Acute respiratory distress syndrome (ARDS) is a common disease that threatens the lives of critically ill patients, with a death rate of 36%-45%. 12 cases of acute respiratory failure from various causes were first reported by Ashbaugh in 1967, and the syndrome has been recognized for half a century, but its definition and diagnostic criteria have been controversial. Currently, the more commonly used diagnostic criteria are the 1994 American and European Joint Conference (AECC), but a large number of studies have shown that the accuracy of the criteria is not satisfactory. Therefore, it is of great significance to seek an accurate and rigorous diagnostic standard for clinical treatment and scientific research.
I. Characteristics of the ideal ARDS criteria
ARDS is a clinical syndrome characterized by respiratory distress and progressive hypoxemia due to diffuse pulmonary interstitial and alveolar edema caused by damage to pulmonary capillary endothelial cells and alveolar epithelial cells from various causes. The typical histopathological changes are characterized by diffuse alveolar injury. Although our understanding of the pathogenesis of ARDS has improved significantly, it is still not possible to accurately determine the course and prognosis of lung injury. Therefore, the diagnostic criteria of ARDS must be defined by combining risk factors, clinical manifestations, oxygenation indicators, imaging changes and biomarkers.
1. Distinction of risk factors The risk factors leading to ARDS are roughly divided into endopulmonary and exopulmonary factors. ARDS caused by different pathogenic factors are different in terms of pathophysiological mechanism, imaging performance, and responsiveness to treatment strategies. Numerous studies have shown that exopulmonary ARDS may be more responsive to treatment strategies such as pulmonary retension, prone ventilation, and high-frequency oscillatory ventilation than endopulmonary ARDS, and their prognosis may also differ because of the responsiveness to treatment. Therefore, it is necessary for the future definition of ARDS to differentiate ARDS risk factors, which may facilitate the adjustment of treatment strategies.
2. Definition of the time of onset The diagnosis of ARDS requires the exclusion of chronic lung disease and needs to be differentiated from interstitial lung disease, the onset of which usually lasts from several weeks to several months. At present, there is relatively little epidemiological data on the time of onset of ARDS, so the definition of the time of onset is unclear for both old and new criteria. Therefore, many scholars believe that it is reasonable to define the acute onset of ARDS at 7 days. The definition of the time of onset can effectively distinguish ARDS from other chronic diseases and thus improve the accuracy of diagnosis. Therefore, the time of onset of ARDS should be clearly defined in the new standard.
3, standardization of hypoxemia The most debated part of the AECC definition is the interpretation of hypoxemia, because of its many influencing factors, among which, the influence of PEEP and Fi02 is particularly prominent. villar et al. found that for ARDS patients who met the AECC criteria, by giving PEEP/Fi02 titration, it was found that after PEEP ≥ 10 cmH2O and FiO2 ≥ Only 99 patients still met the original diagnostic criteria for ARDS, while 55 patients met the criteria for ALI and even 16 patients had an oxygen index ≥300 mmHg. There was also a significant difference in the morbidity and mortality rates of the three categories of patients reclassified after the intervention, 45.5%, 20%, and 6.3%, respectively. , and 6.3%. In addition, Britos et al. showed that FiO2 has a greater impact on the oxygenation index of ARDS patients than PEEP and can be used to determine patient prognosis. It can be seen that in the future, when defining ARDS, mechanical ventilation parameters in hypoxemia, especially PEEP as well as FiO2, should be standardized.
Imaging features play a pivotal role in the diagnosis of ARDS, but abnormalities in X-ray chest films can be influenced by the patient’s position, the reader’s imaging knowledge and experience. A clinical study organized 21 critical care specialists to determine whether the radiographs of ARDS patients met the diagnostic criteria for ARDS established by the AECC. The results showed that the accuracy of the experts’ diagnoses ranged from 36% to 71%, and the agreement rate of their diagnostic conclusions was only 55%. Therefore, the definition of chest imaging should be as exhaustive as possible in the future ARDS criteria. In addition, the application of CT of the lung may obtain more information about the lesion than conventional X-ray chest radiographs, which is more beneficial for accurate determination of lung damage. The use of chest CT for the assessment of pathophysiological changes in ARDS is likely to become an indispensable – item in the new criteria.
5. Exclusion of cardiogenic pulmonary edema The AECC criteria use PAWP <18 mmhg as an index to exclude cardiogenic pulmonary edema, which is unreasonable. First, the measurement of PAWP requires the placement of a swan-ganz catheter, and it is not possible to perform this test in every patient. Second, there is a problem with the accuracy of using the presence or absence of "increased left atrial pressure" as an exclusion criterion for cardiogenic pulmonary edema. In contrast, b-type brain natriuretic peptide (bnp), which can be increased with a mild increase in ventricular load, can be used to monitor cardiac function. In addition, bedside ultrasound is a useful indicator of cardiogenic pulmonary edema because it is simple and noninvasive and can be used to assess cardiac and valvular function. Therefore, cardiogenic pulmonary edema can be excluded by bnp and bedside ultrasound in future aards criteria. < p="">
6. Introduction of biomarkers With the rapid development of ARDS genetic diagnosis and the gradual understanding of the molecular biological mechanism of the disease, biomarkers will definitely be introduced in the future ARDS diagnosis. Suitable biomarkers will play a key role in the early identification, diagnosis, and classification of the severity of ARDS. Existing studies have shown that IL-8 in alveolar lavage fluid and serum lipopolysaccharide-binding protein can be used as indicators of risk factors for ARDS. In addition, Determann et al. found that plasma levels of Clara cell protein (CC16) were significantly higher in patients with ARDS than in those without ARDS. Further analysis revealed that if plasma CC16 ≥18 ng/ml was used as a criterion for the diagnosis of ARDS, its sensitivity was 80% and specificity was 92%. Therefore, the introduction of biomarkers will certainly occupy an important position in the future ARDS diagnostic criteria.
II. Historical evolution of ARDS diagnosis
The definition of ARDS has been evolving since 1967. So far, the more widely used diagnostic criteria include Murray’s Lung Injury Score in 1988, the European and American Joint Conference Diagnostic Criteria (AECC) in 1994 and Delphi’s criteria in 2005.
1, Murray lung injury scoring standards 1988 Murray lung injury score will be the original definition of the expansion. The score consists of four parts: chest X-ray, hypoxemia (oxygenation index), PEEP, and respiratory compliance. 0 means no lung injury, 1~2.5 means mild to moderate lung injury, and more than 2.5 means severe lung injury or ARDS. the advantage of this score is that it takes PEEP and lung compliance into account to differentiate the degree of injury, and at the same time, the imaging changes are more characteristic. . The well-known CESAR study and the 2011 JAMA clinical study on first-line treatment with ECMO used the Murray lung injury criteria as inclusion criteria. However, at the same time, this criterion has some shortcomings: hypoxia due to cardiogenic pulmonary edema is not excluded, risk factors for morbidity are not addressed, and the ability to determine prognosis is poor. In any case, the Murray lung injury score has further improved the understanding of ARDS.
2, AECC criteria The judgment of the severity of ARDS affects the assessment of treatment responsiveness and prognosis. in order to distinguish the degree of lung injury, the AECC diagnostic criteria were adopted in 1994 by the joint meeting of Europe and America. the main advantage of the AECC criteria is the simplicity and convenience of distinguishing ALI and ARDS. Therefore, all studies after ARDSnet have adopted this criterion, and countries have developed their own ARDS guidelines mainly by referring to this criterion. Unfortunately, the AECC criteria are also questionable: they do not take into account the mode of mechanical ventilation and PEEP levels that directly affect oxygenation; they do not routinely apply pulmonary artery catheters; they do not define acute onset; and they do not mention risk factors.
By comparing the AECC criteria with autopsy results, Steban et al. found that the AECC criteria had a sensitivity of 75% and a specificity of 84%. Bruno et al. also reached similar conclusions in a study published in 2007. Therefore, although the AECC diagnostic criteria have made some progress, the accuracy is still not perfect.
3.Delphi criteria
The exploration of ARDS criteria did not stop, and the Delphi criteria came into being in 2005. the main contents of the Delphi criteria are
① Hypoxemia: PaO2/FiO2<200mmhg and peep≥10cmh2O;
②Acute onset: onset <72 hours;
③ abnormal chest imaging: bilateral lung infiltrative shadow >2 intervals;
④No cardiogenic factors: no clinical evidence of congestive heart failure (can be determined by pulmonary artery catheter or ultrasound);
⑤ Decreased pulmonary compliance: static respiratory compliance <50ml/cmH2O (sedated state, Vt 8ml/kg, PEEP ≥10cmH2O);
(6) High risk factors: direct or indirect factors leading to lung injury. the advantages of the Delphi criteria are: defining the time of acute onset, emphasizing risk factors, taking into account the effect of PEEP, and excluding the possibility of cardiogenic hypoxia. It goes further than the two previous criteria, but only includes ARDS patients with P/F values less than 200 mmHg, which is not conducive to early detection of patients with lung injury with P/F values greater than 200 mmHg and less than 300 mmHg. Therefore, the Delphi criteria are still a product of the process of continuous updating of ARDS criteria.
In 2005, Niall et al. compared the accuracy of the AECC criteria, Murray’s lung injury criteria, and Delphi’s criteria in a total of 138 patients who underwent autopsy. The results showed that the AECC definition had a sensitivity of 0.83 and a specificity of 0.51; the Murray lung injury score had a sensitivity of 0.74 and a specificity of 0.77; and the Delphi definition had a sensitivity of 0.69 and a specificity of 0.82. In a subgroup analysis, the study found that if the PEEP ≥10 cmH2O was added to the AECC criteria, the specificity increased to 0.79; and the specificity increased to 0.79. The sensitivity and specificity of any of the current ARDS diagnostic criteria could be further improved, but their accuracy could be improved if they are combined in a reasonable manner.
III. 2011 Berlin Criteria
Against the backdrop of the current ARDS diagnostic criteria, which are not very accurate and have a lot of room for improvement, the Berlin criteria were developed again at the 23rd Annual European Congress of Intensive Care Medicine held in Berlin, Germany, in October 2011. The criteria were developed in consultation with experts in critical care medicine from Europe and the United States, taking into account existing epidemiological evidence, physiological concepts and the results of relevant clinical studies. The Berlin criteria are described in terms of time of onset, degree of hypoxemia, source of pulmonary edema, radiographs and other physiologic disturbances (Table 7-1-1).
Table 7-1-1
Berlin Diagnostic Criteria for ARDS
Berlin criteria
ARDS
Mild
Moderate
Severe
Time of onset
Known injury with acute onset within one week or new onset of respiratory symptoms
Hypoxemia
P/F: 201 to 300 and PEEP ≥ 5 cmH2O
P/F≤200 and PEEP≥5cmH2O
P/F≤100 and PEEP≥10cmH2O
Source of pulmonary edema
Respiratory failure that cannot be explained by cardiac insufficiency or fluid overload**
X-Ray chest film
Bilateral infiltrative shadow*
Bilateral infiltrative shadow*
Cumulative infiltrative shadowing in at least 3 quadrants*
Other physiologic disturbances
no
None
VE Corr>10L/min or CRS<40ml/cmH2O
Not fully explained by pleural effusion, nodules, masses, lung lobe collapse by specialized imaging training
Assessment of objective indicators is required if there are no risk factors.
VE
Corr = VE x PaCO2/40
VE: exhaled tidal volume, CRS: respiratory compliance
The Berlin criteria are a summary and extension of the previous criteria, and were developed based on feasibility, reliability and accuracy, which basically meet the characteristics of ideal diagnostic criteria. The feasibility and reliability of the Berlin criteria are that they help researchers to maximize the study population, standardize the experimental protocols, and make the various clinical studies on ARDS as comparable as possible. The Berlin criteria help clinicians to make early diagnosis, early intervention, early determination of disease severity, and more accurate prognosis estimation, and to translate clinical research results into clinical practice, thus improving patient prognosis.
The accuracy of the Berlin criteria was verified by Gattinoni et al. who found that the mortality rate of patients with mild ARDS was 10%, moderate 32%, and severe 62%. The new Berlin criteria can effectively differentiate the severity of ARDS and help to determine the prognosis more accurately. However, such a conclusion still needs to be verified by subsequent clinical studies.
In summary, the importance of diagnostic criteria for ARDS is clear, but the accuracy of the currently used criteria has been questioned. Therefore, it is necessary to update the diagnostic criteria for ARDS based on the latest theoretical evidence. The Berlin criteria have been proposed as a powerful contribution to the understanding of ARDS, but more clinical studies are needed to confirm them.