Limiting factors in peak oxygen uptake and the relationship with functional ambulation in ambulating children with Spina Bifida
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- De Groot, J.F., Takken, T., Schoenmakers, M.A.G.C. et al. Eur J Appl Physiol (2008) 104: 657. doi:10.1007/s00421-008-0820-9
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The objective of this study is to interpret the outcomes of peak oxygen uptake (VO2peak) in children with SB and explore the relationship between VO2peak and functional ambulation using retrospective cross-sectional study. Twenty-three ambulating children with SB participated at Wilhelmina’s Children’s Hospital Utrecht, the Netherlands. VO2peak was measured during a graded treadmill-test. Eschenbacher’s and Maninna’s algorithm was used to determine limiting factors in reaching low VO2peak values. Energy expenditure during locomotion (both O2 rate and O2 cost) and percentage of VO2peak and HRpeak were determined during a 6-min walking test (6MWT). Differences between community and normal ambulators were analyzed. VO2peak, VO2peak/kg, HRpeak, RERpeak and VEpeak were significantly lower compared to reference values, with significant differences between normal and community ambulators. Limiting factors according to the algorithm were mostly “muscular and/or deconditioning” (47%) and ventilatory “gasexchange” (35%). Distance walked during 6MWT was 48.5% of predicted distance. Both O2 rate and O2 cost were high with significant differences between normal and community ambulators [17.6 vs. 21.9 ml/(kg min) and 0.27 vs 0.43 ml/(kg m)]. Also %HRpeak and %VO2peak were significantly higher in community ambulators when compared to normal ambulators (resp. 97.6 vs. 75% and 90.2 vs. 55.9%). VO2peak seems to be mostly limited by deconditioning and/or muscular components and possible ventilatory factors. For both peak values and functional ambulation, community ambulators were significantly more impaired than normal ambulators. High energy expenditure, %VO2peak and %HRpeak reflect high level of strain during ambulation in the community ambulators. Future exercise testing in children with SB should include assessment of ventilatory reserve. Exercise training in ambulatory children should focus on increasing both VO2peak and muscular endurance, as well as decreasing energy cost of locomotion.
KeywordsExercise testEnergy cost of locomotionSpina Bifida6 min walking testVO2peak
Ambulation level by Hoffer et al. adapted by Schoenmakers et al. (2005)
Level of ambulation
Independent and unrestricted ambulation without use of assisted devices
Independent outdoor ambulation with or without use of braces and/or assisted devices; using wheelchair for longer distances
Using braces or assisted devices for indoor ambulation; using wheelchair for outdoor locomotion
Walking only in therapeutic situations
At the same time, small studies have shown higher levels of energy expenditure during ambulation in patients with SB, a finding that is associated with a pathological gait pattern (Bare et al. 2001; Buffart et al. 2006; Waters and Mulroy 1999). Energy expenditure refers to both O2 rate [ml O2/(kg min)], an indicator of strain or effort and O2 cost [ml O2/(kg m)] (Schwartz 2007). Higher energy expenditure during ambulation may result in higher levels of fatigue while physically active. This combination of reduced exercise capacity and higher cost of locomotion is referred to as “diminished physiological fitness reserve” (McArdle et al. 1996).
Which factors (cardiovascular, pulmonary or muscular) are limiting VO2peak in ambulatory children with SB?
Since components of physical fitness are associated with efficiency of movement (Bar-Or 1996), is VO2peak related to oxygen expenditure during ambulation in children with SB?
The study group consisted of a 23 ambulatory children with SB visiting the SB clinic of the University Children’s Hospital in Utrecht (The Netherlands) for lifestyle and sports advice in 2004. Study procedures were approved by the University Medical Ethics Committee.
Children were included when they were (1) at least community ambulatory (see Table 1), (2) able to follow instructions regarding testing and (3) between 6 and 18 years of age. Parents and children signed informed consent prior to testing.
Exclusion criteria were medical events that might interfere with the outcomes of the testing and medical status that did not allow maximum exercise testing.
Retrospective cross-sectional study, using outcomes of incremental exercise testing and the 6-min walking test (6MWT).
Data concerning medical history were obtained from medical records. These data included type of SB, level of lesion, use of orthotics, ambulation level, age and sex.
Body mass index (BMI)
BMI was calculated as weight (kg)/length (m)2. This index has proven to be a reliable and valid tool to estimate children’s nutritional status, e.g. whether they are over- or underweight (Dietz and Robinson 1998; Mei et al. 2002). Weight was measured using an electronic scale. Height was measured while standing using a wall-mounted centimeter.
Peak oxygen uptake (VO2peak)
In exercise testing, VO2 peak is considered to be the single best indicator of aerobic exercise capacity, which is often referred to as aerobic fitness. Gas exchange analysis during an incremental ergometry test to the point of volitional termination due to exhaustion is considered the gold standard to measure VO2peak (Shephard et al. 1968). Earlier studies employing exercise testing in healthy children show it is possible to test VO2peak in healthy children (Armstrong et al. 1996; Eiberg et al. 2005; Gulmans et al. 1997; Reybrouck et al. 1992; Rowland 1993). In this study, VO2peak was measured using a treadmill test (EnMill, Enraf, Delft, The Netherlands), since all children would be able to perform this test and reference values are available for both young children and adolescents. In previous studies, treadmill protocols have been used to test VO2peak in children with disability (Hoofwijk et al. 1995; Verschuren et al. 2006), including children with Spina Bifida (Agre et al. 1987; Shermans et al. 1997). In order to accommodate children with different ambulatory abilities, two progressive exercise test protocols were used. Children considered community ambulators were tested with a starting speed of 2 km/h, which was gradually increased by 0.25 km/h every minute. Children classified as normal ambulators were started at a speed of 3 km/h, with the speed being increased 0.50 km/h every minute. The protocols were continued until the patient stopped due to exhaustion, despite verbal encouragement of the test leader. During the incremental exercise test, physiologic responses were measured using a heart rate (HR) monitor (Polar) and calibrated mobile gas analysis system (Cortex Metamax B3, Cortex Medical GmbH, Leipzig, Germany). The Cortex Metamax is a valid and reliable system for measuring gas-exchange parameters during exercise (Brehm et al. 2004; Medbo et al. 2002).
Functional ambulation was measured during a 6-min walking test (6MWT). The test was performed on an 8-m track in a straight corridor and gas exchange parameters were measured continuously with a portable Cortex gas analysis system (Cortex Metamax B3, Cortex Medical GmbH, Leipzig, Germany). Patients were instructed to cover the largest possible distance in 6 min at a self-selected walking speed. The test and encouragements during the test were performed in accordance with the ATS guidelines (ATS 2002).
Peak oxygen uptake
Peak exercise parameters were calculated as the average value over the last 30 s during the exercise test. Normalized VO2peak was calculated as VO2peak/kg. Predicted peak values were obtained from established values from age- and sex- matched historical Dutch controls (Binkhorst et al. 1991). For comparison with healthy children Z-scores were calculated for VO2peak, VO2peak/kg, HRpeak RERpeak and VEpeak. Standard deviation scores >2 SD below or above normal were considered to be significantly different from the norm values.
Data were evaluated using the algorithm from Eschenbacher and Maninna (Eschenbacher and Mannina 1990). This algorithm has been developed for the interpretation of outcomes of exercise testing in adults. For this purpose it uses cut-off points routinely measured during exercise testing in order to make a distinction between cardiac, pulmonary or “other” limitations (deconditioning and/or musculoskeletal factors) to explain exercise capacity. The following parameters were measured and used in the algorithm: VO2peak, VCO2peak, VEpeak, VEpeak/VCO2peak, anaerobic threshold (AT) and heart rate response (HRR) expressed as (HRpeak − HRrest)/(VO2peak − VO2rest). Whereas the original algorithm uses adult cut-off points, in this study values were adapted to the pediatric population, based on earlier work from our laboratory regarding maximum exercise testing parameters in healthy children (van Leeuwen et al. 2004).
In this algorithm, VEpeak/VCO2peak is a general indicator of the efficiency of the both the lungs and gas exchange; high values (VEpeak/VCO2peak >36) suggest gas exchange difficulties. Since FEV1 was not measured and no known pulmonary problems were present, it was assumed that ventilatory reserve in all children was normal. HRR refers to the increase in HR in relation to the increase in VO2. An excessive increase in HR (>[−6.25 × age] + 150) might reflect either cardiac disease or deconditioning. In our patients no known cardiac history was present and therefore increased HRR was considered an indicator of deconditioning rather than cardiac disease. AT occurring at less than 40% VO2peak was considered an indicator of poor circulatory or “pump” limitation. When no ventilatory or cardiac limitations were present, patients were considered to be limited by “other limitations”.
Steady state was taken as the average value over the period during which oxygen uptake changed less than 5% (Schwartz 2007); (3) Subsequently, the following parameters were derived: Speed (m/min), calculated as 6MWD/6; O2 cost [ml/(kg m)], calculated as O2 rate/speed (Waters and Mulroy 1999); individual strain (O2ratesteady state/VO2peak × 100% and maximum HR6mwt/HRpeak × 100%)
For all measurements, t tests were used to test differences between normal and community ambulators after testing for normal distribution and equality of means. When this was not the case (VO2peak), Mann–Whitney U test were used. For the correlation between VO2peak and O2 expenditure, a Spearman Rho was calculated. Significance level was set at p < 0.05. Statistical analyses were performed using SPSS for Windows (version 15.0, SPSS Inc, Chicago, Ill.).
Z scores (SD) compared to reference values
Level of lesion and functional ambulation level
Level of lesion
No motor loss
Use of orthotics
Peak oxygen uptake and other peak parameters
Descriptives of exercise testing in 21 children with SB
Mean (SD) all children
Z score (SD)
Mean (SD) NA
Z scores (SD)
Mean (SD) CA
Z scores (SD)
VO2peak/kg [ml/(kg min)]
One tailed t test showed a significant difference between the normal and community ambulators for Z scores of VO2peak, VO2peak/kg, HRpeak, VEpeak scores and outcomes of VCO2peak and VO2peak/kg. Normal ambulators showed higher scores for both ventilation, VO2peak and VCO2peak. Ventilatory equivalents for both carbon dioxide and oxygen (VEpeak/VCO2peak and VEpeak/VO2peak) did not differ, but were high in both groups.
Limiting factors using Eschenbacher’s and Mannina’s algorithm
Eighty-five percent of complete test data (n = 20) scored below 90% of predicted VO2peak, indicating lower levels of fitness than expected.
Looking at the limiting factors, 47% showed signs of “other limitation”, e.g. muscular deficiency and/or deconditioning, as indicated by high heart rate response (HRR).
Cut-off points in the algorithm by Eschenbacher and Maninna as measured in 21 children with SB
Used cut off points
% reaching critical values
VO2peak pred (%)
>(−6.25 × age) + 150
Deconditioning and/or muscular limitations
Outcomes of 6MWT
Mean (SD) all children
Mean (SD) normal ambulators
Mean (SD) community ambulators
Predicted distance (%)
Mean O2 rate [ml/(kg min)]
O2 rate steady state [(ml/(kg min)]
O2 cost [(ml/(kg m)]
Correlation between VO2peak and oxygen utilization during ambulation
Both O2 rate and O2 cost during 6MWT correlated negatively with VO2peak (respectively rsp = −0.56 (p < 0.001) and rsp = −0.76 (p < 0.001)), indicating lower energy expenditure during locomotion in children reaching higher VO2peak.
Peak oxygen uptake
The first purpose of the study was to determine why ambulatory children with SB showed significantly reduced levels of VO2peak compared to healthy peers. Despite subjective signs of peak effort, the treadmill testing resulted in both low HRpeak and RERpeak values, calling into question the true maximal character of the testing procedures. Currently we are using a protocol of Rossiter et al. (2006) using a supra-maximal step (105–110% of last reached speed) to determine whether the regular protocol yields true maximum values or whether a different approach in exercise testing should be used in children with SB. At the same time the low HRpeak seems to be in line with other studies regarding exercise testing in children with SB (Agre et al. 1987; Shermans et al. 1997) with HRpeak ranging from 130 to 185 beats per minute. In one of these studies (Agre et al. 1987) HRpeak seems negatively related to level of lesion. Another explanation for low HRpeak could be that exercise capacity in children with SB is not limited by the cardiovascular system, but by muscular components.
Using the algorithm (Eschenbacher and Mannina 1990), limiting factors in exercise capacity in ambulatory children with SB indeed seem to be mostly “deconditioning and/or muscular” components. Muscular limitations can partly be explained by the disease itself. Lower muscle mass in children with SB results in lower VO2peak. VO2peak/kg was even more reduced. This is likely a result of the different body composition in these children with less active muscle mass and increased fat mass (Liusuwan et al. 2007b). In contrast with the muscular consequences of the disease, atrophy and muscular inefficiency as a result of disuse and sedentary lifestyle can be expected to improve through a training program. In the studied population, not only was exercise capacity reduced, they also showed lower strength above the lesion level and a sedentary lifestyle (Schoenmakers et al. 2008). In combination with a high HRR, the muscular limitations indentified in this study seem partly due to deconditioning. Exercise programs aimed at improving physical fitness in ambulatory children with SB are scarce, but they do show significant improvements in both strength and endurance (Andrade et al. 1991; Liusuwan et al. 2007a; Widman et al. 2006).
In this study high ventilatory equivalents were found for both VCO2 and VO2, which could be an indicator of ventilatory limitations. These findings are consistent with one other study reporting on pulmonary dysfunction due to restrictive lung disease and respiratory muscle weakness in children with SB during exercise (Shermans et al. 1997).
Another possible explanation for these high ventilatory equivalents might be the presence of a Chiari II malformation, often present in children with SB. This malformation affects the brain stem and is known to influence both O2 and CO2 peripheral chemoreceptor function in children with SB (Gozal et al. 1995; Petersen et al. 1995). Future studies should include assessment of ventilatory reserve during exercise, so that a distinction can be been made between the different causes of pulmonary limitations, e.g. diffusion type versus gas exchange versus mechanical limitations.
Our second purpose was to determine the relationship between VO2peak and functional ambulation. The 6MWT is a submaximal test of functional exercise capacity (Li et al. 2007). One of the main outcomes is the distance walked. In our study only half of the predicted distance was reached. A likely reason for reduced 6MWD is reduced muscle strength resulting in decreased motor control and an altered gait pattern leading to high energy expenditure (Gutierrez et al. 2005; Waters and Mulroy 1999). In this study, both O2 rate and O2 cost were indeed high compared to values for healthy children, which range in the literature from 12 to 18 ml/(kg min) and 0.18 to 0.27 ml/(kg m). In the literature values for O2 rate and O2 cost during ambulation in children with SB range from 17.5 to 19 ml/(kg min) and from 0.28 to 0.47 ml/(kg m) (Bartonek et al. 2002; Gutierrez et al. 2005). The O2 rate in our study was higher, while the cost ranged from 0.27 ml/(kg min) in normal ambulators to 0.43 ml/(kg min) in community ambulators. These other studies used different protocols regarding both mode of testing (treadmill vs. level ground), walking speed (self-selected vs. imposed) and preparation of the subjects, factors hinderomg comparison between the studies. Therefore we are using new protocols, proposed in recent literature (Brehm et al. 2007; Schwartz 2007) in our current study.
Another interesting result from this study is the individual level of strain during locomotion. Community ambulators showed a much higher HR during the 6MWT than normal ambulators. Studies in healthy children show HR reached during the 6MWT to be around 134 beats per minute, which is similar to the normal ambulators (Lammers et al. 2007; Li et al. 2005). Looking at the intensity of ambulation, community ambulators performed this task at a very high level of individual strain (91% VO2peak and 97.6% HRpeak). Studies in healthy children reach 65–70% of HRpeak during the 6MWT (Paap et al. 2005). One explanation for this could be the low HRpeak reached during the exercise test. But as mentioned above the community ambulators reached a high HR during the 6MWT. In combination with high oxygen utilization, the effort of walking remains high.
Correlation between VO2peak and oxygen utilization during ambulation
VO2peak values were related to oxygen utilization during locomotion. This indicates lower levels of peak oxygen uptake are associated with both higher oxygen rate and oxygen cost during locomotion. Rate is indicator of strain or effort, which might explain the level of fatigue during locomotion. Reybrouck et al observed similar trends in treadmill testing when comparing children with chronic fatigue with healthy peers, concluding that high individual strain was associated with early fatigue (Reybrouck et al. 2007).
Energy cost is an indicator of efficiency (Schwartz 2007). From the literature it is known that energy cost of locomotion in people with disabilities can be improved by training (Felici et al. 1997; Protas et al. 2001), so future research should also look at the effects of training to reduce the energy cost during locomotion in ambulatory children with SB.
Limitations of the study
Questions could be raised with regards to use of a treadmill protocol. Other studies (Bruinings et al. 2007; van den Berg-Emons et al. 2003a, b; Widman et al. 2007) have used upper extremity ergometry. An advantage of arm ergometry in this population could be that the muscles tested are less involved in the disease process. In this way the outcomes of the test might more closely reflect cardiorespiratory limitations in exercise testing. On the other hand, upper extremity ergometry has been known to result in lower VO2peak values, due to the smaller muscle mass being involved in testing (Franklin 1985). In this study a treadmill protocol was chosen for several reasons. First, for all children, ambulation was the main mode of transportation. In this case it is recommended to use a treadmill for maximum exercise testing, due to the specificity of testing (Stromme et al. 1977). Secondly, we were interested in comparing outcomes from the peak exercise test to other ambulation parameters. If we had used arm ergometry, these comparisons would be hard to interpret due to the differences in physiological responses between arm ergometry and treadmill testing. In this study the 6MWT was performed using an 8-m track. Looking at the studies establishing reference values (Geiger et al. 2007; Lammers et al. 2007; Li et al. 2007) for the 6MWD in children, a 20 m track seems to result in a longer 6MWD. In this study however, the children were walking with a significantly lower speed as compared to healthy children reducing the importance of the shorter distance between the turning points. Despite this shorter track a steady state of O2 utilization was reached by all, but two children. Currently we are working with the more commonly used 20 m track.
Lower levels of VO2peak in ambulatory children with SB seem to be related to muscular and/or deconditioning components rather than cardiopulmonary deficiencies. Future exercise testing in ambulatory children with SB should include evaluation of the ventilatory reserve to better determine possible ventilatory limitations.
Both O2 rate and O2 cost during locomotion are high in ambulatory children with SB, even in those considered to be normal ambulators. Oxygen utilization correlated negatively with VO2peak. Overall, community ambulators showed significantly worse outcomes than normal ambulators. At the same time, the normal ambulators only walked half of the predicted distance at high O2 rate and O2 cost. Future training programs for ambulatory children with SB should focus on improving VO2peak and muscular endurance, as well as decreasing energy expenditure during locomotion to increase physiological reserve.
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