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(Chest. 2002;121:1555-1560.)
© 2002 American College of Chest Physicians

The Effect of Noninvasive Intermittent Positive-Pressure Ventilation During Exercise in Severe Scoliosis*

Martin P. Highcock, MBBS; Ian E. Smith, MD and John M. Shneerson, DM, FCCP

* From the Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge, UK.

Correspondence to: Martin P. Highcock, MBBS, c/o RSSC, Papworth Hospital, Papworth Everard, Cambridge, CB3 8RE, UK; e-mail: mhighcock{at}ukonline.co.uk


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Study objectives: Noninvasive intermittent positive-pressure ventilation (NIPPV) may improve exercise performance in COPD patients. It is not known whether this also applies to other patient groups such as those with restrictive respiratory diseases.

Design: Randomized controlled trial.

Setting: Regional center for assisted ventilation.

Subjects: Eight patients with severe congenital scoliosis.

Interventions: A submaximal treadmill test was performed with NIPPV applied via a mouthpiece. Each subject performed three walks breathing with three different ventilators and one walk breathing through the mouthpiece alone in random order. In addition, four unencumbered walks breathing normally and without monitoring were performed.

Measurements and results: The four unencumbered walks did not show a significant learning effect. The mean (SD) distance walked was 204 m (134.9 m). Using the mouthpiece alone, the walking distance fell to 140 m (75.8 m), and with the addition of the ventilators it fell further to 109 m (59.3 m). Grouped-effects analysis of variance showed this to be a significant difference in walking distance according to the type of walk (p = 0.048). There was no difference shown among the three brands of ventilator. At the breakpoint of exercise, significant increases were seen in tidal volume and minute volume (Mv) in the ventilator-assisted walks (p < 0.05) compared to walks performed breathing with the mouthpiece alone.

Conclusions: Breathing via a mouthpiece impaired exercise performance, and there was no improvement when breathing with a ventilator, despite the observed increase in Mv. NIPPV has no beneficial effect on exercise endurance in patients with severe scoliosis.

Key Words: congenital scoliosis • exercise test • exhaustive treadmill exercise • noninvasive ventilation • positive-pressure ventilation


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Noninvasive intermittent positive-pressure ventilation (NIPPV) may enhance exercise performance in COPD patients.1 2 During exercise, NIPPV can increase tidal volume (VT) and minute volume (Mv) with reduced inspiratory effort3 and less inspiratory muscle loading,4 leading to a reduction in breathlessness. It is not known whether this applies to other patient groups with exercise impairments such as those with restrictive respiratory diseases.

In patients with respiratory failure occurring as a consequence of thoracic scoliosis, regular nocturnal NIPPV improves overnight oxygen saturation, daytime blood gas tensions, and the patient’s symptoms.5 These improvements are maintained over time, and the 5-year survival rate is approximately 80%.6 During NIPPV, Mv is increased despite reduced inspiratory effort.7 8

Healthy individuals are limited by cardiovascular factors during exercise, but subjects with severe scoliosis are usually restricted by their ventilation.9 Maximum exercise ventilation is diminished, and this is proportional to the reduction in vital capacity (VC). In addition, peak oxygen consumption is increased compared to that in healthy individuals at any given level of ventilation, indicating an increased work of breathing.

We hypothesized that the application of NIPPV during exercise in this group may increase ventilation but may reduce the work of breathing and subsequently may lead to an increase in exercise capacity. We also wished to investigate whether any brand of ventilator was particularly effective in this role.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Subjects were recruited from the population of patients with congenital scoliosis who have attended our center. The inclusion criteria were a Cobb angle of 90° or greater and restrictive lung deficit with total lung capacity (TLC) equal to or < 50% of predicted.10 All subjects were already using home nasal ventilation. Exclusion criteria included any pulmonary disorder or other medical condition that is likely to affect exercise capacity. such as cardiovascular or neuromuscular disease. Subjects were excluded if they had experienced any change of symptoms or drug therapy in the 4 weeks prior to entering the study. The hospital’s ethics committee approved the study, and all subjects gave informed consent.

Ventilators
The three following ventilators were compared: BiPAP-ST 30 (Respironics Inc; Monroeville, PA); Nippy2 (B & D Electrical Ltd; Stratford-upon-Avon, UK); and Vpap II ST (ResMed Ltd; Abingdon, Oxfordshire, UK). NIPPV was applied with the subject wearing noseclips and breathing via a mouthpiece. The triggered/timed mode and the minimum backup rate was used with each machine to ensure that all ventilator breaths were triggered by the subject. The minimum expiratory airway pressure was used throughout. Maximum inspiratory airway pressure (IPAP) and inspiratory times (TI) were set for each machine, as determined by patient comfort at rest, and were not altered during exercise. The ventilators were attached to the mouthpiece using identical circuits incorporating an expiratory valve (Whisper swivel II; Respironics Inc). A pneumotachograph (Fleisch, Feraris, Solihull, UK) and a pressure transducer (Vygon, Gloucestershire, UK) were inserted into the circuit between the mouthpiece and the expiratory valve to record the expiratory volumes and pressure within the circuit.

Experimental Protocol
Subjects were asked to perform walking tests on a treadmill to compare their exercise capacity under the three following different conditions: (1) unencumbered; (2) breathing via a mouthpiece with noseclips; and (3) breathing via a mouthpiece with noseclips attached to one of the ventilators.

For all walking tests, pulse oximetry using a finger probe (Ohmeda; Hatfield, Hertfordshire, UK) and heart rate were documented before and after the test. Respiratory rate (RR) and BP also were measured immediately prior to and following the cessation of exercise. On walks with the mouthpiece with or without a ventilator attached, the expiratory VT, RR, IPAP, TI, and expiratory time were recorded continuously. These were stored on a data-logging system (CARDAS; Pilogic, Dyffed, UK) for subsequent analysis. In addition, during these walks each subject also was connected to a three-lead ECG, and the finger probe was used throughout.

All treadmill walks were carried out at a constant speed and were terminated by breathlessness. The speed was set at a pace that each subject thought was equivalent to a brisk walk, and this speed was kept constant for subsequent tests. To complete the protocol, we asked subjects to attend on three occasions at the same time of day within a maximum period of 8 days. Subjects were asked to avoid eating food and drinking caffeinated beverages in the 2 h prior to attendance.

Day 1
On the first attendance, baseline measurements were recorded. These measurements included a penetrated posteroanterior chest radiograph such that the Cobb angle could be calculated, a resting ECG, a resting measurement of peripheral oxygen saturation (SpO2), and measurements of arterial blood gas tension levels while the subject was breathing air. Spirometry was performed using a rolling seal spirometer (Vitalograph Ltd; Buckinghamshire, UK), and TLC was estimated using body plethysmography (Masterlab; Jaeger; Hoechberg, Germany). Gas transfer could not be measured due to low intrathoracic gas volumes. Maximum voluntary ventilation (MVV) was measured over > 12 s using a low-resistance spirometer (Vitalograph Ltd).

To define their maximal performance, subjects performed a practice shuttle-walking test11 and then a further shuttle-walking test with the results recorded. The shuttle-walking test requires the subject to walk up and down a 10-m course. The speed is externally paced by a prerecorded audio signal. The test is therefore highly reproducible and is less likely to be influenced by external factors compared to self-paced timed walks.12 The speed is also incremental, stressing the subject to a symptom-limited maximal performance, which correlates well with peak oxygen consumption,13 unlike the 12-min walk.14 After familiarization with the treadmill, a series of practice walks breathing with each of the ventilators and with the mouthpiece alone were completed by subjects. This allowed the subject to become familiar with the equipment and for the ventilator settings and treadmill speed to be established. Finally, two unencumbered walks were completed on the treadmill. Subjects were excluded if they were able to walk for longer than 10 min at a speed determined to be their maximum on the shuttle-walking test. At least 30 min was left between walks to allow the subject to recover.

Day 2 and Day 3
Spirometry and measurement of resting SpO2 levels were repeated on both days, and subjects were excluded if there was a > 10% change in these values. In random order on each day, one unencumbered walk and two of the four other walks were performed, that is, walking while breathing via a mouthpiece but with no ventilator and breathing via a mouthpiece attached to one of the three ventilators.

Statistical Analysis
The statistical analysis of all data was performed using appropriate software (SPSS for Windows; SPSS; Chicago, IL). In all tests, a p value of < 0.05 was considered to be significant.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
Subjects
Eight subjects (five men) with a mean (SD) age of 64 years (3.6 years) completed the study protocol. The spinal deformity was severe, with a mean Cobb angle of 100° (12.7°), FEV1 of 0.7 L (0.2 L) and 27.5% of predicted, FVC of 1.0 L (0.3 L) and 30.5% of predicted, TLC of 2.4 L (0.4 L) and 40.9% of predicted. All were subjects were receiving treatment with nocturnal NIPPV for respiratory failure (duration range, 6 to 83 months), and measurements of the following resting arterial blood gas tensions confirmed that the subjects were being adequately treated: PO2, 68.4 mm Hg (8.4 mm Hg); and PCO2, 47.9 mm Hg (6.1 mm Hg). The mean shuttle-walking distance was 206.3 m (73.5 m), and the subsequent treadmill speed was 78.4% (13.8%) of the maximum speed determined for the shuttle-walking test. The mean preset IPAP during the ventilator walks was 13.7 cm H2O (4.8 cm H2O).

Distances
To look for the effect of fatigue, on each study day the first and last walks were compared using a paired Student’s t test. There was no significant difference in the distances walked. The mean (SD) values were as follows: day 2/walk 1, 136.0 m (80.4 m); day 2/walk 3, 121.9 m (67.7 m; p = 0.37); day 3/walk 1, 122.0 m (60.6 m); day 3/walk 3, 218.9 m (261.7 m; p = 0.30). There was a small increase in the unencumbered walking distance with practice. However, using analysis of variance (ANOVA) for repeated measures, no significant differences in walking distance were found among the four unencumbered walks (Fig 1 ). ANOVA for the ventilator walks showed no difference in distance according to the brand of ventilator used. The data were therefore combined, and a mixed-effects ANOVA was used to compare the distances completed according to type of walk (ie, unencumbered vs mouthpiece alone vs mouthpiece with ventilator) [Fig 2 ]. The mean (SD) distance walked during the unencumbered walks was 203.7 m (134.9 m). The addition of the mouthpiece and monitoring equipment reduced the mean distance to 140.4 m (75.8 m), and a further fall to 109.3 m (59.3 m) was seen following the application of NIPPV. The differences among the groups were significant (p = 0.048). Post hoc analysis with the Scheffé test showed that only the comparison between the unencumbered walks and the ventilator walks was significant (p < 0.01).



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  		Figure 1.. Distances walked, with individual data points and group means are shown. The p values were calculated using ANOVA for repeated measures.

 


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  		Figure 2.. Distances walked according to type, with individual data points and group means are shown. The p values were calculated using mixed-effects ANOVA and comparing walks according to type.

 
Exercise Physiology
A mixed-effects ANOVA was used to compare the degree of desaturation, the cardiovascular response, and the RR measured immediately post-exercise among the three types of walks (Table 1 ). No significant differences were observed. Of note is the high RR in all the types of walks.


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  		Table 1.. Post-Exercise Results Among Walks*

 
For the walks using the mouthpiece, measured parameters were compared for the last 20 s of exercise using mixed-effects ANOVA (Table 2 ). Significant increases in VT, Mv, and inspiratory flow were seen during the ventilator walks. VT was a significantly higher proportion of VC.


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  		Table 2.. Parameters at Breakpoint of Exercise*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
Our results show that although ventilation was increased during exercise with NIPPV, this did not lead to an improvement in exercise capacity. A number of factors may be important in explaining these results.

First, the potential weaknesses of the experimental methods need to be considered. The number of subjects included was small but was comparable to those of other studies that have shown positive results of NIPPV on exercise performance in different disease groups.1 15 16 The interpretation of exercise tests can be difficult due to learning effects and the influence of encouragement and motivation.12 It can be seen from the time-ordered walks that there was a small but statistically insignificant learning effect. It is possible that this may have influenced our overall results, particularly as our protocol involved four unencumbered walks compared to three ventilator walks. However, this alone is unlikely to account for the differences seen among the types of walking tests. There was no demonstrable effect of fatigue on the distances walked.

No verbal encouragement was given during the tests. A constant work rate was used, but this was a high proportion of each subject’s maximal speed, and subjects were excluded if they were not exhausted after 10 min of treadmill exercise. All subjects stopped due to breathlessness. At exercise breakpoint, the Mv/MVV was close to 1, indicating a ventilatory limit to the exercise. There were no significant differences in the degree of arterial desaturation and cardiovascular responses seen among the different types of tests, suggesting that the effort exerted was uniform in each test.

The addition of monitoring equipment during exercise tests may impair performance.13 17 Our data show that exercise capacity was reduced when the mouthpiece and monitoring equipment were used. However, the addition of NIPPV did not overcome this handicap. It is important when considering the effect of NIPPV during exercise tests that performance is compared with unencumbered control subjects. In clinical practice, if NIPPV is to have a genuine benefit during exercise, then the handicap of the ventilator circuit and mask also must be overcome.

There are a number of theoretical reasons why NIPPV may be unsuited to exercise in scoliosis. As in healthy individuals, VT increases initially during exercise to a maximum and then remains constant while the respiratory frequency rises. The maximal VT, although less than normal, is a higher percentage of the VC than in healthy subjects.9 Our subjects utilized an even higher proportion of VC when exercising with NIPPV. Although this was the objective of using ventilation, it may be that this in itself is related to the sensation of dyspnea that terminated exercise prematurely.

The high RR observed in these subjects during exercise also may be a handicap for the use of NIPPV. All ventilator breaths were triggered by the subjects. Inspiratory and expiratory effort is therefore required to trigger the ventilators to IPAP and expiratory airway pressure during each breath cycle. There is a delay in triggering that may be up to 0.25 s during inspiration and 0.4 s during expiration with the machines used in our study.18 With the RR of approximately 40 breaths/min seen at peak exercise, the total breathing cycle time (TTOT) is only 1.5 s. Therefore, at peak exercise a large proportion of the TTOT may involve triggering the ventilators, and thus the duration of ventilatory assistance will be relatively short. The work of breathing will therefore be high, leading to breathlessness and the termination of exercise.

Similar rate-related problems also may apply to CO2 rebreathing. Using the expiratory valve, up to 60% of the expired volume of air may remain in the ventilator circuit at the end of expiration.19 Stable intubated patients compensate for this by increasing Mv to maintain equivalent blood gas levels, with the work of breathing subsequently increasing.20 This may be of no consequence with resting tidal respiration but may be a limiting factor at the high rate of respiration in our subjects at the breakpoint of exercise. Rebreathing may be eliminated by the use of alternative exhalation devices,21 and the inclusion of such a valve in our study may have produced different results. The use of a mouthpiece alone increases the dead space and could lead to rebreathing in subjects with limited VC. This contributes to the inevitable handicap of the ventilator circuit. However, the mouthpiece that we employed has a volume of 43 mL, which is less than half that of a small nasal mask (98 mL, allowing for the volume of the nose; Respironics). A nasal mask also was not used, because, although nasal breathing is common at rest, oronasal breathing appears to be universal during exercise.22

Ventilation is not the only limit to exercise in patients with scoliosis. Cardiac output and left ventricular function are usually normal, but pulmonary artery pressure rises rapidly during exercise. The rate of rise is inversely proportional to VC, functional residual capacity, and TLC but is unrelated to the angle of scoliosis or arterial oxygen tension and is hardly affected by breathing pure oxygen.23 General deconditioning24 and a reduction in lean muscle mass25 also are seen within the population of scoliosis patients as a consequence of reduced physical activity. NIPPV increases systolic pulmonary artery pressure in subjects with COPD26 and would be expected to increase pulmonary hypertension further in our subjects. NIPPV would not be expected to have any direct effect on deconditioning, unless exercise capacity was increased, leading to a physical training effect.


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
We have shown that although ventilation is increased by NIPPV during exercise in scoliosis patients, exercise capacity is impaired. The use of a mouthpiece during exercise tests leads to reduced performance, but the addition of NIPPV had no further effect. The physiologic variables that we have measured do not explain why performance is impaired, but there are a number of theoretical reasons why NIPPV may be unsuited to exercise in scoliosis patients. Further study with the measurement of respiratory effort, end-tidal CO2, and pulmonary artery pressure would help to clarify this, but there appears to be no role for NIPPV in attempts to enhance exercise capacity in patients with severe scoliosis.


   Footnotes
 
Abbreviations: ANOVA = analysis of variance; IPAP = inspiratory airway pressure; Mv = minute volume; MVV = maximum voluntary ventilation; NIPPV = noninvasive intermittent positive-pressure ventilation; RR = respiratory rate; SpO2 = peripheral oxygen saturation; TI = inspiratory time; TLC = total lung capacity; TTOT = total breathing cycle time; VC = vital capacity; VT = tidal volume

Dr. Highcock was supported in this work by a grant from the British Scoliosis Research Foundation.

Received for publication March 13, 2001. Accepted for publication November 9, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

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