Introduction
Acute respiratory distress syndrome (ARDS) is a common cause of mortality in the ICU [
1]. The diagnosis of ARDS is established using the new Berlin criteria which consists of four elements: 1) onset within a week of a known clinical insult or new respiratory symptoms, 2) bilateral opacities on chest radiograph or computed tomography scan, 3) respiratory failure not fully explained by cardiac failure or fluid overload, and 4) impaired oxygenation defined as partial pressure of oxygen (PaO
2)/fraction of inspired oxygen (FiO
2) ≤300 on positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥5 cmH
2O. Diagnosis of ARDS requires an arterial blood gas (ABG) test and chest radiography or computed tomography in the appropriate clinical scenario.
In much of the world where medical resources are limited, blood gas analysis and imaging technologies may not be available, impairing the ability to make the diagnosis of ARDS. In one study, half of all patients who clinically had ARDS in a hospital in Rwanda had a chest radiograph available for review [
2]. However, both pulse oximetry and ultrasound are becoming increasingly accessible worldwide [
3,
4]. The pulse oximetric saturation to inspired oxygen ratio (SpO
2/FiO
2) has been correlated with the PaO
2/FiO
2 ratio in ARDS [
5,
6]. Pulmonary ultrasound is a rapidly developing technology in which the diagnosis of lung disease is being explored in diverse settings, and new diagnostic criteria are being developed for multiple pulmonary processes [
7]. Some of the first patterns of pulmonary ultrasound to be recognized were the distinct “A line” and “B line” artifacts [
8]. The “A-line” pattern, characterized by horizontal reflection artifacts of the pleural line deep into the lung, is seen with alveoli that are physiologically filled with air. The “B-line” pattern, characterized by the presence of three or more vertical artifacts obliterating any A-lines, correlates with the ultrasound interstitial syndrome (UIS) [
9]. The presence of UIS diffusely on ultrasound is considered consistent with either cardiogenic pulmonary edema or ARDS [
10‐
12]. The A line and B line patterns have proven to be easily distinguished by a bedside clinician after relatively brief teaching [
13,
14]. Therefore, it is conceivable that the diagnosis of ARDS could be made using pulse oximetry and pulmonary ultrasound at the point of care.
We hypothesized that data derived from pulse oximetry and bedside pulmonary ultrasound could be used in lieu of ABG and chest radiography to meet oxygenation and radiographic criteria for ARDS. We designed a prospective study in patients with respiratory failure in the ICU to test this hypothesis.
Discussion
The purpose of this pilot study was to assess the performance of rapid assessment with bedside pulmonary ultrasound and use of pulse oximetry as alternatives to chest radiograph and ABG in the diagnosis of ARDS. The results of this study showed that, in mechanically ventilated ICU patients, SpO2/FiO2 and PaO2/FiO2 are highly correlated, that SpO2/FiO2 ≤ 315 is quite sensitive for PaO2/FiO2 ≤ 300, and that SpO2/FiO2 ≤ 235 is highly specific for PaO2/FiO2 ≤ 200. Our study confirms reasonable sensitivity of simplified six-point lung ultrasound in identifying patients with bilateral pulmonary opacities consistent with ARDS on chest radiograph using a threshold of bilateral UIS involving at least three lung fields in total, although specificity was lower. Finally, our data on a relatively small number of patients indicate that the combination of SpO2/FiO2 ≤ 315 and bilateral/3 field UIS on ultrasound is sensitive for the classification of traditional oxygenation and radiographic criteria for ARDS in mechanically ventilated patients; in contrast, the combination of SpO2/FiO2 ≤ 235 and bilateral/3 field UIS on ultrasound is specific for moderate–severe ARDS.
Overall, we found that the SpO
2/FiO
2 cutoffs established by Rice et al. were less predictive of the PaO
2/FiO
2 than originally described [
5]. Rice et al. found higher sensitivity in their study, with SpO
2/FiO
2 ≤ 235 resulting in 85 % sensitivity with 85 % specificity for PaO
2/FiO
2 ≤ 200, and 91 % sensitivity with 56 % specificity of SpO
2/FiO
2 ≤ 315 to predict PaO
2/FiO
2 ≤ 300. Several explanations may account for this. First, the use of the SpO
2/FiO
2 ratio is limited by flattening of the oxyhemoglobin dissociation curve at high SpO
2; this effect is exacerbated when FiO
2 is not maximally reduced. Many patients in our study were administered a “minimum” FiO
2 of 0.4. Rice et al. report that their studies targeted SpO
2 values between 92 and 94 %, whereas very few of our subjects had SpO
2 < 97 %. Second, Rice et al. analyzed 1,076 patients enrolled in ARDS studies; this contrasts markedly with our smaller, relatively unfiltered cohort of 77 mechanically ventilated patients. Third, our study is a single-center observational study, in contrast to the multicenter interventional ARDSNet studies. Future studies refining test characteristics of new ARDS criteria should determine SpO
2/FiO
2 at the lowest possible FiO
2, which would require cooperation with respiratory therapists and nursing staff.
The sensitivity and specificity of ultrasound assessments of UIS for radiographic criteria of ARDS in our study were also less than was predicted based on prior studies. There are several possible reasons for this. The original diagnostic algorithm for the BLUE protocol includes an assessment of the lung sliding by ultrasound [
10]. This specific criterion was removed from our study, as in trauma patients with chest injuries one might expect a loss of lung sliding without ruling out ARDS or cardiogenic pulmonary edema. An additional challenge in the trauma patient is the evaluation in the setting of significant subcutaneous emphysema. In this setting ultrasound images are difficult to interpret, and may provide false reassurance to novice sonographers simply counting B lines or looking for hepatization. A phased-array probe was used in this study instead of the micro convex probe used in many other studies. This was chosen based on an assessment that the two probes most likely to be found in a resource limited setting were a linear probe (for superficial assessments and procedures) and a phased-array probe (for cardiac, intra-abdominal, and obstetric assessment). In addition, unlike other studies [
10,
11,
18], our study used only chest radiographs and not chest computed tomography imaging to determine radiographic criteria for ARDS.
About a third of ultrasound assessments we performed had at least one lung field for which the imaging clip was considered difficult to interpret. Specifically, trauma patients with subcutaneous emphysema and supine obese patients with significant distance to the lung tissue represent a technical challenge. The division of the chest into six zones as performed in the BLUE protocol and the ICU-SOUND protocol allows rapid assessment of anterior and posterior-lateral fields [
15,
18]. Other studies have utilized more lung fields, with the international consensus statement specifying an eight-zone protocol published by Volpicelli et al. [
7]. Our study was designed as a rapid diagnostic tool leading to a binary outcome, but the diagnosis of ARDS in other ultrasound studies was one of several potential outcomes at the end of a diagnostic algorithm. By distilling the process to simply an “A-line” or “B-line” determination for each lung field, much of the information we acquired in the process of ultrasound was disregarded, including the presence or absence of lung sliding and images that showed clear signs of consolidation, hepatization or effusions. In the BLUE protocol these findings would have potentially changed the final ultrasound-based diagnosis, and likely contributed to the moderate interobserver agreement we observed. Six points of examination may also not be sufficient for clear identification of alternative processes, as the study that most accurately identified ARDS using pulmonary ultrasound did so by scanning each intercostal space [
11].
Alternative methods for ascertainment of imaging and oxygenation criteria for ARDS may be useful in a variety of settings where critically ill patients are managed. Ultrasound evaluation may be faster and offer additional benefits compared to chest radiography [
12,
19]. In low-resource settings without portable chest radiography and ABG testing capacity, pulse oximeters and ultrasound machines are increasingly available [
3,
4]. Ultrasound is a useful imaging modality in these settings due to its versatility and portability. Moreover, dependence on traditional tools for diagnosing ARDS in low-resource settings may substantially underestimate the incidence of disease [
2]. The diagnosis of ARDS is important even when resources are limited because two of the management strategies demonstrated to improve mortality in ARDS – lung protective ventilation and proning [
20,
21] – are cheap and potentially feasible to implement in a range of settings. While some evidence supports more liberal use of lung protective ventilation in respiratory failure [
22], understanding the prevalence of ARDS is one element in a necessary effort to improve detection and treatment of respiratory diseases and critical illness in low-resource settings globally [
23‐
27].
Our study offers several strengths. First, our study was conducted by a novice sonographer quickly and without moving the patient. While several other studies have examined the ability of ultrasound to identify findings consistent among patients with ARDS [
10‐
12,
18], conditions were optimized: patients were positioned carefully and expert sonographers obtained multiple ultrasound findings in combination. Thus our study was pragmatic and modeled “real-world” conditions for busy ICU practitioners. Second, we methodically evaluated a sequentially enrolled cohort of critically ill medical and surgical patients at risk for ARDS in a large referral center, suggesting external validity of our study to other busy critical care centers. Third, we enrolled patients with a range of diseases and PaO
2/FiO
2 ratios; thus our tests of diagnostic accuracy measures should apply to similar spectra of disease. Fourth, we carefully considered the timing of various diagnostic tests in relation to each study observation in order to minimize effects of temporal changes in clinical condition on the analysis. Fifth, although we treated each assessment as independent, we confirmed that intraindividual correlation did not alter our findings. Finally, we tested interobserver effects by performing a secondary analysis of ultrasound characteristics using an independent ultrasound-trained physician to classify images.
Our study also has several limitations. Most notably, this was a small, single-center study with ultrasound data obtained by only one sonographer. Furthermore, few patients had SpO
2 < 97 %, limiting the number of observations that could be analyzed according to the methodology of Rice et al. [
5]. As this was an observational study, additional patients were excluded from analysis if the duration of time between their radiograph or ABG and the study observation was too long. These restrictions resulted in a small population for final analyses. In addition, if less ill patients had less frequent diagnostic tests, our analyses may have been biased towards sicker patients. While the study physician was blinded to the clinical picture for initial assessments, repeat assessments were performed after medical record review, potentially leading to bias. Evaluating only intubated patients limits the generalizability of our results, particularly to lower resourced settings. As noted above, a six-point protocol may be insufficient and a binary “B-line predominant” determination may result in disregarding potentially important clinical information. Avoiding patient repositioning meant that there was limited visualization of the posterior lung fields, which is particularly relevant as ARDS is a posterior predominant condition. Potentially, diagnostic yield would have been higher had assistance been sought. Furthermore, chest radiography is a suboptimal gold standard when compared to chest computed tomography imaging [
12].
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
CMB, DRS and TEW participated in the design of the study. CMB performed all ultrasound assessments and acquired data. CMB and AAA interpreted all ultrasound assessments. CMB and TEW performed statistical analysis and drafted the manuscript. All authors read and approved the final manuscript.