Lung collapse is an important cause of deteriorated oxygenation and gas exchange after major surgery, in acute lung injury (ALI) and in acute respiratory distress syndrome (ARDS) 12. Although the logical therapy for lung collapse, namely a lung recruitment maneuver (LRM) in combination with high positive end-expiratory pressure (PEEP), improves oxygenation in these conditions, it has not conclusively been found to improve important outcome measures, for example length of stay in the hospital or mortality 3456.The reasons for the latter might be that in the studies the positive effects of LRM in patients with recruitable lung collapse are evened out by the negative effects such as circulatory compromise and barotrauma/volutrauma in non-recruiters. This indicates that LRM preferably should be performed only in patients with lung collapse that it is possible to recruit 78. Although examination of the lungs by computed tomography could assess the effect of LRMs, it is complicated and the patient will be exposed to radiation and needs to be moved to the computed tomography suite 910. Therefore an easy method for predicting the effect of LRMs would be useful.

Superimposed plots of inspiratory airway pressure against lung volume (pressure–volume; PV) obtained from different PEEP levels were originally described by Ranieri and coworkers, and have been further developed by others, for assessing PEEP-induced lung recruitment 1112. However, this method does not predict whether an LRM would be successful, but instead shows the volume effect of derecruitment caused by removal or reduction of PEEP 13. Vieillard-Baron and coworkers proposed a slow inflation–deflation (upper airway pressure of 20 cmH₂O) PV loop method for predicting the volume effect by PEEP-induced lung recruitment 14. They found in ARDS that the increase in lung volume, from zero end-expiratory pressure (ZEEP) to the airway pressure equal to the subsequent PEEP, assessed from the difference between the expiratory and inspiratory limbs of the loop, agreed well with decrease in volume found at removal of PEEP. In addition, they found in patients with lower inflexion points at high pressures that PEEP recruited more lung volume than it did in patients without any obvious lower inflexion points. We hypothesized that a modification of this method, by measuring end-expiratory lung volume (EELV), using higher airway pressures (which is commonly used in LRM) and measuring the volume difference between the limbs of the PV loop (hysteresis), might predict the effects of a subsequent LRM (evaluated by changes in EELV, oxygenation, compliance of the respiratory system (Crs) and CO₂ elimination).

In ALI/ARDS, the inspiratory limb reflects mainly lung recruitment and the expiratory limb reflects derecruitment 1516. At a specific pressure, the volume hysteresis reflects the volume recruited (and the expansion of the recruited volume) by the PV-loop maneuver. Thus, a substantial hysteresis would predict that an LRM would be effective, whereas a minor hysteresis would indicate that an LRM would not be beneficial.

The aim of the present study was to test this hypothesis in a porcine model with normal lungs, lungs subjected to lavage and finally lungs subjected to lavage and injurious ventilation (1) by registering PV loops and volume hysteresis under the three conditions and then compare hysteresis (assumed predicted recruited lung volume) at 10 cmH₂O airway pressure with the measured difference in EELV at 10 cmH₂O PEEP before and after an LRM (the recruited volume plus expansion of recruited lung units), (2) to relate the maximal volume hysteresis (MH) on the PV curve standardized to total lung capacity (TLC) to changes in EELV, Crs and blood gases caused by an LRM (Figure 1), and (3) to calculate the sensitivity and specificity of using the MH/TLC ratio for predicting the effect of an LRM.

We found that the volume hysteresis at 10 cmH₂O agreed with the increase in EELV, that MH/TLC was related to changes in EELV, Crs and PaCO₂, and that a MH/TLC ratio of 0.3 predicted with high sensitivity and specificity whether an LRM would improve EELV, Crs, partial pressure of arterial CO₂ (PaCO₂) and partial pressure of arterial oxygen (PaO₂).

This animal interventional study was performed at the laboratory of the Clinical Institute, Aarhus University Hospital. The study was approved by the Danish National Animal Ethics Committee.

The main finding in this study is that specific information from a PV loop could predict the potential for lung recruitment in a porcine model of acute lung injury.

The PV loop and lung volume measurement methods have been evaluated previously and are found to be reliable 171819. The short time of the PV loop procedure makes it improbable that gas exchange had a major impact of the shape of the PV loop. To obtain different lung conditions to test our hypothesis we used three models: normal lung, lung collapse, and mechanical lung injury. We used a maximal pressure of 40 cmH₂O for the PV loops in all lung conditions to permit easy comparison of the different loops. Furthermore, 40 cmH₂O is commonly considered safe and it would create a transpulmonary pressure high enough for obtaining an accurate TLC under the lung conditions studied. The PV loops and EELV obtained agree with previous findings: the normal lung has a crescent PV loop and the collapsed and the mechanical injured lung have a convex PV loop with reduced EELV 2122. In the present study, the more pronounced the convexity, as indicated by a larger MH/TLC ratio, the higher was the probability for improvements in EELV, Crs and PaCO₂ by an LRM. This agrees well with theoretical considerations by Hickling and by Jonson and Svantesson 1516. Unexpectedly, although the shape of the PV loop was different from that in the injured lungs, in the normal lungs the hysteresis was substantial, with a MH/TLC ratio up to 0.3. Because the hysteresis of the PV loop at 10 cmH₂O was equal to the increase in EELV by the LRM at similar airway pressure it could be debated whether the hysteresis found in the normal lungs was a sign of lung recruitment produced by the PV loop maneuver and thus predicted the recruitment of collapsed lung tissue. We do not believe this is the main explanation, because only minor changes were found in Crs, PaO₂ and PaCO₂ by the LRM. In fact, PaCO₂ increased in four of the animals. Instead, we suggest that the probable cause was that the pressure used in the PV loop maneuver and in the LRM squeezed blood out from the lungs that was replaced by an increased amount of air in previously open lung units 23.

We used 10 cmH₂O PEEP for two reasons: first, it is a clinically relevant PEEP level in ALI/ARDS, and second, if higher PEEP levels had been used, the inspiratory pressures would presumably have been high enough to allow tidal lung recruitment. Theoretically, tidal recruitment could inadvertently have increased EELV before LRM, because tidal recruitment might not always be followed by tidal derecruitment. This is because the PEEP used might prevent derecruitment and because the time constant for derecruitment in the lavage model is substantial 24. In our study the inspiratory pressures were less than 22 cmH₂O, which is well below the airway pressure needed to recruit collapsed lung parenchyma 3. Our finding that EELV at 10 cmH₂O before LRM was similar to the lung volume registered from the inspiratory PV loop at the same airway pressure indicates that tidal recruitment was minimal. After the LRM, EELV as measured at 10 cmH₂O PEEP increased in all animals to similar lung volumes, as registered from the expiratory limb of the PV loop. Thus, in agreement with the findings by Vieillard-Baron and coworkers, the PV loop seems to predict the volume gain that could be achieved by an LRM 14. However, because recruitment is dependent on time and pressure, the PV loop might not always predict the full volume effect of an LRM.

Clinically, improvement in oxygenation is often used for evaluating the effect of LRM, and it has been suggested to indicate whether recruitment of collapsed regions has occurred 10. However, oxygenation could be improved and shunt could be decreased by a reduction in cardiac output induced by the high intrathoracic pressure during the LRM and by high PEEP 25. It should be noted that improvements in lung mechanics or in EELV by an LRM do not necessarily indicate improvements in oxygenation, intrapulmonary shunt or CO₂ elimination 26. In our study, although MH/TLC was related to changes in Crs and EELV we could not find any relation to changes in PaO₂, and the sensitivity and specificity were lower for PaO₂ and PaCO₂ than for Crs and EELV. However, a low MH/TLC ratio suggested that LRM would not markedly improve oxygenation, PaCO₂, lung mechanics or EELV.

We are not aware that any simple methods have previously been reported to predict whether LRM would be effective in ALI/ARDS. The other simple clinical methods using a combination of changes in Crs, PaO₂ and PCO₂, or in EELV, do only evaluate a posteriori whether an LRM combined with high PEEP has been effective 13.

We believe that this method, using measurement of EELV combined with a PV loop, might be found valuable clinically. Registration of PV loops obtained by slowly increasing and decreasing airway pressures as well as EELV measurement methods have been incorporated in modern ventilators. Thus, in patients with low Crs and low PaO₂/FiO₂ ratios, EELV measurements could determine whether lung volume is reduced. Then an analysis of the shape of a PV loop could be used to predict whether an LRM and increased PEEP would be effective. Although this concept needs to be tested in patients, both the method described by Vieillard-Baron and coworkers and the method using superimposed inspiratory PV curves from different PEEP levels are conceptually similar to the method used in this study and have been found to give reliable results in patients with ARDS 11121427.

Our study has several limitations. First, it is an experiment in young previously healthy animals. Second, the lung collapse and lung injury are induced by surfactant deficiency and mechanical stress and not, as in ALI/ARDS, by local or systemic inflammation. Thus, the models used do not capture all aspects of the human disease. Third, we did not use an imaging method such as computed tomography to assess lung recruitment. Fourth, the statistics used could be criticized because the changes in EELV or lung mechanics caused by the collapse and mechanical lung injury are not independent. However, previous studies with similar models have been consistent, and therefore a priori we decided to use a limited number of animals.

In this porcine model, specific information from a PV loop, namely a MH/TLC of 0.3, predicted better whether an LRM would improve EELV and Crs – that is, lung mechanics – than PaCO₂ and PaO₂ – that is, gas exchange – in the range of the studied PEEP and PV loop.

• Registering airway pressure – lung volume loops and measurements of end-expiratory lung volume are easily obtained at the bedside with modern ventilators.

• This animal study indicates that these measures might predict whether a lung recruitment maneuver would be effective in the treatment of acute lung injury.

ALI = acute lung injury; ARDS = acute respiratory distress syndrome; Crs = compliance of the respiratory system; ΔEELV = increase in end-expiratory lung volume at 10 cmH₂O positive end-expiratory pressure associated with a lung recruitment maneuver; ΔV = difference in lung volume at 10 cmH₂O airway pressure between the expiratory and inspiratory limbs of a static airway pressure – lung volume loop; EELV = end-expiratory lung volume; EELV-10_LRM = end-expiratory lung volume at 10 cmH₂O positive end-expiratory pressure after a lung recruitment maneuver; EELV-10_noLRM = end-expiratory lung volume at 10 cmH₂O positive end-expiratory pressure before a lung recruitment maneuver; EELV_ZEEP = end-expiratory lung volume at zero end-expiratory pressure; ELV-10 = the absolute lung volumes at an airway pressure of 10 cmH₂O obtained from the expiratory limb of a static airway pressure – lung volume loop; ILV-10 = the absolute lung volumes at an airway pressure of 10 cmH₂O obtained from the inspiratory limb of an airway pressure – lung volume loop; i.m. = intramuscularly; i.v. = intravenously; MH = maximal volume hysteresis obtained from an airway pressure – lung volume loop; LRM = lung recruitment maneuver; PaCO₂ = partial pressure of arterial CO₂; PaO₂ = partial pressure of arterial oxygen; PEEP = positive end-expiratory pressure; PV loop = static airway pressure – lung volume loop; TLC = total lung capacity; ZEEP = zero end-expiratory pressure.

The authors declare that they have no competing interests.

JKN participated in the design, performed the study and drafted the manuscript. NDN and AJK participated in the acquisition of the data for the study. AL participated in the design of the study, participated in the acquisition of data and helped to draft the manuscript. All authors read and approved the final manuscript.