American Journal of Respiratory and Critical Care Medicine

Rationale: Response to positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome depends on recruitability. We propose a bedside approach to estimate recruitability accounting for the presence of complete airway closure.

Objectives: To validate a single-breath method for measuring recruited volume and test whether it differentiates patients with different responses to PEEP.

Methods: Patients with acute respiratory distress syndrome were ventilated at 15 and 5 cm H2O of PEEP. Multiple pressure–volume curves were compared with a single-breath technique. Abruptly releasing PEEP (from 15 to 5 cm H2O) increases expired volume: the difference between this volume and the volume predicted by compliance at low PEEP (or above airway opening pressure) estimated the recruited volume by PEEP. This recruited volume divided by the effective pressure change gave the compliance of the recruited lung; the ratio of this compliance to the compliance at low PEEP gave the recruitment-to-inflation ratio. Response to PEEP was compared between high and low recruiters based on this ratio.

Measurements and Main Results: Forty-five patients were enrolled. Four patients had airway closure higher than high PEEP, and thus recruitment could not be assessed. In others, recruited volume measured by the experimental and the reference methods were strongly correlated (R2 = 0.798; P < 0.0001) with small bias (−21 ml). The recruitment-to-inflation ratio (median, 0.5; range, 0–2.0) correlated with both oxygenation at low PEEP and the oxygenation response; at PEEP 15, high recruiters had better oxygenation (P = 0.004), whereas low recruiters experienced lower systolic arterial pressure (P = 0.008).

Conclusions: A single-breath method quantifies recruited volume. The recruitment-to-inflation ratio might help to characterize lung recruitability at the bedside.

Clinical trial registered with (NCT02457741).

Scientific Knowledge on the Subject

In acute respiratory distress syndrome, the effect of positive end-expiratory pressure (PEEP) depends on the amount of nonaerated and poorly aerated lung tissue that can be reopened or recruited. There is no simple accessible and reliable method to assess recruitability at the bedside.

What This Study Adds to the Field

Using a drop in PEEP over a single-breath maneuver, one can measure the recruited volume over a given range of PEEP. Taking into account the possible presence of airway closure and, therefore, of the effective change in pressure permits one to calculate the compliance of the recruited lung; the latter is compared to the baby lung compliance using the recruitment-to-inflation ratio, which helps to differentiate recruiters and nonrecruiters.

Since the first description of the acute respiratory distress syndrome (ARDS), positive end-expiratory pressure (PEEP) has remained an essential component of its management (1). The rationale of using PEEP is to keep airways and alveoli open. The response to positive pressure, however, varies enormously among patients (2). Increasing PEEP may improve or worsen gas exchange (3, 4), depending on the corresponding reaeration of nonaerated and poorly aerated lung tissue, also defined as lung recruitability (2, 5, 6), and alterations in intrapulmonary and intracardiac shunt (7, 8). Although improved oxygenation can be explained by lung recruitment (9, 10), the relationship between oxygenation and recruitment is often weak owing to the complex circulatory effects of PEEP (7, 8). Application of excessive PEEP in the absence of recruitability can lead to lung overdistension, cardiac dysfunction, and a reduction in oxygen delivery to tissues (2, 11). In lowly recruitable lungs, higher PEEP may provide only minimal benefit or cause harm by increasing strain (12). In highly recruitable lungs, higher PEEP may increase the size of the aerated lung and reduce alveolar strain, and also reduce the cyclic closing-reopening of alveoli and small airways during tidal breaths (“atelectrauma”) (13). Knowing whether PEEP has an effect on lung recruitment is thus fundamental.

Until now, clinicians have had no reliable and easily accessible tool to assess lung recruitment at the bedside. Computed tomography (CT) has been used in research but is infeasible in clinical practice, not the least because of risks of transport (2, 5, 14). The measurements require repeated CT examinations at different pressures, the analysis is time-consuming, and also the definition of lung recruitment by CT is controversial (15, 16). Other morphological approaches, such as ultrasound and electrical impedance tomography, seem to be promising but require specific equipment and validation with other established methods. Alternatively, the multiple pressure–volume (P–V) curves technique is based on a “hysteresis-like” behavior of the lung and has been proposed to assess recruitment. Although this technique does not require patient transport, it is still relatively complex owing to the need for merging two or more P–V curves starting from different lung volumes. Setting PEEP based on tidal compliance has been shown to be unreliable (17). Randomized clinical trials comparing different levels of PEEP did not determine the potential for lung recruitment (1821) and patients having different responses to PEEP could not be stratified or phenotyped in subgroup analyses. The inconsistent results from these trials and the likelihood of heterogeneity of treatment effect raise an urgent need for developing a reliable and valid bedside tool to assess lung recruitability.

We propose to validate a simplified single-breath method to quantitate lung recruitment at the bedside that does not require any specialized equipment. We propose the concept of the compliance of the recruited lung (Crec) as the recruited volume divided by the effective change in pressure accounting for patients with complete airway closure, as recently described (2224). We propose a new approach to define lung recruitability by measuring the ratio of the Crec to the compliance of the “baby lung.” We hypothesized that our new definition of lung recruitability would reliably differentiate patients with different response to PEEP in terms of gas exchange, lung mechanics, and hemodynamics.


This was a prospective clinical study ( NCT02457741) conducted in two quaternary academic ICUs at St. Michael’s Hospital and Toronto General Hospital (Toronto, Canada), with approval by the relevant institutional research ethics boards. Informed consent was obtained from each patient or their legal substitute decision-maker before onset of any study procedures.


All mechanically ventilated patients in the ICUs were screened Monday to Friday. Inclusion criteria were 1) age older than 16 years, 2) presence of moderate or severe ARDS (PaO2/FiO2 ≤200 mm Hg) (25) and within 10 days of onset, 3) assist/control mechanical ventilation with continuous sedation, and 4) an arterial line in place. Exclusion criteria were 1) undrained pneumothorax or ongoing air leak, 2) hemodynamic instability (>30% increase in vasopressors in the last 6 h or norepinephrine >0.5 μg/kg/min), 3) PaO2/FiO2 <80 mm Hg, 4) severe or very severe chronic obstructive pulmonary disease according to the Global Initiative for Chronic Obstructive Lung Disease criteria (26), and 5) clinically suspected elevated intracranial pressure (>18 mm Hg).


During the study, all patients were ventilated with a dedicated ventilator (Engstrom Carestation; General Electric). Airway pressure (Paw), flow, carbon dioxide (CO2), and oxygen concentrations were measured by flowmeters (D-Lite; GE) integrated in the ventilator. If an esophageal balloon catheter was already available (4), esophageal pressure (Pes) was measured by connecting the catheter with the auxiliary pressure transducer on the ventilator and was validated by performing an occlusion test (27). Pressure and flow transducers were calibrated (error < 4%) before the measurements. Potential gas leak was carefully excluded before and after connecting the ventilator (see online supplement).

Changes in lung volume, such as Vt and change in end-expiratory lung volume between two PEEP levels (∆EELV) were measured with the flowmeter (i.e., the integral of flow); for example, ∆EELV was measured by comparing the difference in expiratory Vt when reducing PEEP from high PEEP (PEEPhigh) to low PEEP (PEEPlow) over a 9-second expiration (see Single-breath experimental method). Similarly, we measured ∆EELV when reducing PEEPlow to zero end-expiratory pressure. In addition, we measured the absolute end-expiratory lung volume using the nitrogen wash-out/in technique integrated on the ventilator (28).

An elastic P–V curve was obtained by performing a low-flow (5 L/min) inflation, ensuring that the resistive pressure was negligible (29).

Assessment of Recruitment
The multiple P–V curve method: reference method

The multiple P–V curve was the reference method to assess lung recruitment. This method was first proposed to interpret the hysteresis-like behavior of the respiratory system (30) and then used to detect lung recruitment (9, 31). The rationale is to detect a difference in lung volume for a given elastic pressure between two P–V curves starting from two PEEP levels. If the ventilated, open, lung units are the same (no recruitment) after a higher PEEP, the lung volume at a given elastic pressure should remain unchanged. If the higher PEEP applied for several minutes results in improved respiratory mechanics due to recruitment (i.e., increased number of aerated lung units), an upward volume shift on P–V curves is observed, the difference between the two volumes at a given pressure indicating recruited volume.

We measured two elastic P–V curves traced along the Vt and starting from PEEPhigh and PEEPlow. We plotted these two curves starting from different end-expiratory lung volumes on the same graph. To do this, we measured the ∆EELV between PEEPhigh and PEEPlow (Figures 1 and 2]) with a single prolonged expiration, as explained above. The figures started from zero end-expiratory pressure and its corresponding volume, the FRC. The recruited volume (∆Vrec) was calculated as the amount of upward shift in volume between two P–V curves at a same pressure (PEEPhigh).

Of note, to simplify the terminology and although we went down from PEEPhigh to PEEPlow, we do not use the term “derecruitment” (9).

Complete airway closure: a confounder

∆Vrec assessed lung recruitability over a certain range of PEEP. We needed first to identify if complete airway closure, a confounder for measurement of alveolar pressure, was present (22). During an interim analysis of this study, we found that 8 out of 30 patients had complete airway closure (22). Their lungs required an airway opening pressure (AOP) between 5 and 20 cm H2O to reopen airways before initiating lung inflation. In such cases, the airways are not communicating with the alveoli below the AOP, until the airways reopen. The real change in alveolar pressure can therefore be remarkably different from the change in Paw (32). When AOP was higher than PEEP, we considered the AOP to be the nearest measurable alveolar pressure. Depending on AOP, the same change in alveolar pressure could not be applied to all patients. For assessing lung recruitment reliably, we thus indexed ∆Vrec by the effective pressure change.


We defined the Crec as the ∆Vrec divided by the effective change in pressure over which recruitment is assessed (∆Prec):

In patients without complete airway closure at PEEPlow, ∆Prec is the difference between PEEPhigh and PEEPlow:
In patients with complete airway closure and an AOP greater than the PEEPlow, ∆Prec is then the difference between PEEPhigh and AOP:
We explain this concept in Figures 1 and 2 using two representative patients without and with airway closure, respectively. Crec is essentially an indexed ∆Vrec. This denomination represents how much volume can be regained from the recruitable lung by each centimeter of water of pressure increment. Crec allowed us to compare ∆Vrec measured in patients with or without airway closure.

Recruitment-to-inflation ratio

Conceptually, Crec can be integrated in a three-compartment model of the ARDS lung, with a nonrecruitable part, a recruitable part, and the baby lung. The term “baby lung” is used to describe the lung tissue that remains aerated at PEEPlow or at FRC. A recruitable part refers to the lung tissue that can be recruited over a clinically acceptable range of PEEP. An analogy of this model is three serially connected springs with different stiffness. By comparing Crec with the compliance of the baby lung, one might predict the likelihood of the distribution of volume between the recruited lung (recruitment) and the baby lung (inflation/hyperinflation). The respiratory system compliance (Crs) at PEEPlow or above AOP (depending on the presence of airway closure; see below) can be used as a surrogate for the compliance of the baby lung. The ratio of Crec to the compliance of the baby lung was called the recruitment-to-inflation ratio (R/I ratio):

RI ratio=CrecCrs at PEEPlow or above AOP.
The higher the R/I ratio is, the higher the potential for lung recruitment is. For example, an R/I ratio of 1.0 indicates that the likelihood of recruitment (volume distributed in the recruited lung) is the same as inflation/hyperinflation (volume distributed in the already aerated baby lung). Note, however, that hyperinflation can coexist with recruitment.

Single-breath experimental method

Our simplified method mainly requires a single-breath PEEP reduction. It has a similar rationale as the multiple P–V curve method but does not require complex offline analysis and can be performed without additional equipment. The ∆EELV is measured by the flowmeter during a PEEP reduction maneuver using the expired Vt (Figure E2 in the online supplement). In parallel, the predicted ∆EELV in the absence of PEEP-induced recruitment can be calculated under the assumption of a linear recoil process of the respiratory system without any change in aerated lung units. The difference between the measured ∆EELV and the predicted one is the recruitment caused or maintained by higher PEEP:

Vrec=measured EELVpredicted EELV.

In patients without airway closure, the predicted ∆EELV is the product of the Crs at PEEPlow and the change in PEEP (4):

Predicted ΔEELV=VT(Pplat at PEEPlow)PEEPlow×(PEEPhighPEEPlow),
where Pplat is plateau pressure. In patients with airway closure, we measured the Crs above AOP when lungs were “effectively” ventilated:
Predicted ΔEELV=VT(Pplat at PEEPlow)AOP×(PEEPhighAOP).
AOP can be identified by either a P–V curve or by a pressure–time curve on the ventilator at low flow (see Figure E4). Crec can then be calculated as the quotient of ∆Vrec and ∆Prec. We previously showed the feasibility of assessing ∆Vrec (4). Finally, the R/I ratio is calculated by normalizing the Crec to the Crs at PEEPlow or above AOP. We provide a Web page including videos to demonstrate the measurements in patients with or without airway closure, and to perform the calculations (


A detailed protocol and a flow chart (see Figure E1) are provided in the online supplement. Briefly, all patients were passively ventilated (no spontaneous effort) in a standardized volume control mode (4). After a baseline assessment at a PEEP preset by clinicians, we used the following steps: 1) PEEPhigh, being 15 to 18 cm H2O; 2) PEEPlow, being 5 to 8 cm H2O; and 3) PEEPhigh. The difference between PEEPhigh and PEEPlow was 10 cm H2O but the exact level of PEEP was adjusted slightly to allow better clinical tolerance. Each step lasted 30 minutes. At each step, the following order was used: arterial blood gases at 10 minutes after initiation of the PEEP level, end-expiratory and end-inspiratory occlusions, absolute lung volume, and low-flow inflation. FiO2 was planned to be kept unchanged during the study but some patients required increased FiO2 at PEEPlow (oxygen saturation as measured by pulse oximetry [SpO2] < 88%). Because PaO2/FiO2 usually changes with FiO2 (33), SpO2 at the same FiO2 was also used for comparisons.

Signal analysis

We recorded real-time ventilator signals (Paw, flow, Pes, CO2, and oxygen) by connecting the ventilator to a computer. Recordings were processed and analyzed automatically by a customized program in MATLAB (Mathworks). Auto-PEEP was measured by performing end-expiratory hold. All other parameters of respiratory mechanics, such as airway Pplat, and Pes at the end of inspiration (using a brief set end-inspiratory pause) and at the end-expiration, were measured by a 40-breath ensemble averaging process (see Figure E3) (34, 35). This allowed cancelling out the cardiac artifacts, particularly in the Pes signal. The alveolar dead space fraction was calculated by (PaCO2 − PetCO2)/PaCO2, where PetCO2 is the partial pressure of end-tidal CO2. An average of PetCO2 during 40 consecutive breaths was used for each patient. The AOP was identified as previously described (22).

Endpoints and statistical analysis

The primary endpoints were the correlation and agreement in measuring ∆Vrec between our experimental method and the reference method. The correlation was assessed by simple linear regression. Bias and limits of agreement were compared by Bland-Altman analysis (36). We separated patients as low-recruiters and high-recruiters using the median of the R/I ratio measured by our experimental method and compared the response to PEEP within group by the paired t test. In particular, we compared tidal respiratory system compliance and lung compliance to see how they would be changed by altering PEEP. Statistical analyses were conducted in R version 3.5.1 (37).

Forty-five consecutively identified patients were enrolled into this study. Their characteristics are reported in Table 1.

Table 1. Characteristics of the Patients

CharacteristicsOverall (N = 45)Non–Airway Closure (n = 30)Airway Closure (All, n = 15)Airway Closure and AOP > PEEPhigh (n = 4)
Sex, M, n (%)36 (80.0)24 (80.0)12 (80.0)3 (75.5)
Age, yr58 ± 1660 ± 1755 ± 1448 ± 11
Height, cm171 ± 16174 ± 13165 ± 20154 ± 31
Body mass index, kg/m233 (27–39)31 (26–39)36 (30–40)35 (30–37)
COPD/asthma/smoking history, n (%)15 (33.3)9 (30.0)6 (40.0)0 (0.0)
APACHE II at admission25 ± 926 ± 824 ± 1023 ± 12
ICU stay before enrollment, d4 (2–8)4 (2–9)6 (3–8)9 (8–10)
Total fluid balance from admission, L7.3 (3.7–14.2)7.3 (3.4–12.7)8.9 (4.7–16.2)15.6 (12.0–19.0)
SOFA at the day of enrollment13 ± 313 ± 413 ± 312 ± 2
Clinical PEEP at enrollment, cm H2O15 (12–16)14 (12–16)16 (15–17)15 (14–16)
PaO2/FiO2 at clinical PEEP, mm Hg145 (105–168)151 (106–170)120 (104–149)115 (106–126)
V˙e,corr, L/min12.2 (10.2–14.0)12.3 (10.5–14.4)12.0 (9.7–13.2)11.0 (8.0–14.3)
Estimated shunt at high PEEP*, %39 (29–45)36 (27–45)41 (34–48)41 (39–44)
Risk factors of ARDS, n (%)    
 Pneumonia15 (33.3)10 (33.3)5 (33.3)2 (50.0)
 Aspiration7 (15.6)3 (10.0)4 (26.7)1 (25.0)
 Extrapulmonary sepsis8 (17.8)8 (26.7)0 (0.0)0 (0.0)
 Trauma2 (4.4)1 (3.3)1 (6.6)0 (0.0)
 Other13 (28.9)8 (26.7)5 (33.3)1 (25.0)
Severity of ARDS, n (%)    
 Moderate36 (80.0)25 (83.3)11 (73.3)3 (75.0)
 Severe9 (20.0)5 (16.7)4 (26.7)1 (25.0)
ICU mortality, n (%)18 (40.0)14 (46.7)4 (26.7)1 (25.0)

Definition of abbreviations: AOP = airway opening pressure; APACHE II = Acute Physiology and Chronic Health Evaluation II score; ARDS = acute respiratory distress syndrome; COPD = chronic obstructive pulmonary disease; PEEP = positive end-expiratory pressure; SOFA = Sepsis-related Organ Failure Assessment; V˙e,corr = expired volume per minute corrected by arterial carbon dioxide.

Dichotomous or nominal categorical variables are described as number (percentage); continuous variables are described as mean ± SD or median (interquartile range), as appropriate. V˙e,corr was calculated using the method described in Reference 25.

*Intrapulmonary shunt was estimated by using the PaO2 when FiO2 was set at 1.0, proposed by Reske and colleagues (48). We performed this measurement at the end of the study at the high PEEP level to avoid alternation in FiO2 during other measurements.

Airway Closure

One-third (n = 15) of the 45 patients presented with complete airway closure with AOP ranging from 5 to 20 cm H2O (see characteristics in Table 1). All patients with airway closure displayed auto-PEEP during regular tidal breath at PEEPlow. The level of auto-PEEP was always lower than the AOP and could be “eliminated” after prolonged expiration (see Figures E4 and E5). Pes was measured in 13 of the 15 patients with airway closure (87%), allowing us to calculate transpulmonary pressure. At AOP, transpulmonary pressure ranged from −9 to 3 cm H2O. Four patients had AOP greater than PEEPhigh. In these four patients, no analysis of recruitability could be performed because PEEPhigh was insufficient to keep the airways open at end-expiration. We report their characteristics in Table 1.

ΔVrec by Experimental versus Reference Method

In 41 patients with or without airway closure, ∆Vrec values measured with the experimental and the reference methods were strongly correlated (R2 = 0.798; P < 0.0001) (Figure 3A). The bias was −21 ml with limits of agreement from −119 to 76 ml (see Figure 3B).

Crec to Index ΔVrec and R/I Ratio to Normalize Crec

Figures 1 and 2 show ∆Vrec and Crec in two patients. Both have a low ∆Vrec (143 and 191 ml) compared with the median level of the cohort (228 ml). One (see Figure 2) had complete airway closure and the effective change in pressure was only about 3 cm H2O. The calculated Crec were remarkably different (14 vs. 60 ml/cm H2O), as well as the R/I ratio (0.37 vs. 1.67).

R/I Ratio to Define Lung Recruitability

The median value of the R/I ratio measured by our experimental method in all 41 analyzed patients was 0.5, ranging from 0 to 2.0. We dichotomized the R/I ratio by using the median to define lung recruitability: high recruiters were defined by an R/I ratio greater than or equal to 0.5 and low recruiters were defined by an R/I ratio less than 0.5 (see grouped characteristics in Table E1). Average R/I ratios were 0.90 ± 0.39 in high recruiters and 0.30 ± 0.15 in low recruiters (see Table E2 for ∆Vrec and Crec). We compared their response to PEEP (Table 2). At PEEPhigh, only high recruiters had a significant oxygenation response, whereas only low recruiters had a lower systolic arterial pressure. Tidal Crs [Vt/(Pplat − total PEEP)] and tidal lung compliance (Vt/lung driving pressure) were higher at PEEPlow in both groups.

Table 2. Response to Postive End-Expiratory Pressure in High Recruiters (Recruitment-to-Inflation Ratio ≥ 0.5) and Low Recruiters (Recruitment-to-Inflation Ratio < 0.5)

 High Recruiters (n = 21*)Low Recruiters (n = 20)
 High PEEPLow PEEPP ValueHigh PEEPLow PEEPP Value
PEEP, cm H2O16 ± 16 ± 116 ± 16 ± 1
Gas exchange      
 SpO2 at fixed FiO2, %95 ± 293 ± 40.00296 ± 395 ± 40.340
  FiO2 where ABG was measured0.69 ± 0.210.73 ± 0.210.1150.56 ± 0.100.56 ± 0.100.330
  PaO2/FiO2, mm Hg132 ± 52111 ± 510.004181 ± 62178 ± 600.853
 Vd,alv/Vt, %33 ± 1035 ± 110.10921 ± 921 ± 90.616
 Absolute EELV, ml1,765 ± 5561,103 ± 416<0.0011,922 ± 7731,341 ± 593<0.001
 Pl,end-exp, cm H2O0 ± 3−7 ± 3<0.0010 ± 3−7 ± 4<0.001
 Elastance-derived Pl,plat, cm H2O24 ± 415 ± 3<0.00120 ± 212 ± 3<0.001
 Tidal Crs, ml/cm H2O29 ± 835 ± 8<0.00132 ± 939 ± 13<0.001
 Tidal Cl, ml/cm H2O38 ± 1446 ± 13<0.00149 ± 1462 ± 180.006
 Tidal Ccw, ml/cm H2O139 ± 60151 ± 520.342126 ± 62154 ± 840.080
 Heart rate, beats/min88 ± 2188 ± 210.69387 ± 1884 ± 180.882
 SBP, mm Hg123 ± 24123 ± 140.178118 ± 24124 ± 220.008
 DBP, mm Hg60 ± 1161 ± 110.76260 ± 1061 ± 80.492

Definition of abbreviations: ABG = arterial blood gas; DBP = diastolic blood pressure; EELV = end-expiratory lung volume; elastance-derived Pl,plat = elastance-derived transpulmonary plateau pressure, calculated using airway plateau pressure times the ratio of lung elastance to respiratory system elastance; PEEP = positive end-expiratory pressure; Pl,end-exp = transpulmonary pressure at end-expiration; SBP = systolic blood pressure; SpO2 = oxygen saturation as measured by pulse oximetry; tidal Ccw = chest wall compliance during tidal breath; tidal Cl = lung compliance during tidal breath; tidal Crs = respiratory system compliance during tidal breath; Vd,alv/Vt = alveolar dead space fraction.

Continuous variables are described as mean ± SD and were compared using the paired t test. Bold indicates significant P values.

*n = 19 (90% of high recruiters) for those parameters requiring esophageal pressure, such as transpulmonary pressures, tidal lung, and chest wall compliances.

n = 16 (80% of low recruiters) for those parameters requiring esophageal pressure.

Continuous R/I Ratio Correlates with Gas Exchange

At PEEPlow, the R/I ratio was inversely correlated with PaO2/FiO2 and correlated with alveolar dead space fraction (R2 = 0.223 and R2 = 0.164, respectively) (Figures 4A and 4B). Four patients required a higher FiO2 at PEEPlow. All were high recruiters with a median of R/I ratio of 1.04 (range, 0.87–1.15). Overall, the response to PEEP in SpO2 and in alveolar dead space both correlated with the R/I (R2 = 0.315 and R2 = 0.284, respectively) (see Figures 4C and 4D). The changes in SpO2 and alveolar dead space were normalized by the effective change in pressure because the effective changes in alveolar pressure varied depending on AOP. The correlations remained significant when the changes in SpO2 and alveolar dead space were not normalized (P = 0.009 and P = 0.014, respectively).

The main findings of this study are: 1) complete airway closure is not rare in patients with moderate or severe ARDS, especially at PEEPlow, and can confound the assessment of respiratory mechanics and lung recruitment; 2) a single-breath method provides a reliable and accurate estimation for recruited volume in one maneuver; 3) the R/I ratio differentiates patients with different responses to PEEP; and 4) the R/I ratio correlates with oxygenation and alveolar dead space, both at baseline and in response to PEEP.

Airway Closure

The prevalence of airway closure found in this cohort is consistent with recent reports (23, 38). This phenomenon, ignored until recently, needs to be assessed before any measurement of respiratory mechanics and for defining lung recruitability as well because it makes airway and alveolar pressure different. The concern that Paw could poorly reflect alveolar pressure has been raised previously (32) but was mostly considered for auto-PEEP. Auto-PEEP can coexist but differs from AOP, and we assumed that AOP was the closest estimate of the alveolar pressure (see justifications in the online supplement). The classical auto-PEEP needs the presence of expiratory flow at end-expiration. When the expiratory time is modified, AOP remains constant, whereas auto-PEEP greatly varies. Auto-PEEP can be easily suppressed by prolonging the expiratory time without altering the level of AOP at the next insufflation (see Figures E5 and E6A from the same patient). The difference between and the coexistence of auto-PEEP and airway closure is further discussed in the online supplement.

Definition of Recruitment

Different techniques and definitions exist to assess recruitment (15, 3942). We discussed their important differences and associations in the online supplement. The recruited volume measured by the hysteresis-like behavior methods include reversal of lung collapse and improved mechanical properties of an already partially inflated lung. Such recruitment reduces regional transpulmonary pressure; stress; and, probably to a certain extent, strain on the lung.

When assessing lung recruitability, we implicitly mean recruitability over a clinically acceptable range of PEEP (9, 4042). Greater recruitment can be achieved by higher and often excessive positive pressure (43, 44), but this might result in lung overdistension, right ventricular dilatation, severe hypotension, and potentially worse outcomes (2, 12, 21).

Lung Recruitability and Gas Exchange

Our experimental method was strongly correlated with the reference method in measuring ∆Vrec in patients with and without airway closure. The biases were small and the limits of agreement acceptable. Airway closure was not previously considered, and not considering the effective pressure change to interpret ∆Vrec may be misleading. To assess recruitment reliably, the determination of AOP is first required, which is also essential for any calculation of respiratory mechanics.

In two representative patients (see Figures 1 and 2), they both would be classified as “low recruiters” if one simply used the median of ∆Vrec to define lung recruitability as described in the literature. Crec and R/I ratio are new concepts proposed in this study and thus no available threshold exists yet. We decided to use the median of R/I ratio by the experimental method to define lung recruitability in this series and then checked if this definition could differentiate patients with different PEEP responses.

Our definition of recruitability was able to separate patients having opposite oxygenation and hemodynamic responses to PEEP. At PEEPlow, there was a negative correlation between the R/I ratio and PaO2/FiO2, and a positive correlation between this ratio and the alveolar dead space. These are consistent with Gattinoni and colleagues’(2) study, which showed that the high recruiters had worse oxygenation and dead space. The correlations between the normalized change in SpO2 at constant FiO2 and the R/I ratio, and between the normalized change in alveolar dead space and the ratio, also support this concept. The correlation with gas exchange is expected to be weak owing to the circulatory effects of PEEP and the complex shunt Q. relationship. Chiumello and colleagues (45) have demonstrated that the oxygenation-based PEEP strategy was the only bedside method correlated with lung recruitability defined by CT scan and the correlation was weak (R2 = 0.29; P < 0.0001). Oxygenation or oxygenation response is thus an indirect indicator of lung recruitment, which can be individually misleading.

Changes in Tidal Compliance

It might be counterintuitive that the Crs and lung compliance during tidal breathing decreased at higher PEEP, especially in high recruiters. This can be explained by a greater tidal recruitment at lower PEEP (17, 46). A low tidal compliance at higher PEEP can be caused by less ongoing tidal recruitment during the insufflation. On the other hand, tidal hyperinflation is also possible, making the interpretation of tidal compliance even more complicated. Moreover, the lung tissue that is recruited by a higher PEEP level could have different mechanical properties than the baby lung, as already suggested from experimental work (47). The recruited lung improves lung aeration but may present different regional compliances. The Crec tissue could therefore be lower than that of the preexisting baby lung.

Clinical Implications

The single-breath method permits an easy assessment of ∆Vrec and does not need additional complex analysis. Our study is the first to distinguish patients with and without airway closure in the assessment of lung recruitability. A low-flow inflation is mandatory to detect airway closure (see Video E1) but a simple pressure–time curve starting from PEEP 5 is sufficient to detect and measure it (see Figure E4). Overall, our technique permits a direct assessment of the “potential for recruitment.”

The R/I ratio, mathematically, reflects the proportion of volume distributed into the recruited lung to that into the baby lung when PEEP is changed. For example, the lower the R/I ratio, the greater the volume that will be distributed into the already aerated baby lung and therefore the greater the risk of hyperinflation. This will need future validation and may need to be tested prospectively as a new method to titrate PEEP in ARDS. Indeed, the R/I ratio may provide an indicator for both the risk of atelectrauma (setting PEEPlow in patients with a high R/I ratio) and hyperinflation (setting PEEPhigh in patients with a low R/I ratio), and can help in developing a strategy for preventing ventilator-induced lung injury.

Increasing PEEP in high recruiters does not guarantee the absence of hyperinflation. It is reassuring to see a lack of negative hemodynamic effect in the high recruiters, but any inflation of the baby lung can coexist with hyperinflation.


Our study involves careful measurements to assess lung recruitability and respiratory mechanics. We calibrated flowmeters and carefully excluded potential leaks. Ideally, this should also be recommended during clinical practice in which less accurate flow sensors may be used and unrecognized leaks could exist. Implementing our single-breath method into clinical practice may require a careful check on ventilators (e.g., pretest and leak-test).

Our experimental method assumes a linear P–V relationship. To increase the chance of keeping the measurements within a linear P–V relationship, we kept the recruitability test within 10 cm H2O of changes in pressure (e.g., from 15 to 5 cm H2O of PEEP) and kept the inflated volume at 6 ml/kg predicted body weight. In addition, we used the tidal Crs above AOP [i.e., Vt/(Pplat − AOP)] to overcome the nonlinearity of the P–V curve due to airway closure.

A fixed order of measurements (see online supplement) is a potential limitation.

Also, lung recruitability was tested over a fixed change in PEEP and the lack of a wider range of PEEP is a limitation to completely assess the potential for recruitment. Four patients were excluded from analyses on lung recruitability. Setting a PEEPhigh greater than AOP is thus necessary if one wants to use the recruitability test. Other limitations in this study include the lack of biological or imaging correlations to support the findings, and the lack of investigation on the regional versus global distribution of recruitment or the effects of positioning.


Our single-breath method can accurately measure ∆Vrec at the bedside and, to avoid the confounding effect of airway closure, Crec needs to be calculated. By comparing Crec with the compliance of the baby lung, the R/I ratio differentiates patients with, on average, different oxygenation and circulation responses to PEEP. This ratio correlates with both oxygenation and alveolar dead space, indicating further validity of this index. It provides clinicians a bedside tool to characterize lung recruitability over a clinical range of PEEP, which can be used to personalize PEEP.

The authors thank Jianing Gu and Audery Kim for their essential work on data collection and organization. They also thank Gyan Sandhu, Jennifer Hodder, Thomas Piraino, and Orla Smith for their help with the research coordination. Thomas Piraino also dedicated his precious time to make the video for demonstration and the Web page for automating calculations. This study is a part of L.C.’s Ph.D. program, supervised by L.B. and the Program Advisory Committee: Drs. Brian Kavanagh, John Laffey, and Haibo Zhang. Brian Patrick Kavanagh passed away on June 15, 2019, and we will greatly miss his immense talent.

1. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 1967;2:319323.
2. Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 2006;354:17751786.
3. Goligher EC, Kavanagh BP, Rubenfeld GD, Adhikari NK, Pinto R, Fan E, et al. Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome: a secondary analysis of the LOVS and ExPress trials. Am J Respir Crit Care Med 2014;190:7076.
4. Chen L, Chen GQ, Shore K, Shklar O, Martins C, Devenyi B, et al. Implementing a bedside assessment of respiratory mechanics in patients with acute respiratory distress syndrome. Crit Care 2017;21:84.
5. Malbouisson LM, Muller JC, Constantin JM, Lu Q, Puybasset L, Rouby JJ; CT Scan ARDS Study Group. Computed tomography assessment of positive end-expiratory pressure-induced alveolar recruitment in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2001;163:14441450.
6. Camporota L, Caricola EV, Bartolomeo N, Di Mussi R, Wyncoll DLA, Meadows CIS, et al. Lung recruitability in severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. Crit Care Med 2019;47:11771183.
7. Dantzker DR, Lynch JP, Weg JG. Depression of cardiac output is a mechanism of shunt reduction in the therapy of acute respiratory failure. Chest 1980;77:636642.
8. Mekontso Dessap A, Boissier F, Leon R, Carreira S, Campo FR, Lemaire F, et al. Prevalence and prognosis of shunting across patent foramen ovale during acute respiratory distress syndrome. Crit Care Med 2010;38:17861792.
9. Maggiore SM, Jonson B, Richard JC, Jaber S, Lemaire F, Brochard L. Alveolar derecruitment at decremental positive end-expiratory pressure levels in acute lung injury: comparison with the lower inflection point, oxygenation, and compliance. Am J Respir Crit Care Med 2001;164:795801.
10. Ranieri VM, Eissa NT, Corbeil C, Chassé M, Braidy J, Matar N, et al. Effects of positive end-expiratory pressure on alveolar recruitment and gas exchange in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1991;144:544551.
11. Suter PM, Fairley B, Isenberg MD. Optimum end-expiratory airway pressure in patients with acute pulmonary failure. N Engl J Med 1975;292:284289.
12. Caironi P, Cressoni M, Chiumello D, Ranieri M, Quintel M, Russo SG, et al. Lung opening and closing during ventilation of acute respiratory distress syndrome. Am J Respir Crit Care Med 2010;181:578586.
13. Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 1994;149:13271334.
14. Chen L, Brochard L. Lung volume assessment in acute respiratory distress syndrome. Curr Opin Crit Care 2015;21:259264.
15. Chen L, Sklar M, Dres M, Goligher EC. Different definitions of lung recruitment by computed tomography scan. Am J Respir Crit Care Med 2016;193:13141315.
16. Amato MB, Santiago RR. The recruitability paradox. Am J Respir Crit Care Med 2016;193:11921195.
17. Jonson B, Richard JC, Straus C, Mancebo J, Lemaire F, Brochard L. Pressure-volume curves and compliance in acute lung injury: evidence of recruitment above the lower inflection point. Am J Respir Crit Care Med 1999;159:11721178.
18. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, et al.; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004;351:327336.
19. Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, et al.; Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2008;299:646655.
20. Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, et al.; Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2008;299:637645.
21. Cavalcanti AB, suzumura EA, Laranjeira LN, paisani DM, Damiani LP, Guimaraes HP, et al.; Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA 2017;318:13351345.
22. Chen L, Del Sorbo L, Grieco DL, Shklar O, Junhasavasdikul D, Telias I, et al. Airway closure in acute respiratory distress syndrome: an underestimated and misinterpreted phenomenon. Am J Respir Crit Care Med 2018;197:132136.
23. Yonis H, Mortaza S, Baboi L, Mercat A, Guérin C. Expiratory flow limitation assessment in patients with acute respiratory distress syndrome: a reappraisal. Am J Respir Crit Care Med 2018;198:131134.
24. Grieco DL, Anzellotti GM, Russo A, Bongiovanni F, Costantini B, D’Indinosante M, et al. Airway closure during surgical pneumoperitoneum in obese patients. Anesthesiology 2019;131:5873.
25. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al.; ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA 2012;307:25262533.
26. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013;187:347365.
27. Henderson WR, Chen L, Amato MBP, Brochard LJ. Fifty years of research in ARDS: respiratory mechanics in acute respiratory distress syndrome. Am J Respir Crit Care Med 2017;196:822833.
28. Dellamonica J, Lerolle N, Sargentini C, Beduneau G, Di Marco F, Mercat A, et al. Accuracy and precision of end-expiratory lung-volume measurements by automated nitrogen washout/washin technique in patients with acute respiratory distress syndrome. Crit Care 2011;15:R294.
29. Lu Q, Rouby JJ. Measurement of pressure-volume curves in patients on mechanical ventilation: methods and significance. Crit Care 2000;4:91100.
30. Katz JA, Ozanne GM, Zinn SE, Fairley HB. Time course and mechanisms of lung-volume increase with PEEP in acute pulmonary failure. Anesthesiology 1981;54:916.
31. Ranieri VM, Giuliani R, Fiore T, Dambrosio M, Milic-Emili J. Volume-pressure curve of the respiratory system predicts effects of PEEP in ARDS: “occlusion” versus “constant flow” technique. Am J Respir Crit Care Med 1994;149:1927.
32. Loring SH, Topulos GP, Hubmayr RD. Transpulmonary pressure: the importance of precise definitions and limiting assumptions. Am J Respir Crit Care Med 2016;194:14521457.
33. Aboab J, Louis B, Jonson B, Brochard L. Relation between PaO2/FIO2 ratio and FIO2: a mathematical description. Intensive Care Med 2006;32:14941497.
34. Aliverti A, Carlesso E, Dellacà R, Pelosi P, Chiumello D, Pedotti A, et al. Chest wall mechanics during pressure support ventilation. Crit Care 2006;10:R54.
35. Chiumello D, Carlesso E, Cadringher P, Caironi P, Valenza F, Polli F, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med 2008;178:346355.
36. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307310.
37. R Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2018.
38. Coudroy R, Lu C, Chen L, Demoule A, Brochard L. Mechanism of airway closure in acute respiratory distress syndrome: a possible role of surfactant depletion. Intensive Care Med 2019;45:290291.
39. Hubmayr RD. Perspective on lung injury and recruitment: a skeptical look at the opening and collapse story. Am J Respir Crit Care Med 2002;165:16471653.
40. Lu Q, Constantin JM, Nieszkowska A, Elman M, Vieira S, Rouby JJ. Measurement of alveolar derecruitment in patients with acute lung injury: computerized tomography versus pressure-volume curve. Crit Care 2006;10:R95.
41. Chiumello D, Marino A, Brioni M, Cigada I, Menga F, Colombo A, et al. Lung recruitment assessed by respiratory mechanics and computed tomography in patients with acute respiratory distress syndrome: what is the relationship? Am J Respir Crit Care Med 2016;193:12541263.
42. Dellamonica J, Lerolle N, Sargentini C, Beduneau G, Di Marco F, Mercat A, et al. PEEP-induced changes in lung volume in acute respiratory distress syndrome: two methods to estimate alveolar recruitment. Intensive Care Med 2011;37:15951604.
43. Pelosi P, Goldner M, McKibben A, Adams A, Eccher G, Caironi P, et al. Recruitment and derecruitment during acute respiratory failure: an experimental study. Am J Respir Crit Care Med 2001;164:122130.
44. Crotti S, Mascheroni D, Caironi P, Pelosi P, Ronzoni G, Mondino M, et al. Recruitment and derecruitment during acute respiratory failure: a clinical study. Am J Respir Crit Care Med 2001;164:131140.
45. Chiumello D, Cressoni M, Carlesso E, Caspani ML, Marino A, Gallazzi E, et al. Bedside selection of positive end-expiratory pressure in mild, moderate, and severe acute respiratory distress syndrome. Crit Care Med 2014;42:252264.
46. Hickling KG. The pressure-volume curve is greatly modified by recruitment: a mathematical model of ARDS lungs. Am J Respir Crit Care Med 1998;158:194202.
47. Grasso S, Stripoli T, Sacchi M, Trerotoli P, Staffieri F, Franchini D, et al. Inhomogeneity of lung parenchyma during the open lung strategy: a computed tomography scan study. Am J Respir Crit Care Med 2009;180:415423.
48. Reske AW, Costa EL, Reske AP, Rau A, Borges JB, Beraldo MA, et al. Bedside estimation of nonaerated lung tissue using blood gas analysis. Crit Care Med 2013;41:732743.
Correspondence and requests for reprints should be addressed to Laurent Brochard, M.D., St. Michael’s Hospital in Toronto, Li Ka Shing Knowledge Institute, Keenan Research Centre, 209 Victoria Street, Room 408, Toronto, ON, M5B 1T8 Canada. E-mail: .

*L.B. is Deputy Editor of AJRCCM. His participation complies with American Thoracic Society requirements for recusal from review and decisions for authored works.

Author Contributions: L.C., L.D.S., J.-C.M.R., and L.B. conceived the study. L.C., L.D.S., N.R., N.D.F., E.F., and L.B. participated in its design and coordination. L.C., L.D.S., D.L.G., D.J., N.R., I.S., M.C.S., and M.R. made substantial contributions to data acquisition. L.C. conducted the signal and statistical analysis. L.C. and L.B. drafted the manuscript. All authors helped to revise the draft of the manuscript. All authors read and approved the final manuscript.

This article has an online supplement, which is accessible from this issue’s table of contents at

Originally Published in Press as DOI: 10.1164/rccm.201902-0334OC on October 2, 2019

Author disclosures are available with the text of this article at

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