To our knowledge, this is the first study to analyze inspiratory PV curves in mechanically ventilated patients with IPF, revealing a sigmoidal shape and the presence of a region of low compliance of the respiratory system at low airway pressures. Despite technical aspects of our study (muscle paralysis and a supine position) that may have interfered with the mechanical behavior of the respiratory system and impacted the shape of the PV curve, the controls had a much less pronounced sigmoidal shape in their PV curves than did the IPF patients.
The lower (LIP) and upper (UIP) inflection points were statiscally higher in the patients than in controls receiving the same level of deep sedation and muscle paralysis and briefly ventilated before the performance of the pressure-volume curve under the same ventilatory conditions: volume control ventilation using low FIO2
(0.3-0.4) and moderate PEEP (5 cm H2
O). The LIP has been used to titrate PEEP during mechanical ventilation in ARDS30
, but more recent studies have suggested that the LIP is not the pressure at which maximal recruitment is achieved and that it may not be the best guide to setting appropriate PEEP in ARDS.14,15,19
Using parameters from the sigmoidal fit could be an alternative. The sigmoidal equation had a good fit to the PV curves of these patients in our study, who had been recently diagnosed with IPF. Parameters a, b, c
are physiologically meaningful and may be useful for guiding mechanical ventilation, which is particularly challenging in IPF since patients ventilated for acute exacerbations have poor outcomes,7-11
and patients who undergo an open lung biopsy are at increased risk of complications.12
estimates how close the lung volume at EELV is to the residual volume. Patients with smaller absolute a
had higher LIP, although the correlation did not reach significance (p
0.064). Parameter b
is analogous to vital capacity and could be useful for assessing disease severity in intubated patients in whom standard maneuvers to measure vital capacity cannot be performed. Parameters c
characterize the shape of the curve, information that is not available from standard tests. Parameter c
can be particularly useful during mechanical ventilation because it represents the pressure at which maximal respiratory system compliance is reached. This information could guide the titration of PEEP and inspiratory pressure to generate a mean airway pressure close to c
, thereby minimizing both airway and alveolar collapse and hyperinflation. Parameter d
estimates the dispersion of the critical opening and hyperinflation pressures for a given patient. Small absolute values indicate that major volume changes occur when the airway pressure is close to c
, suggesting avalanche recruiting as the critical opening pressure is achieved. Large values of d
suggest that the patient has a heterogeneous distribution of critical opening pressures. These parameters may be useful to guide a protective ventilatory strategy using small tidal volumes to avoid high plateau pressures, similarly to what is recommended for ARDS,30,31
and titrating PEEP to move tidal ventilation to the central, linear part of the curve,32,33
but more study is required before specific guidance can be provided.
The sigmoidal equation had a good fit to the PV curves from the controls; however, unlike the patients, all the controls had LIPs between 0 and 6 cm H2O and Pmci values lower than 2 cm H2O. Although a sigmoidal shape was evident, it was less pronounced than in the IPF patients, and a linear pressure-volume relationship is evident at pressures commonly used for mechanical ventilation.
Interestingly, although the LIP and Pmci were consistently low in the controls, for the patients with IPF, the PV curve could either have a linear initial portion, with a low LIP and Pmci, or have a more pronounced sigmoidal shape, with a higher LIP and Pmci. Individual analyses of the PV curve using the sigmoidal fit could help identify each pattern and titrate mechanical ventilation accordingly.
Previous investigators have fit an exponential equation to the deflation PV curves of the lungs of spontaneously breathing patients with fibrotic lung diseases.16-18
However, most of the curves had few points at low lung volumes, close to FRC, where the slope of the curve decreases. By excluding points below 50% of the TLC, researchers were able to fit deflation PV curves from patients with pulmonary fibrosis using an exponential equation; they concluded that this method generated a good fit and that parameter k
was useful for characterizing changes in lung mechanics16
and the degree of fibrosis.17
Although this exponential model has been shown to be clinically useful when applied to the deflation limb of the PV curve of spontaneously breathing patients, our results indicate that a sigmoidal model is superior when an inflation PV curve is captured in anesthetized patients and may also be useful for guiding mechanical ventilation.
The finding of a region of low compliance at low lung volumes suggests that small airway and alveolar collapse may be present in IPF patients during mechanical ventilation and general anesthesia, which could be a result of small airways dysfunction. Small airways compromise in early IPF has been previously reported,34-36
but most of the studies of IPF focus on the alveoli, not the airways.5
Recently, Mello and coworkers37
used lung tissues from diagnostic biopsies to show morphological abnormalities in the airways of patients with IPF and overexpression of matrix metalloproteinase (MMP)-7 and MMP-9, suggesting that bronchiolar epithelial cells could contribute to local remodeling of the peribronchial interstitial lung tissue and promote fibrotic activity. Further studies may be warranted to evaluate small airway dysfunction in patients with IPF.37,38
The primary limitation of this study is the number of patients studied. However, despite the small number of patients and the early stage of their disease, a sigmoidal shape of the PV curve was noted in all the patients, and it was more pronounced than in the controls. Our control patients had myasthenia gravis, which is associated with chest wall abnormalities that could impact the shape of a pressure volume curve. This impact, however, would be expected for spontaneously breathing patients who were not under general anesthesia or muscle paralysis. To minimize any concerns about the contribution of the chest wall to the shape of the pressure-volume curve, we used esophageal catheters to monitor chest wall activity during curve recording and found that it was always absent. The controls were younger and had smaller body mass indexes than the patients, a finding that should be kept in mind when interpreting our results.
We studied inflation PV curves of the total respiratory system, which is in contrast to the deflation PV curves of the lung used in previous studies,16,17
a difference that should be considered when comparing results. We used the inflation PV curve because it usually has more points at low lung volumes than does the deflation curve. Total respiratory system PV curves were used instead of lung PV curves because the signal from the esophageal balloon was damped in some cases and because information on the respiratory system as a whole is more commonly used at the bedside to guide mechanical ventilation, given that it does not require an esophageal balloon. In all cases, patient respiratory effort was absent, none of the patients had chest wall abnormalities, and the shapes of the PV curves using airway pressure and transpulmonary pressure were similar (see supplementary material). The PV curves were performed with patients in the supine position while under anesthesia with muscle paralysis, a condition that has been associated with a reduction in the FRC and lung collapse in healthy subjects.39
However, the occurrence of lung collapse during anesthesia is related to mechanical ventilation without PEEP and with a high FIO2
. The use of a recruitment maneuver has been shown to completely reverse anesthesia-induced collapse in supine anesthetized patients, and an FIO2
≤0.4 prevents its recurrence.40
Our patients were ventilated with FIO2
values between 0.3 and 0.4 and PEEPs of 5 cm H2
O, and a recruitment maneuver was performed immediately before the PV curves. The controls received the same ventilatory strategy and did not demonstrate as pronounced a sigmoidal shape in their PV curves.
In conclusion, our results show that a sigmoidal equation is superior to an exponential equation for fitting inflation PV curves of the respiratory system from IPF patients under general anesthesia. The PV curve's sigmoidal shape reveals, for the first time, that total respiratory system compliance is decreased at low lung volumes during general anesthesia and mechanical ventilation in patients with IPF, a characteristic that should be considered for adjustment of mechanical ventilator settings.