such as PaCO2 were determined by stepwise multiple linear regression analysis (StatView 5.0; SAS Institute; Cary, NC). The Bland-Altman method was used to compare the validity of our equation and the Jones equation to predict PaCO2.19 Validity for estimations of VD/VT during exercise testing based on the two estimated values of PaCO2 was also evaluated by the same method. Data are expressed as mean ± SD; p < 0.05 was considered significant.


   Results of Study 1 (Prediction)
TOP
 Abstract
 Introduction
 Materials and Methods
 Results of Study 1...
Results of Study 2...
 Discussion
 Conclusions
 References
 
In each group, 64 points in total (8 points in each subject) were plotted against each corresponding cardiopulmonary variable throughout exercise testing, and the relations were evaluated.

Determinants of P(ET-a)CO2
Control Subjects: P(ET-a)CO2 correlated with VCO2 (r = 0.59, p < 0.0001), R (r = 0.31, p < 0.05), VE (r = 0.46, p = 0.0001), VE/VCO2 (r = – 0.86, p < 0.0001), VT (r = 0.70, p < 0.0001), arterial oxygen saturation (SaO2) [r = – 0.65, p < 0.0001], and VD/VT (r = – 0.86, p < 0.0001). In a stepwise multiple regression analysis among these variables, VD/VT and VE/VCO2 were the major determinants of P(ET-a)CO2 during exercise (p < 0.0001).

Fontan Procedure: P(ET-a)CO2 correlated with age (r = 0.29, p < 0.05), VCO2 (r = 0.41, p < 0.001), VE (r = 0.27, p < 0.05), VE/VCO2 (r = – 0.71, p < 0.0001), VT (r = 0.31, p < 0.01), SaO2 (r = 0.38, p < 0.005), and VD/VT (r = – 0.58, p < 0.0001). Of the above variables, age, VT, VE/VCO2, SaO2, and VD/VT were major determinants of P(ET-a)CO2 (p < 0.0001).

RVOTR Patients: P(ET-a)CO2 correlated with VCO2 (r = 0.53, p < 0.0001), VE (r = 0.44, p < 0.001), VE/VCO2 (r = – 0.62, p < 0.0001), VT (r = 0.71, p < 0.0001), and VD/VT (r = – 0.79, p < 0.0001). Of these variables, VT, VCO2, and VD/VT were major determinants of P(ET-a)CO2 (p < 0.0001).

Determinants of PETCO2
Control Subjects: PETCO2 correlated with age (r = 0.43, p < 0.001), VCO2 (r = 0.56, p < 0.0001), VE (r = 0.38, p < 0.01), VE/VCO2 (r = – 0.90, p < 0.0001), VT (r = 0.71, p < 0.0001), SaO2 (r = – 0.68, p < 0.0001), and VD/VT (r = – 0.68, p < 0.0001). Of these variables, VCO2, VE, VE/VCO2, and VD/VT were the major determinants (p < 0.0001).

Fontan Procedure: PETCO2 correlated with age (r = 0.55, p < 0.0001), VCO2 (r = 0.26, p < 0.05), VE/VCO2 (r = – 0.71, p < 0.0001), and SaO2 (r = 0.29, p < 0.05). Of these variables, age, VE/VCO2, and SaO2 were the major determinants (p < 0.0001).

RVOTR: PETCO2 correlated with VCO2 (r = 0.56, p < 0.0001), VE (r = 0.42, p < 0.001), VE/VCO2 (r = – 0.88, p < 0.0001), VT (r = 0.67, p < 0.0001), VD/VT (r = – 0.51, p < 0.0001), and SaO2 (r = – 0.36, p < 0.01). Of these variables, VE/VCO2 was the major determinant.

Determinants of PaCO2
Control Subjects: PaCO2 correlated with age (r = 0.53, p < 0.0001), VE/VCO2 (r = – 0.56, p < 0.0001), VCO2 (r = 0.29, p < 0.05), R (r = – 0.26, p < 0.05), respiratory rate (r = – 0.28, p < 0.05), VT (r = 0.42, p < 0.001), SaO2 (r = – 0.42, p < 0.001), and PETCO2 (r = 0.76, p < 0.0001). In a stepwise multiple regression analysis among all these variables relating to P(ET-a)CO2, PETCO2, or PaCO2, the major determinants were age, VE/VCO2, R, and PETCO2:


(1)

Fontan Procedure: PaCO2 correlated with age (r = 0.47, p < 0.001), VE/VCO2 (r = – 0.39, p < 0.01), and PETCO2 (r = 0.83, p < 0.0001). In a multiple regression analysis among all these variables relating to P(ET-a)CO2, PETCO2, or PaCO2, the major determinants were PETCO2, SaO2 (p < 0.0001 for both), and VE/VCO2:


(2)

RVOTR: PaCO2 correlated with VE/VCO2 (r = – 0.53, p < 0.0001), SaO2 (r = – 0.35, p < 0.01), and PETCO2 (r = 0.61, p < 0.0001). In a stepwise multiple regression analysis among all these variables relating to P(ET-a)CO2, PETCO2, or PaCO2, the major determinants were PETCO2, VT, and VE/VCO2:

(3)


   Results of Study 2 (Validation)
TOP
 Abstract
 Introduction
 Materials and Methods
 Results of Study 1...
 Results of Study 2...
Discussion
 Conclusions
 References
 
The equations derived in study 1 were applied to the study 2 subjects to evaluate their validity in estimating PaCO2 during exercise testing in the control children and in the same categories of postoperative patients.

Control Subjects
Using equation 1, estimated PaCO2 correlated with measured PaCO2 (slope = 1.0, r = 0.86, p < 0.0001). With the Jones equation, estimated PaCO2 also correlated with measured PaCO2 (slope = 0.59, r = 0.72, p < 0.0001).

According to the Bland-Altman method, differences between measured and estimated PaCO2 were plotted against the mean values of the measured and estimated PaCO2 in our equation and the Jones equation (Figs 1234 ). Our equation gives a slightly lower mean PaCO2 by – 0.1, and there was no relationship between the difference of the two values and the mean PaCO2. The limits of agreement were – 3.3 and 3.2. The Jones estimation also gives a slightly lower mean PaCO2 by – 0.8. However, there was a significant inverse correlation between the measured and predicted PaCO2 and the mean value of the two PaCO2 values (p < 0.05). In addition, the limits of agreement were greater than our findings.



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  		Figure 1.. Correlations between P(ET-a)CO2 and VD/VT during exercise in control subjects (left, a), Fontan procedure (center, b), and RVOTR patients (right, c).

 


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  		Figure 2.. Correlations between measured PaCO2 and age (left, a), VE/VCO2 (center, b), and R (VCO2/VO2) [right, c] during exercise testing in control subjects.

 


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  		Figure 3.. Correlations between PETCO2 and measured PaCO2 in control subjects (left, a), Fontan procedure (center, b), and RVOTR patients (right, c).

 


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  		Figure 4.. Difference and average of the measured and estimated PaCO2. The limits of agreement are shown in control subjects (top panels), Fontan procedure (center panels), and RVOTR (bottom panels) groups. Oh-PaCO2 = estimated PaCO2 based on our equation; J-PaCO2 = estimated PaCO2 based on the Jones equation.

 
Fontan Procedure
With equation 2, estimated PaCO2 correlated with the measured PaCO2 (slope = 1.06, r = 0.69, p < 0.0001). With the Jones equation, the estimated PaCO2 also correlated with the measured PaCO2 (slope = 0.75, r = 0.72, p < 0.0001).

Our equation gives a slightly lower mean PaCO2 by – 0.1, and the limits of agreement were – 4.5 and 4.4. However, there was a significant positive relationship between the difference and the mean PaCO2 (p < 0.001). The Jones estimation gives a slightly higher mean PaCO2 by 1.2 without any relationship between the two variables. The limits of agreement were – 3.4 and 5.8.

RVOTR
With equation 3, estimated PaCO2 correlated with measured PaCO2 (slope = 0.84, r = 0.74, p < 0.0001). With the Jones equation, estimated PaCO2 also correlated with measured PaCO2 (slope = 0.38, r = 0.61, p < 0.0001).

Our equation gives a slightly lower mean PaCO2 by – 0.9 mm Hg, and the limits of agreement were – 4.0 and 2.2. The Jones estimation gives a higher mean PaCO2 by 1.5, and there was a significant inverse correlation between the difference between the measured and predicted PaCO2 and the mean value of the two PaCO2 values (p < 0.001). In addition, the limits of agreement were greater than our findings (Fig 4).

Evaluation of VD/VT
VD/VT during and after exercise was evaluated on the basis of the two estimated PaCO2 values and compared with that calculated with measured PaCO2 (Fig 5 ). Our estimations were more appropriate than those based on the Jones equation in terms of the limits of agreement, especially in the control and RVOTR groups. However, even with the better estimation of PaCO2 in our equations, the difference of ± 5% may be a significant discrepancy for evaluating VD/VT.



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  		Figure 5.. Difference and average of the measured and estimated values of VD/VT. The limits of agreement are shown in control subjects (top panels), Fontan procedure (center panels), and RVOTR (bottom panels) groups. Oh-Vd/Vt = estimated Vd/Vt based on our estimated PaCO2; J-Vd/Vt = estimated Vd/Vt based on Jones’ estimated PaCO2.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results of Study 1...
 Results of Study 2...
 Discussion
Conclusions
 References
 
P(ET-a)CO2
VD /VT was the major determinant of P(ET-a)CO2 in all study groups. As Liu et al20 demonstrated in healthy adults and patients with lung disease, VD /VT has a great impact on the P(ET-a)CO2 , and this is also true in children. In addition, as Jones et al12 demonstrated, metabolic rate (VCO2) and VT were common determinants of P(ET-a)CO2 in all groups, although they were not major factors.12 Thus, the explanations for the change in P(ET-a)CO2 during exercise are similar in children to those in adults. Namely, an efficient shift to the alveoli of the additional VCO2 during exercise mainly determines the PETCO2 , and the efficiency can be modified by alveolar VD /VT . In fact, VCO2 was one of the determinants of PETCO2 in all our groups. In addition, longer expiration also enables PETCO2 to rise toward the mixed venous PCO2 level.21 PCO2 is higher in mixed venous blood than in arterial blood, especially during and after exercise. Consequently, an efficient and large VCO2 shift with larger VT results in a positive value of P(ET-a)CO2 during exercise testing. In other words, the following are possible explanations for the abnormal P(ET-a)CO2 during exercise testing in children and cardiac patients. For normal children, a smaller VCO2 due to immature metabolic development in the working muscle22 and less ventilatory efficiency in conjunction with a smaller VT ,16 while for cardiac patients, an impaired increase in VCO2 due to impaired hemodynamics and disease and/or surgery-related ventilation/perfusion mismatch combined with the restrictive lung (smaller VT) are major factors. Because these factors are sensitively reflected in a high value of VE/VCO2, it is understandable that VE/VCO2 is closely related to P(ET-a)CO2. We and other investigators have demonstrated that PETCO2 is not high enough to cause a significant negative P(ET-a)CO2 during exercise even in normal children and older subjects,623 as well as in pediatric cardiac or pulmonary patients.91120

In addition to these mechanisms, the relation of P(ET-a)CO2 to age and SaO2 as well as VE/VCO2 implies that additional explanations may be needed in Fontan procedure patients in terms of the determinants. Some Fontan procedure patients show a significantly lower PaCO2 than control subjects, and the lower PaCO2 is associated with lower SaO2 that is often seen in Fontan procedure patients.24 Because significant exercise-related SaO2 decline indicates a significant increase in right-to-left shunting flow through residual anatomic structures, such as pulmonary arteriovenous fistulae and leakage, a significant amount of right-to-left VCO2 shift occurs. This VCO2 shift may significantly impact PaCO2 change during exercise in Fontan procedure patients. The reason for the significant contribution of age to the P(ET-a)CO2 is unclear; however, aging-related PaCO2 changes may also be associated with this relationship as shown in our control subjects. In addition to the mechanisms for abnormal P(ET-a)CO2 in the RVOTR patients and growing children, impaired perfusion of the apex of the lung or other lung segments due to heterogeneity of the vascular resistance25 together with the lack of a subpulmonic ventricle may exaggerate the failure of PETCO2 to be closer to the mixed venous PCO2; consequently, P(ET-a)CO2 remains negative. Thus, the control of P(ET-a)CO2 may be more multifactored in Fontan procedure patients than in subjects with biventricular physiology.

Estimation of PaCO2
Application of the Jones equation to young healthy adults was validated during mild-to-moderate exercise and at rest.1423 However, it is questionable to apply the equation to healthy children or to subjects during severe exercise including healthy young adults. The PaCO2 level remains relatively constant up to moderate exercise; however, PaCO2 begins to decline during moderate-to-severe exercise and immediately after peak exercise in normal children and young adults. In regard to ventilatory efficiency, although efficiency improves as the exercise intensity increases during moderate exercise, the efficiency becomes worse during heavy exercise, while it improves rapidly again immediately after exercise while showing a transient postexercise increase in SaO2. The ventilatory efficiency is usually better than before exercise. Therefore, in situations in which worse or better ventilatory efficiency occurs, application of the Jones equation to estimate PaCO2 is suspect. Based on the equation, impaired ventilatory efficiency (lower PETCO2) makes a predicted PaCO2 lower and better ventilatory efficiency than normal (higher PETCO2) makes it higher. These situations resulted in our significantly flatter slopes of regression lines between estimations based on the Jones equation and measured PaCO2, especially in control subjects and RVOTR patients (p < 0.001 for both). In fact, Williams and Babb23 demonstrated that estimated PaCO2 at peak exercise is significantly lower than the actual PaCO2 in young adults. In addition, a lower PaCO2 set point may cause significant error for the estimation in children.

According to the Bland-Altman method, our estimations for PaCO2 were more accurate than those based on the Jones equation in our patients. Adoption of age as a major determinant of PaCO2 in normal children is reasonable because many investigators have demonstrated the lower PaCO2 set point in normal children.1 A dynamic change in R (VCO2/VO2) may be able to adjust the estimation during heavy and after peak exercise. However, SaO2 is closely associated with PaCO2 in Fontan procedure patients. In addition to being one of the major determinants for ventilation, SaO2 decline indicates impaired VCO2 excretion ability (elevation of PaCO2) during exercise. In RVOTR patients with restrictive ventilatory impairment, smaller VT has a significant adverse effect on the impaired rise in PETCO2. Despite the better estimation of PaCO2 based on our equations, these limits of agreement are ± 3 mm Hg for control subjects and RVOTR patients and ± 4 mm Hg for Fontan procedure patients. Therefore, our equations also may have some limitations for the precise assessment of ventilatory response during exercise testing in pediatric subjects.

In regard to exercise-related VD/VT, our noninvasive assessment was also more accurate than that based on the Jones equation. However, the limits of agreement are ± 5%, indicating some limitation of the noninvasive evaluation for VD/VT.

Study Limitations
First, our study is not prospective. Fortunately, there was no difference in the clinical backgrounds between study 1 and study 2 groups. However, confirmation of the present findings is needed using different exercise protocols, although there may be ethical restrictions in normal healthy children. Second, we compared our estimations with data from the Jones equation, which is based on a steady-state exercise protocol. Our exercise protocol is a progressive one. Therefore, direct comparison of the two estimations may be inappropriate. However, steady-state conditions are rare in the real-life setting of children, and there is no steady state at peak or after exercise. In these respects, our results are clinically useful. Studies in a steady state would provide more information on this point. Third, the small number of subjects in each group is a definite limitation of our study. Analyses with large numbers at each stage during exercise testing may be more ideal than our analyses with a whole stage of exercise testing. Finally, our control subjects are not entirely normal. However, our clinical evaluation did not show any cardiorespiratory-related abnormalities. Therefore, considering the ethical constraints of studies in normal healthy children, we believe that our control subjects are good substitutes for healthy children.


   Conclusions
TOP
 Abstract
 Introduction
 Materials and Methods
 Results of Study 1...
 Results of Study 2...
 Discussion
 Conclusions
References
 
We have made the following conclusions: (1) In growing children, VE/VCO2, R, and age in addition to PETCO2 are major determinants of PaCO2 during and after exercise, and estimation of PaCO2 is possible with our derived equation. (2) Estimation of PaCO2 with PETCO2 and VE/VCO2 is, to some extent, possible in Fontan procedure and RVOTR patients by adding SaO2 and VT, respectively. Finally, metabolic immaturity and dynamic change in ventilatory efficiency during and after exercise in normal children and impaired hemodynamics as well as ventilatory impairment in pediatric postoperative cardiac patients make the estimation of PaCO2 based on the Jones equation questionable.


   Acknowledgements
 
We are grateful to Drs. Peter M. Olley, Adjunct Professor of Pediatrics, Sapporo Medical University, and Setsuko Olley for assistance in preparing the article.


   Footnotes
 
Abbreviations: PETCO2 = end-tidal carbon dioxide tension; P(ET-a)CO2 = difference between PETCO2 and PaCO2; R = gas exchange ratio; RVOTR = right ventricular outflow tract reconstruction; SaO2 = arterial oxygen saturation; VC = vital capacity; VCO2 = carbon dioxide production; VD/VT = physiologic dead space/tidal volume ratio; VE = minute ventilation; VO2 = oxygen uptake; VT = tidal volume

Received for publication February 16, 2005. Accepted for publication June 17, 2005.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results of Study 1...
 Results of Study 2...
 Discussion
 Conclusions
 References
 

  1. Cooper, DM, Kaplan, MR, Baumgarten, L, et al (1987) Coupling of ventilation and CO2 production during exercise in children. Pediatr Res 21,568-572[ISI][Medline]
  2. Springer, C, Cooper, DM, Wasserman, K Evidence that maturation of the peripheral chemoreceptors is not complete in childhood. Respir Physiol 1988;74,55-64[CrossRef][ISI][Medline]
  3. Gratas-Delamarche, A, Mercier, J, Ramonatxo, M, et al Ventilatory response of prepubertal boys and adults to carbon dioxide at rest and during exercise. Eur J Appl Physiol 1993;66,25-30[CrossRef]
  4. Marcus, CL, Glomb, WB, Basinski, DJ, et al Developmental pattern of hypercapnic and hypoxic ventilatory responses from children to adulthood. J Appl Physiol 1994;76,314-320[Abstract/Free Full Text]
  5. Nagano, Y, Baba, R, Kuraishi, K, et al Ventilatory control during exercise in normal children. Pediatr Res 1998;43,704-707[Medline]
  6. Ohuchi, H, Kato, H, Tasato, H, et al Ventilatory response and arterial blood gases during exercise in children. Pediatr Res 1999;45,389-396[Medline]
  7. Rowland, T Developmental exercise physiology. 1990,27-157 Human Kinetics. Champaign IL:
  8. Eriksson, BO, Bjarke, B Oxygen uptake, arterial blood gases and blood lactate concentration during submaximal and maximal exercise in adult subjects with shunt-opened tetralogy of Fallot. Acta Med Scand 1975;197,187-193[ISI][Medline]
  9. Ohuchi, H, Katou, Y, Arakaki, Y, et al Alveolar-arterial gas tension differences during progressive exercise in patients after the Fontan operation. Jpn Circ J 1997;61,402-412[Medline]
  10. Wasserman, K, Zhang, YY, Gitt, A, et al Lung function and exercise gas exchange in chronic heart failure. Circulation 1997;96,2221-2227[Abstract/Free Full Text]
  11. Ohuchi, H, Yasuda, K, Suzuki, H, et al Ventilatory response to exercise in patients with major aortopulmonary collateral arteries after definitive surgery. Am J Cardiol 2000;85,1223-1229[Medline]
  12. Jones, NL, Robertson, DG, Kane, JW Difference between end-tidal and arterial PCO2 in exercise. J Appl Physiol 1979;47,954-960[Abstract/Free Full Text]
  13. Rhodes, J, Garofano, RP, Bowman, FO, Jr, et al Effect of right ventricular anatomy on the cardiopulmonary response to exercise: implication for the Fontan procedure. Circulation 1990;81,1811-1817[Abstract/Free Full Text]
  14. Robbins, PA, Conway, J, Cunningham, DA, et al Comparison of indirect methods for continuous estimation of arterial PCO2 in men. J Appl Physiol 1990;68,1727-1731[Abstract/Free Full Text]
  15. Ohuchi, H, Nakajima, T, Kawade, M, et al Measurement and validity of the ventilatory threshold in patients with congenital heart disease. Pediatr Cardiol 1996;17,7-14[Medline]
  16. Sue, DY, Hansen, JE, Blais, M Measurement and analysis of gas exchange during exercise using a programmable calculator. J Appl Physiol 1980;49,456-461[Abstract/Free Full Text]
  17. Beaver, WL, Wasserman, K, Whipp, BJ A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol 1986;60,2020-2027[Abstract/Free Full Text]
  18. Wasserman, K, Hansen, JE, Sue, DY, et al Principles of exercise testing and interpretation: including pathophysiology and clinical applications 2005,559 Lippincott, Williams & Wilkins. Philadelphia, PA:
  19. Bland, JM, Altman, DG Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1,307-310[CrossRef][ISI][Medline]
  20. Liu, Z, Vargas, F, Stansbury, D, et al Comparison of the end-tidal arterial PCO2 gradient during exercise in normal subjects and in patients with severe COPD. Chest 1995;107,1218-1224[Abstract/Free Full Text]
  21. DuBois, AB, Britt, AG, Fenn, WO Alveolar CO2 during the respiratory cycle. J Appl Physiol 1951;4,535-548
  22. Eriksson, BO, Karlsson, J, Saltin, B Muscle metabolites during exercise in pubertal boys. Acta Paediatr Scand 1971;217(suppl),154-157
  23. Williams, JS, Babb, TG Difference between estimates and measured PaCO2 during rest and exercise in older subjects. J Appl Physiol 1997;83,312-316[Abstract/Free Full Text]
  24. Ohuchi, H, Ohashi, H, Takasugi, H, et al Restrictive ventilatory impairment and arterial oxygenation characterize rest and exercise ventilation in patients after the Fontan operation. Pediatr Cardiol 2004;25,513-521[CrossRef][Medline]
  25. Matsushita, T, Matsuda, H, Ogawa, M, et al Assessment of the intrapulmonary ventilation-perfusion distribution after the Fontan procedure for complex cardiac anomalies: relation to pulmonary hemodynamics. J Am Coll Cardiol 1990;15,842-848[Abstract]




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