Journal of Critical Care (2013) 28, 534.e1534.

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Effectiveness of end-expiratory lung volume measurements during the lung recruitment maneuver for patients with atelectasis
Susumu Nakahashi PT, MS , Satoshi Gando MD, PhD, Takehiko Ishikawa MD, PhD, Takeshi Wada MD, PhD, Yuichiro Yanagida MD, Nobuhiko Kubota MD, PhD, Shinji Uegaki MD, Mineji Hayakawa MD, PhD, Atsushi Sawamura MD, PhD
Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N15W7 Kita-ku, Sapporo 060-8638, Japan

Keywords:
Recruitement maneuver; Atelectasis; Functional residual capacity; End-expiratory lung volume; Respiratory therapy

Abstract Purpose: The aim of this study was to determine whether the relative change in the end-expiratory lung volume (EELV) obtained by the recruitment maneuver (RM) can serve as an indicator of the change in the P/F ratio. Materials and Methods: The effects of the intermittent stepwise increases in the RM (peak inspiratory pressure, 45, 50, and 55 cm H2O) were compared in 21 patients with atelectasis under mechanical ventilation. The EELV, the ratio of arterial oxygen concentration to the fraction of inspired oxygen P/F ratio, and relative change rate () in these parameters were evaluated after each RM. Results: A greater improvement in the EELV (1157 344 mL vs 1469 396 mL) and P/F ratio (250 99 vs 320 92) was observed after the RM. The EELV was correlated with the P/F ratio ( = 0.73, P b .01) and was identified as an accurate predictor of the improvement of the P/F ratio by the receiver operating characteristic curve (the area under the curve, 0.93; P b .01). Conclusions: These results suggest that the EELV obtained by intermittent stepwise RM can serve as an indicator of the change in the P/F ratio. 2013 Elsevier Inc. All rights reserved.

1. Introduction
The lung recruitment maneuver (RM) is a method used for reinflation (recruitment) to achieve the recovery of lung volume by transiently increasing the transpulmonary pres Corresponding author. Tel.: + 81-011-7067377; fax: + 81-0117067378. E-mail address: n14w4@s3.dion.ne.jp (S. Nakahashi). 0883-9441/$ see front matter 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcrc.2012.11.003

sure to reopen collapsed alveoli [1,2]. Recruitment is achieved in the inspiratory phase; however, insufficient inspiratory pressure fails to achieve reopening. On the other hand, the alveolar overinflation and increase in transpulmonary pressure induced by applying high pressure can cause lung injury [3] and circulatory depression, resulting in decreased cardiac output and arrhythmia. Therefore, safe and effective settings for the application of pressure are required. An assessment that could be performed during RM

534.e2 was needed to determine whether the collapsed alveoli were reopened. The most accurate assessment of the reopening of collapsed alveoli is provided by a computed tomographic (CT) scan, but this method is not a reasonable bedside system in the intensive care unit (ICU). Although an arterial blood gas analysis is also used as an indicator of reopening [4], it is invasive and cumbersome when it has to be measured frequently in a short period. In addition, it does not indicate the lung volume directly. Therefore, it is critical to develop a simple bedside method for evaluating the effects of the RM for reopening collapsed alveoli in the clinical setting. Recently, it has become possible to measure the endexpiratory lung volume (EELV) automatically, and it is identical to the EELV measured by CT [5,6]. In addition, it is well known that the EELV increases when the collapsed alveoli are reopened after the RM [6-9]. However, no studies have discussed the effects of stepwise increases in the inspiratory pressure using the change in the EELV as an indicator for the improvement of the P/F ratio induced by the reopening of collapsed alveoli. The present study was conducted to test the hypothesis that the change in the EELV (EELV) obtained by RM can serve as an accurate indicator of the change in the P/F ratio.

S. Nakahashi et al. this study. Patients were excluded if they had a chronic obstructive lung disease, interstitial lung disease, pneumothorax, pulmonary thromboembolism, pneumonia, acute respiratory distress syndrome (ARDS), the ratio of arterial oxygen concentration to the fraction of inspired oxygen (P/F ratio) P/F ratio less than 100, hemodynamic instability, or copious secretion retention (need for suctioning N 3 times/2 h or the need for bronchofiberscopy) or if they were receiving percutaneous cardiopulmonary support and extracorporeal membrane oxygenation. Additional exclusion criteria were the deterioration of the general condition of the patient during the study period and hemodynamic instability (change in the blood pressure and/or heart rate 15%) caused by the RM.

2.2. Ventilator settings and measurements

During the study period, the patients were ventilated with an EC ventilator (GE Healthcare, Madison, Wis) with a COVX module (GE Healthcare, Helsinki, Finland). The patients were initially ventilated in a synchronized-intermittent mandatory ventilation mode with volume control, with a tidal volume of 8 mL/kg ideal body weight, an inspiratory/expiratory (I/E) ratio of 1:2 without an inspiratory pause, a respiratory rate adjusted to achieve normocapnia, and appropriate levels of positive end-expiratory pressure (PEEP) based on the experienced clinical judgment of their physicians (baseline ventilation conditions). The patients were ventilated under deep sedation (Richmond Agitation Sedation Scale 5) and had no spontaneous breathing efforts during the study period because EELV measurements are affected by spontaneous breathing variations. No muscle relaxants were used. The RM composed of consecutive 3 breaths with a PEEP of 20 cm H2O and a peak inspiratory pressure (PIP) of 45, 50, or 55 cm H2O were performed 3 times [10,11]. A schematic diagram of the protocol is shown in Fig. 1. Owing to the accurate control of inspiratory pressure, we changed the ventilatory mode from the volume-controlled mode to the pressure-controlled mode during the RM. The EELV was

2. Materials and methods

2.1. Patient selection
The present study was approved by the Human Ethics Committee of the Hokkaido University Hospital, and written informed consent was obtained from each patient's next of kin. This study was conducted between July 2010 and December 2011. Twenty-one postoperative mechanically ventilated patients with atelectasis on their chest radiograph in the ICU of Hokkaido University Hospital were enrolled in

Fig. 1 The study protocol. The RM was conducted under pressure-controlled ventilation with a PEEP of 20 cm H2O and a PIP of 45, 50, or 55 cm H2O. The EELV and P/F ratio were measured 10 minutes after each RM (RMs 1, 2, and 3) and 5 minutes before the first RM.

EELV measurements for patients with atelectasis measured twice using an automated procedure available on the ventilator based on the wash-out/wash-in method with an inspiratory oxygen fraction step change of 0.1, as previously described [12]. Under the baseline ventilator conditions (at the same PEEP setting), the EELV measurements were calculated after 10 minutes of the steady state at each RM to avoid any influence of the RM on the nitrogen wash-out/ wash-in test. At the same time, an arterial blood gas analysis was performed. The presence and degree of atelectasis were evaluated by chest radiographs obtained 5 minutes before performing the initial RM and 10 minutes after the final RM. Atelectasis was graded using the radiologic atelectasis score [13]. Improvements in the EELV and P/F ratio were expressed as a relative change ratio () compared with previous values at each RM (ie, EELV of RM3 = EELV of RM3 EELV of RM2/EELV of RM2). A significant improvement in oxygenation was defined as a 15% P/F ratio or greater in the present study, based on the previous 2 studies [14,15]. The threshold value of improvement for oxygenation was defined as a P/F ratio of 10% in the postoperative patients after cardiac surgery in a previous study, with a P/F ratio of 300 [14]. Another study defined an improvement as a P/F ratio of 20% in ARDS patients with a P/F ratio of 124 [15]. In the present study, the mean P/F ratio was 249, which is between these studies [14,15]; therefore, the P/F ratio was set at 15%, which was the intermediate value of the 2 studies.
Table 1 Patient characteristics

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2.3. Statistical analysis

The statistical analysis was performed using the GraphPad 5.0 software package (GraphPad software Inc, San Diego, Calif). Regarding the effects of the RM, a 1-way analysis of variance for repeated measurements was used to compare the changes before and after the RM. When appropriate, the post hoc analyses were performed using Bonferroni test. Correlations between the EELV and the P/F ratio were analyzed using Spearman rank correlation coefficients. The optimal cutoff point for the EELV to predict the improvement of the P/F ratio by more than 15% was evaluated using the area under the receiver operating characteristic curve. All plus/minus values, including those in the figures, are presented as the means SD. P b .05 was considered statistically significant.

Age (y) 67.8 13.2 Sex (male/female) 13/8 Height (cm) 165.1 9.5 Weight (kg) 73.7 8.5 Body mass index (kg/m2) 27.1 2.7 Primary diagnosis Thoracic aortic aneurysm 1 Abdominal aortic aneurysm 2 Aortic dissection 1 Acute myocardial infarction 2 Hepatocellular carcinoma 4 Alcoholic liver cirrhosis 1 Viral hepatitis 1 Primary sclerosing cholangitis 1 Fulminant hepatitis 1 Hepatic cirrhosis 1 Gastric cancer 1 Pancreatic cancer 2 Colon cancer 1 Acute epidural hematoma 1 Spinal cord injury 1 Baseline ventilation condition FIO2 0.5 0.1 Tidal volume (mL) 468.9 68.7 PEEP (cm H2O) 6.4 2.1 PIP (cm H2O) 19.5 5.5 Atelectasis score 3.0 1.1 0: Complete resolution 0 1: Partial collapse of 1 lobe 3 2: Partial collapse of 2 lobes 3 3: Complete collapse of 1 lobe 6 4: Complete collapse of 2 lobes 9 Clinical course Duration of MV before the study enrollment (d) 7.3 3.8 ICU stay (d) 13.4 5.5
Data are expressed as mean SD or number. ARF indicates acute respiratory failure; FIO2, inspiratory oxygen fraction; MV, mechanical ventilation.

3. Results
The demographic data of the patients are presented in Table 1. A total of 21 patients were enrolled in the study: 10 had undergone abdominal surgery, 8 had undergone cardiovascular surgery, and 3 had undergone another type of surgery. The systemic inflammatory response syndrome score was 2.0 0.2, and the C-reactive protein level was 3.1 2.8. Fig. 2 demonstrates the changes in the EELV and

Fig. 2 Changes in the EELV and P/F ratio after RM. Data are the means SD. *P b .01: control vs RM2, RM3. P b .05: control vs RM1.

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S. Nakahashi et al.

4. Discussion
Using the changes in the EELV, we demonstrated that the RM with stepwise increases in inspiratory pressure has significant effects on alveolar recruitment in mechanically ventilated patient. Our present results lead us to believe that the RM reopened the collapsed alveoli, which was accompanied by the improvement of the EELV, the P/F ratio, and the radiologic atelectasis score. In addition, a strong positive correlation was obtained between the EELV and the P/F ratio. In the process of performing the intermittent and stepwise increases in inspiratory pressure for the RM, the EELV increased depending on the degree of recruitment, and this was followed by improvement of the P/F ratio in conjunction with the recovered lung volume. In our study, the improvement of oxygenation by RM was defined as a 15% or greater change in the P/F ratio. The optimal cutoff value of the EELV to predict a 15% increase in the P/F ratio was around 10% (9.25%), which was consistent with the report by Heinze et al [8]. In their study, when the EELV was increased by 9%, the improvement of the P/F ratio was 16%. These results suggest that, when the EELV is less than 10%, a further increase in inspiratory pressure should not be considered because of the insufficient improvement of P/F ratio. This is because when the EELV is less than 10%, considering that the opening pressure in the alveoli is normally distributed [16], the collapsed alveoli may already be reopened. To conduct RM safely, a minimally invasive method to assess the best opening pressure at the bedside for each patient is required. The present study suggests that the intermittent and stepwise RM under the measurement of the EELV to predict the P/F ratio can be safely applied for patients with atelectasis. The EELV increases not only on the reopening of collapsed alveoli but also by overdistention of alveoli without recruitment [14]. Therefore, the measurement of the EELV does not accurately reflect the reopening of the collapsed alveoli when the RM with continuous increases of the PEEP or inspiratory pressure is applied because there is a mixture of reopening and overdistention of the alveoli [17]. When using the EELV as an indicator for the effects of RM, it is necessary to assess the effects using baseline ventilation conditions, as were used in the present study. The large dispersion of the values in Fig. 3 indicates the individual variation of the responsiveness to the P/F ratio with the EELV among the patients. We surmised that this difference was caused by the presence of hypoxemic factors other than atelectasis (eg, interstitial fluid and remaining inflammation of the alveolar wall) and the variations in the baseline PEEP values. The baseline PEEP was not determined using the pressure-volume curve for each patient. Therefore, the end-expiratory transpulmonary pressure was different among the patients under the baseline PEEP condition. The inhomogeneity of the end-expiratory

Fig. 3 Spearman rank correlation coefficients between the EELV and the P/F ratio. The solid line is the regression line. The dotted lines indicate the 95% confidence band. The indicates the relative change rate after each RM. CI indicates confidence interval.

P/F ratio. The RM induced significant increases in the EELV, from 1157 344 mL at the baseline to 1250 353 mL (P b .05), 1386 360 mL (P b .01), and 1469 396 mL (P b .01) after RM1, RM2, and RM3, respectively. The P/F ratio also significantly improved to 304 99 (P b .01) and 320 92 (P b .01) after RM2 and RM3 compared with the baseline (250 99). The radiologic atelectasis score significantly improved between the baseline and RM3 (3.0 1.1 vs 0.6 1.1, P b .01). There was a significant correlation between the EELV and the P/F ratio (Spearman = 0.7332, P b .01; Fig. 3). The area under the receiver operating characteristic curve required to achieve 15% changes in the P/F ratio was 0.9304 (SE, 0.03). The optimal cutoff value of the EELV to predict a 15% change in the P/F ratio was 9.25% (sensitivity, 86.7%; specificity, 84.4%; Fig. 4). None of the patients showed any hemodynamic instability.

Fig. 4 The receiver operating characteristic curve of the EELV for predicting the improvement in oxygenation (P/F 15%). The indicates the relative change rate after each RM.

EELV measurements for patients with atelectasis transpulmonary pressure among the patients may be at least partly responsible for the variations in the responsiveness of the P/F ratio when the EELV increased. The PIP was up to 55 cm H2O in this study. For maximum recruitment of alveoli [18], a 65 cm H2O pressure or greater was required in patients with severe hypoxemia; however, complications (pneumothorax and subcutaneous emphysema) occurred in these patients. The opening pressure for perioperative atelectasis is expected to be 40 to 45 cm H2O, and RM using 35 to 55 cm H2O is recommended [19]. Although there was still some residual atelectasis, the peak pressure of 55 cm H2O could be safely applied for all patients in our study. Based on the previous studies [14,15], the P/F ratio was defined as an increase of 15% or larger to set the optimal PIP. Further investigations will be needed to determine the optimal P/F ratio in the patients with atelectasis. This study has limitations in that we did not perform assessments using CT or lung compliance together with our EELV measurements. We could not verify whether the PaCO2 and Vt were associated with the RM. It is possible that if the EELV is below 10%, all collapsed alveoli may have already been reopened. However, we did not identify which inspiratory pressure is the best to optimize the recruitment. In addition, a study to verify the present results in patients with more severely impaired pulmonary function, such as ARDS, will be necessary and is a future goal. The number of cases was not large enough to draw any definitive conclusions, and possibilities of type III errors cannot be ruled out.

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5. Conclusion
The present study demonstrated that the EELV obtained by intermittent stepwise RM can serve as an accurate indicator of the change in the P/F ratio.

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