Usefulness and limitations of the acute respiratory distress syndrome definitions in non-intubated patients. A narrative review.

According to the Berlin Definition of acute respiratory distress syndrome (ARDS), a positive end-expiratory pressure (PEEP) of at least 5 cmH2O is required to diagnose and grade ARDS. While the Berlin consensus statement specifically acknowledges the role of non-invasive ventilation (NIV) in mild ARDS, this stratification has traditionally presumed a mechanically ventilated patient in the context of moderate to severe ARDS. This may not accurately reflect today's reality of clinical respiratory care. NIV and high-flow nasal cannula oxygen therapy (HFNO) have been used for managing of severe forms of acute hypoxemic respiratory failure with growing frequency, including in patients showing pathophysiological signs of ARDS. This became especially relevant during the COVID-19 pandemic. The levels of PEEP achieved with HFNO have been particularly controversial, and the exact FiO2 it achieves is subject to variability. Pinpointing the presence of ARDS in patients receiving HNFO and the severity in those receiving NIV therefore remains methodically problematic. This narrative review highlights the evolution of the ARDS definition in the context of non-invasive ventilatory support and provides an overview of the parallel development of definitions and ventilatory management of ARDS. It summarizes the methodology applied in clinical trials to classify ARDS in non-intubated patients and the respective consequences on treatment. As ARDS severity has significant therapeutic and prognostic consequences, and earlier treatment in non-intubated patients may be beneficial, closing this knowledge gap may ultimately be a relevant step to improve comparability in clinical trial design and outcomes.

Comparison of the Montreux definition with the Berlin definition for neonatal acute respiratory distress syndrome.

To compare the similarities and differences between the Montreux definition and the Berlin definition in terms of the prevalence, mortality, and complications of neonatal acute respiratory distress syndrome (ARDS). We retrospectively analyzed the data of neonates with respiratory failure treated in a neonatal intensive care unit (NICU) between 1 November 2019 and 31 December 2021. In total, 554 infants had neonatal ARDS (524 infants, Montreux definition; 549 infants, Berlin definition). The prevalence (3.1% vs. 3.3%, p = 0.438) and mortality (18.9% vs.18.0%, p = 0.716) of neonatal ARDS did not differ between the definitions. Among the 519 infants meeting both definitions, key clinical outcomes did not differ between the definitions such as ventilation duration, NICU stay, complication rates, and antibiotic use, except for nitric oxide inhalation. The Montreux and Berlin definitions identified an additional 5 and 30 patients, respectively, not captured by the other definition. The rate of inhaled nitric oxide treatment (20.0% vs. 0%, p = 0.013), air leaks (20.0% vs. 0%, p = 0.013), and invasive ventilation duration (110.00 vs.0.00 h, p = 0.002) significantly differed between the above two groups. Sixty-two patients had moderate and severe ARDS according to the Montreux and Berlin definitions, respectively. The rates of adverse outcomes (e.g., mortality, invasive ventilation time) among these patients were similar to the rates among patients with moderate ARDS according to both definitions than among patients with severe ARDS according to both definitions.  Conclusion: The prevalence, mortality, and most complications of neonatal ARDS were similar between the Montreux and Berlin definitions, which mainly differed in terms of the severity of neonatal ARDS. What is Known: • The Montreux definition was first proposed for the diagnosis of neonatal acute respiratory distress syndrome and was established in 2017. To date, the Montreux definition has not been compared with other diagnostic definitions of ARDS. What is New: • The study suggests that perinatal lung disease need not be excluded in the diagnosis of neonatal ARDS, and that the Montreux definition is more applicable to neonates, taking into account their specific physiological characteristics.

An expanded definition of acute respiratory distress syndrome: Challenging the status quo.

Although the Berlin definition of acute respiratory distress syndrome (ARDS), 2012 has been widely used in clinical practice, issues have occasionally been raised regarding various criteria since it was proposed. High-flow nasal oxygen (HFNO) is widely used for effective respiratory support in acute respiratory failure. As patients who do not require ventilation but meet the Berlin criteria have similar characteristics to those with ARDS, the definition of ARDS may be broadened to include patients receiving HFNO. As the PaO2/FiO2 under-recognizes the diagnosis of ARDS, a SpO2/FiO2 value of ≤315 may be considered instead of a PaO2/FiO2 value of ≤300 for diagnosing the condition in resource-constrained settings. In this context, patients with severe COVID-19 always meet other criteria for ARDS except for 7-day acute onset. Therefore, the timeframe for the onset of ARDS may be extended to up to 14 days. An expanded definition of ARDS may allow early identification of patients with less severe diseases and facilitate testing and application of new therapies in patients with a high risk of poor outcomes. Here, we discuss the major controversies regarding the extension of the ARDS definition with a view to improving clinical implementation and patient outcomes.

Definition of Acute Respiratory Distress Syndrome on the Plateau of Xining, Qinghai: A Verification of the Berlin Definition Altitude-PaO2/FiO2-Corrected Criteria.

Background: Acute respiratory distress syndrome (ARDS) is a common critical respiratory illness. Hypoxia at high altitude is a factor that influences the progression of ARDS. Currently, we lack clear diagnostic criteria for high-altitude ARDS. The purpose of this study was to determine the value of the application of the Berlin Definition altitude-PaO2/FiO2-corrected criteria for ARDS in Xining, Qinghai (2,261 m). Methods: We retrospectively analyzed the clinical data of patients with ARDS admitted to the Department of Critical Care Medicine of the Affiliated Hospital of Qinghai University from January 2018 to December 2018. The severity of ARDS was categorized according to the Berlin Definition, Berlin Definition altitude-PaO2/FiO2-corrected criteria, and the diagnostic criteria for acute lung injury (ALI)/ARDS at high altitudes in Western China (Zhang criteria). In addition, the differences between the three criteria were compared. Results: Among 1,221 patients, 512 were treated with mechanical ventilation. In addition, 253 met the Berlin Definition, including 49 (19.77%) with mild ARDS, 148 (58.50%) with moderate ARDS, and 56 (22.13%) with severe ARDS. A total of 229 patients met the altitude-PaO2/FiO2-corrected criteria, including 107 with mild ARDS (46.72%), 84 with moderate ARDS (36.68%), and 38 (16.59%) with severe ARDS. Intensive care unit (ICU) mortality increased with the severity of ARDS (mild, 17.76%; moderate, 21.43%; and severe, 47.37%). Twenty-eight-day mortality increased with worsening ARDS (mild 23.36% vs. moderate 44.05% vs. severe 63.16%) (p < 0.001). There were 204 patients who met the Zhang criteria, including 87 (42.65%) with acute lung injury and 117 (57.35%) with ARDS. The area under receiver operating characteristics (AUROCs) of the Berlin Definition, the altitude-P/F-corrected criteria, and the Zhang criteria were 0.6675 (95% CI 0.5866-0.7484), 0.6216 (95% CI 0.5317-0.7116), and 0.6050 (95% CI 0.5084-0.7016), respectively. There were no statistically significant differences between the three diagnostic criteria. Conclusion: For Xining, Qinghai, the altitude-PaO2/FiO2-corrected criteria for ARDS can distinguish the severity of ARDS, but these results need to be confirmed in a larger sample and in multicenter clinical studies. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04199650.

Performance of acute respiratory distress syndrome definitions in a high acuity paediatric intensive care unit.

BACKGROUND: For years, paediatric critical care practitioners used the adult American European Consensus Conference (AECC) and revised Berlin Definition (BD) for acute respiratory distress syndrome (ARDS) to study the epidemiology of paediatric ARDS (PARDS). In 2015, the paediatric specific definition, Paediatric Acute Lung Injury Consensus Conference (PALICC) was developed. The use of non-invasive metrics of oxygenation to stratify disease severity were introduced in this definition, although this potentially may lead to a confounding effect of disease severity since it is more common to place indwelling arterial lines in sicker patients. We tested the hypothesis that PALICC outperforms AECC/BD in our high acuity PICU, which employs a liberal use of indwelling arterial lines and high-frequency oscillatory ventilation (HFOV). METHODS: We retrospectively collected data from children < 18 years mechanically ventilated for at least 24 h in our tertiary care, university-affiliated paediatric intensive care unit. The primary endpoint was the difference in the number of PARDS cases between AECC/BD and PALICC. Secondary endpoints included mortality and ventilator free days. Performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC). RESULTS: Data from 909 out of 2433 patients was eligible for analysis. AECC/BD identified 35 (1.4%) patients (mortality 25.7%), whereas PALICC identified 135 (5.5%) patients (mortality 14.1%). All but two patients meeting AECC/Berlin criteria were also identified by PALICC. Almost half of the cohort (45.2%) had mild, 33.3% moderate and 21.5% severe PALICC PARDS at onset. Highest mortality rates were seen in patients with AECC acute lung injury (ALI)/mild Berlin and severe PALICC PARDS. The AUC-ROC for Berlin was the highest 24 h (0.392 [0.124-0.659]) after onset. PALICC showed the highest AUC-ROC at the same moment however higher than Berlin (0.531 [0.345-0.716]). Mortality rates were significantly increased in patients with bilateral consolidations (9.3% unilateral vs 26.3% bilateral, p = 0.025). CONCLUSIONS: PALICC identified more new cases PARDS than the AECC/Berlin definition. However, both PALICC and Berlin performed poorly in terms of mortality risk stratification. The presence of bilateral consolidations was associated with a higher mortality rate. Our findings may be considered in future modifications of the PALICC criteria.

Rule-Based Cohort Definitions for Acute Respiratory Distress Syndrome: A Computable Phenotyping Strategy Based on the Berlin Definition.

Accurate identification of acute respiratory distress syndrome is essential for understanding its epidemiology, patterns of care, and outcomes. We aimed to design a computable phenotyping strategy to detect acute respiratory distress syndrome in electronic health records of critically ill patients. DESIGN: This is a retrospective cohort study. Using a near real-time copy of the electronic health record, we developed a computable phenotyping strategy to detect acute respiratory distress syndrome based on the Berlin definition. SETTING: Twenty multidisciplinary ICUs in Mayo Clinic Health System. SUBJECTS: The phenotyping strategy was applied to 196,487 consecutive admissions from year 2009 to 2019. INTERVENTIONS: The acute respiratory distress syndrome cohort generated by this novel strategy was compared with the acute respiratory distress syndrome cohort documented by clinicians during the same period. The sensitivity and specificity of the phenotyping strategy were calculated in randomly selected patient cohort (50 patients) using the results from manual medical record review as gold standard. MEASUREMENTS AND MAIN RESULTS: Among the patients who did not have acute respiratory distress syndrome documented, the computable phenotyping strategy identified 3,169 adult patients who met the Berlin definition, 676 patients (21.3%) were classified to have severe acute respiratory distress syndrome (Pao2/Fio2 ratio ≤ 100), 1,535 patients (48.4%) had moderate acute respiratory distress syndrome (100 < Pao2/Fio2 ratio ≤ 200), and 958 patients (30.2%) had mild acute respiratory distress syndrome (200 < Pao2/Fio2 ratio ≤ 300). The phenotyping strategy achieved a sensitivity of 94.4%, specificity of 96.9%, positive predictive value of 94.4%, and negative predictive value of 96.9% in a randomly selected patient cohort. The clinicians documented acute respiratory distress syndrome in 1,257 adult patients during the study period. The clinician documentation rate of acute respiratory distress syndrome was 28.4%. Compared with the clinicians' documentation, the phenotyping strategy identified a cohort that had higher acuity and complexity of illness suggested by higher Sequential Organ Failure Assessment score (9 vs 7; p < 0.0001), higher Acute Physiology and Chronic Health Evaluation score (76 vs 63; p < 0.0001), higher rate of requiring invasive mechanical ventilation (99.1% vs 71.8%; p < 0.0001), higher ICU mortality (20.6% vs 16.8%; p < 0.0001), and longer ICU length of stay (5.1 vs 4.2 d; p < 0.0001). CONCLUSIONS: Our rule-based computable phenotyping strategy can accurately detect acute respiratory distress syndrome in critically ill patients in the setting of high clinical complexity. This strategy can be applied to enhance early recognition of acute respiratory distress syndrome and to facilitate best-care delivery and clinical research in acute respiratory distress syndrome.

Characteristics of Nonpulmonary Organ Dysfunction at Onset of ARDS Based on the Berlin Definition.

BACKGROUND: The Berlin definition of ARDS does not account for nonpulmonary organ failure, which is a major determinant of outcome. We examined whether an increasing severity of hypoxemia across the Berlin definition classifications also corresponded with evidence of multiple organ dysfunction on the day of ARDS onset. We also examined the representation of major etiologies for ARDS across the Berlin definition classifications. METHODS: This single-center, retrospective study examined 15 years of data from a quality assurance program that monitored the use of lung-protective ventilation in ARDS. We analyzed 1,747 subjects without chronic kidney disease or severe chronic liver disease at ARDS onset. The most abnormal laboratory values at ARDS onset were analyzed as cutoff values to assess organ dysfunction. Data were analyzed by using non-parametric analysis of variance (Kruskall-Wallis test) and the Dunn post test. Categorical variables were compared by using the Fisher exact test. Alpha was set at 0.05. Factors independently associated with mortality were assessed by multivariate logistic regression modeling. RESULTS: Nonpulmonary organ dysfunction was present in at least 1 system at ARDS onset that increased with severity: 80% (mild), 83% (moderate), and 90% (severe). ARDS etiologies varied as severity increased: trauma-associated lung injury steadily decreased, whereas lung injury associated with aspiration and pneumonia steadily increased. Hospital mortality also increased significantly with the Berlin definition classifications: mild (22%), moderate (30%), and severe (47%). Multivariate logistic regression modeling revealed that the Berlin definition of severe ARDS was independently associated with mortality, as were cutoff values for renal and hepatic function as well as acidemia. Normal hematologic function and the absence of standard exclusion criteria used for therapeutic clinical trials in ARDS were protective. CONCLUSIONS: Nonpulmonary organ dysfunction was present at ARDS onset in most subjects and was more pronounced as ARDS severity increased. The Berlin definition classification of ARDS provided an elegant scheme for studying the syndrome because it coincided with increasing multiple organ dysfunction.

Prognostic values of the Berlin definition criteria, blood lactate level, and fibroproliferative changes on high-resolution computed tomography in ARDS patients.

BACKGROUND: In the Berlin definition, acute respiratory distress syndrome (ARDS) is stratified into three stages according to oxygenation severity at the onset. The relevance between ARDS severity and prognosis varies among published reports and has not been verified, especially in Asian patients. METHODS: In this study, we examined the associations between the Berlin definition criteria and prognosis and clinical parameters, including high-resolution computed tomography (HRCT) scores of fibroproliferative changes of the lungs. One hundred fifty-three patients (45 females; mean age, 67 y/o), who met the Berlin definition and received treatment in our intensive care unit between January 2012 and December 2015, were enrolled. RESULTS: The severity of ARDS was mild in 42 patients, moderate in 71, and severe in 40. The underlying diseases included pneumonia in 56 patients and aspiration in 43. Forty-two (27.5%) patients were deceased within 30 days, and the 30-day mortality was 10% in mild ARDS, 23% in moderate, and 55% in severe, which were significantly different (P <  0.05). In the non-survivors, APACHE II, SOFA, and SAPS II scores were higher than in the survivors (P <  0.001). Multivariate analyses revealed that elevated blood lactate level (≥ 2.0 mmol/L) and increased HRCT scores were significantly associated with weaning failure and 30-day mortality of the patients with ARDS. CONCLUSIONS: These results suggested that the severity criteria in the Berlin definition might be associated with the prognosis of the patients. Blood lactate levels and HRCT score might be predictive of the outcome of patients with ARDS.

Acute Respiratory Distress Syndrome following Cardiac Surgery: Comparison of the American-European Consensus Conference Definition versus the Berlin Definition.

BACKGROUND: Lung injury with development of the acute respiratory distress syndrome (ARDS) is a serious complication which can occur after major surgery, including cardiac surgery. OBJECTIVE: The aim of our study was to compare the prevalence, risk factors, and mortality of ARDS following cardiac surgery according to the American-European Consensus Conference (AECC) definition and the new Berlin definition of ARDS. METHODS: We performed a retrospective, observational study that included prospectively collected data from consecutive adult patients, aged from 18 to 92 years, who had undergone cardiac surgery (both on and off pump) at a large tertiary university hospital over 5 years (from September 2012 to September 2017). RESULTS: During the study period, 3,972 patients underwent cardiac surgery, and 3,946 patients were included in the study. Fifty-five patients developed ARDS (1.14%) according to the AECC definition and 59 patients (1.15%) according to the Berlin definition, with a mortality of 32.7 and 30.5%, respectively (18 patients). Multivariate regression analysis identified prior cardiac surgery, complex cardiac surgery, emergency procedures, and transfusion of > 3 packed red blood cell units as predictors for ARDS. CONCLUSION: The development of ARDS in patients after cardiac surgery is a rare but serious complication associated with significant mortality. Moreover, our findings showed that prevalence, mortality, and risk factors for developing ARDS were similar according to both the AECC and the new Berlin definition.

Extended use of the modified Berlin Definition based on age-related subgroup analysis in pediatric ARDS.

BACKGROUND: Pediatric acute respiratory distress syndrome (pARDS) is a rare but very severe condition. Management of the condition remains a major challenge for pediatric intensive care specialists. OBJECTIVE: To perform a descriptive assessment of pARDS based on the modified Berlin Definition by using the SpO2/FiO2 ratio in order to establish an extended patient registry divided into age-related subgroups. METHODS: The data of all children on mechanical ventilation for respiratory failure admitted between 2005 and 2012 were reviewed retrospectively for this study. The age of patients ranged from newborns >37 weeks, up to children <18 years. Inclusion criteria were based on the modified Berlin Definition of pARDS. The following data were collected: demographic data, primary diagnosis, ventilation settings, and use of supportive treatment, in addition to mechanical ventilation (inhaled nitric oxide, surfactant, corticosteroids, prone positioning, and extracorporeal membrane oxygenation). RESULTS: In all, 93 children where included: 35% were newborns, 29% infants, 24% toddlers, and 12% school children; 66% were male and 34% were female patients. The most common primary diagnosis was viral pneumonia (21%) and 55% of the children were diagnosed with severe ARDS. The median duration of stay on the pediatric intensive care unit was 16 days (10/27). In total, 66 children (71%) had direct lung injury and 18 (19%) had indirect lung injury. More than 80% of all children needed more than one supportive care therapy. The overall survival rate was 77%. CONCLUSION: This study is a valuable report about pediatric patients with ARDS and allows for an important extension of the application of the modified Berlin Definition in all age groups.

Clinical application of the Pediatric Acute Lung Injury Consensus Conference definition of acute respiratory distress syndrome

PURPOSE: Despite improved quality of intensive care, acute respiratory distress syndrome (ARDS) significantly contributes to mortality in critically ill children. As pre-existing definitions of ARDS were adult-oriented standards, the Pediatric Acute Lung Injury Consensus Conference (PALICC) group released a new definition of pediatric ARDS. In this study, we aimed to assess the performance of PALICC definition for ARDS risk stratification. METHODS: Total 332 patients who admitted to the intensive care unit at Severance Hospital from January 2009 to December 2016 and diagnosed as having ARDS by either the PALICC definition or the Berlin definition were retrospectively analyzed. Patient characteristics and mortality rates were compared between the individual severity groups according to both definitions. RESULTS: The overall mortality rate was 36.1%. The mortality rate increased across the severity classes according to both definitions (26% in mild, 37% in moderate and 68% in severe by the PALICC definition [P<0.001]; 20% in mild, 32% in moderate and 64% in severe by the Berlin definition [P<0.001]). The mortality risk increased only for severe ARDS in both definitions (hazard ratio [95% confidence interval]: 2.279 [1.414–3.672], P=0.001 by the PALICC definition; 2.674 [1.518–4.712], P=0.001 by the Berlin definition). There was no significant difference in mortality discrimination between the 2 definitions (difference in integrated area under the curve: 0.017 [−0.018 to 0.049]). CONCLUSION: The PALICC definition demonstrated similar discrimination power on PARDS' severity and mortality as the Berlin definition.

Acute Respiratory Distress Syndrome: An Update and Review.

Acute respiratory distress syndrome (ARDS) is a life threatening condition characterized by severe hypoxemia due to pulmonary gas exchange failure and was first recognized in 1960s.Since its first description, it has undergone intensive research in the past few decades to understand its pathogenesis and therapies. Despite this, the recommended therapies to decrease mortality in ARDS remain limited and include low-tidal volume mechanical ventilation, prone ventilation and recently, the ECMO rescue therapy in extreme cases. This review article will summarize the key features of ARDS with a brief overview of the therapeutic options in the management of ARDS.

Comparison of Prevalence and Outcomes of Pediatric Acute Respiratory Distress Syndrome Using Pediatric Acute Lung Injury Consensus Conference Criteria and Berlin Definition.

OBJECTIVES: Our objective was to compare the prevalence and outcomes of pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria and Berlin definitions. METHODS: We screened case records of all children aged 1 month to 17 years of age admitted to the Pediatric Intensive Care Unit (PICU) over a 3-year period (2015-2017) for presence of any respiratory difficulty at admission or during PICU stay. We applied both PALICC and Berlin criteria to these patients. Data collection included definition and outcome related variables. Data were compared between the "PALICC only group" and the "Berlin with or without PALICC" group using Stata 11. RESULTS: Of a total of 615 admissions, 246 were identified as having respiratory difficulty at admission or during PICU stay. A total of 61 children (prevalence 9.9%; 95% CI: 7.8-12.4) fulfilled the definition of acute respiratory distress syndrome (ARDS) with either of the two criteria. While 60 children (98%) fulfilled PALICC criteria, only 26 children (43%) fulfilled Berlin definition. There was moderate agreement between the two definitions (Kappa: 0.51; 95% CI: 0.40-0.62; observed agreement 85%). Greater proportion of patients had severe ARDS in the "Berlin with or without PALICC group" as compared to the "PALICC only" group (50 vs. 19%). There was no difference between the groups with regard to key clinical outcomes such as duration of ventilation (7 vs. 8 days) or mortality [51.4 vs. 57.7%: RR (95% CI): 0.99 (0.64-1.5)]. CONCLUSION: In comparison to Berlin definition, the PALICC criteria identified more number of patients with ARDS. Proportion with severe ARDS and complications was greater in the "Berlin with or without PALICC" group as compared to the "PALICC only" group. There were no differences in clinical outcomes between the groups.

Diagnostic and prognostic values of Club cell protein 16 (CC16) in critical care patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a critical condition characterized by bilateral pulmonary infiltrates and severe hypoxemia. This study aimed to evaluate the diagnostic and prognostic values of Club cell protein 16 (CC16) in critical care patients with ARDS. METHODS: In this retrospective observational study, 83 patients with ARDS and 129 non-ARDS patients on ICU admission were enrolled. The differences in serum CC16 and other laboratory indicators between two groups were analyzed. The sensitivity, specificity, positive and negative predictive values, and accuracy of CC16 as a diagnostic marker on ICU admission were determined by receiver operating characteristic (ROC) curve analysis. The correlation between serum CC16 levels and the severity of ARDS as quantified by PaO2 /FiO2 ratio were further assessed. CC16 levels were compared between survivors and non-survivors. The relationships between CC16 levels and duration of ICU and hospitalization were evaluated. RESULTS: The serum CC16 levels in ARDS patients were significantly higher than that in non-ARDS patients (54.44±19.62 vs 24.13±12.32 ng/mL, P=.001). ROC analysis showed that the sensitivity, specificity, positive predictive value, and negative predictive value were 90.4%, 79.8%, 74.2%, and 92.8%, respectively, when the cut-off value was set at 33.3 ng/mL. CC16 levels were correlated with the severity of ARDS. The serum CC16 levels were significantly greater in non-survivors than in survivors from the ARDS group. CC16 levels were associated with ICU stay but not hospital stay. CONCLUSIONS: CC16 may serve as a diagnostic and stratification marker for ARDS. However, it provided limited prognostic information for ARDS.

Polytrauma Defined by the New Berlin Definition: A Validation Test Based on Propensity-Score Matching Approach.

Background: Polytrauma patients are expected to have a higher risk of mortality than that obtained by the summation of expected mortality owing to their individual injuries. This study was designed to investigate the outcome of patients with polytrauma, which was defined using the new Berlin definition, as cases with an Abbreviated Injury Scale (AIS) ≥ 3 for two or more different body regions and one or more additional variables from five physiologic parameters (hypotension [systolic blood pressure ≤ 90 mmHg], unconsciousness [Glasgow Coma Scale score ≤ 8], acidosis [base excess ≤ -6.0], coagulopathy [partial thromboplastin time ≥ 40 s or international normalized ratio ≥ 1.4], and age [≥70 years]). Methods: We retrieved detailed data on 369 polytrauma patients and 1260 non-polytrauma patients with an overall Injury Severity Score (ISS) ≥ 18 who were hospitalized between 1 January 2009 and 31 December 2015 for the treatment of all traumatic injuries, from the Trauma Registry System at a level I trauma center. Patients with burn injury or incomplete registered data were excluded. Categorical data were compared with two-sided Fisher exact or Pearson chi-square tests. The unpaired Student t-test and the Mann-Whitney U-test was used to analyze normally distributed continuous data and non-normally distributed data, respectively. Propensity-score matched cohort in a 1:1 ratio was allocated using the NCSS software with logistic regression to evaluate the effect of polytrauma on patient outcomes. Results: The polytrauma patients had a significantly higher ISS than non-polytrauma patients (median (interquartile range Q1-Q3), 29 (22-36) vs. 24 (20-25), respectively; p < 0.001). Polytrauma patients had a 1.9-fold higher odds of mortality than non-polytrauma patients (95% CI 1.38-2.49; p < 0.001). Compared to non-polytrauma patients, polytrauma patients had a substantially longer hospital length of stay (LOS). In addition, a higher proportion of polytrauma patients were admitted to the intensive care unit (ICU), spent longer LOS in the ICU, and had significantly higher total medical expenses. Among 201 selected propensity score-matched pairs of polytrauma and non-polytrauma patients who showed no significant difference in sex, age, co-morbidity, AIS ≥ 3, and Injury Severity Score (ISS), the polytrauma patients had a significantly higher mortality rate (OR 17.5, 95% CI 4.21-72.76; p < 0.001), and a higher proportion of patients admitted to the ICU (84.1% vs. 74.1%, respectively; p = 0.013) with longer stays in the ICU (10.3 days vs. 7.5 days, respectively; p = 0.003). The total medical expenses for polytrauma patients were 35.1% higher than those of non-polytrauma patients. However, there was no significant difference in the LOS between polytrauma and non-polytrauma patients (21.1 days vs. 19.8 days, respectively; p = 0.399). Conclusions: The findings of this propensity-score matching study suggest that the new Berlin definition of polytrauma is feasible and applicable for trauma patients.

Does the applied polytrauma definition notably influence outcome and patient population? - a retrospective analysis.

BACKGROUND: Although the term "polytrauma" has been in use for decades, no generally accepted definition exists. The aim of this study was to demonstrate that different polytrauma definitions applied to a specific patient population result in diverse subgroups of individuals, who in turn present a varying outcome. METHODS: All patients (≥18 years) treated at our level I trauma center within a time period of three years were classified according to 11 selected polytrauma definitions and included in our study, if they were rated "polytraumatized" by at least one of these definitions. All patients, who met the criteria of a certain definition, were combined to the relevant definition-positive group, thus resulting in 11 patient subgroups. Their demographic data (number of patients, mean patient age, mean Injury Severity Score value, median number of ventilator days, median length of stay at the intensive care unit and at the hospital, mortality rate and odds ratio) were statistically compared. RESULTS: Three hundred seventy-five patients (73% male) with a mean age of 47 years met the inclusion criteria and were allocated to the relevant subgroups; their patient number varied from 55 to 346 and their mean Injury Severity Score value ranged from 4 to 75. Not surprisingly, all examined parameters were subject to variations. Whereas most definition-positive groups showed a mortality rate of about 21% to 30%, 18% of the individuals, who met the criteria according to Blacker, and 40% of the polytrauma victims according to Schalamon died. The Pape 1-, Schalamon-, and Berlin-positive groups presented a significant odds ratio with regard to mortality that considerably exceeded 1. DISCUSSION: A polytrauma definition can only be a reliable tool in classifying trauma victims if it provides a significant odds ratio with regard to mortality that considerably exceeds 1 and if it succeeds in capturing patients with multiple severe injuries and a higher mortality rate without reducing the number of polytraumatized patients to a not representatively small number. CONCLUSIONS: Solely the Berlin definition resulted in a patient number reflecting clinical reality, thus enabling a transparent evaluation of treatment results provided by different institutions and allowing objective comparison of published studies.

Lung Injury Etiology and Other Factors Influencing the Relationship Between Dead-Space Fraction and Mortality in ARDS.

BACKGROUND: In ARDS, elevated pulmonary dead-space fraction (VD/VT) is a particularly strong indicator of mortality risk. Whether the magnitude of VD/VT is modified by the underlying etiology of ARDS and whether this influences the strength of its association with mortality remains unknown. We sought to elucidate the impact of ARDS etiology on VD/VT and also to determine whether ARDS severity, as classified by the Berlin definition, has correspondence with changes in VD/VT. METHODS: This single-center, retrospective, observational study (2010-2016) measured VD/VT in 685 subjects with ARDS as part of clinical management with lung-protective ventilation. Volumetric capnography was used to measure VD/VT with 99% of measurements occurring within 48 h of ARDS onset. Demographic information as well as illness severity scores and pulmonary mechanics data also were collected. Multivariate logistic regression modeling was done to assess the strength of association between VD/VT and mortality. RESULTS: VD/VT was elevated across etiologies, with aspiration and pneumonia having significantly higher VD/VT than non-pulmonary sepsis or trauma. Differences in the magnitude of VD/VT across etiologies did not necessarily correspond with mortality between etiologies. However, within each etiology grouping, VD/VT was significantly elevated in non-survivors versus survivors. The same results were found in both moderate and severe (but not mild) ARDS using the Berlin definition. In the final adjusted model, the strongest mortality risk was VD/VT, wherein the risk of death increased by 22% for every 0.05 increase in VD/VT. CONCLUSIONS: VD/VT magnitude varies by ARDS etiology, as does mortality. Only in mild ARDS does VD/VT fail to distinguish non-survivors from survivors. Nonetheless, VD/VT has the strongest association with mortality risk in those with ARDS.

Etiologies, diagnostic work-up and outcomes of acute respiratory distress syndrome with no common risk factor: a prospective multicenter study.

BACKGROUND: Patients meeting the Berlin definition for the acute respiratory distress syndrome (ARDS) might lack exposure to one or more "common" risk factors and exhibit different clinical phenotype and outcomes. We aimed to compare the clinical presentation and outcome of ARDS patients with or without risk factors, the impact on hospital mortality, and to assess the diagnostic work-up performed. The current study is an ancillary analysis of an international, multicenter, prospective cohort study (the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure, LUNG SAFE). Patients meeting ARDS criteria within 2 days of acute hypoxemic respiratory failure onset were included in the study and categorized as having risk factors or not. Outcomes were compared using propensity score matching. RESULTS: Among 2813 patients, 234 (8.3% [7.3-9.3]) had no ARDS risk factor identified. These were older, had more frequent chronic diseases and presented with less severe SOFA and non-pulmonary SOFA scores (p < 0.001). Compared to other ARDS, CT scan (32.1 vs 23.9%, p < 0.001) and open lung biopsy (2.6 vs 0.2%, p < 0.001) were slightly more frequent but left heart filling pressures assessment was not (69.4 vs 68.4%, p > 0.99). Among ARDS with no risk factor, 45 patients (19.2%) had a specific diagnosis made. As compared to others, patients having ARDS with no risk factor had a lower ICU but not hospital mortality (34.6 vs 40.0%; p = 0.12). A matched cohort analysis confirmed the lack of significant difference in mortality. CONCLUSION: Eight percent of ARDS patients have no identified risk factor, 80% of whom have no etiological diagnosis made. The outcome of ARDS with no risk factor was comparable to other ARDS but few had a comprehensive diagnostic work-up, potentially leading to missed curable diseases. Trial registration clinicaltrials.gov Identifier: NCT02010073.

The Acute Respiratory Distress Syndrome (ARDS) in mechanically ventilated burn patients: An analysis of risk factors, clinical features, and outcomes using the Berlin ARDS definition.

BACKGROUND: The Berlin definition of Acute Respiratory Distress Syndrome (ARDS) has been applied to military burns resulting from combat-related trauma, but has not been widely studied among civilian burns. This study's purpose was to use the Berlin definition to determine the incidence of ARDS, and its associated respiratory morbidity, and mortality among civilian burn patients. METHODS: Retrospective study of burn patients mechanically ventilated for ≥48h at an American Burn Association-verified burn center. The Berlin criteria identified patients with mild, moderate, and severe ARDS. Logistic regression was used to identify variables predictive of moderate to severe ARDS, and mortality. The outcome measures of interest were duration of mechanical ventilation and in-hospital mortality. Values are shown as the median (Q1-Q3). RESULTS: We included 162 subjects [24% female, age 48 (35-60), % total body surface area (TBSA) burn 28 (19-40), % body surface area (BSA) full thickness (FT) burn 13 (0-30), and 62% with inhalation injury]. The incidence of ARDS was 43%. Patients with ARDS had larger %TBSA burns [30.5 (23.1-47.0) vs. 24.8 (17.1-35), p=0.007], larger FT burns [20.5(5.4-35.5) vs. 7 (0-22.1), p=0.001], but had no significant difference in the incidence of inhalation injury (p=0.216), compared to those without ARDS. The % FT burn predicted the development of moderate to severe ARDS [OR 1.034, 95%CI (1.013-1.055), p=0.001]. ARDS developed in the 1st week after burn in 86% of cases. Worsening severity of ARDS was associated with increased days of mechanical ventilation in survivors (p=0.001), a reduction in ventilator-free days/1st 30 days in all subjects (p=0.004), and a strong indication of increased mortality (0% in mild ARDS vs. 50% in severe ARDS, unadjusted p=0.02). Neither moderate ARDS nor severe ARDS were significant predictors of death. CONCLUSIONS: ARDS is common among mechanically ventilated civilian burn patients, and develops early after burn. The extent of full thickness burn predicted development of moderate to severe ARDS. Increasing severity of ARDS based upon the Berlin definition was associated with a significantly greater duration of mechanical ventilation and a trend toward higher mortality.

Acute Respiratory Distress: from syndrome to disease.

The acute respiratory distress syndrome (ARDS) is currently one of the most important critical entities given its high incidence, rate of mortality, long-term sequelae and non-specific pharmacological treatment. The histological hallmark of ARDS is diffuse alveolar damage (DAD). Approximately 50% of ARDS patients present DAD, the rest is made up of a heterogeneous group of histological patterns, many of which correspond to a well-recognized disease. For that reason, if these patterns could be diagnosed, patients could benefit from a treatment. Recently, the effect of DAD in clinical and analytical evolution of ARDS has been demonstrated, so the classical approach to ARDS as an entity defined solely by clinical, radiological and gasometrical variables should be reconsidered. This narrative review aims to examine the need to evolve from the concept of ARDS as a syndrome to ARDS as a specific disease. So we have raised 4 critical questions: a) What is a disease?; b) what is DAD?; c) how is DAD considered according to ARDS definition?, and d) what is the relationship between ARDS and DAD?