Lung imaging for titration of mechanical ventilation

REVIEW URRENT C OPINION

Lung imaging for titration of mechanical ventilation Thomas Luecke a, Francesco Corradi b, and Paolo Pelosi b

Purpose of review Computed tomography (CT) has fostered pivotal advancements in the understanding of acute lung injury/ acute respiratory distress syndrome and ventilator-induced lung injury. Apart from CT-based studies, the past years have seen fascinating work using positron emission tomography, electrical impedance tomography and lung ultrasound as diagnostic tools to optimize mechanical ventilation. This review aims to present the major findings of recent studies on lung imaging. Recent findings Patients presenting with a focal loss of aeration on CT may not be suitable candidates for recruitment maneuvers and high levels of positive end-expiratory pressure (PEEP) in supine position. PET/CT has provided valuable insights into the inflammatory response of the lung. Electrical impedance tomography has been used to assess lung recruitability and to titrate PEEP. Finally, lung ultrasound has proven to be reliable diagnostic tool for assessing PEEP-induced recruitment. Summary Whereas quantitative CT remains the gold standard to assess lung morphology, recruitment and hyperinflation of lung tissue at different inflation pressures, EIT and LUS have emerged as valuable, radiation-free, noninvasive bedside lung imaging tools that should be used together with global parameters like lung mechanics and gas exchange to acquire additional information on recruitability and ventilation distribution. Keywords acute respiratory distress syndrome, computed tomography, electrical impedance tomography, imaging, lung ultrasound, mechanical ventilation, positron emission tomography

INTRODUCTION Mechanical ventilation, albeit being the cornerstone of therapy for acute lung injury/acute respiratory distress syndrome (ALI/ARDS), also has the potential to induce lung injury per se when leading to unphysiological stress and strain of the lung parenchyma, resulting in inflammatory responses and mechanical lesions up to stress at rupture [1 ]. Whereas protective mechanical ventilation using low tidal volumes (VT) and limited inspiratory plateau pressures (Pplat) has been established as a key therapeutic strategy for treating ALI/ARDS [2], controversy still exists about the optimum approach to minimize ventilator-induced lung injury (VILI) [3]. The two basic pathophysiological mechanisms causing VILI are cyclic overdistention caused by excessive transpulmonary pressure (Ptp) and cyclic opening and closing of atelectatic alveoli and distal small airways with tidal ventilation [4]. Lung protective strategies aim at preventing cyclic overdistention by limiting tidal volume to 6 ml/kg predicted body weight (PBW) and/or plateau pressure below 30 cmH2O as well as preventing intratidal &

collapse of pulmonary units by providing a positive end-expiratory pressure (PEEP) sufficient to keep the lung open throughout the respiratory cycle [1 ]. Whereas the first part of this strategy (limiting strain and stress by limiting tidal volume and inspiratory pressures) had been tested in a large randomized trial [5], a study by Terragni et al. [6] using computed tomography (CT) of the lungs demonstrated that one-third of the patients with severe ARDS being ventilated with low tidal volume showed alveolar overdistention, calling into question safe general thresholds for tidal volume or inspiratory plateau &

a

Department of Anesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Mannheim, Germany and bDepartment of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy Correspondence to Professor Thomas Luecke, Department of Anesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Mannheim, Germany. Fax: +49 621 383 2122; e-mail: [email protected] Curr Opin Anesthesiol 2012, 25:131–140 DOI:10.1097/ACO.0b013e32835003fb

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Intensive care and resuscitation

KEY POINTS Quantitative CT still presents the gold standard to assess lung morphology and to quantify recruitment and hyperinflation of lung tissue at different inflation pressures.

whole-lung helical CT due to large craniocaudal gradients in the injured lungs. Whole lung quantitative CTs, however, result in substantial x-ray exposure and considerable amount of work required to manually segment the CT images to obtain quantitative data [12]. To address these problems, Reske et al. [13 ] showed that extrapolation from only 10 thoracic CT scans can provide reliable information on the aeration of the entire lung, thus reducing radiation exposure and time required for quantitative analysis. We believe that this study is a crucial step towards a broader acceptance of quantitative CT as a routine diagnostic tool to titrate PEEP and tidal volume early in the course of acute lung injury. &

PET offers the unique possibility to image lung inflammatory response, providing valuable insights into ventilator-induced lung injury. Electrical impedance tomography and lung ultrasound may evolve as bedside imaging techniques to titrate mechanical ventilation.

pressures. Even more controversy exists on the second part of the ‘lung protective strategy’ related to the PEEP selection. The results of the large clinical trials [7–9] testing ‘higher versus lower’ PEEP strategies may not provide sufficient guidance to set PEEP in a given patient, whereas individualized approaches to titrate PEEP lack external validity and agreement about endpoints [10]. Therefore, it is not surprising that there is continued and even increasing interest in the use of different imaging techniques to better guide mechanical ventilation in ALI/ARDS.

COMPUTED TOMOGRAPHY Quantitative analysis of CT has enabled pivotal advancements in the understanding of ALI/ARDS pathophysiology.

Technical aspects The digital images produced by CT scans consist of a matrix of voxels, that is, volume elements that attenuate the radiation of the CT scanner according to the density of the tissue contained in the voxel. CT attenuation, expressed in Hounsfield units (HU), is referenced to distilled water and air, with values of 0 and -1000 HU, respectively, assuming that tissue has the same density as water and that pulmonary gas has the same density as air [11 ]. According to their HU, voxels can be grouped into different aeration compartments, which allows quantification of lung parenchyma as overinflated, normally aerated, poorly aerated and nonaerated (Fig. 1). When repeated at different inflation pressures, lung CT can quantify recruitment and overinflation (Fig. 2), thus providing the ‘anatomical basis’ for individualized ventilator settings. Whereas early CT studies mostly used one or three CT scan slices, those studies may lead to inaccurate estimates of recruitment and overdistention compared to &

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Computed tomography to assess recruitability and to titrate mechanical ventilation Several recent studies have used CT to assess recruitability and to titrate mechanical ventilation. In a landmark study, Gattinoni et al. [14] evaluated lung recruitability in 68 ALI/ARDS patients by whole lung CT scans taken at 5 cmH2O of PEEP and at 45 cmH2O plateau pressure. To assess the effects of high PEEP, another CT scan series was performed at PEEP ¼ 15 cmH2O. The percentage of potentially recruitable lung varied widely and was strictly associated with the overall severity of the lung injury as detected by CT scan and respiratory physiologic variables. Of note, respiratory physiologic variables, particularly the changes in oxygenation, were poor predictors of lung recruitability. On the basis of these results, the authors concluded that evaluation of the potentially recruitable lung seems to be essential when approaching how to set the optimal level of PEEP. More recently, the same group [15 ] investigated how lung recruitability influences alveolar strain and intratidal opening and closing after the application of high PEEP. Reanalyzing the CT data from the multicenter study [14], they showed that in patients with greater lung recruitability, the impact of reducing the amount of opening and closing lung tissue by increasing PEEP seems to prevail over the potentially harmful effects of increasing alveolar strain. Based on the uncertainty of how much PEEP would be necessary during ALI/ARDS, this study suggests evidence in favor of the application of high (15–20 cmH2O) levels of PEEP, especially in patients with high lung recruitability. Notably, this conclusion, based on firm pathophysiological data, fits into the result of the recent meta-analysis on the use of PEEP by Briel et al. [16], showing a reduced mortality for higher levels of PEEP in patients meeting ARDS criteria. Albeit somewhat reassuring, it has to be kept in mind, however, that alveolar strain, &&

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Lung imaging for titration of mechanical ventilation Luecke et al.

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FIGURE 1. Analysis of distribution of Hounsfield units (HU) in whole-lung computed tomography obtained from a normal (a) and an ARDS (b) patient allows quantification of lung parenchyma as overinflated (%O), normally aerated (%N), poorly aerated (%P) and nonaerated (%No). ARDS, acute respiratory distress syndrome.

defined as the ratio between the amount of gas volume delivered during tidal breath and the amount of aerated lung receiving it, may become too high and inevitably result in tidal hyperinflation in patients with a larger nonaerated compartment. This has been shown by Terragni et al. [6] and is highly relevant, as CT can identify the subgroup of patients that will not be protected even by tidal volumes as low as 6 ml/kg PBW. Therefore, CT has a unique role in identifying patients not suitable for ‘lung protective conventional mechanical ventilation’ who need further reduction in tidal volume and probably alternative ventilatory strategies like extracorporeal CO2 removal and/or high frequency oscillatory ventilation (HFOV) [17]. On the basis of these findings, we believe that in patients with severe ARDS and inspiratory plateau pressures still above 28 cmH2O after titration of PEEP and tidal volume of 6 ml/kg PBW, lung CT is highly warranted in order to decide on alternative ventilatory techniques.

Alveolar recruitment maneuvers are commonly applied as an integral part of ‘open lung strategies’ [18] and – together with a sufficient level of PEEP – aim at reducing the repetitive opening and closing of unstable lung units. As the amount of potentially recruitable lung volume varies widely in ALI/ARDS patients [14], it is not surprising that the routine use of recruitment maneuvers yielded variable results [19]. In order to determine whether differences in lung morphology, defined as differences in the pulmonary distribution of aeration loss and assessed by whole lung CT, can predict the response to recruitment maneuvers, Constantin et al. [20 ] studied 19 consecutive patients with early ALI/ARDS at zero end-expiratory pressure (ZEEP) during open lung ventilation [VT 6 ml/kg, PEEP set at 2 cmH2O above the lower inflection point of the inspiratory pressure-volume (PV) curve], during a recruitment maneuver and 5 min after the recruitment maneuver during open lung ventilation. Nine patients presented focal and 10 patients presented nonfocal


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FIGURE 2. Representative computed tomography images and their distribution of Hounsfield units at low PEEP (a) and high PEEP (b) levels allow quantifying lung recruitability of consolidations and overdistension of normally aerated parenchyma. In this example, high levels of PEEP result in an increase in overinflated lung parenchyma (%O) and a moderate decrease in poorly (%P) and nonaerated (%No) lung parenchyma with no changes in normally aerated lung parenchyma (%N). This quantitative analysis demonstrates poor recruitability by high PEEP. PEEP, positive end-expiratory pressure.

lung morphology at ZEEP. Patients with focal lung morphology were at substantial risk for significant hyperinflation during the recruitment maneuver, whereas lung recruitment was very limited. The authors conclude that recruitment maneuver and high levels of PEEP should be discouraged in patients with focal loss of aeration and that chest CT must be considered if lung morphology is not evident on chest radiograph.

Computed tomography to assess the effects of new ventilatory modes Two recent studies used CT to study the effects of biologically variable ventilation in experimental lung injury. Ruth Graham et al. [21 ] compared conventional mechanical ventilation to biologically &

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variable ventilation in a porcine oleic injury lung injury model. Using quantitative CT analysis, they showed that biologically variable mechanical ventilation significantly increased total and normally aerated lung, most likely owing to the recruiting effects of the certain numbers of high tidal volume breaths, or ‘sighs’ [22]. Carvalho et al. [23 ] assessed the distribution of regional aeration and perfusion during conventional and noisy pressure support ventilation (PSV) as well as during pressure controlled ventilation (PCV) in a porcine surfactantdepletion lung injury model. The distribution of lung aeration was determined by static and dynamic CT, whereas the distribution of pulmonary blood flow (PBF) was determined by intravenously injected fluorescent microspheres. PSV and noisy PSV did not decrease nonaerated areas but led to a &




redistribution of PBV from dorsal to ventral lung regions and reduced tidal reaeration and hyperinflation compared with PCV, with the positive effects of noisy PSV being more pronounced.

involved regions that appeared ‘normally aerated’, suggesting that no region of the lung is spared by the presence of activated inflammatory cells, whereas the intensity of this activation and its regional distribution vary widely within and between patients. In a second study [28 ], the same group performed a PET scan of the chest and three CT scans (at mean airway pressure, end-expiration and endinspiration) in 13 patients with ALI ventilated at relatively high levels of PEEP (13.4 2.7 cmH2O). They showed that inflammation of the normally aerated tissue and of the whole lung is associated both with plateau pressure, showing a pronounced increase above 26–27 cmH2O, and with the ratio between regional VT and end-expiratory lung volume. Of note, the steep increase in inflammation seen at plateau pressure above 26–27 cmH2O calls into question the commonly held notion that plateau pressures up to 30 cmH2O might be ‘safe’ and corresponds well to the findings by Terragni et al. [6] who identified a threshold for plateau pressure around 27 cmH2O as discriminating the patients between ‘more’ and ‘less’ protected from mechanical ventilation. Even based on these preliminary data, it seems reasonable to conclude that PET/CT holds a great promise to better assess lung inflammatory response and to help titrate mechanical ventilation not only to optimize lung morphology but rather lung function and inflammatory response. To further address the relationship between inflammation and regional mechanical stress, de Prost et al. [29 ] studied sheep undergoing unilateral saline lung lavage with the nonlavaged lungs serving as controls. They showed highest metabolic activity in poorly aerated dependent regions following lung lavage suggesting local increased inflammation. The authors also used injected [13N2] to compute regional perfusion and ventilation. Thus, this work also can be viewed as one of the most comprehensive imaging studies to date, allowing quantification of regional aeration, ventilation, perfusion and metabolic activity. &&

POSITRON EMISSION TOMOGRAPHY PET is a functional imaging technique based on the detection of a labeled molecule administered to a patient. Combined with CT, PET has recently been used in ALI/ARDS as an imaging tool to study pathophysiology in vivo noninvasively on a regional basis. Two recent review articles [24 ,25 ] provide excellent in-depth discussion on the principles and use of this evolving technique in the setting of ALI/ARDS and VILI. Therefore, only the most recent and important studies are discussed here. Wellman et al. [26 ] used PET of equilibrated [13N2] to measure regional specific lung volume change. They showed that during low tidal volume ventilation, application of high PEEP to endotoxin-injured lungs allowed achievement of a degree of uniformity in ventral-to-dorsal tidal expansion that was higher than that of healthy lungs ventilated at ZEEP. Whereas specific volume change, which is conceptually equivalent to changes in lung aeration during tidal breathing derived from CT, reflects the gas content of a region, PET also allows true assessment of regional alveolar ventilation by tracing [13N2] washout. In contrast to plain CT, which cannot answer the question whether effective alveolar gas turnover takes place in a given aerated lung volume, PET/CT allows to specifically address this important point. Recently, there has been growing interest in the use of [18F]fluoro-2-deoxy-D-glucose (FDG) to measure regional lung inflammation in ALI/ARDS with PET. The rationale for this approach is that activated neutrophils have a rate of glucose utilization much higher than other inflammatory cells and lung parenchyma because neutrophil metabolism is almost exclusively supported by anaerobic glycolysis. [18F]FDG as an analog of glucose is taken up by cells by the same transporters and the same rate as glucose, but cannot proceed any further in the glycolytic pathway and therefore remains trapped in the cells. Two recent clinical studies have used PET with [18F]FDG to image lung metabolic activity (which is likely to reflect inflammation) [24 ]. In the first study [27], 10 patients with ALI/ARDS undergoing mechanical ventilation for 5.4 4.3 days were studied. The metabolic activity of the lungs was markedly increased and correlated with the derangement in oxygenation. Of note, inflammation was not confined to regions with density abnormalities on the CT scan, but also &

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ELECTRICAL IMPEDANCE TOMOGRAPHY Functional electrical impedance tomography (EIT) of the lung noninvasively measures relative impedance changes in lung issue during tidal breathing and creates images of the local ventilation distribution at the bedside. EIT has been the subject of two recent concise reviews [30 ,31 ] that cover technical aspects, open questions, potential applications as well as recent studies. Therefore, we would just like to remind the reader on some basic methodological aspects that should be kept in mind when


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interpreting study results or using the technique at the bedside: The primary physical parameter ‘imaged’ by EIT is the change of electrical resistivity, that is the specific electrical resistance, in relation to a physiological reference state. The resistivity of lung tissue depends on its morphology, air content, the amount of intracellular and extracellular fluids and blood volume in the examined part of the lung [30 ]. As emphasized by Moerer et al. [30 ], clinical application of EIT is nearly exclusively based on image reconstruction techniques that require at least one measurement on a well defined reference state. All quantitative data are related to this reference and can only indirectly quantify changes in local lung volume but not absolute local lung volume. If reference states of two measurements differ markedly, an identical change in lung volume can result in differing quantitative EIT images. Whereas these and other technical and methodological problems should be taken into account, EIT nevertheless for the first time provides the opportunity to visualize online and noninvasively the effects of ventilation and ventilatory maneuvers at the bedside and there is growing evidence that supports the use of EIT to individually titrate mechanical ventilation at the bedside. &

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Electrical impedance tomography to assess potential lung recruitability and to set PEEP As shown by Gattinoni et al. [14], the amount of potentially recruitable lung volume (PRLV) is extremely variable in ALI/ARDS. To overcome the potential drawbacks of the CT-based assessment of recruitability, Lowhagen et al. [32 ] assessed whether an EIT-based technique (together with end-expiratory lung volume measurements using a modified nitrogen wash-out/wash-in procedure and volumedependent compliance) could determine PRLV. Sixteen mechanically ventilated patients with early ALI/ARDS were studied. A considerable heterogeneity in lung recruitability (PRLV range 11–47%) was observed. The authors concluded that EIT-based methods may be used to determine the need for recruitment maneuvers and to select PEEP on the basis of lung recruitability. The same group [33] investigated regional intratidal gas distribution before and after a step increase in PEEP and an ensuing decremental PEEP trial using EIT in ALI/ ARDS patients. Analyzing regional impedance changes over time curves, they evaluated intratidal gas distribution and collected information on regional lung mechanics, assessing for the first time volume-dependent initial and final regional compliance. The principal finding of this study was that using regional alveolar pressure–volume curves, &

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obtained by combining regional volume measurements from the EIT with global volume-dependent pressure–volume curves, it was possible to identify different gas distributions and volume-dependent compliance patterns in individual patients. The authors concluded that online intratidal gas distribution monitoring by EIT offered additional information on recruitability and PEEP. Whereas the first clinical study on PEEP selection by EIT by Erlandsson et al. [34] proposed to set PEEP to maintain a stable end-expiratory lung volume, other approaches have recently been described. Most of them focus on minimization of ventilation inhomogeneities, like the study by Zhao et al. [35], who used the global inhomogeneity index based on EIT images. Likewise, Dargaville et al. [36] performed a stepwise vital capacity maneuver in different experimental lung conditions and were able to identify a PEEP level at which tidal ventilation is relatively homogeneous in all lung regions. Finally, Karsten et al. [37] studied the effect of 10 cmH2O of PEEP compared to ZEEP during laparoscopic surgery. Differences in regional ventilation were analyzed by the EIT-based center-of-ventilation (COV) index, which quantifies the distribution of ventilation and indicates ventilation shifts. They showed that PEEP and recruitment maneuver preserved homogeneous regional ventilation during laparoscopic surgery in most patients. It should be noted, however, that homogenization of lung ventilation somewhat became synonymous with protecting the lungs, assuming that reopened lung units can improve the ventilation distribution by accommodating part of the tidal volume, thus minimizing tidal hyperinflation as well. As outlined by Costa and Amato [38], however, in normal lungs with minimal collapse, heterogeneity of lung ventilation is a physiologic phenomenon which is mirrored by the heterogeneity of lung perfusion. Therefore, looking at ventilation homogeneity may be a useful approach to titrate PEEP, but in order to explore its fullest potential, EIT most likely has to be combined with additional techniques like end-expiratory lung volume (EELV) measurements, gas exchange data and lung mechanics as part of a multimodal monitoring approach. As EIT images a definite volume around the planes of electrodes but not the entire lungs, redistribution of air in the craniocaudal direction between different states (e.g. PEEP levels) presents a potential source of error. Whereas EIT can be measured at different cranio-caudal levels of the thoracic cage, the caudal thoracic level just above the diaphragm is most commonly used. From CT analysis, however, it is well known that this level is not representative for the entire lung and this reason Volume 25 Number 2 April 2012



may well explain the conflicting results found between regional lung parameters measured with EIT and global lung parameters, such as compliance or EELV. To address this problem, Bikker et al. [39 ] evaluated whether ventilation distribution measured by EIT, and the relation between EIT regional compliance and global dynamic compliance, differs between a cranial to caudal thoracic level in response to decremental PEEP steps. Measurements were performed at four levels of PEEP (0–15 cmH2O) in 12 mechanically ventilated patients after cardiac surgery and revealed different behavior between caudal and cranial lung levels with optimal regional compliance at 10 and 5 cmH2O of PEEP at the cranial slice and 15 and 10 cmH2O of PEEP at the caudal slice for the dependent and nondependent lung regions, respectively. &

LUNG ULTRASOUND Until recently, transthoracic lung ultrasound (LUS) was considered a poorly accessible method, due to the inability to penetrate the air-filled lung. Despite its limitations, LUS is being increasingly used in a growing number of pathological situations such as pneumonia, atelectasis, pneumothorax and pleural effusion. LUS is relatively easy to learn, repeatable and without the need of exposure to ionizing radiation. It is very sensitive to detect acute interstitial syndromes and consolidations especially when localized to basal and upper lung fields. However,

Electrical impedance tomography to guide lung recruitment in high-frequency ventilated infants &

Miedema et al. [40 ] used EIT to measured changes in lung volume and ventilation in 15 high-frequency oscillatory ventilated preterm infants during oxygenation-guided recruitment maneuvers. The inflation and the deflation limbs were mapped, and the lower and upper inflection points were calculated using both oxygenation and impedance data. They demonstrated large lung hysteresis in preterm infants with respiratory distress syndrome. Whereas optimal recruitment increased the oscillation volume, the distribution of ventilation was relatively homogeneous along a ventral–dorsal axis.

FIGURE 3. (a) Massive atelectasis of the left lung. Instead of an acoustic barrier, a tissue image is visible on lung ultrasound, showing complete consolidation of lower left lobe with static air bronchograms (). (b) Lung re-expansion after recruitment maneuvers.

FIGURE 4. (a) Lung ultrasound image of normally aerated parenchyma when the probe is applied in a longitudinal axis over the thorax. The superficial layers are visible at the top of the screen. The large horizontal arrow represents the pleural line. The small arrows represent the a lines that are deep repetitions of the pleural line. The vertical arrow represents the rib posterior acoustic shadow. (b–d) Lung scans from interstitial to diffuse alveolar edema. (b) B-line artefacts () arising from the pleural line with vertical orientation that are comet tails with well defined laser-like lines that spread up to the edge of the image without fading. The distance between each comet tail is approximately 7 mm and represents the thickening of the interlobular septa with 95% degree of lung aeration. When the distance between comet tails drop to 3 mm the degree of lung aeration is approximately 80%. However, in these image superficial layers, ribs acoustic shadow and pleural line are still present. (c) Multiple B-line artefacts () with abnormal and inhomogeneous thickening of the pleural line and small subpleural consolidation (white arrow) with spared areas in lung parenchyma; (d) The ribs (vertical arrows) are recognized by their curved shape with posterior acoustic shadow (bath sign). Between rib shadows ‘white lung’ parenchyma with concomitant disappearance of horizontal and vertical artefacts representative of groundglass areas with 80% or lower degree of aeration compatible with diffuse alveolar flooding and/or alveolar edema.



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it is difficult to differentiate between different types of consolidation (e.g. pneumonia, atelectasis) and LUS does not allow a quantitative analysis of the distribution of aeration. Its basic principles and current applications have been concisely illustrated in a recent review [41 ]. LUS has yielded a considerably better diagnostic performance than chest radiography in an unselected ICU population [42]. Bouhemad et al. [43] studied lung reaeration by LUS in patients with ventilator-associated pneumonia treated by antibiotics. LUS of the entire chest was performed and four entities were defined: consolidation; multiple irregularly spaced B-lines; multiple abutting ultrasound lung ‘comets’ issued from the pleural line or a small subcostal consolidation; normal aeration (Figs 3 and 4). Ultrasound changes were measured between days 0 and 7 and a reaeration score was calculated. A highly significant correlation was found between CT and ultrasound reaeration, whereas the chest radiograph was inaccurate. Using this reaeration score, the same group [44 ] used LUS to assess PEEP-induced lung recruitment in 30 patients with ALI/ARDS as compared to the PVcurve method. A highly significant correlation was found between PEEP-induced lung recruitment measured by PV curves and ultrasound reaeration score. In addition, LUS reaeration score correlated &

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with the PEEP-induced increase in PaO2. As LUS cannot assess PEEP-induced hyperinflation, however, the authors emphasize that LUS should not be the sole method for PEEP titration. In keeping with these findings, LUS was shown to detect the nonaerated lung area changes during a PEEP trial in 10 patients with early ARDS [45].

CONCLUSION Apart from quantitative CT, which still has to be regarded as the gold standard to assess lung morphology and to quantify recruitment and hyperinflation, new imaging tools have emerged over the past years. Whereas PET/CT may provide the most comprehensive insights, additionally covering the inflammatory response and/or ventilation/perfusion distributions, bedside, radiation-free and noninvasive techniques like EIT and lung ultrasound hold great promise to support optimal ventilator settings in clinical practice. Given their inherent limitations, however, findings need to be interpreted with some caution and those techniques should be regarded to provide adjunctive information used as a part of a multimodal monitoring approach. The major advantages and disadvantages of the imaging techniques described are summarized in Table 1.

Table 1. Overview on imaging techniques to titrate mechanical ventilation Imaging technique

Advantages

Disadvantages

Computed tomography (CT)

Gold standard for objective and quantitative assessment of:

High radiation exposure

Lung morphology and volumes

Requires patient transportation

Recruitment and overinflation

Data analysis cumbersome

Gold standard to titrate PEEP and VT

Expensive

Positron emission tomography (PET)

Allows imaging of lung inflammatory response

Limited to few specialized centers See CT

Electrical impedance tomography (EIT)

Most comprehensive technique (combined with CT) Bedside technique Radiation-free and noninvasive

No evaluation of pleural effusion, atelectasis and consolidation

Online monitoring

No quantitative measurement of aeration distribution

Detects regional aeration and recruitment

Measures impedance changes rather than true lung volumes

Regional measurements only Endpoints for titration of MV ill defined

Lung ultrasound

Bedside technique

No quantitative measurement of aeration distribution

Radiation-free and noninvasive

Cannot assess overinflation

Online monitoring Detects pleural effusion, atelectasis, consolidation and recruitment PEEP, positive end-expiratory pressure; VT, tidal volume.

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Acknowledgements None. Conflicts of interest This study was not supported by any financial support. There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 261). 1. Gattinoni L, Carlesso E, Brazzi L, et al. Positive end-expiratory pressure. Curr & Opin Crit Care 2010; 16:39–44. This important review thoroughly discusses the rationale as well as the methods to titrate optimal PEEP levels in patients with ALI/ARDS. 2. Putensen C, Theuerkauf N, Zinserling J, et al. Meta-analysis: ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury. Ann Intern Med 2009; 151:566–576. 3. Del Sorbo L, Slutsky AS. Ventilatory support for acute respiratory failure: new and ongoing pathophysiological, diagnostic and therapeutic developments. Curr Opin Crit Care 2010; 16:1–7. 4. Tremblay LN, Slutsky AS. Ventilator-induced lung injury: from the bench to the bedside. Intensive Care Med 2006; 32:24–33. 5. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301– 1308. 6. Terragni PP, Rosboch G, Tealdi A, et al. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 2007; 175:160–166. 7. Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive endexpiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004; 351:327–336. 8. Meade MO, Cook DJ, Guyatt GH, et al. 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. J Am Med Assoc 2008; 299:637–645. 9. Mercat A, Richard JC, Vielle B, et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. J Am Med Assoc 2008; 299:646–655. 10. Rubenfeld GD. How much PEEP in acute lung injury. J Am Med Assoc 2010; 303:883–884. 11. Pelosi P, Rocco PR, de Abreu MG. Use of computed tomography scanning to & guide lung recruitment and adjust positive-end expiratory pressure. Curr Opin Crit Care 2011; 17:268–274. A recent and comprehensive review on the use of computed tomography scanning to titrate ventilator settings. 12. Gattinoni L, Cressoni M. Quantitative CT in ARDS: towards a clinical tool? Intensive Care Med 2010; 36:1803–1804. 13. Reske AW, Reske AP, Gast HA, et al. Extrapolation from ten sections can & make CT-based quantification of lung aeration more practicable. Intensive Care Med 2010; 36:1836–1844. An important methodological study showing that the use of 10 slices combined with a simple trapezoidal interpolation procedure permits an accurate estimation of lung aeration. This technique will allow quantitative CT scanning at much lower radiation exposure and faster image analysis. 14. Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 2006; 354:1775–1786. 15. Caironi P, Cressoni M, Chiumello D, et al. Lung opening and closing during && ventilation of acute respiratory distress syndrome. Am J Respir Crit Care Med 2010; 181:578–586. An important study in patients with ARDS, showing that – in the presence of high recruitability – the benefical impact of reducing intratidal alveolar opening and closing by increasing PEEP prevails over the effects of increasing alveolar strain. 16. Briel M, Meade M, Mercat A, et al. Higher vs. lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. J Am Med Assoc 2010; 303:865–873. 17. Terragni PP, Del Sorbo L, Mascia L, et al. Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal. Anesthesiology 2009; 111:826–835. 18. Lachmann B. Open up the lung and keep the lung open. Intensive Care Med 1992; 18:319–321.

19. Fan E, Wilcox ME, Brower RG, et al. Recruitment maneuvers for acute lung injury: a systematic review. Am J Respir Crit Care Med 2008; 178:1156– 1163. 20. Constantin JM, Grasso S, Chanques G, et al. Lung morphology predicts && response to recruitment maneuver in patients with acute respiratory distress syndrome. Crit Care Med 2010; 38:1108–1117. This study showed that lung morphology at ZEEP predicts the response to recruitment maneuvers. Patients with focal lung morphology were at substantial risk for significant hyperinflation during the recruitment maneuver, whereas lung recruitment was very limited. On the basis of these findings, the authors strongly advise a computed tomography assessment of the patient if lung morphology is not evident on chest radiograph. 21. Ruth Graham M, Goertzen AL, Girling LG, et al. Quantitative computed & tomography in porcine lung injury with variable versus conventional ventilation: recruitment and surfactant replacement. Crit Care Med 2011; 39:1721– 1730. By using quantitative computed tomography, this study showed that biologically variable ventilation resulted in significant recruitment, probably because of the intermittent high tidal volume breaths, or ‘sighs’. 22. Gattinoni L, Carlesso E, Cressoni M. Recruitability, recruitment, and tidal volume interactions: is biologically variable ventilation a possible answer? Crit Care Med 2011; 39:1839–1840. 23. Carvalho AR, Spieth PM, Guldner A, et al. Distribution of regional lung & aeration and perfusion during conventional and noisy pressure support ventilation in experimental lung injury. J Appl Physiol 2011; 110:1083– 1092. Another study supporting the benefits of biologically variable ventilation using a remarkable technique combining dynamic CT and microsphere-based perfusion measurements. 24. Bellani G, Amigoni M, Pesenti A. Positron emission tomography in ARDS: a & new look at an old syndrome. Minerva Anestesiol 2011; 77:439–447. Excellent review on the principles and use of positron emission tomography in ALI/ARDS. 25. Musch G. Positron emission tomography: a tool for better understanding of & ventilator-induced and acute lung injury. Curr Opin Crit Care 2011; 17:7–12. Excellent review on the principles and use of positron emission tomography in ALI/ARDS. 26. Wellman TJ, Winkler T, Costa EL, et al. Measurement of regional specific lung & volume change using respiratory-gated PET of inhaled 13N-nitrogen. J Nucl Med 2010; 51:646–653. An important PET/CT study illustrating the difference between aeration and ventilation. 27. Bellani G, Messa C, Guerra L, et al. Lungs of patients with acute respiratory distress syndrome show diffuse inflammation in normally aerated regions: a [18F]-fluoro-2-deoxy-D-glucose PET/CT study. Crit Care Med 2009; 37:2216–2222. 28. Bellani G, Guerra L, Musch G, et al. Lung regional metabolic activity and gas && volume changes induced by tidal ventilation in patients with acute lung injury. Am J Respir Crit Care Med 2011; 183:1193–1199. A landmark study using PET/CT to assess lung inflammation. This study showed a pronounced increase in lung inflammation at plateau pressures above 26– 27 cmH2O, reemphasizing that the concept of ‘safe plateau pressures’ needs reevaluation. 29. de Prost N, Costa EL, Wellman T, et al. Effects of surfactant depletion on & regional pulmonary metabolic activity during mechanical ventilation. J Appl Physiol 2011; 111:1249–1258. A remarkable study revealing the full potential of PET/CT by assessing lung regional ventilation, perfusion and inflammation. 30. Moerer O, Hahn G, Quintel M. Lung impedance measurements to monitor & alveolar ventilation. Curr Opin Crit Care 2011; 17:260–267. Excellent review on electrical impedance tomography with a strong focus on methodological aspects and limitations of this technique. 31. Muders T, Luepschen H, Putensen C. Impedance tomography as a new & monitoring technique. Curr Opin Crit Care 2010; 16:269–275. A comprehensive review on the current use of impedance tomography with a detailed discussion of different approaches to optimize ventilation. 32. Lowhagen K, Lindgren S, Odenstedt H, et al. A new nonradiological method & to assess potential lung recruitability: a pilot study in ALI patients. Acta Anaesthesiol Scand 2011; 55:165–174. Using a sophisticated technique incorporating electrical impedance data, the authors show how EIT-based approaches can be used to determine lung recruitability. As a high difference in potentially recruitable lung volume was observed, this technique may be useful to determine the need for recruitment maneuver and higher levels of PEEP. 33. Lowhagen K, Lundin S, Stenqvist O. Regional intratidal gas distribution in acute lung injury and acute respiratory distress syndrome: assessed by electric impedance tomography. Minerva Anestesiol 2010; 76:1024–1035. 34. Erlandsson K, Odenstedt H, Lundin S, et al. Positive end-expiratory pressure optimization using electric impedance tomography in morbidly obese patients during laparoscopic gastric bypass surgery. Acta Anaesthesiol Scand 2006; 50:833–839. 35. Zhao Z, Steinmann D, Frerichs I, et al. PEEP titration guided by ventilation homogeneity: a feasibility study using electrical impedance tomography. Crit Care 2010; 14:R8.



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Intensive care and resuscitation 36. Dargaville PA, Rimensberger PC, Frerichs I. Regional tidal ventilation and compliance during a stepwise vital capacity manoeuvre. Intensive Care Med 2010; 36:1953–1961. 37. Karsten J, Luepschen H, Grossherr M, et al. Effect of PEEP on regional ventilation during laparoscopic surgery monitored by electrical impedance tomography. Acta Anaesthesiol Scand 2011; 55:878–886. 38. Costa EL, Amato MB. Can heterogeneity in ventilation be good? Crit Care 2010; 14:134. 39. Bikker IG, Preis C, Egal M, et al. Electrical impedance tomography measured & at two thoracic levels can visualize the ventilation distribution changes at the bedside during a decremental positive end-expiratory pressure (PEEP) trial. Crit Care 2011; 15:R193. This study using simultaneous EIT measurements at a cranial and caudal thoracic level showed different behavior between caudal and cranial lung levels during a decremental PEEP trial. This work is helpful to better understand the differences in ventilation distribution throughout the lung. 40. Miedema M, de Jongh FH, Frerichs I, et al. Changes in lung volume and & ventilation during lung recruitment in high-frequency ventilated preterm infants with respiratory distress syndrome. J Pediatr 2011; 159:199–205; e2. A very informative study showing the use of EIT in preterm infant in order to optimize lung recruitment during high-frequency oscillatory ventilation.

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41. Stefanidis K, Dimopoulos S, Nanas S. Basic principles and current applications of lung ultrasonography in the intensive care unit. Respirology 2011; 16:249–256. A current review on lung ultrasonography, nicely explaining an illustrating the different lung signs, points, lines and patterns. 42. Xirouchaki N, Magkanas E, Vaporidi K, et al. Lung ultrasound in critically ill patients: comparison with bedside chest radiography. Intensive Care Med 2011; 37:1488–1493. 43. Bouhemad B, Liu ZH, Arbelot C, et al. Ultrasound assessment of antibioticinduced pulmonary reaeration in ventilator-associated pneumonia. Crit Care Med 2010; 38:84–92. 44. Bouhemad B, Brisson H, Le-Guen M, et al. Bedside ultrasound assessment of && positive end-expiratory pressure-induced lung recruitment. Am J Respir Crit Care Med 2011; 183:341–347. This landmark study provides evidence that lung ultrasound ca be used as a diagnostic tool for assessing positive end-expiratory pressure-induced lung recruitment. 45. Stefanidis K, Dimopoulos S, Tripodaki ES, et al. Lung sonography and recruitment in patients with early acute respiratory distress syndrome: a pilot study. Crit Care 2011; 15:R185. &

