Hypoventilation is defined as ventilation below that which is needed to maintain adequate gas exchange. It can be a feature in lung diseases as diverse as chronic bronchitis and pulmonary fibrosis but determining whether it is present of not is often complicated by defects in gas exchange. When desaturation occurs during a CPET (i.e. a significant decrease in SaO2 below 95%) this is a strong indication that the primary exercise limitation is pulmonary in nature and from that point the maximum minute ventilation and the Ve-VCO2 slope can show whether the limitation is ventilatory or instead due to a gas exchange defect. But in this circumstance what what does it mean when both the maximum minute ventilation and Ve-VCO2 slope are normal?
Recently a CPET came across my desk for an individual with chronic SOB. The individual recently had a full panel of pulmonary function tests:
| Observed: | %Predicted: | |
| FVC (L): | 1.73 | 62% |
| FEV1 (L): | 1.39 | 66% |
| FEV1/FVC: | 80 | 106% |
| TLC (L): | 2.99 | 62% |
| DLCO (ml/min/mmHg): | 14.66 | 84% |
| DL/VA: | 5.45 | 124% |
| MIP (cm H2O): | 11.5 | 18% |
| MEP(cm H2O): | 21.3 | 24% |
The reduced TLC showed a mild restrictive defect. At the same time the relatively normal DLCO indicates that the restriction is probably not due to interstitial lung disease and more likely either a chest wall or a neuromuscular disorder, both of which can prevent the thorax from expanding completely but where the lung tissue remains normal. The reduced MIP and MEP tends to suggest that a neuromuscular disorder is the more likely of the two.
I take this with a grain of salt however, and that is because this individual never had pulmonary function tests before and for this reason there is no way to know what their baseline DLCO was prior to the restriction. At the same time far too many individuals perform the MIP/MEP test poorly and low results are not definitive, and in this case in particular the results are so low the individual should have been in the ER, not the PFT Lab.
The CPET results were somewhat complicated, in that a close inspection showed both pulmonary and cardiovascular limitations.
| Rest: | %Predicted: | AT: | %Predicted: | Maximum: | %Predicted: | |
| VO2 (LPM): | 0.26 | 24% | 0.49 | 44% | 0.54 | 48% |
| VCO2 (LPM): | 0.21 | 0.43 | 0.65 | |||
| RER: | 0.84 | 0.87 | 1.27 | |||
| SpO2 (%) | 97% | 94% | 92% | |||
| PetCO2 (mm Hg): | 41.2 | 46.5 | 53.4 | |||
| Ve/VCO2: | 49 | 39 | 30 | |||
| Ve (LPM): | 9.7 | 16% | 15.7 | 28% | 18.2 | 31% |
| Vt (L): | 0.37 | 0.46 | 0.48 | |||
| RR (f): | 27 | 36 | 39 | |||
| Heart Rate (BPM: | 72 | 48% | 86 | 58% | 89 | 60% |
| BP (mm Hg) | 156/78 | 162/82 | 170/84 | |||
| O2 Pulse (ml/beat) | 3.6 | 48% | 6.0 | 79% | 6.2 | 80% |
In addition, the chronotropic index was 0.68 (normal 0.80 to 1.30), the Ve-VCO2 slope from rest to AT was 14.5 and the Ve-VCO2 slope from rest to peak exercise was 16.4. Although the maximum minute ventilation and maximum heart rate are well below their ULN of 85% of predicted, the RER of 1.27 at peak exercise indicates that there was an adequate exercise test effort.
That there is a cardiovascular limitation is indicated first by the reduced VO2 at anaerobic threshold. The LLN for this individual based on their age and gender was 54% so the observed value of 44% is well below normal. This shows that there was an oxygen delivery problem and this is usually related to a decrease in cardiac output. In addition, the chronotropic index is also reduced and since the individual is taking metoprolol, a beta blocker, this is not a major surprise. Together these factors could indicate that the individual’s primary exercise limitation was cardiovascular but the reduced SaO2 at maximum exercise indicates that the primary limitation has to be pulmonary.
But even though the individual has a restrictive ventilatory defect the maximum minute ventilation is well below the ULN of 85% so there was a large ventilatory reserve at peak exercise. Moreover, the ULN for the Ve-VCO2 slope from rest to AT is 34 and for the Ve-VCO2 slope from rest to peak exercise it is 40. The respective Ve-VCO2 slope values of 14.5 and 16.4 are well below this ULN and this (as well as the normal DLCO) is a strong indication that gas exchange was normal. So why is did this individual desaturate?
There are two strong clues. First, PetCO2 was elevated, both somewhat at rest and most distinctly at peak exercise. A normal resting PetCO2 is usually between 30 and 35 and at peak exercise between 35 and 45.
Note: A maximum PetCO2 above 40 is usually seen only in subjects with above average fitness and usually only at higher levels of exercise. PetCO2 can become elevated because an increased cardiac output decreases pulmonary capillary transit time and end-expiratory alveolar air therefore begins to reflect the venous PCO2. In these instances however, even though the PetCO2 is elevated, arterial PCO2 is usually normal and less than PetCO2.
In this case a resting PetCO2 of 41 is a touch high but not necessarily abnormal, but the pattern during exercise was. A normal PetCO2 pattern is a peak near AT (usually slightly after) and then a decline thereafter. For this individual however, PetCO2 actually increased throughout exercise. In addition the maximum PetCO2 of 53.4 is well above any normal.
Second, the Ve-VCO2 slopes, although technically within normal limits, are actually much too low. A normal Ve-VCO2 slope from rest to AT should have been around 29 for this individual.
Note: Ve/VCO2 is the relationship between minute ventilation and CO2 production at any one instant whereas the Ve-VCO2 slope is the relationship between the change in minute ventilation and the change in CO2 production over time. Traditionally the Ve/VCO2 at AT has been used to assess ventilatory efficiency and in this case the Ve/VCO2 of 39 at AT is elevated (ULN is 35). However, it has been pointed out that AT is where the nadir of Ve/VO2 occurs, not Ve/VCO2, and that because the AT is in this sense an arbitrary point at which to assess Ve/VCO2 the lowest observed Ve/VCO2 is a better indicator of of ventilatory efficiency. The lowest observed Ve/VCO2 for this individual is 30 and WNL.
In addition, it has been shown that the Ve/VCO2 at AT is a function of the Ve-VCO2 slope from rest to AT and it’s offset (i.e. , what Ve would be if VCO2 was zero). The offset of the Ve-VCO2 is different between individuals and disease states for reasons that remain unclear. Because of all this, and given that the Ve-VCO2 slope is generated from a relatively large number of data points, it’s my opinion that the Ve-VCO2 slope from rest to AT is a more reliable indicator of ventilatory efficiency than Ve/VCO2.
The Ve-VCO2 slopes of 14.5 and 16.4 are abnormally low and indicate little change in minute ventilation when compared to the change in VCO2 and given the large ventilatory reserves at peak exercise there is no apparent reason for this.
Finally, in addition there is one minor additional point and that is that there was only a small increase in tidal volume during exercise. Tidal volume normally doubles or triples during exercise and a low increase in tidal volume along with all the other factors:
- Mild restriction with a relatively preserved DLCO
- Reduced MIP and MEP
- Elevated PetCO2
- Reduced Ve-VCO2 slope
- Elevated ventilatory reserve
is a strong suggestion that the individual in question is hypoventilating due to respiratory muscle weakness. Their exercise limitation may be exacerbated by their chronotropic incompetence, but the primary limitation is still hypoventilation. There are a variety of possible causes for this weakness but the individual was referred to my lab by a physician outside the hospital network and for this reason there is no history available for review (and unfortunately any follow up will probably also occur outside the hospital network so I may never find out what the cause was).
It is moderately unusual to find hypoventilation by itself, without any gas exchange defect, as a primary exercise limitation. Hypoventilation can be a factor in both COPD and interstitial diseases, but in these cases there is usually a mix of both ventilatory and gas exchange limitations. The primary difference between those cases and the present one, and which showed a lack of underlying lung disease, was the Ve-VCO2 slope and PetCO2. Given that there was no ventilatory or gas exchange limitations, the only reasonable cause can be hypoventilation.
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