Nội dung

Huang et al. BMC Pulmonary Medicine (2018) 18:136 https://doi.org/10.1186/s12890-018-0666-9 RESEARCH ARTICLE Open Access Diagnostic value of cardiopulmonary ultrasound in elderly patients with acute respiratory distress syndrome Daozheng Huang1,4† , Huan Ma1†, Zhiyuan Xiao2†, Michael Blaivas3, Ying Chen4, Jianyi Wen4, Weixin Guo4, Jun Liang4, Xiaolong Liao4, Zhonghua Wang4, Hanbiao Li4, Jie Li4, Yangong Chao5, Xiao ting Wang6, Yan Wu4, Tiehe Qin4, Ke Su7*, Shouhong Wang4* and Ning Tan1* Abstract Background: Lung ultrasound and echocardiography are mainly applied in critical care and emergency medicine. However, the diagnostic value of cardiopulmonary ultrasound in elderly patients with acute respiratory distress syndrome (ARDS) is still unclear. Methods: Consecutive patients admitted to ICU with the diagnosis of suspected ARDS based on clinical grounds were enrolled. Cardiopulmonary ultrasound was performed as part of monitoring on day 1, day 2 and day 3. On each day a bedside ultrasound was performed to examine the lungs and calculate the Left Ventricular Ejection Fraction (LVEF). On day 3, a thoracic CT was performed on each patient as gold standard for ARDS imaging diagnosis. According to the results from CT scan, patients were grouped into ARDS group or Non-ARDS group. The relation between the cardiopulmonary ultrasound results on each day and the results of CT scan was analyzed. (Continued on next page) * Correspondence: huang1huang2@163.com; mina0511@hotmail.com; hdzdoctor@sina.com † Daozheng Huang, Huan Ma and Zhiyuan Xiao are contributed equally to this work as Co-first authors 7 Department of Critical Care Medicine, Zhongshan Dongsheng Hospital, Zhongshan 528400, China 4 Department of Critical Care Medicine, Guangdong Geriatric Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, China 1 Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, China Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Huang et al. BMC Pulmonary Medicine (2018) 18:136 Page 2 of 9 (Continued from previous page) Results: Fifty one consecutive patients aged from 73 to 97 years old were enrolled. Based on CT criteria, 33 patients were classified into the ARDS group, while 18 patients were included in non-ARDS group. There was no significant difference between the two groups in baseline characteristics, including gender, age, underlying disease, comorbidities, APACHE II score, SOFA score, and PaO2/FiO2 ratio (P > 0.05). Lung ultrasound (LUS) examination results were consistent with the CT scan results in diagnosis of pulmonary lesions. The Kappa values were 0.55, 0.74 and 0.82 on day 1, day 2 and day 3, respectively. The ROC analysis showed that the sensitivity, specificity and area under curve of ROC (AUROC) for lung ultrasound in diagnose ARDS were 0.788,0.778,0.783;0.909,0.833,0.871;0.970,0. 833,0.902 on day 1, day 2 and day 3, respectively. However, cardiopulmonary ultrasound performed better in diagnosing ARDS in elderly patients. The sensitivity, specificity and AUROC were 0.879,0.889,0.924;0.939,0.889,0.961; and 0.970,0.833,0.956 on day 1, day 2 and day 3, respectively. The combined performances of cardiopulmonary ultrasound, N-terminal pro-brain natriuretic peptide (NT-proBNP), and PaO2/FiO2 ratio improved the specificity of the diagnosis of ARDS in elderly patients. Conclusions: LUS examination results were consistent with the CT scan results in diagnosis of pulmonary lesions. Cardiopulmonary ultrasound has a greater diagnostic accuracy in elderly patients with ARDS, compared with LUS alone. The combined performances of cardiopulmonary ultrasound, NT-proBNP, and PaO2/FiO2 increased the specificity of the diagnosis of ARDS in elderly patients. Keywords: ARDS, Lung ultrasound, Cardiopulmonary ultrasound, Diagnostic value, Elderly Background Acute respiratory distress syndrome (ARDS) is a clinical syndrome, which is a type of acute diffuse, inflammatory lung injury, leading to increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue [1]. ARDS has a high incidence rate and caries mortality of nearly 50% for patients with severe ARDS [2]. At present, there are limited methods of improving the accuracy of ARDS diagnosis in patients [3–5]. Elderly patients generally have a higher number of comorbidities and poorer homeostatic capability. The diagnosis of ARDS in this patient population is even more challenging and needs improvement [2]. Therefore, early diagnosis and intervention are very important to improve the prognosis for elderly patients with ARDS. The diagnosis of ARDS at our institution is largely based on change noted on lung ultrasonography (LUS). The data collection of thoracic X-ray, especially bedside X-ray examination, can be affected by various factors. Hence we found it to not be valuable in the diagnosis of ARDS [6, 7]. Even with advantages over chest X-ray, thoracic CT has limited usage among critically ill patients, due to its high risk in patient transport, high cost, and risk of radiation exposure. Therefore, there are various underlying difficulties in early diagnosis of ARDS, especially imaging diagnosis. LUS has drawn increasing attention among clinical physicians recently [8–12]. The guideline of international evidence-based recommendations for point-of-care lung ultrasound [13] aimed to improve and standardize the clinical application and scientific research of lung ultrasound. However, there has yet to be a good comparison between point-of-care ultrasound (PoCUS) and the imaging gold standard of CT diagnosis of ARDS. Persistent questions include: what ultrasound signs are best for the diagnosis diagnose ARDS? What are the sensitivity and specificity of PoCUS in diagnosing ARDS? What is the effect of the underlying diseases of the patients in diagnosis, especially those in lungs? In order to answer these questions, we performed a prospective observational study using dynamic ultrasound monitoring and other clinical indicators on 51 elderly patients with suspected ARDS, in order to investigate the diagnostic value of cardiopulmonary ultrasound in this patient group. Methods Subjects Elderly patients with suspected ARDS based on clinical grounds, admitted to the department of Critical Care Medicine, Guangdong Geriatric Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences between January 2014 February 2016 [1]. Inclusion criteria: age is greater than or equal to 65 years old; risk factors of ARDS, including pneumonia, aspiration pneumonia, sepsis, septic shock, coma, multiple injuries, pancreatitis or large quantity of infusion of blood products; acute onset within 1 week or occurrence of severe acute respiratory system syndrome; Respiratory rate of more than 20 breaths per minute or presence of respiratory distress; PaO2/FiO2 < 300 mmHg; acute respiratory failure which cannot be explained by cardiac insufficiency or fluid overload [2]. Exclusion criteria: age < 65 years; end stage malignant neoplasms; no consent given or not able to have thoracic CT. Fifty-one patients were enrolled to this study, in which, fifteen patients with aspiration pneumonia, eleven patients with severe pneumonia, 10 patients with Huang et al. BMC Pulmonary Medicine (2018) 18:136 Page 3 of 9 acute exacerbation of chronic obstructive pulmonary disease (AECOPD), eight patients with septic shock, seven patients with other diseases (including three cases with acute severe pancreatitis, two cases with multiple injury and two cases with cerebral hemorrhage). These included patients were divided into ARDS group (n = 33) and NonARDS group (n = 18), based on the results of thoracic CT scan on day 3. This study protocol was approved by the ethics committee of Guangdong General Hospital and Guangdong Academy of Medical Sciences [No. GDREC2015106H (R1)], and written informed consent was obtained from each patient’s next of kin. Instrument and diagnosis criteria 1.2.1 A Phillips EPIQ5 ultrasonic diagnostic apparatus was used. An abdominal convex array probe (Frequency 1>5 MHz) was used for the lung ultrasound examination; A phased array probe (frequency 0.6. There was 91 % of patients had adequate US views for LVEF and SV to be measured, and five patients were excluded for poor US images. The cardiac US images were collected and analyzed by two investigators and the inter-observer variability was good. Definition of ARDS Bedsides onset time, risk factors and chest radiography, the Berlin definition proposed three mutually exclusive categories of ARDS according to PaO2/FIO2 ratios: mild (200 mmHg 0.90 on day 1, day 2 and day 3. The combination of LUS + LVEF+NTproBNP had the highest diagnostic value on day 2, with sensitivity, specificity and AUROC of 0.939, 0.889 and 0.965, respectively (Table 6). 2.6 ROC curve analysis of cardiopulmonary ultrasound +NT-proBNP+ PaO2/FiO2 diagnosing ARDS: The above combination was of high value with AUROC> 0.920 on day 1, day 2 and day 3; In which, the diagnostic value was the highest on day 2, with sensitivity, specificity and AUROC of 0.939,0.889 and 0.965, respectively (Table 7). Discussions Chinese society is aging [19],and resulting in an increasing number of critically ill elderly patients. The mortality and morbidity of those patients may be much higher than younger patients. This may be attributed to a lower reserve capacity in most important organs and systems functions, which will reduce ability to deal with physical stress and the presence of acute or chronic comorbidities. Therefore, early diagnosis maybe have a marked impact on interventions and outcomes of elderly patients with ARDS. However, the Berlin diagnostic criteria of ARDS widely used in clinical practice, is not very clear about the evaluation standard of pulmonary imaging, especially thoracic X-ray, which may Table 4 Analysis of ROC curve of pulmonary dynamic monitoring results in patients with ARDS LUS Cutoff values Sensitivity Specificity Youden index AUROC day1 1.0 0.788 0.778 0.566 0.783 day2 1.0 0.909 0.833 0.742 0.871 day3 1.0 0.970 0.833 0.803 0.902 lead to poor reliability of ARDS diagnosis [8]. The development of clinical application and research of PoCUS provides a novel way of ARDS diagnosis in imagine. Cardiopulmonary ultrasound can help evaluate the cardiopulmonary morphology and function, but more exploration is needed to investigate the relation between cardiopulmonary ultrasound and chest CT scan in chest imagines for diagnosis of ARDS. If ultrasound proved sensitive and specific in early ARDS diagnosis, it may become part of a novel diagnostic imaging standard of ARDS diagnosis. This study was a single-center, prospective observational study. Patients were divided into ARDS group (n = 33) and control group (n = 18), based on the results of chest CT scan on day 3. There were no significant differences between the two groups in gender, age, underlying disease, APACHEII score, SOFA score, PaO2/FiO2 ratio and PEEP levels day 1. It’s reported that NT-proBNP is an important biomarker of heart failure [20]. Previous studies suggested that patients with diagnosis of ARDS often had right ventricular dysfunction [21, 22], which would damage cardiopulmonary function. This study showed that, the levels of NT-proBNP on day 1 were increased in both groups, while the levels in control group were statistically significantly higher than those in the ARDS group (p = 0.046). Respiratory failure of patients without ARDS was mainly caused by cardiogenic factors, whereas for patients with ARDS, other factors, such as hypoxia, can also affect the cardiac function. There are obvious limitations to using NT-proBNP alone to differentiate ARDS from acute or chronic heart failure. Our study showed that the results of LUS examinations were comparable with those of ARDS diagnosis using CT scan. Consistent with the results of the preliminary animal experiment in the research group, the Kappa value was 0.82 on day 3,indicating early ARDS diagnosis using LUS was of similar clinical value as a CT scan. In our study, the results of CT scan in 33 patients with ARDS on day 3 showed different degrees of pulmonary consolidation, especially obvious in the gravity-dependent areas, such as lateral chest and back. This is a characteristic finding of ARDS on chest CT scan. The relation between ultrasound signs and ARDS diagnostic criteria through chest CT scan was analyzed according to the ARDS diagnosis standard using ultrasound suggested in this study. The sensitivity, specificity and AUROC of LUS on day 1, day 2 and day 3 were high and increased between day 1 and day 3. Our Huang et al. BMC Pulmonary Medicine (2018) 18:136 Page 8 of 9 Table 6 ROC curve analysis of ARDS diagnosis with cardiopulmonary ultrasound combined with NT-proBNP or PaO2/FiO2 ratio Combination Index Cutoff Value Sensitivity Specificity Youden index Cardiopulmonary ultrasound +NT-proBNP day1 0.556 0.879 0.889 0.768 AUROC 0.938 Cardiopulmonary ultrasound +NT-proBNP day2 0.487 0.939 0.889 0.828 0.965 Cardiopulmonary ultrasound +NT-proBNP day3 0.745 0.939 0.889 0.828 0.961 Cardiopulmonary ultrasound + PaO2/FiO2 day1 0.764 0.848 0.944 0.793 0.919 Cardiopulmonary ultrasound + PaO2/FiO2 day2 0.496 0.939 0.889 0.828 0.962 Cardiopulmonary ultrasound + PaO2/FiO2 day3 0.442 0.970 0.833 0.803 0.958 results indicated that diagnostic imaging of ARDS could be partially based on LUS signs. The results on day 3 were of higher diagnostic value, since the third day may be the peak of the inflammation. Pulmonary ultrasound yields considerable advantage in the diagnosis and management of various pleural cavity and pulmonary diseases [23–26]. Change in pulmonary ventilation area can be determined by LUS before the reduction of PaO2/FiO2 [27]. Our previous animal experiment showed that LUS could semi-quantify pulmonary edema [28, 29]. Inevitably, the diagnosis of ARDS must be differentiated from acute left heart failure, and cardiac ultrasound is an important means of comprehensive evaluation of cardiac function. Previous studies showed that cardiopulmonary ultrasound had obvious advantages in investigating the etiology of acute respiratory failure [30, 31]. Therefore, we believe that a cardiopulmonary ultrasound approach will have broad application prospects in ARDS diagnosis. The sensitivity, specificity and AUROC of ARDS diagnosis using cardiopulmonary ultrasound on day 1, day 2 and day 3 were 0.879,0.889,0.924;0.939,0.889,0.961;and 0.970, 0.833,0.956, respectively. Our study’s main aim was to investigate the diagnostic value of cardiopulmonary ultrasound in elderly patients with ARDS. According to the guideline of point of care LUS [13], there are no consistent standards in diagnosing ARDS using LUS findings. Combined with Berlin criteria of ARDS [1] and our clinical experience, pulmonary edema and consolidation are the main imaging findings in ARDS patients. If there is normal LVEF or even hyperdynamic state in patients, combined with the results of LUS,we basically believe that the patient’s respiratory distress is caused by pulmonary edema caused by ARDS. Our results showed that cardiopulmonary ultrasound was of greater advantage Table 7 The ROC curse analysis of Cardiopulmonary Ultrasound combined with NT-proBNP and PaO2/FiO2 ratio in the diagnosis of ARDS Time Cut-off value Sensitivity Specificity Youden index AUROC day1 0.726 0.848 0.944 0.793 0.928 day2 0.486 0.939 0.889 0.828 0.965 day3 0.738 0.939 0.889 0.828 0.961 compared with LUS alone in ARDS diagnosis. The reason may be that cardiopulmonary ultrasound can exclude the interference of heart failure in ARDS diagnosis. Both NTproBNP and PaO2/FiO2 are important clinical indicators in pathophysiology. We also evaluated the combination of cardiopulmonary ultrasound and NT-proBNP or PaO2/FiO2 in ARDS diagnosis, with sensitivity, specificity and AUROC on day 2:0.938,0.887,0.964;0.939,0.889,0.965, respectively. These results suggest a combination of ultrasound signs and pathophysiology indicators was of greater application value in ARDS diagnosis. This study investigated the ARDS diagnosis in elderly patients using PoCUS. Lung ultrasound, especially cardiopulmonary ultrasound was of important clinical application value in ARDS diagnosis in elderly patients. A combination of ultrasound signs and pathophysiology indicators was of more application value than ultrasound signs alone. PoCUS is mainly applied not only in critical care, emergency medicine, and trauma surgery, but also in pulmonary and internal medicine, especially in the assessment of cardiopulmonary function. Respiratory failure of patients without ARDS was mainly caused by cardiogenic factors, whereas for patients with ARDS may be promoted in the diagnosis and treatment management in elderly patients with ARDS. This study had a few of limitations including its observational design and finite study arms. Initial indications are promising for cardiopulmonary ultrasound in the diagnosis of ARDS. However, the effect of underlying disease of elderly patients on its diagnostic value needs to be investigated in larger prospective and also interventional studies to evaluate any effect on outcomes. Conclusions Cardiopulmonary ultrasound has a greater diagnostic accuracy in elderly patients with ARDS, compared with lung ultrasound alone. The combined performances of cardiopulmonary ultrasound, NT-proBNP, and PaO2/FiO2 increased the specificity of the diagnosis of ARDS in elderly patients. Abbreviations ACCF: American College of Cardiology Foundation; AECOPD: Acute exacerbation of chronic obstructive pulmonary disease; ARDS: Acute respiratory distress syndrome; AUROC: Area under the ROC; LUS: Lung ultrasound; LVEF: Left ventricular ejection fraction; NT-proBNP: N-terminal Huang et al. BMC Pulmonary Medicine (2018) 18:136 Page 9 of 9 pro-brain natriuretic peptide; PoCUS: Point-of-care ultrasound; ROC: Receiver operating characteristic curve; SV: Stroke volume; US: Ultrasonography 7. Acknowledgements This work was supported by grant from Medical Scientific Research Foundation of Guangdong Province, Guangdong, People’s Republic of China. (Grant number: C2015046 and B2015076). 8. Ethics of approval and consent to participate The study protocol was approved by the ethics committee of Guangdong General Hospital/ Guangdong Academy of Medical Sciences (No.GDREC2015106H(R1)). Written informed consent was obtained from each patient’s next of kin as patients were in a critically ill status, incapacitated and unable to make decisions. 10. Funding This work was supported by grant from Medical Scientific Research Foundation of Guangdong Province, Guangdong, People’s Republic of China. (Grant number: C2015046 and B2015076). 13. Availability of data and materials The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Authors’ contributions (I) Conception and design: DH and HM. (II) Administrative support: TQ, NT and JW. (III) Provision of study materials or patients: SW, ZX and YC. (IV) Collection and assembly of data: DH, SW, WG and XL. (V) Data analysis and interpretation: DH, KS and ZW. (VI) Manuscript writing: All authors. (VII) Final approval of manuscript: All authors. Competing interests The authors declare that they have no competing interests. Publisher’s Note 9. 11. 12. 14. 15. 16. 17. 18. 19. 20. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details 1 Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, China. 2Department of Critical Care Medicine, Yunnan Cancer Hospital and the Third Affiliated Hospital of Kunming Medical University, Kunming 650000, China. 3Department of Emergency Medicine, Piedmont Hospital, Newnan, GA, USA. 4Department of Critical Care Medicine, Guangdong Geriatric Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, China. 5Department of Critical Care Medicine, the First Hospital of Tsing Hua University, Beijing 100730, China. 6Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. 7Department of Critical Care Medicine, Zhongshan Dongsheng Hospital, Zhongshan 528400, China. Received: 6 March 2018 Accepted: 29 May 2018 21. 22. 23. 24. 25. 26. 27. References 1. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the berlin definition. JAMA. 2012;307(23):2526–33. 2. Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788–800. 3. 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(8):566–76. 4. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159–68. 5. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107–16. 6. Alves GC, Silva JG, Lima RS, et al. Risk factors for death among critically ill elderly patients. Rev Bras Ter Intensiva. 2010;22(2):138–43. 28. 29. 30. 31. Li Q, Zhang J, Wan X. Analysis of characteristics and related risk factors of prognosis in elderly and young adult patients with acute respiratory distress syndrome. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014;26(11):794–8. Li G, Malinchoc M, Cartin-Ceba R, et al. Eight-year trend of acute respiratory distress syndrome: a population-based study in Olmsted County, Minnesota. Am J Respir Crit Care Med. 2011;183(1):59–66. Mozzini C, Fratta PA, Garbin U, et al. Lung ultrasound in internal medicine: training and clinical practice. Crit Ultrasound J. 2016;8(1):10. See KC, Ong V, Wong SH, et al. Lung ultrasound training: curriculum implementation and learning trajectory among respiratory therapists. Intensive Care Med. 2016;42(1):63–71. Georgopoulos D, Xirouchaki N, Volpicelli G. Lung ultrasound in the intensive care unit: let's move forward. Intensive Care Med. 2014;40(10):1592–4. Volpicelli G, Boero E, Sverzellati N, et al. Semi-quantification of pneumothorax volume by lung ultrasound. Intensive Care Med. 2014;40(10):1460–7. Volpicelli G, Elbarbary M, Blaivas M, et al. International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med. 2012;38(4):577–91. de Hemptinne Q, Remmelink M, Brimioulle S, et al. ARDS: a clinicopathological confrontation. CHEST. 2009;135(4):944–9. Posterior Consolidation KLT. An important clue for differentiating ARDS from cardiogenic pulmonary edema. CHEST. 2016;149(4):1108–9. Sekiguchi H, Schenck LA, Horie R, et al. Critical care ultrasonography differentiates ARDS, pulmonary edema, and other causes in the early course of acute hypoxemic respiratory failure. CHEST. 2015;148(4):912–8. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. J Thorac Cardiovasc Surg. 2011;142(6):e153–203. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637. Wang L, Li Y, Li H, et al. Regional aging and longevity characteristics in China. Arch Gerontol Geriatr. 2016;67:153–9. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the heart failure association (HFA) of the ESC. Eur J Heart Fail 2016;18(8):891–975. Wadia SK, Shah TG, Hedstrom G, et al. Early detection of right ventricular dysfunction using transthoracic echocardiography in ARDS: a more objective approach. Echocardiography. 2016;33(12):1874–9. Repesse X, Charron C, Vieillard-Baron A. Right ventricular failure in acute lung injury and acute respiratory distress syndrome. Minerva Anestesiol. 2012;78(8):941–8. Lichtenstein D, Goldstein I, Mourgeon E, et al. Comparative diagnostic performances of auscultation, chest radiography, and lung ultrasonography in acute respiratory distress syndrome. ANESTHESIOLOGY. 2004;100(1):9–15. Anile A, Russo J, Castiglione G, et al. A simplified lung ultrasound approach to detect increased extravascular lung water in critically ill patients. Crit Ultrasound J. 2017;9(1):13. Soldati G, Demi M. The use of lung ultrasound images for the differential diagnosis of pulmonary and cardiac interstitial pathology. J Ultrasound. 2017;20(2):91–6. Lichtenstein DA, Meziere GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol. CHEST. 2008;134(1):117–25. Caltabeloti F, Monsel A, Arbelot C, et al. Early fluid loading in acute respiratory distress syndrome with septic shock deteriorates lung aeration without impairing arterial oxygenation: a lung ultrasound observational study. Crit Care. 2014;18(3):R91. Ma H, Huang D, Guo L, et al. Strong correlation between lung ultrasound and chest computerized tomography imaging for the detection of acute lung injury/ acute respiratory distress syndrome in rats. J Thorac Dis. 2016;8(7):1443–8. Ma H, Huang D, Zhang M, et al. Lung ultrasound is a reliable method for evaluating extravascular lung water volume in rodents. BMC Anesthesiol. 2015;15:162. Bataille B, Riu B, Ferre F, et al. Integrated use of bedside lung ultrasound and echocardiography in acute respiratory failure: a prospective observational study in ICU. CHEST. 2014;146(6):1586–93. Volpicelli G. Interpreting lung ultrasound B-lines in acute respiratory failure. CHEST. 2014;146(6):e230.