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Airway management

Pressure safety range of barotrauma with lung recruitment manoeuvres: A randomised experimental study in a healthy animal model

García-Fernández, Javier; Canfrán, Susana; de Segura, Ignacio A. Gómez; Suarez-Sipmann, Fernando; Aguado, Delia; Hedenstierna, Göran

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European Journal of Anaesthesiology: September 2013 - Volume 30 - Issue 9 - p 567-574
doi: 10.1097/EJA.0b013e3283607875
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Lung collapse invariably occurs during mechanical ventilation and commonly develops after induction of general anaesthesia.1–4 The use of recruitment manoeuvres has been proposed as a useful technique to reverse atelectasis induced by general anaesthesia.5–7

Recently, an open lung approach (OLA) ventilation strategy has been described in patients with acute respiratory distress syndrome (ARDS) and acute lung injury, which might have therapeutic advantages over conventional ventilation strategies. OLA is based on the use of a recruitment manoeuvre, during which maximal inspiratory pressure (MIP) is transiently increased to fully re-open collapsed lung regions. This is followed by sequential decrements in positive end-expiratory pressure (PEEP) to identify ‘open-lung PEEP’ which maintains the recruited lung open. The aim of this strategy is to prevent ventilator-induced lung injury by reversing lung collapse, avoiding cyclical tidal recruitment and minimising lung overdistension by limiting the driving pressure above the set open lung PEEP.8–11

Although potentially benefiting from the same principles for lung protection, recruitment manoeuvres have not gained widespread acceptance during routine mechanical ventilation in anaesthesia. One of the main reasons relates to concerns regarding its potential risks. These include haemodynamic impairment,12 lung barotrauma and effects on distal organ function.13,14 Of these, barotrauma is of major immediate clinical concern. Most studies regarding recruitment manoeuvres have been conducted in diseased lungs with ARDS,1,6,10,11 but information regarding the response to recruitment manoeuvres and risk of barotrauma in patients with healthy lungs is lacking.

The development of atelectasis during general anaesthesia is also a consistent finding in paediatric patients.7,15,16 In these patients, pressures needed to recruit lung alveoli and safety of recruitment manoeuvres are largely unknown and are very likely different in healthy than in diseased lungs. However, to our knowledge, very few studies have addressed this issue. If recruitment manoeuvres are to be implemented in healthy patients, their safety and efficacy should be explored in more detail. In particular, it would be useful to have an estimate of the pressure levels needed to reopen collapsed alveoli and also the pressure range that may cause direct barotrauma. Therefore, the aim of this study was to determine the open lung and barotrauma pressures in an experimental model using small healthy open-chest rabbit lungs. This model was chosen because of its sensitivity to barotrauma once the influence of the chest wall is eliminated. Because only two different maximum PEEP levels are generally available in anaesthesia workstations (20 cmH2O) and critical care ventilators (50 cmH2O), we explored two different recruitment manoeuvres based on the maximal available PEEP.



The study was approved by the ethical committee for experimental research of La Paz University Hospital (Ethical Committee N° 26–2010), Madrid, Spain on 25 October 2010. The experimental work was performed in accordance with national and institutional guidelines for the care and use of experimental animals. We prospectively studied 14 female New Zealand rabbits (Granja San Bernardo, Tulebras, Navarra, Spain) weighing 2.5 to 3.0 kg and aged 12 weeks. Animals were housed in specific cages recommended for this species from their arrival until the experimental procedure day. They were fed with dry pellets for rabbits and had free access to water. The animals were sedated with ketamine [Ketolar; Pfizer, Madrid, Spain; 15 mg kg−1 intramuscularly (i.m.)] and medetomidine (Domtor; Pfizer, Madrid, Spain; 0.1 mg kg−1 i.m.) in a specific restraint cage for rabbits, and then euthanised with pentobarbital (Dolethal; Vetoquinol, Cedex, France; 100 mg kg−1 intravenously).

Lung preparation

A 3.5-mm internal diameter cuffless tracheal tube with a secondary lateral lumen to monitor intratracheal pressure (Vygon, Ecouen, France) was inserted via a tracheostomy and sealed to the trachea by fixing it with a 1/0 silk suture to prevent air leakage. A median sternotomy was performed and sharp osseous areas were protected with soaked gauze. The thorax was kept open with a neonatal Finochietto sternal retractor. The lungs were exposed by carefully opening the thoracic cavity and parietal pleura, and the pleural cavity was filled with physiological saline solution. After surgical preparation lasting 20 to 45 min, mechanical ventilation (SERVO-i ventilator; Maquet Critical Care, Solna, Sweden) was started in pressure-controlled mode with zero end-expiratory pressure (ZEEP), a MIP of 15 cmH2O, an inspiratory to expiratory ratio 1 : 1 and a respiratory rate of 30 breaths per minute. Baseline data were collected after 10 min of stabilisation at these settings.

Recruitment manoeuvre protocol

The animals were allocated randomly into one of two recruitment manoeuvre groups: PEEP-20, reaching a maximum PEEP of 20 cmH2O (n = 6), and PEEP-50, reaching a maximum PEEP of 50 cmH2O, (n = 7). The recruitment manoeuvre sequence was performed in pressure-controlled mode by sequential increases in PEEP in 5-cmH2O PEEP steps each lasting 1 min. A fixed driving pressure of 15 cmH2O was maintained until the maximum PEEP was reached in each group or direct barotrauma appeared. Thereafter, driving pressure was further increased in both groups in 5-cmH2O steps, again maintained for 1 min, until direct barotrauma was observed (Fig. 1). The study was completed when barotrauma was observed in all lungs.


Because the sternal retractor maintained an open thorax during the protocol, the anterior and medial aspects and most of the dependent lung were macroscopically visible at all times. We could, therefore, define three study conditions by visual inspection of the lungs.


Ten minutes after starting mechanical ventilation, gross macroscopic end-expiratory collapse in the dependent regions was seen in all animals.

Anatomically open lung

The lungs were macroscopically fully re-expanded with no visible atelectasis.

Direct barotrauma

Direct barotrauma was characterised by a clear visual air leak (appearance of air bubbles in the saline-filled pleural space) combined with detection of all the following sudden specific changes in the respiratory waveforms: volume–time curve, a sudden two-fold or more increase in the inspiratory tidal volume together with the loss of expiratory tidal volume, displaying a value of zero; flow–time curve, a sudden at least two-fold increase in peak inspiratory flow which remained above zero along the entire available inspiratory time combined with the disappearance of the expiratory flow waveform; pressure–time curve, a decrease in set PEEP of at least 2 cmH2O, resulting in pressure auto-triggering (Fig. 2).


Respiratory variables such as MIP, PEEP, mean airway pressure (Paw) and driving pressure were continuously recorded during the entire protocol. The values obtained during each progressive lung condition were compared and the safety margin of MIP was calculated. This safety margin was defined as the difference between barotrauma and anatomically open lung MIP.

Statistical analysis

Data are expressed as the mean ± standard deviation, and mode, minimum and maximum values as appropriate. We used the mode, because MIP was studied in 5-cmH2O increments, as performed in the clinical setting. Once the normality of the data was assessed with the Kolmogorov–Smirnov test, a one-way analysis of variance test was completed. Correlation between quantitative data was tested with Pearson's correlation test. A value of P less than 0.05 was considered statistically significant. The power analysis for the studied variables in each group showed an observed power more than 90% in all cases. The statistical analysis was performed using SPSS for Windows (SPSS Statistics for Windows, Version 17.0. Chicago: SPSS Inc., Illinois, USA).


No differences in weight were observed between the groups (weight 2.8 ± 0.1 kg in each group). One animal in the PEEP-20 group was discarded from the study due to inappropriate surgical preparation. Consequently, six animals were included in the PEEP-20 group and seven animals in the PEEP-50 group.

Anatomically open lung pressures

Macroscopic lung atelectasis disappeared at similar anatomically open lung MIP in both groups. This resulted in a similar anatomically open lung MIP (23.3 ± 4.1 vs. 23.6 ± 3.8 cmH2O; P = 0.91), PEEP (8.3 ± 4.1 vs. 8.6 ± 3.8 cmH2O; P = 0.91) and Paw (16.3 ± 4.1 vs. 16.6 ± 3.7 cmH2O; P = 0.91) in the PEEP-20 and PEEP-50 groups, respectively (Fig. 3). Considering both groups together, 46% of the lungs were opened at MIP of 20 cmH2O, 85% at MIP of 25 cmH2O and all lungs were opened at MIP of 30 cmH2O.


Barotrauma pressures

We found significant differences in all barotrauma pressures between the study groups. Barotrauma MIP was 56.7 ± 5.2 and 65.7 ± 3.4 cmH2O in the PEEP-20 and PEEP-50 groups, respectively (P = 0.003). Barotrauma PEEP was 49.3 ± 1.9 cmH2O in the PEEP-50 group, whereas all animals in the PEEP-20 group reached 20 cmH2O of PEEP without developing barotrauma (P <0.001). Barotrauma Paw was 38.7 ± 2.7 and 57.9 ± 2.3 cmH2O in the PEEP-20 and PEEP-50 groups, respectively (P <0.001; Table 1, Fig. 3). Barotrauma PEEP and Paw were directly correlated with barotrauma MIP (r = 0.773; P = 0.002 and r = 0.879; P <0.001, respectively).

Table 1
Table 1:
Direct barotrauma pressures and safety ranges during two different recruitment manoeuvres in healthy rabbit lungs

Pressure safety range

The difference between barotrauma MIP and anatomically open lung MIP (i.e. the pressure safety range) was significantly higher in the PEEP-50 group than in the PEEP-20 group (42.1 ± 3.9 vs. 33.3 ± 8.7 cmH2O; P = 0.035; Table 1). Barotrauma PEEP and Paw were directly correlated with the pressure safety range (r = 0.61; P = 0.027 and r = 0.727; P = 0.005, respectively).

Barotrauma driving pressure

Driving pressure differences between groups in barotrauma conditions were significantly different (37.5 ± 6.1 and 16.4 ± 2.4 cmH2O in the PEEP-20 and PEEP-50 groups, respectively; P <0.001).

All relevant pressures obtained during a recruitment manoeuvre are shown in Table 1.


In this study, we explored the pressure levels needed to re-expand collapsed lung and the pressure limits resulting in barotrauma of ex-vivo healthy lungs submitted to two different recruitment strategies. We found similar opening pressures but substantially lower barotrauma pressures when the recruitment strategy was extended with a combination of a lower PEEP and progressively higher driving pressure (PEEP-20 group) when compared with the combination of a higher PEEP and fixed lower driving pressure (PEEP-50). Consequently, we found a larger margin of safety between recruitment and barotrauma pressures in the PEEP-50 group, suggesting that this recruitment strategy might be a safer means to recruit the lung when higher pressures are needed.

We describe a MIP threshold, which corresponds to transpulmonary pressure, after which direct barotrauma occurs. Such a threshold has, to our knowledge, never been established for healthy lungs before. We have found that barotrauma is not so much related to a high PEEP level or mean airway pressure per se because lungs exposed to incrementally higher PEEP and Paw had higher barotrauma MIP (PEEP-50 group) than those exposed to lower PEEP and Paw (PEEP-20 group). Our results suggest that, together with the absolute MIP reached, the most relevant factor determining the risk of barotrauma is the use of a larger driving pressure to achieve a given MIP. In other words, a lower cyclical stretch determined by the level of driving pressure (in our study 15 cmH2O), even at the expense of higher PEEP levels (up to 45 cmH2O), better protects the lung from high pressures.

Barotrauma MIP varied between animals but was always within 50 to 70 cmH2O, much higher than the anatomically open lung MIP of 20 to 30 cmH2O. Our data indicate that there seems to be a rather large margin of safety because the maximum pressures needed to recruit the lung are almost half of those needed to induce barotrauma in healthy lungs. Therefore, in the model used representing small healthy lungs, direct barotrauma can be considered a very low or non-existent hazard at MIP values below 50 cmH2O. This margin of safety is even larger when a higher PEEP with a constant low driving pressure is provided. Conversely, the animals with a lower maximum PEEP (20 cmH2O) developed barotrauma at a MIP approximately 10 cmH2O lower than in the PEEP-50 group (Figs 1 and 3).

Regarding recruitment pressures, we found that anatomically open lung MIP values of 20 to 30 cmH2O were observed in all animals, suggesting that higher pressures are not necessary to fully recruit healthy lungs. These pressures are consistent with, and even lower than, those described for recruitment manoeuvres in adults with healthy lungs, in whom maximum airway pressures typically vary between 40 and 45 cmH2O,6 and in paediatric patients, in whom documented effective recruitment pressures are as high as 20 cmH2O.7,17–19

Recruitment manoeuvres have been described mainly for patients with diseased lungs,20 although they are increasingly used in patients with healthy lungs under general anaesthesia.6 Among patients with healthy lungs, intraoperative benefits of lung recruitment have been described for patients undergoing cardiac surgery,21–23 laparoscopic surgery,24,25 thoracic surgery with one lung ventilation,26,27 morbidly obese patients28–32 and paediatric patients.7,33 Our results provide useful information which may apply to healthy lungs including those of children, among whom data regarding recruitment pressures and, more importantly, upper safety pressure thresholds which should not be exceeded are completely lacking. In ARDS patients, pressures needed to fully recruit the lung are higher34,35 and, due to the heterogeneous nature of the disease, the pressures needed to rupture the lung is very probably lower than the ones obtained in this model.34 Surprisingly, the reported incidence of barotrauma is as low as 1%36 and a recent Cochrane review concluded that recruitment manoeuvres did not increase the rate of barotrauma in ARDS patients.37

There are several limitations of this study that need to be addressed.

The experimental model used in this study does not completely represent a paediatric patient. In children, lung alveolarisation occurs at the age of 2 to 3 years, reaching complete maturity only at 6 to 8 years.38 Nevertheless, in 12-week-old rabbits, lung alveolarisation is still not complete,39 and the use of an open-chest condition avoiding the influence of the thoracic wall resembles children's high chest wall compliance.40 This, together with the fact that the mechanical characteristics of the lung are similar among different mammalian species,41 suggests that our model shares important characteristics of paediatric patients 2 to 3 years of age.

Extrapolation of our results to the clinical environment has further limitations. The open thorax eliminates the effects of the chest wall and pleural pressure and this must be considered when interpreting our results. However, it is important to remember that in small children, the effect of the chest wall is minor.40 An open-chest condition may be even more sensitive to barotrauma because the modulation of pleural pressure is lost and transpulmonary pressure always equals alveolar pressure because, by definition, pleural pressure is zero (i.e. atmospheric pressure). Accordingly, barotrauma pressures in healthy lungs with an intact chest wall may be higher than those described in this study. Equally, open lung pressures were probably underestimated because transpulmonary pressure was higher for any given airway pressure when compared with the intact chest wall. This might explain the differences observed with the recruitment manoeuvre pressures described in previous studies.7,17–19

The open chest model allows for visual confirmation of the absence of atelectasis because transpulmonary pressure should be the same throughout the lung. Thus, absence of atelectasis in the lung exposed to view, which included the ventral and medial aspects and most of the dorsal part, allowed us to identify the anatomically open lung condition. Nevertheless, we cannot rule out the possibility of persistence of small atelectatic regions in the most dorsal dependent portions of the lung that remained hidden from view.

The high transpulmonary pressures applied in this protocol would certainly have caused severe haemodynamic impairment, especially at the highest pressures applied. Even though barotrauma pressures should never be reached in healthy patients with normal chest wall compliance, the recruitment pressures determined can have profound haemodynamic effects, especially in hypovolaemic patients. Therefore, recruitment manoeuvres should always be performed with caution and only in normovolaemic patients because the pressures resulting in haemodynamic detrimental effects are far below those which cause barotrauma. Therefore, haemodynamic monitoring and stability should be the main concern during recruitment manoeuvres.

The lack of pulmonary vascular pressure potentially contributing to alveolar tethering and lung damage introduces further uncertainties when relating our findings to the clinical setting. However, the use of high PEEP and inspiratory pressures are associated with a decrease in right ventricular function and hence decreased pulmonary blood flow, so that the vascular contribution to lung injury during a brief recruitment manoeuvre is likely to be small.

Finally, this study focused only on the mechanical effects on the lung of increases in airway pressure. Given the fact that the experiments were intended to detect barotrauma, an evidently stressful terminal event, the authors considered that it was advisable to conduct the study in euthanised animals. By doing so, we assumed the limitations but also the potential advantages of using an ex-vivo open chest model.

In conclusion, we found a large margin of safety with respect to the risk of barotrauma when performing recruitment manoeuvres in healthy lungs. This safety range can be further increased when a constant low driving pressure is applied in combination with high PEEP levels to recruit the lung.


Assistance with the study: the authors would like to thank the staff of the Experimental Unit of La Paz University Hospital (Madrid, Spain) for their assistance with the study.

Financial support and sponsorship: this work was supported by the Foundation of La Paz University Hospital, Madrid, Spain.

Conflicts of interest: none declared.


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