Introduction
The low tidal volume trial of the ARDS Network (the ARMA trial), supported by a long list of preclinical and clinical studies, has unequivocally established that mechanical ventilation with large tidal volumes (VTs) can be injurious to the lungs of patients with acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) [
1]. However, neither ARMA nor subsequent clinical trials resolved questions and controversies about 'best PEEP [positive end-expiratory pressure]' management, about the efficacy of recruitment maneuvers, or about the efficacy of specific modes of ventilation or, most importantly, how to best tailor ventilator mode and settings, including VT, to the needs of individual patients. ARMA established that a VT of 6 mL/kg of predicted body weight (PBW) was safer than one of 12 mL/kg PBW and was associated with a survival benefit. Since the main determinants of PBW and those of the size of the normal lung are the same (namely, height and gender [
2,
3]), the ARMA protocol, in effect, targeted VT to the size of the lung before it was injured. Because it is widely acknowledged that the size of the recruitable lung (Gattinoni's 'baby lung') is decreased in ALI [
4] and because that decrease was undoubtedly nonuniform across ARMA patients, it is probable that, in both trial arms, patients with severe disease were ventilated with VTs that were disproportionately larger than those patients with mild disease. Indeed, this argument was put forth recently by Chiumello and colleagues [
5], who measured the functional residual capacity of the lungs of patients with ALI. The ARMA protocol did provide a mechanism for lowering VT to 4 mL/kg PBW in patients in whom plateau airway pressure (Pplat) would have otherwise exceeded 30 cm H
2O. However, the use of this threshold as a surrogate for severe lung impairment has yet to be validated and is obviously influenced by the choices of PEEP, VT, respiratory muscle activity, and the mechanical properties of the chest wall [
6]. Indeed, esophageal manometry-based estimates of intrathoracic pressure in recumbent patients with ALI or ARDS suggest that the recoil properties of the chest wall may in fact dominate Pplat [
7,
8].
This small observational study on 14 mechanically ventilated patients was motivated by our belief that scaling VT to the size of the injured lung is safer and more 'physiologic' than scaling it to PBW (that is, to its size before it was injured). Considering this premise, we set out to measure the total lung capacity (TLC) of 14 mechanically ventilated patients with respiratory failure and to test whether measuring the volume of gas that enters the lungs during a brief inflation to 40 cm H
2O is sufficient to predict TLC at the bedside. We show that there is a reasonable correlation between the inflation maneuver-derived inspiratory capacity (IC) and the thoracic gas volume (TGV) at relaxed end-expiration (Vrel) and that, in the supine posture, Vrel/TLC is determined in large part by the body mass index (BMI). We also confirm earlier reports that suggested great variability in parenchymal deformation of patients with injured lungs when VT is targeted to PBW as opposed to effective lung size [
5] and address the feasibility and challenges of making IC measurements by means of commercially available mechanical ventilators.
Discussion
The main conclusion from this small observational study is that measuring the IC of intubated patients helps predict effective lung size. Our premise entering this study was that sizing the recruitable lung is important for individualizing patient care. Our research did not test the imperative of this premise. Nevertheless, we find its underlying rationale compelling. It is generally accepted that lungs, particularly when injured, are vulnerable to additional damage by both cyclic recruitment/derecruitment and overinflation. The two injury mechanisms frequently coexist in the same lung. While prevention of the former calls for an increase in parenchymal stress (usually in the form of PEEP), prevention of the latter mandates a stress reduction, which is usually accomplished by limiting Pplat. With increasing lung impairment, the upper and lower volumes and hence stress safety boundaries within which both imperatives may be accomplished approach one another. In other words, the 'safe' inflation pressure amplitude, defined as the difference between optimal PEEP (one that maximizes recruitment) and a 'safe' Plat (one that minimizes the risk of overdistension), approaches zero or may even assume a negative value. Whereas sizing the recruitable lung does not address the choice of best PEEP or mean airway pressure per se, it does provide information about the probability that a chosen VT will encroach on upper or lower lung volume (or both) or stress safety boundaries.
We assumed that the TGV at a transrespiratory system pressure (PRS) of 40 cm H
2O provides a reasonable estimate of the injured lungs' total capacity. In normal humans, TLC is almost completely determined by the size and recoil properties of the lungs because the lungs' compliance near TLC approaches zero whereas that of the chest wall remains finite. As a result, in upright normal humans, the intrathoracic pressure near TLC approximates 10 cm H
2O [
14]. The widely accepted plateau pressure threshold of 30 cm H
2O as a surrogate of stress injury risk is implicitly based on these estimates. It is now apparent that the lungs of many recumbent patients, particularly those with increased BMI or distended abdomens or both, are not fully expanded at a PRS of 30 cm H
2O [
6]. Therefore, we defined TLC as the TGV at a PRS of 40 cm H
2O. It is nevertheless likely that, in patients with extensive alveolar flooding and collapse or with morbid obesity or with both, even a PRS of 40 cm H
2O does not guarantee full lung inflation. The choice of 40 cm H
2O thus represents a compromise between patient safety and biologic certainty.
Our data are entirely in line with observations by Chiumello and colleagues [
5], who emphasized the large between-patient variability in lung strain when VT is scaled to PBW. Since Chiumello and colleagues defined strain as the fractional volume change between Vrel and the lung volume at end-inflation, it may be assumed that patients with the smallest Vrel, those with the largest PBW, and those who were ventilated with high levels of PEEP generated the largest strain estimates. In contrast, TLC and IC were not measured directly or reported, so that lung deformation relative to lung capacity (that is, VT/TLC) cannot be inferred from the data of Chiumello and colleagues [
5]. We favor VT/TLC as a surrogate of the deformation experienced by aerated alveoli. In a normal lung, alveolar size is uniform at TLC, so that regional VT/TLC may be treated as an index of regional alveolar ventilation [
15]. Since in patients with ARDS the mechanical properties of aerated alveoli were found to be relatively normal [
5], our reasoning applies to injured lungs as well.
We set out to measure Vrel and consequently IC at/from a volume at ZEEP. We abandoned this approach after four patients because reducing airway pressure to ZEEP frequently induced coughing, always runs the risk of oxygen desaturation, and was not essential for the objectives of our experiment. While the small sample size precludes a statistical evaluation of this change in experimental design, we are unable to detect the expected bias (lower Vrel/TLC and greater IC when Vrel is measured at ZEEP) in our data. Over 50% of inflations to 40 cm H
2O yielded an acceptable IC estimate, even though we refrained from using neuromuscular blocking agents. Repeat IC estimates (available in 10 of 14 patients) varied by less than 12%, averaging ± 5% for the group. None of our attempts to inflate the thorax to 40 cm H
2O pressure had to be aborted for cardiovascular reasons. Limiting the duration of inflation to 5 seconds undoubtedly enhanced the tolerance of the IC 'recruitment' maneuver. It is of note that, within the limits of our flow detection capabilities (>1 L/minute), a 5-second inflation appeared sufficient to fully expand all recruitable lung units. This observation is in keeping with computer tomography-based estimates of alveolar recruitment of atelectatic lung regions [
12].
While we expected that Vrel and, by inference, IC would serve as surrogates of lung impairment, namely of disease-related loss of lung units, we were surprised how strongly Vrel/TLC correlated with BMI. This observation underscores the importance of chest wall mechanics on lung function of recumbent patients with injured lungs. It is very much in line with recent esophageal manometry-based estimates of chest wall recoil in this population and undermines the rationale for limiting airway inflation pressure and, by inference, PEEP therapy to a singular Pplat value [
8,
16]. On a related note, we note that lung injury had little effect on the expected relationships between Vrel, IC, and TLC. This implies that mass loading of the lung by chest wall and abdomen more or less offsets the anticipated effects of dependent 'lung collapse' on Vrel of aerated units and that the potential for lung recruitment in our small patient sample was modest [
17,
18]. In this context, it should be noted that the elastance of the chest wall in contrast to chest wall recoil pressure may well have been normal. As previously reported in obese volunteers with normal lungs, abdominal distension is expected to cause a rightward shift of the chest wall pressure volume curve without necessarily altering its shape [
19].
Measuring the IC by means of the inherent hardware/software systems of commercially available mechanical ventilators can be challenging. Bench tests of mechanical ventilators used in our practice generally support the manufacturer's stated volume accuracy of ± 10% (data not shown). Compensation algorithms accounting for tubing compliance, gas temperature, and humidity vary greatly among vendors [
13]. Therefore, we caution against an uncritical acceptance of exhaled volume displays when estimating IC or TLC in intubated, mechanically ventilated patients.
Conclusions
We have provided evidence that measuring the volume of gas that enters the lungs during a brief inflation to 40 cm H
2O, when adjusted for body weight/habitus, is sufficient to estimate the capacity of the injured lung at the bedside. We did not and cannot offer an opinion on the critical size of any IC- or TLC-based VT scaling factor nor do we know of specific data on its interactions with mean lung volume or PEEP. Consistent with hypotheses put forth by Chiumello and colleagues [
5], we believe that many prior studies on the topic of ventilator-associated lung injury, including those dealing with best PEEP, were confounded by variability in VT/TLC and related lung injury mechanisms. Eliminating this variability in future studies might be a step forward.
The dependence of Vrel on BMI, which we have observed, indirectly supports the esophageal manometry-based conclusions of Talmor and colleagues [
8] and those of Loring and Weiss [
16] and thereby undermines reliance on a uniform plateau pressure target. While keeping Pplat below 30 cm H
2O remains a reasonable initial care goal, we draw attention to the importance of BMI as a determinant of Vrel/TLC and will be less hesitant to exceed this threshold in patients with abdominal distension, but preserved TLC. Alternatively, we are likely to reduce VT to less than 6 mL/kg PBW long before Pplat reaches 30 cm H
2O in nonobese patients with small effective lung capacities. Needless to say, validation of these approaches will require preclinical and clinical efficacy trials.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
JSM and SRH screened and identified patients, obtained informed written consent, carried out all bedside measurements, and contributed to the data analysis. RAO contributed to study design and participated in study conduct and data analysis. RWS and CFB participated in study conduct and, together with SRH, were responsible for validating methods and approach at the bench. RDH conceived the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.