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Additionally&#44; the definition of a disease promotes the development of related scientific research&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The definitions of ARDS over time</span><p id="par0155" class="elsevierStylePara elsevierViewall">The original definition of ARDS dates to 1967 and was issued by Petty and Ashbaugh&#44; who described a group of 12 patients with acute respiratory failure&#44; profound hypoxemia secondary mainly to intrapulmonary shunt&#44; bilateral infiltrates on CXR and decreased thoraco-pulmonary compliance&#44; with no history of chronic respiratory failure&#44; and in absence of left ventricular failure&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> This condition occurred after exposure to what they called a &#34;catastrophic event&#34; &#40;which are now the risk factors for ARDS&#41;&#44; of pulmonary or extrapulmonary origin &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Because of its clinical and radiological similarity to respiratory distress syndrome secondary to surfactant deficiency in newborns&#44; the authors named this entity &#34;Adult Respiratory Distress Syndrome&#34;&#46; Petty and Ashbaugh&#39;s definition identified what is currently known as severe ARDS&#44; since from the point of view of oxygenation impairment it referred to patients with PaO<span class="elsevierStyleInf">2</span> &#60; 50&#8239;mmHg with an inspired oxygen fraction &#40;FiO<span class="elsevierStyleInf">2</span>&#41; &#62; 0&#46;6&#59; that is&#44; with deep hypoxemia&#44; evidenced by a PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> ratio of approximately 80 mmHg&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">Since this initial approach&#44; several modifications of the definition have been made&#46; In 1988&#44; Murray et al&#46; proposed the Lung Injury Score &#40;LIS&#41; with the intention of quantifying the severity of the syndrome&#46; The LIS was the average value of 4 variables&#44; expressed as a score from 0 to 4 reflecting increasing severity&#58; hypoxemia &#40;defined as the PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> ratio&#41;&#59; extent of pulmonary infiltrates on chest radiograph &#40;in quadrants&#41;&#44; thoraco-pulmonary compliance &#40;ml&#47;cmH<span class="elsevierStyleInf">2</span>O&#41; and use of positive end-expiratory pressure &#40;PEEP&#44; cmH<span class="elsevierStyleInf">2</span>O&#41;&#46; ARDS was defined by an LIS &#62; 2&#46;5&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The LIS was adopted for use&#44; but the definition remained a construction of few experts&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">In 1994&#44; the American-European Consensus Conference &#40;AECC&#41; definition was published&#44; in which the syndrome known until then as Adult Respiratory Distress Syndrome was considered as compounded by two conditions of progressive severity&#58; acute lung injury &#40;ALI&#41; and ARDS &#40;Acute Respiratory Distress Syndrome&#41;&#44; defined by the compromise of oxygenation&#58; PaO2&#47;FiO2&#8239;&#8804;&#8239;300 and &#8804;200&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The acute characteristics of the syndrome and the exclusion of cardiovascular causes for pulmonary edema development were maintained&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">The AECC definition&#44; like the LIS score&#44; suffered from several criticisms&#44; centered mainly on two aspects&#46; First&#44; experts highlighted the diagnostic difficulties for the evaluation of CXR infiltrates on CXR&#44; due to the great intra- and interobserver variation&#46; In addition&#44; the decision to exclude any standardized level of PEEP for oxygenation assessment produced further variability&#44; secondary to PEEP great impact on the definition of ARDS&#46; Patients could quickly move from one category of hypoxemia to another&#44; without implying a real change in the underlying disease and in its severity&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The publication of the Berlin definition published in 2012 produced other significant changes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The timing of onset of the acute respiratory failure was incorporated to the preexistent AECC definition&#58; ARDS had to appear within 1 week of exposure to a risk factor&#46; In addition&#44; clarification was added for the origin of edema and of lung images&#44; allowing definition by CT&#46; Three mutually exclusive categories of ARDS severity were established based on the PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> ratio&#44; evaluated with a minimum PEEP level of 5 cmH<span class="elsevierStyleInf">2</span>O&#46; In cases of mild ARDS the possibility of considering ARDS in patients who met the diagnostic criteria and were receiving noninvasive ventilation &#40;NIV&#41; was acknowledged&#46; Up till then&#44; ARDS could only be diagnosed in patients undergoing invasive mechanical ventilation&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The Berlin definition was a great advance&#46; One of its strengths was its empirical validation in 3670 patients&#44; unlike previous consensus definitions which only involved agreement between experts&#46; An attempt was also been made to make the new definition compatible with previous ones&#44; especially with the AECC&#46; Another positive feature is Berlin definition&#8217;s predictive validity for mortality&#46; Thus&#44; as severity of ARDS increases&#44; an increase in mortality and comorbidities was observed&#46; The experts sought to ensure that the variables defining ARDS were easily measurable&#44; that is to say&#44; that the application of the definition was feasible&#46; For example&#44; the increase in extravascular lung water was considered the variable that best reflected ARDS&#44; but its incorporation into the definition was discarded due to the technical difficulties and expensive technology involved&#46; In addition&#44; the experts established a &#34;conceptual model&#34; of ARDS&#44; which was mentioned at the beginning of this review&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Berlin&#39;s definition&#44; however&#44; had limitations&#46; The first is that it requires the use of a minimum level of PEEP for diagnosis&#44; either with invasive or noninvasive ventilation&#8213;in the latter case in mild ARDS only&#46; The assessment of bilateral infiltrates on CXR continues to lack intra- and interobserver reproducibility &#40;reliability&#41;&#44; and the consideration of a 7-day interval within which the syndrome should develop after exposure to a risk factor is completely arbitrary&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Another historical debate&#44; which is reinforced after the presentation of each new definition&#44; is whether the syndrome called ARDS really exists or is simply a compilation of multiple&#44; very heterogeneous diseases causing acute hypoxemic respiratory failure&#46; Thus&#44; all definitions of ARDS would necessarily be &#34;unsatisfactory and superficial&#34;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;16</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Despite these criticisms&#44; the utilization of AECC definition and the homogenization it implied helped to establish crucial therapeutic achievements which decreased mortality&#44; such as protective ventilation&#46; In addition&#44; the use of high PEEP&#44; compared to the conventional approach of intermediate PEEP&#44; was shown to have no benefit&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> The Berlin definition was also widely adopted&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">In 2016&#44; in a study conducted in Kigali&#44; Rwanda&#44; the researchers noted that with the previous definitions no patient with acute hypoxemic respiratory failure could be diagnosed as having ARDS&#44; because blood gas measurements were unavailable&#59; it was therefore impossible to know the PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Only a single daily measurement of peripheral oxygen saturation measured with pulse oximetry &#40;SpO<span class="elsevierStyleInf">2</span>&#41; was available&#46; The typical images of ARDS could also not be considered for diagnosis since less than 50&#37; of patients with hypoxemia had access to CXR&#46; However&#44; lung ultrasound was available&#46; Furthermore&#44; less than 30&#37; of the hypoxemic patients could receive mechanical ventilation&#44; due to the lack of ventilators&#59; therefore&#44; the PEEP&#8239;&#8805;&#8239;5 cmH<span class="elsevierStyleInf">2</span>O criteria could not be applied either&#46; Finally&#44; due to lack of beds&#44; only 30&#37; of patients with hypoxemic acute respiratory failure could be admitted ICU&#59; thus&#44; patients with less severe ARDS were possibly underdiagnosed&#46; These profound deficiencies in critical care provision are also present in other low-resource areas&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The researchers proposed the Kigali definition of ARDS as a modification of the Berlin definition &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8226;</span><p id="par0210" class="elsevierStylePara elsevierViewall">The PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 300 required for the diagnosis of ARDS was replaced by SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 315&#44; based on the acceptable linear correlation between PaO<span class="elsevierStyleInf">2</span> and SpO<span class="elsevierStyleInf">2</span>&#44; provided that SpO<span class="elsevierStyleInf">2</span> is &#8804; 97&#37;&#44; there are no hemoglobin abnormalities&#44; and that peripheral perfusion is adequate&#46; The Rice equation reflects this relationship&#58;</p><p id="par0215" class="elsevierStylePara elsevierViewall">SpO<span class="elsevierStyleInf">2</span> &#47;FiO<span class="elsevierStyleInf">2</span>&#8239;&#61;&#8239;64&#8239;&#43;&#8239;0&#8211;84 &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span>&#41;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">However&#44; above the 97&#37; threshold&#44; changes in PaO<span class="elsevierStyleInf">2</span> generate minimal impact on SpO<span class="elsevierStyleInf">2</span>&#44; due to the shape of the oxyhemoglobin dissociation curve&#59; therefore&#44; in the flat part of the curve the correlation between both methods of oxygenation assessment is lost&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8226;</span><p id="par0225" class="elsevierStylePara elsevierViewall">Lung ultrasound was added as diagnostic method for diagnosis of the syndrome&#44; in the absence of access to CXR or lung CT&#46; Even though these variables were not incorporated at that time into the Berlin definition as it would have been appropriate&#44; what occurred shows the importance of constituting panels of experts with members from all regions of the world&#46; The Berlin definition of ARDS&#44; like the previous AECC definition&#44; had been designed by experts from high-income countries &#40;mostly North America and Europe&#41; without the involvement of researchers from middle- and low-income countries&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></li></ul></p><p id="par0230" class="elsevierStylePara elsevierViewall">The Kigali definition also reflected the recent expansion of ultrasound as a diagnostic method in the ICU&#44; which might be more reliable than CXR for evaluation of lung infiltrates when trained operators are involved&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">The SARS-CoV-2 pandemic that devastated the world and generated maximum stress on health care systems&#44; particularly on the ICUs and emergency departments&#44; prompted a reevaluation of the definition of ARDS&#46; Thousands of patients with acute hypoxemic respiratory failure secondary to COVID-19 were simultaneously admitted to hospitals worldwide&#59; about 15&#8211;20 &#37; presented severe disease and 5&#37; required admission to the ICU&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> This trigged the need of continuous monitoring of oxygenation in patients who could rapidly worsen and require some type of respiratory support&#44; from oxygen therapy to invasive mechanical ventilation&#46; Thus&#44; the usual PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> monitoring with arterial blood gases&#44; which is intermittent&#44; laborious&#44; invasive and resource-intensive&#44; was replaced by the continuous&#44; noninvasive and less costly SpO<span class="elsevierStyleInf">2</span> measurement&#44; capable of detecting changes rapidly&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Additionally&#44; during the pandemic&#44; the use of high-flow nasal cannula &#40;HFNC&#41;&#44; which was increasingly used in acute hypoxemic respiratory failure&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> became widespread&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">As a result of these changes&#44; in 2021&#44; 54 years after Petty and Ashbaugh&#39;s publication&#44; an update of the definition of ARDS that could also be universally applicable was proposed&#46; An evolution from the &#34;expert consensus&#34; to &#34;a scientific system of categorization&#34; using approaches adopted in other fields of knowledge to build definitions of syndromes &#40;also called &#34;constructs&#34;&#41; for which there are no gold standards&#44; was deemed crucial&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Lack of a gold standard for definition not only occurs in ARDS but also in other well-known syndromes such as fragility&#44; heart failure&#44; and irritable bowel syndrome&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">For these reasons&#44; the construction of the New Global definition followed a rigorous methodology&#58; description of the clinical phenomenon &#40;or syndrome&#44; or &#34;construct&#34;&#41; to be &#34;captured&#34;&#59; justification of the changes proposed for the new definition&#59; explicit criteria for the selection of experts for the panel&#44; which should reflect not only expertise but gender&#44; cultural&#44; geographic&#44; socioeconomic&#44; and ethnic diversity&#59; and specification of the method by which agreements would be reached&#46; Usually&#44; an agreement implies a majority of at least 70&#37; when voting to accept or discard a variable or a statement&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Another objective was to reevaluate the conceptual model of ARDS recommended by the Berlin definition and to develop a New Global Definition of ARDS &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The feasibility of the New Global Definition was also evaluated&#44; i&#46;e&#46;&#44; whether its components are easily measurable&#44; both in clinical situations and in research&#44; and can be measured worldwide&#46; The reliability &#40;or reproducibility&#41;&#44; namely&#44; the ability of the definition to diagnose the same patient equally in different scenarios and when applied by different professionals&#44; was also analyzed&#46; Finally&#44; the validity of the new definition was explored&#44; that is to say&#44; its ability to reflect what clinicians really want to identify&#46; These concepts include surface validity &#40;the ability to identify the characteristics that are obviously part of ARDS and together distinguish patients with the condition from those without it&#41;&#59; and predictive validity &#40;whether the definition predicts outcomes&#44; such as mortality&#44; which should be more frequent in patients with the syndrome compared to those without it&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0260" class="elsevierStylePara elsevierViewall">In addition&#44; it was intended that the New Global Definition of ARDS should be supported by different critical care societies worldwide&#46; After a meticulous review process&#44; the following updates were incorporated into the Berlin consensus definition&#58;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">New Global Definition of ARDS<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conceptual model</span><p id="par0265" class="elsevierStylePara elsevierViewall">The conceptual model presented in the Berlin definition<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> was preserved&#44; and it was added that clinical presentation might be greatly influenced by the medical treatments administered&#58; change in position&#44; sedation&#44; paralysis&#44; PEEP&#44; and fluid balance&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Timing of diagnosis and consideration of extrapulmonary risk factors</span><p id="par0270" class="elsevierStylePara elsevierViewall">Regarding the time of disease onset and exposure to the risk factor&#44; the 7 days established by the Berlin criteria were retained&#46; ARDS is an inflammatory edema due to increased permeability&#44; excluding cardiogenic factors or hydric overload&#46; However&#44; ARDS can be diagnosed in the presence of these conditions if a predisposing risk factor for ARDS exists and if hydrostatic factors are not considered to be the main cause of hypoxemia&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Chest images</span><p id="par0275" class="elsevierStylePara elsevierViewall">Imaging criteria should include bilateral infiltrates on CXR or CT&#46; Additionally&#44; lung ultrasound &#40;evidence of B-lines or consolidation&#44; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A and B&#41; is incorporated in this update&#46; Whichever modality is used&#44; it should suggest loss of aeration not fully explained by lobar collapse&#44; pulmonary nodules or pleural effusion&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0280" class="elsevierStylePara elsevierViewall">CXR is the most widely used modality in critically ill patients&#46; However&#44; one of its limitations is the existence of high interobserver variability for identifying bilateral opacities&#46; In fact&#44; this was demonstrated when a CXR was evaluated by the same experts in mechanical ventilation and ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> A recent study showed an improvement in the interpretation of CXR using the RALE &#40;Radiographic Assessment of Lung Edema&#41; score&#46; It quantifies the number of affected quadrants in each hemithorax in 0&#8211;4 points&#44; together with the radiographic density of each quadrant&#44; assigning 1&#8211;3 points to it&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> The RALE score showed high interobserver agreement &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;0&#46;83 &#91;0&#46;8&#8722;0&#46;85&#93;&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;0001 for 488 studies&#41;&#44; and correlated with biomarker concentrations and with progression to prolonged mechanical ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Therefore&#44; the New Global Definition of ARDS integrates lung ultrasound to detect the loss of aeration&#44; especially when CXR or CT is not available&#46; This technique is especially useful when the operator is trained to detect bilateral consolidations and noncardiogenic pulmonary edema&#46; In the modified definition for resource-limited countries&#44; the lack of operator expertise could lead to overdiagnosis of ARDS&#44; since PEEP is eliminated as a diagnostic criterion&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Although the use of lung ultrasound for this purpose could be questioned&#44; there is evidence that supports it as an appropriate complement for imaging diagnosis of ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> On the other hand&#44; a very recent multicenter study evaluated pulmonary edema with the LUS &#40;Lung Ultrasound Score&#41; score for diagnosis of ARDS&#46; It was demonstrated&#44; through a model then applied successfully to a validation cohort&#44; that LUS has a very good diagnostic performance and could detect ARDS correctly&#44; comparable to that of expert evaluators&#46; these conclusions&#44; however&#44; require validation in larger numbers of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Oxygenation</span><p id="par0295" class="elsevierStylePara elsevierViewall">The creation of three new categories of ARDS with the aim of broadening the definition in line with the knowledge gathered during the COVID-19 pandemic was one of the major innovations&#46; Thus&#44; three groups were established&#58; <ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">&#8226;</span><p id="par0300" class="elsevierStylePara elsevierViewall">ARDS in non-intubated patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">&#8226;</span><p id="par0305" class="elsevierStylePara elsevierViewall">ARDS in intubated patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">&#8226;</span><p id="par0310" class="elsevierStylePara elsevierViewall">Modified ARDS category for resource-limited settings&#46;</p></li></ul></p><p id="par0315" class="elsevierStylePara elsevierViewall">The non-intubated category includes patients with NIV &#40;already considered in the Berlin definition&#41; and also with HFNC&#46; In addition&#44; to ensure that the definition is applicable in regions with scarce resources&#44; a third category was created&#46; For this purpose&#44; the Kigali modification was taken as a reference for settings where advanced ventilatory support devices are not available&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">This flexibility of the criteria has benefits as well as possible disadvantages&#46; For example&#44; it might be possible to make the diagnosis of ARDS earlier&#44; from the moment the patient is receiving HFNC support&#46; This allows the early implementation of different treatments&#44; which might even prevent progression to invasive mechanical ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Some special considerations are needed to keep in mind when utilizing HFNC&#46; With respect to the FiO<span class="elsevierStyleInf">2</span> delivered&#44; there is a relationship between the flow programmed in the device and the patient&#39;s inspiratory tidal flow&#44; which might impact on the FiO<span class="elsevierStyleInf">2</span> delivered and cause errors in the calculation of PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Moreover&#44; the inclusion of HFNC in the diagnosis of ARDS might be questioned due to its capacity to generate pressure&#46; In the new definition of ARDS the authors assume that 30&#8239;L&#47;m of flow achieves 5 cmH<span class="elsevierStyleInf">2</span>O of PEEP&#59; however&#44; the airway pressure generated by HFNC will be determined by the programmed flow and patient factors&#44; such as compliance of the respiratory system and whether the mouth is open or closed&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> However&#44; it is noteworthy that patients with severe hypoxemia who receive HFNC might continue to meet ARDS criteria after being intubated&#44; although they can be considered as a less severe form of ARDS&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">The gold standard for severity assessment is the use of arterial blood gases to determine PaO<span class="elsevierStyleInf">2</span>&#46; However&#44; as previously mentioned&#44; the wide use of SpO<span class="elsevierStyleInf">2</span> and the SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> index has proven a valid alternative for diagnosis&#44; given that patients diagnosed by either SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> or PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> have similar clinical characteristics and outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Although the absolute value of the SpO<span class="elsevierStyleInf">2</span> may differ from that of the arterial oxygen saturation measured invasively&#44; the good correlation between both methods and with PaO<span class="elsevierStyleInf">2</span> has led to the universal adoption of continuous SpO<span class="elsevierStyleInf">2</span> measurement&#44; and its subsequent incorporation to the New Global Definition of ARDS as a standard of care&#46; Likewise&#44; SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> cut-off points have been included for mild&#44; moderate and severe ARDS&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;37&#44;38</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">Based on these previous points&#44; the committee agreed to allow the use of SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> as an alternative to PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> for the diagnosis of ARDS&#46; Sensitivity and specificity of SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> for the diagnosis of ARDS according to the AECC definition are good &#40;around 85&#37; for both&#41; but the specificity drops sharply &#40;56&#37;&#41; for PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> values between 300 and 200&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In addition&#44; the devices used for SpO<span class="elsevierStyleInf">2</span> measurement &#40;digital pulse oximeters&#41; have considerable margins of error in the recordings&#44; which exposes patients to potential misdiagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#44;39</span></a></p><p id="par0335" class="elsevierStylePara elsevierViewall">When balancing the benefits and limitations listed&#44; the committee felt that the widespread availability of pulse oximetry in all healthcare settings outweighed the disadvantage of overlooking or miscategorizing hypoxemia in some patients&#46; And&#44; most importantly&#44; the overall effect of the New Global Definition will be to increase health equity in settings where ARDS is currently underdiagnosed&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">The New Global Definition of ARDS will have a significant impact on epidemiological studies and on interventional clinical trials&#44; since by reflecting a global panorama&#44; additional data on risk factors&#44; disease course and outcomes of different treatments in different populations will be available&#46; However&#44; it might increase diagnostic sensitivity&#44; as patients with atelectasis&#44; for example&#44; could be diagnosed as ARDS in low-resource regions&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The incorporation of non-intubated patients also increases the heterogeneity of the population diagnosed as ARDS&#44; but might allow&#44; as already mentioned&#44; earlier diagnosis and therefore rapid initiation of treatment&#46; In the future&#44; the identification of distinct ARDS subphenotypes &#40;subgroups of patients that can be reliably discriminated from other subgroups based on a pattern of measurable properties&#41; might reduce the impact of heterogeneity on clinical&#44; physiological&#44; or biological effects of any treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Issues not included in the New Global Definition</span><p id="par0345" class="elsevierStylePara elsevierViewall">There are several topics that might have been considered in this new global definition&#46; For example&#44; the discussion about prognosis enrichment&#44; which might help to optimize validity and applicability of the results obtained in clinical trials on ARDS&#46; As such&#44; the consideration of stricter inclusion criteria&#44; such as limiting participation to intubated patients with moderate to severe ARDS&#44; or to those meeting the definition of ARDS with a programmed PEEP value of 10 cmH<span class="elsevierStyleInf">2</span>O&#44; could identify more homogeneous subgroups of patients&#46; In turn&#44; this would improve the understanding of clinical variability and facilitate translation to clinical practice of the findings&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">Another aspect that was not addressed is how to assess unilateral infiltrates on CXR&#46; In clinical practice&#44; they are considered an exclusion criterion for ARDS&#44; which may preclude the application of protective ventilation strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> However&#44; it is known that CXR is susceptible to biases and limitations&#44; as bilateral infiltrates may go unrecognized especially when taken with the equipment commonly used in ICUs&#44; and in patients with pre-existing lung disease&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Another common misconception is that patients with unilateral infiltrates on mechanical ventilation have better oxygenation and lower mortality&#44; compared to those with bilateral infiltrates and ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Yet data from the LUNG SAFE study reveal that while patients with unilateral infiltrates usually have lower initial severity&#44; mortality does not differ significantly from that of patients with ARDS&#46; Furthermore&#44; in patients with unilateral infiltrates&#44; ventilatory monitoring variables such as driving pressure are important risk factors for developing ARDS&#44; highlighting the importance of implementing protective ventilatory strategies also in this population&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">On the other hand&#44; there is still debate over some issues&#46; Researchers could choose to focus on subjects with ARDS who continue to meet the definition beyond 24&#8239;h if they wish to exclude those who improve rapidly or introduce a stabilization period as proposed by Guerin in the PROSEVA study&#44; therefore achieving more homogeneous subgroups to evaluate a response to a therapeutic maneuver&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#8211;46</span></a> Other subcategories of ARDS &#40;subgroups and subphenotypes&#41; that were not included in the current definition have been proposed to assess possible different responses to treatment&#46; These subcategories might be defined by biomarker levels&#44; types of images &#40;focal or diffuse lung infiltrates&#41;&#44; recruitment potential&#44; or physiological variables such as inspiratory pressure&#44; elasticity behavior&#44; or the ventilatory ratio&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#8211;53</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Final considerations</span><p id="par0360" class="elsevierStylePara elsevierViewall">The New Global Definition of ARDS is an extension of the Berlin definition in matters of diagnosis and monitoring of the disease&#46; The category of intubated patients preserves the previously described PaO2&#47;FiO2 severity cut-off points but allows the use of equivalent SpO2&#47;FiO2 cutoff values in situations where arterial blood gases are not available&#46; The two new categories added&#58; ARDS in non-intubated patients&#44; and ARDS in patients assisted in regions with low health resources&#44; constitute a relevant innovation&#44; but it is especially highlighted that the diagnostic modifications proposed for these regions should be considered only in them&#46; It is recommended that researchers continue to report their data based on the Berlin definition when possible&#46; The epidemiological impact of the modified definition for low-resource areas is still uncertain&#46; Looking ahead&#44; there is great hope that the identification of ARDS subphenotypes may facilitate the assessment of response to different treatments and the development of personalized treatments&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interest</span><p id="par0365" class="elsevierStylePara elsevierViewall">GAP has received funding for teaching programs from <span class="elsevierStyleGrantSponsor" id="gs0005">Medtronic LATAM</span> and <span class="elsevierStyleGrantSponsor" id="gs0010">Vapotherm Inc&#46; USA</span>&#46;</p></span></span>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Increase in shunt and dead space</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Impaired distensibility of the respiratory system present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Thoraco-pulmonary compliance &#60; 50&#8239;mL&#47;cmH<span class="elsevierStyleInf">2</span>O &#40;usually 20&#8211;30&#8239;ml&#47;cmH<span class="elsevierStyleInf">2</span>O&#41;</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3522331.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Adult respiratory distress syndrome definition&#44; according to Ashbaugh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AECC &#40;1994&#41;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Berl&#237;n &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Kigali &#40;2016&#41;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Timing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Within 1 week of a known clinical insult or new or worsening respiratory symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Within 1 week of a known clinical insult or new or worsening respiratory symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chest image&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilateral infiltrates on frontal chest radiograph&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilateral opacities not fully explained by effusions&#44; lobar&#47;pulmonary collapse or nodules on chest radiograph or CT scan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilateral opacities not fully explained by effusions&#44; lobar&#47;pulmonary collapse or nodules on radiography&#44; computed tomography or lung ultrasonography&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Edema cause&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiogenic edema should be ruled out&#46; Wedge pressure &#60; 18&#8239;mmHg if measurable&#44; or absence of clinical or ultrasound signs of left atrial hypertension&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Respiratory failure not fully explained by heart failure or fluid overload&#46; Need objective evaluation &#40;e&#46;g&#46;&#44; echocardiography&#41; to exclude hydrostatic edema if no risk factors are present&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Respiratory failure not fully explained by heart failure or fluid overload&#46; Need objective evaluation &#40;e&#46;g&#46;&#44; echocardiography&#41; to exclude hydrostatic edema if no risk factors are present&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oxygenation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 categories&#58; a&#41; ALI&#58; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 300b&#41; ARDS&#58; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ARDS Mild&#58;</span> 200 &#60; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 300 <span class="elsevierStyleItalic">ARDS Moderate&#58;</span> 100 &#60; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 200 <span class="elsevierStyleItalic">ARDS Severe&#58;</span> PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ARDS&#58; SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 315&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PEEP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Independent of PEEP level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">At least 5 cmH<span class="elsevierStyleInf">2</span>O through invasive mechanical ventilation &#40;or noninvasive in mild ARDS&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No PEEP required&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3522330.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">ARDS different definitions&#46;</p>"
        ]
      ]
      5 => array:9 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Taken from Matthay et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>"
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0030"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Conceptual model&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ARDS is an inflammatory&#44; diffuse&#44; acute&#44; lung injury precipitated by a predisposing risk factor&#44; such as pneumonia&#44; nonpulmonary infection&#44; trauma&#44; transfusion&#44; burns&#44; aspiration&#44; or shock&#46; The resulting injury leads to increased pulmonary vascular and epithelial permeability&#44; pulmonary edema&#44; and severity-dependent atelectasis&#44; all of which contribute to loss of aerated lung tissue&#46; The clinical features are arterial hypoxemia and diffuse radiological opacities associated with increased shunt&#44; increased alveolar dead space and decreased pulmonary compliance&#46; The clinical presentation is influenced by medical treatment &#40;position&#44; sedation&#44; paralysis&#44; PEEP and fluid balance&#41;&#46; Histological findings vary and may include intra-alveolar edema&#44; inflammation&#44; hyaline membrane formation and alveolar hemorrhage&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Criteria that apply to all ARDS categories</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risk factors and edema cause&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Precipitated by an acute predisposing risk factor&#44; such as pneumonia&#44; nonpulmonary infection&#44; trauma&#44; transfusion&#44; aspiration&#44; or shock&#46; Pulmonary edema is not attributable exclusively or primarily to cardiogenic pulmonary edema&#47;fluid overload&#44; and hypoxemia or gas exchange abnormalities are not primarily attributable to atelectasis&#46; However&#44; ARDS can be diagnosed in the presence of these conditions if a predisposing risk factor for ARDS is also present&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Timing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute onset or worsening of hypoxemic respiratory failure within one week of the estimated onset of the predisposing risk factor or new or worsening respiratory symptoms&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chest image&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilateral opacities on chest radiograph and computed tomography or bilateral B-lines and&#47;or consolidations on ultrasound that are not fully explained by effusions&#44; atelectasis or nodules&#47;masses&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab3522329.png"
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria applied to specific ARDS categories</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-intubated ARDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intubated ARDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Definition modified for countries with limited resources&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oxygenation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 300 or SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 315 &#40;if SpO<span class="elsevierStyleInf">2</span> &#60; 97 &#37;&#41; in HFNC with flow &#62; 30&#8239;L&#47;min&#46; oNIV&#47;CPAP&#8239;&#8805;&#8239;5 cmH<span class="elsevierStyleInf">2</span>O of PEEP&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mild&#58;</span>200 &#60; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 300 or235 &#60; SpO2&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 315 &#40;si SpO<span class="elsevierStyleInf">2</span> &#60; 97&#37;&#41;&#46;<span class="elsevierStyleItalic">Moderate&#58;</span>100 &#60; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 200 or148 &#60; SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 235 &#40;si SpO<span class="elsevierStyleInf">2</span> &#60; 97&#37;&#41;&#46;<span class="elsevierStyleItalic">Severe&#58;</span>PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 100 orSpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 148 &#40;si SpO<span class="elsevierStyleInf">2</span> &#60; 97&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 315 &#40;if SpO<span class="elsevierStyleInf">2</span> &#60; 97 &#37;&#41;No PEEP or minimum oxygen flow is required for diagnosis in resource-limited settings&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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Review article
Post-pandemic acute respiratory distress syndrome: A New Global Definition with extension to lower-resource regions
Síndrome de distrés respiratorio agudo en la post-pandemia: una nueva definicion global con extensión a regiones de menos recursos
Elisa Estenssoroa,b,1,
Corresponding author
estenssoro.elisa@gmail.com

Corresponding author at: Dirección postal: 42 No. 577, La Plata 1900, BA, Argentina.
, Iván Gonzálezc, Gustavo A. Plotnikowc,d
a Escuela de Gobierno en Salud, Ministerio de Salud, Buenos Aires, Argentina
b Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Buenos Aires, Argentina
c Servicio de Rehabilitación, Área de Kinesiología Crítica, Hospital Británico de Buenos Aires, CABA, Argentina
d Facultad de Medicina y Ciencias de la Salud, Universidad Abierta Interamericana, Argentina
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">The conceptual model of Acute Respiratory Distress Syndrome &#40;ARDS&#41;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Conceptually&#44; ARDS consists in an acute respiratory failure caused by inflammatory pulmonary edema&#44; characterized by increased vascular permeability with extravasation of fluids into the interstitial space with consequent flooding of the alveolar spaces&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The loss of aerated lung tissue&#44; due to atelectasis in gravity-dependent areas produced by the increased weight of the overlying lung tissue&#44; leads to profound oxygenation impairment secondary to increased intrapulmonary shunt and alveolar dead space&#44; along with a marked decrease in respiratory system compliance&#46; ARDS is also characterized by the presence of lung infiltrates on CXR &#40;CXR&#41; and computed tomography &#40;CT&#41; scans &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and B&#41;&#46; Anatomically and pathologically&#44; the main feature of ARDS is an histological pattern known as diffuse alveolar damage &#40;DAD&#41;&#44; which includes the presence of hyaline membranes&#44; edema&#44; type I and II alveolar cell necrosis&#44; and hemorrhage&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> This description constitutes the &#34;conceptual model of ARDS&#34; and reflects how clinicians &#34;perceive&#34; the syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">ARDS can develop secondary to a multitude of risk factors of pulmonary &#40;direct&#41; and extrapulmonary &#40;indirect&#41; cause&#46; This etiological heterogeneity likely reflects the activation of different mechanisms of injury &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Another crucial aspect is the lack of gold standard for defining ARDS&#46; Even DAD is not pathognomonic since it might not be identified in all clinically diagnosed ARDS cases&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Given the pathophysiological complexity of ARDS and the diverse causes that generate it -although all ultimately converge in the activation of proinflammatory mechanisms- a definition to standardize diagnosis&#44; clinical management&#44; and use of various therapeutic approaches was required&#46; Additionally&#44; the definition of a disease promotes the development of related scientific research&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The definitions of ARDS over time</span><p id="par0155" class="elsevierStylePara elsevierViewall">The original definition of ARDS dates to 1967 and was issued by Petty and Ashbaugh&#44; who described a group of 12 patients with acute respiratory failure&#44; profound hypoxemia secondary mainly to intrapulmonary shunt&#44; bilateral infiltrates on CXR and decreased thoraco-pulmonary compliance&#44; with no history of chronic respiratory failure&#44; and in absence of left ventricular failure&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> This condition occurred after exposure to what they called a &#34;catastrophic event&#34; &#40;which are now the risk factors for ARDS&#41;&#44; of pulmonary or extrapulmonary origin &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Because of its clinical and radiological similarity to respiratory distress syndrome secondary to surfactant deficiency in newborns&#44; the authors named this entity &#34;Adult Respiratory Distress Syndrome&#34;&#46; Petty and Ashbaugh&#39;s definition identified what is currently known as severe ARDS&#44; since from the point of view of oxygenation impairment it referred to patients with PaO<span class="elsevierStyleInf">2</span> &#60; 50&#8239;mmHg with an inspired oxygen fraction &#40;FiO<span class="elsevierStyleInf">2</span>&#41; &#62; 0&#46;6&#59; that is&#44; with deep hypoxemia&#44; evidenced by a PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> ratio of approximately 80 mmHg&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">Since this initial approach&#44; several modifications of the definition have been made&#46; In 1988&#44; Murray et al&#46; proposed the Lung Injury Score &#40;LIS&#41; with the intention of quantifying the severity of the syndrome&#46; The LIS was the average value of 4 variables&#44; expressed as a score from 0 to 4 reflecting increasing severity&#58; hypoxemia &#40;defined as the PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> ratio&#41;&#59; extent of pulmonary infiltrates on chest radiograph &#40;in quadrants&#41;&#44; thoraco-pulmonary compliance &#40;ml&#47;cmH<span class="elsevierStyleInf">2</span>O&#41; and use of positive end-expiratory pressure &#40;PEEP&#44; cmH<span class="elsevierStyleInf">2</span>O&#41;&#46; ARDS was defined by an LIS &#62; 2&#46;5&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The LIS was adopted for use&#44; but the definition remained a construction of few experts&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">In 1994&#44; the American-European Consensus Conference &#40;AECC&#41; definition was published&#44; in which the syndrome known until then as Adult Respiratory Distress Syndrome was considered as compounded by two conditions of progressive severity&#58; acute lung injury &#40;ALI&#41; and ARDS &#40;Acute Respiratory Distress Syndrome&#41;&#44; defined by the compromise of oxygenation&#58; PaO2&#47;FiO2&#8239;&#8804;&#8239;300 and &#8804;200&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The acute characteristics of the syndrome and the exclusion of cardiovascular causes for pulmonary edema development were maintained&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">The AECC definition&#44; like the LIS score&#44; suffered from several criticisms&#44; centered mainly on two aspects&#46; First&#44; experts highlighted the diagnostic difficulties for the evaluation of CXR infiltrates on CXR&#44; due to the great intra- and interobserver variation&#46; In addition&#44; the decision to exclude any standardized level of PEEP for oxygenation assessment produced further variability&#44; secondary to PEEP great impact on the definition of ARDS&#46; Patients could quickly move from one category of hypoxemia to another&#44; without implying a real change in the underlying disease and in its severity&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The publication of the Berlin definition published in 2012 produced other significant changes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The timing of onset of the acute respiratory failure was incorporated to the preexistent AECC definition&#58; ARDS had to appear within 1 week of exposure to a risk factor&#46; In addition&#44; clarification was added for the origin of edema and of lung images&#44; allowing definition by CT&#46; Three mutually exclusive categories of ARDS severity were established based on the PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> ratio&#44; evaluated with a minimum PEEP level of 5 cmH<span class="elsevierStyleInf">2</span>O&#46; In cases of mild ARDS the possibility of considering ARDS in patients who met the diagnostic criteria and were receiving noninvasive ventilation &#40;NIV&#41; was acknowledged&#46; Up till then&#44; ARDS could only be diagnosed in patients undergoing invasive mechanical ventilation&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The Berlin definition was a great advance&#46; One of its strengths was its empirical validation in 3670 patients&#44; unlike previous consensus definitions which only involved agreement between experts&#46; An attempt was also been made to make the new definition compatible with previous ones&#44; especially with the AECC&#46; Another positive feature is Berlin definition&#8217;s predictive validity for mortality&#46; Thus&#44; as severity of ARDS increases&#44; an increase in mortality and comorbidities was observed&#46; The experts sought to ensure that the variables defining ARDS were easily measurable&#44; that is to say&#44; that the application of the definition was feasible&#46; For example&#44; the increase in extravascular lung water was considered the variable that best reflected ARDS&#44; but its incorporation into the definition was discarded due to the technical difficulties and expensive technology involved&#46; In addition&#44; the experts established a &#34;conceptual model&#34; of ARDS&#44; which was mentioned at the beginning of this review&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Berlin&#39;s definition&#44; however&#44; had limitations&#46; The first is that it requires the use of a minimum level of PEEP for diagnosis&#44; either with invasive or noninvasive ventilation&#8213;in the latter case in mild ARDS only&#46; The assessment of bilateral infiltrates on CXR continues to lack intra- and interobserver reproducibility &#40;reliability&#41;&#44; and the consideration of a 7-day interval within which the syndrome should develop after exposure to a risk factor is completely arbitrary&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Another historical debate&#44; which is reinforced after the presentation of each new definition&#44; is whether the syndrome called ARDS really exists or is simply a compilation of multiple&#44; very heterogeneous diseases causing acute hypoxemic respiratory failure&#46; Thus&#44; all definitions of ARDS would necessarily be &#34;unsatisfactory and superficial&#34;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;16</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Despite these criticisms&#44; the utilization of AECC definition and the homogenization it implied helped to establish crucial therapeutic achievements which decreased mortality&#44; such as protective ventilation&#46; In addition&#44; the use of high PEEP&#44; compared to the conventional approach of intermediate PEEP&#44; was shown to have no benefit&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> The Berlin definition was also widely adopted&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">In 2016&#44; in a study conducted in Kigali&#44; Rwanda&#44; the researchers noted that with the previous definitions no patient with acute hypoxemic respiratory failure could be diagnosed as having ARDS&#44; because blood gas measurements were unavailable&#59; it was therefore impossible to know the PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Only a single daily measurement of peripheral oxygen saturation measured with pulse oximetry &#40;SpO<span class="elsevierStyleInf">2</span>&#41; was available&#46; The typical images of ARDS could also not be considered for diagnosis since less than 50&#37; of patients with hypoxemia had access to CXR&#46; However&#44; lung ultrasound was available&#46; Furthermore&#44; less than 30&#37; of the hypoxemic patients could receive mechanical ventilation&#44; due to the lack of ventilators&#59; therefore&#44; the PEEP&#8239;&#8805;&#8239;5 cmH<span class="elsevierStyleInf">2</span>O criteria could not be applied either&#46; Finally&#44; due to lack of beds&#44; only 30&#37; of patients with hypoxemic acute respiratory failure could be admitted ICU&#59; thus&#44; patients with less severe ARDS were possibly underdiagnosed&#46; These profound deficiencies in critical care provision are also present in other low-resource areas&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The researchers proposed the Kigali definition of ARDS as a modification of the Berlin definition &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8226;</span><p id="par0210" class="elsevierStylePara elsevierViewall">The PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 300 required for the diagnosis of ARDS was replaced by SpO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#8804; 315&#44; based on the acceptable linear correlation between PaO<span class="elsevierStyleInf">2</span> and SpO<span class="elsevierStyleInf">2</span>&#44; provided that SpO<span class="elsevierStyleInf">2</span> is &#8804; 97&#37;&#44; there are no hemoglobin abnormalities&#44; and that peripheral perfusion is adequate&#46; The Rice equation reflects this relationship&#58;</p><p id="par0215" class="elsevierStylePara elsevierViewall">SpO<span class="elsevierStyleInf">2</span> &#47;FiO<span class="elsevierStyleInf">2</span>&#8239;&#61;&#8239;64&#8239;&#43;&#8239;0&#8211;84 &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span>&#41;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">However&#44; above the 97&#37; threshold&#44; changes in PaO<span class="elsevierStyleInf">2</span> generate minimal impact on SpO<span class="elsevierStyleInf">2</span>&#44; due to the shape of the oxyhemoglobin dissociation curve&#59; therefore&#44; in the flat part of the curve the correlation between both methods of oxygenation assessment is lost&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8226;</span><p id="par0225" class="elsevierStylePara elsevierViewall">Lung ultrasound was added as diagnostic method for diagnosis of the syndrome&#44; in the absence of access to CXR or lung CT&#46; Even though these variables were not incorporated at that time into the Berlin definition as it would have been appropriate&#44; what occurred shows the importance of constituting panels of experts with members from all regions of the world&#46; The Berlin definition of ARDS&#44; like the previous AECC definition&#44; had been designed by experts from high-income countries &#40;mostly North America and Europe&#41; without the involvement of researchers from middle- and low-income countries&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></li></ul></p><p id="par0230" class="elsevierStylePara elsevierViewall">The Kigali definition also reflected the recent expansion of ultrasound as a diagnostic method in the ICU&#44; which might be more reliable than CXR for evaluation of lung infiltrates when trained operators are involved&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">The SARS-CoV-2 pandemic that devastated the world and generated maximum stress on health care systems&#44; particularly on the ICUs and emergency departments&#44; prompted a reevaluation of the definition of ARDS&#46; Thousands of patients with acute hypoxemic respiratory failure secondary to COVID-19 were simultaneously admitted to hospitals worldwide&#59; about 15&#8211;20 &#37; presented severe disease and 5&#37; required admission to the ICU&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> This trigged the need of continuous monitoring of oxygenation in patients who could rapidly worsen and require some type of respiratory support&#44; from oxygen therapy to invasive mechanical ventilation&#46; Thus&#44; the usual PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> monitoring with arterial blood gases&#44; which is intermittent&#44; laborious&#44; invasive and resource-intensive&#44; was replaced by the continuous&#44; noninvasive and less costly SpO<span class="elsevierStyleInf">2</span> measurement&#44; capable of detecting changes rapidly&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Additionally&#44; during the pandemic&#44; the use of high-flow nasal cannula &#40;HFNC&#41;&#44; which was increasingly used in acute hypoxemic respiratory failure&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> became widespread&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">As a result of these changes&#44; in 2021&#44; 54 years after Petty and Ashbaugh&#39;s publication&#44; an update of the definition of ARDS that could also be universally applicable was proposed&#46; An evolution from the &#34;expert consensus&#34; to &#34;a scientific system of categorization&#34; using approaches adopted in other fields of knowledge to build definitions of syndromes &#40;also called &#34;constructs&#34;&#41; for which there are no gold standards&#44; was deemed crucial&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Lack of a gold standard for definition not only occurs in ARDS but also in other well-known syndromes such as fragility&#44; heart failure&#44; and irritable bowel syndrome&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">For these reasons&#44; the construction of the New Global definition followed a rigorous methodology&#58; description of the clinical phenomenon &#40;or syndrome&#44; or &#34;construct&#34;&#41; to be &#34;captured&#34;&#59; justification of the changes proposed for the new definition&#59; explicit criteria for the selection of experts for the panel&#44; which should reflect not only expertise but gender&#44; cultural&#44; geographic&#44; socioeconomic&#44; and ethnic diversity&#59; and specification of the method by which agreements would be reached&#46; Usually&#44; an agreement implies a majority of at least 70&#37; when voting to accept or discard a variable or a statement&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Another objective was to reevaluate the conceptual model of ARDS recommended by the Berlin definition and to develop a New Global Definition of ARDS &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The feasibility of the New Global Definition was also evaluated&#44; i&#46;e&#46;&#44; whether its components are easily measurable&#44; both in clinical situations and in research&#44; and can be measured worldwide&#46; The reliability &#40;or reproducibility&#41;&#44; namely&#44; the ability of the definition to diagnose the same patient equally in different scenarios and when applied by different professionals&#44; was also analyzed&#46; Finally&#44; the validity of the new definition was explored&#44; that is to say&#44; its ability to reflect what clinicians really want to identify&#46; These concepts include surface validity &#40;the ability to identify the characteristics that are obviously part of ARDS and together distinguish patients with the condition from those without it&#41;&#59; and predictive validity &#40;whether the definition predicts outcomes&#44; such as mortality&#44; which should be more frequent in patients with the syndrome compared to those without it&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0260" class="elsevierStylePara elsevierViewall">In addition&#44; it was intended that the New Global Definition of ARDS should be supported by different critical care societies worldwide&#46; After a meticulous review process&#44; the following updates were incorporated into the Berlin consensus definition&#58;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">New Global Definition of ARDS<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conceptual model</span><p id="par0265" class="elsevierStylePara elsevierViewall">The conceptual model presented in the Berlin definition<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> was preserved&#44; and it was added that clinical presentation might be greatly influenced by the medical treatments administered&#58; change in position&#44; sedation&#44; paralysis&#44; PEEP&#44; and fluid balance&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Timing of diagnosis and consideration of extrapulmonary risk factors</span><p id="par0270" class="elsevierStylePara elsevierViewall">Regarding the time of disease onset and exposure to the risk factor&#44; the 7 days established by the Berlin criteria were retained&#46; ARDS is an inflammatory edema due to increased permeability&#44; excluding cardiogenic factors or hydric overload&#46; However&#44; ARDS can be diagnosed in the presence of these conditions if a predisposing risk factor for ARDS exists and if hydrostatic factors are not considered to be the main cause of hypoxemia&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Chest images</span><p id="par0275" class="elsevierStylePara elsevierViewall">Imaging criteria should include bilateral infiltrates on CXR or CT&#46; Additionally&#44; lung ultrasound &#40;evidence of B-lines or consolidation&#44; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A and B&#41; is incorporated in this update&#46; Whichever modality is used&#44; it should suggest loss of aeration not fully explained by lobar collapse&#44; pulmonary nodules or pleural effusion&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0280" class="elsevierStylePara elsevierViewall">CXR is the most widely used modality in critically ill patients&#46; However&#44; one of its limitations is the existence of high interobserver variability for identifying bilateral opacities&#46; In fact&#44; this was demonstrated when a CXR was evaluated by the same experts in mechanical ventilation and ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> A recent study showed an improvement in the interpretation of CXR using the RALE &#40;Radiographic Assessment of Lung Edema&#41; score&#46; It quantifies the number of affected quadrants in each hemithorax in 0&#8211;4 points&#44; together with the radiographic density of each quadrant&#44; assigning 1&#8211;3 points to it&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> The RALE score showed high interobserver agreement &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;0&#46;83 &#91;0&#46;8&#8722;0&#46;85&#93;&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;0001 for 488 studies&#41;&#44; and correlated with biomarker concentrations and with progression to prolonged mechanical ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Therefore&#44; the New Global Definition of ARDS integrates lung ultrasound to detect the loss of aeration&#44; especially when CXR or CT is not available&#46; This technique is especially useful when the operator is trained to detect bilateral consolidations and noncardiogenic pulmonary edema&#46; In the modified definition for resource-limited countries&#44; the lack of operator expertise could lead to overdiagnosis of ARDS&#44; since PEEP is eliminated as a diagnostic criterion&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Although the use of lung ultrasound for this purpose could be questioned&#44; there is evidence that supports it as an appropriate complement for imaging diagnosis of ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> On the other hand&#44; a very recent multicenter study evaluated pulmonary edema with the LUS &#40;Lung Ultrasound Score&#41; score for diagnosis of ARDS&#46; It was demonstrated&#44; through a model then applied successfully to a validation cohort&#44; that LUS has a very good diagnostic performance and could detect ARDS correctly&#44; comparable to that of expert evaluators&#46; these conclusions&#44; however&#44; require validation in larger numbers of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Oxygenation</span><p id="par0295" class="elsevierStylePara elsevierViewall">The creation of three new categories of ARDS with the aim of broadening the definition in line with the knowledge gathered during the COVID-19 pandemic was one of the major innovations&#46; Thus&#44; three groups were established&#58; <ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel"&g