Failing categorization of severe COVID-19 ARDS into ventilatory subphenotypes studied via the clinical-histopathologic relationship.

BACKGROUND: Categorization of severe COVID-19 related acute respiratory distress syndrome (CARDS) into subphenotypes does not consider the trajectories of respiratory mechanoelastic features and histopathologic patterns. This study aimed to assess the correlation between mechanoelastic ventilatory features and lung histopathologic findings in critically ill patients who died because of CARDS. METHODS: Mechanically ventilated patients with severe CARDS who had daily ventilatory data were considered. The histopathologic assessment was performed through full autopsy of deceased patients. Patients were categorized into two groups according to the median worst respiratory system compliance during ICU stay (CrsICU). RESULTS: Eighty-seven patients admitted to ICU had daily ventilatory data. Fifty-one (58.6%) died in ICU, 41 (80.4%) underwent full autopsy and were considered for the clinical-histopathological correlation analysis. Respiratory system compliance at ICU admission and its trajectory were not different in survivors and non-survivors. Median CrsICU in the deceased patients was 22.9 ml/cmH2O. An inverse correlation was found between the CrsICU and late-proliferative diffuse alveolar damage (DAD) (r = -0.381, p = 0.026). Late proliferative DAD was more extensive (p = 0.042), and the probability of stay in ICU was higher (p = 0.004) in the "low" compared to the "high" CrsICU group. Cluster analysis further endorsed these findings. CONCLUSIONS: In critically ill mechanically ventilated patients, worsening of the respiratory system compliance correlated pathologically with the transition from early damage to late fibroproliferative patterns in non-survivors of CARDS. Categorization of CARDS into ventilatory subphenotypes by mechanoelastic properties at ICU admission does not account for the complexity of the histopathologic features.

Physiological response to prone positioning in intubated adults with COVID-19 acute respiratory distress syndrome: a retrospective study.

BACKGROUND: COVID-19 related acute respiratory distress syndrome (ARDS) has specific characteristics compared to ARDS in other populations. Proning is recommended by analogy with other forms of ARDS, but few data are available regarding its physiological effects in this population. This study aimed to assess the effects of proning on oxygenation parameters (PaO2/FiO2 and alveolo-arterial gradient (Aa-gradient)), blood gas analysis, ventilatory ratio (VR), respiratory system compliance (CRS) and estimated dead space fraction (VD/VT HB). We also looked for variables associated with treatment failure. METHODS: Retrospective monocentric study of intubated COVID-19 ARDS patients managed with an early intubation, low to moderate positive end-expiratory pressure and early proning strategy hospitalized from March 6 to April 30 2020. Blood gas analysis, PaO2/FiO2, Aa-gradient, VR, CRS and VD/VT HB were compared before and at the end of each proning session with paired t-tests or Wilcoxon tests (p < 0.05 considered as significant). Proportions were assessed using Fischer exact test or Chi square test. RESULTS: Forty-two patients were included for a total of 191 proning sessions, median duration of 16 (5-36) hours. Considering all sessions, PaO2/FiO2 increased (180 [148-210] vs 107 [90-129] mmHg, p < 0.001) and Aa-gradient decreased (127 [92-176] vs 275 [211-334] mmHg, p < 0.001) with proning. CRS (36.2 [30.0-41.8] vs 32.2 [27.5-40.9] ml/cmH2O, p = 0.003), VR (2.4 [2.0-2.9] vs 2.3 [1.9-2.8], p = 0.028) and VD/VT HB (0.72 [0.67-0.76] vs 0.71 [0.65-0.76], p = 0.022) slightly increased. Considering the first proning session, PaO2/FiO2 increased (186 [165-215] vs 104 [94-126] mmHg, p < 0.001) and Aa-gradient decreased (121 [89-160] vs 276 [238-321] mmHg, p < 0.001), while CRS, VR and VD/VT HB were unchanged. Similar variations were observed during the subsequent proning sessions. Among the patients who experienced treatment failure (defined as ICU death or need for extracorporeal membrane oxygenation), fewer expressed a positive response in terms of oxygenation (defined as increase of more than 20% in PaO2/FiO2) to the first proning (67 vs 97%, p = 0.020). CONCLUSION: Proning in COVID-19 ARDS intubated patients led to an increase in PaO2/FiO2 and a decrease in Aa-gradient if we consider all the sessions together, the first one or the 4 subsequent sessions independently. When considering all sessions, CRS increased and VR and VD/VT HB only slightly increased.

Trajectories of hypoxemia and pulmonary mechanics of COVID-19 ARDS in the NorthCARDS dataset.

BACKGROUND: Understanding heterogeneity seen in patients with COVIDARDS and comparing to non-COVIDARDS may inform tailored treatments. METHODS: A multidisciplinary team of frontline clinicians and data scientists worked to create the Northwell COVIDARDS dataset (NorthCARDS) leveraging over 11,542 COVID-19 hospital admissions. The data was then summarized to examine descriptive differences based on clinically meaningful categories of lung compliance, and to examine trends in oxygenation. FINDINGS: Of the 1536 COVIDARDS patients in the NorthCARDS dataset, there were 531 (34.6%) who had very low lung compliance (< 20 ml/cmH2O), 970 (63.2%) with low-normal compliance (20-50 ml/cmH2O), and 35 (2.2%) with high lung compliance (> 50 ml/cmH2O). The very low compliance group had double the median time to intubation compared to the low-normal group (107.3 h (IQR 25.8, 239.2) vs. 39.5 h (IQR 5.4, 91.6)). Overall, 68.8% (n = 1057) of the patients died during hospitalization. In comparison to non-COVIDARDS reports, there were less patients in the high compliance category (2.2% vs. 12%, compliance ≥ 50 mL/cmH20), and more patients with P/F ≤ 150 (59.8% vs. 45.6%). There is a statistically significant correlation between compliance and P/F ratio. The Oxygenation Index is the highest in the very low compliance group (12.51, SD(6.15)), and lowest in high compliance group (8.78, SD(4.93)). CONCLUSIONS: The respiratory system compliance distribution of COVIDARDS is similar to non-COVIDARDS. In some patients, there may be a relation between time to intubation and duration of high levels of supplemental oxygen treatment on trajectory of lung compliance.

Respiratory system compliance at the same PEEP level is similar in COVID and non-COVID ARDS.

BACKGROUND: The comparison of respiratory system compliance (Crs) between COVID and non-COVID ARDS patients has been the object of debate, but few studies have evaluated it when considering applied positive end expiratory pressure (PEEP), which is one of the known determinants of Crs itself. The aim of this study was to compare Crs taking into account the applied PEEP. METHODS: Two cohorts of patients were created: those with COVID-ARDS and those with non-COVID ARDS. In the whole sample the association between Crs and type of ARDS at different PEEP levels was adjusted for anthropometric and clinical variables. As secondary analyses, patients were matched for predicted functional residual capacity and the same association was assessed. Moreover, the association between Crs and type of ARDS was reassessed at predefined PEEP level of 0, 5, 10, and 15 cmH2O with a propensity score-weighted linear model. RESULTS: 367 patients were included in the study, 276 patients with COVID-ARDS and 91 with non-COVID ARDS. The association between Crs and type of ARDS was not significant in both the complete cohorts (p = 0.17) and in the matched cohorts (p = 0.92). This was true also for the propensity score weighted association at PEEP 5, 10 and 15 cmH2O, while it was statistically significant at PEEP 0 (with a median difference of 3 ml/cmH2O, which in our opinion is not clinically significant). CONCLUSIONS: The compliance of the respiratory system is similar between COVID ARDS and non-COVID ARDS when calculated at the same PEEP level and while taking into account patients' anthropometric characteristics.

Individualized positive end-expiratory pressure setting in patients with severe acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Patients with acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation benefit from higher positive end-expiratory pressure combined with conventional ventilation during the early extracorporeal membrane oxygenation period. The role of incremental positive end-expiratory pressure titration in patients with severe acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation remains unclear. This study aimed to determine the preferred method for setting positive end-expiratory pressure in patients with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation support. METHODS: We retrospectively reviewed all subjects supported with veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from 2009 to 2019 in the intensive care units in Tianjin Third Central Hospital. Subjects were divided into two groups according to the positive end-expiratory pressure titration method used: P-V curve (quasi-static pressure-volume curve-guided positive end-expiratory pressure setting) group or Crs (respiratory system compliance-guided positive end-expiratory pressure setting) group. RESULTS: Forty-three subjects were included in the clinical outcome analysis: 20 in the P-V curve group and 23 in the Crs group. Initial positive end-expiratory pressure levels during veno-venous extracorporeal membrane oxygenation were similar in both groups. Incidence rates of barotrauma and hemodynamic events were significantly lower in the Crs group (all p < 0.05). Mechanical ventilation duration, intensive care unit length of stay, and hospital length of stay were significantly shorter in the Crs group than the P-V curve group (all p < 0.05). Subjects in the Crs group showed non-significant improvements in the duration of extracorporeal membrane oxygenation support and 28-day mortality (p > 0.05). CONCLUSION: Respiratory system compliance-guided positive end-expiratory pressure setting may lead to more optimal clinical outcomes for patients with severe acute respiratory distress syndrome supported by veno-venous extracorporeal membrane oxygenation. Moreover, the operation is simple, safe, and convenient in clinical practice.

Effect of prone positioning on oxygenation and static respiratory system compliance in COVID-19 ARDS vs. non-COVID ARDS.

BACKGROUND: Prone positioning is recommended for patients with moderate-to-severe acute respiratory distress syndrome (ARDS) receiving mechanical ventilation. While the debate continues as to whether COVID-19 ARDS is clinically different from non-COVID ARDS, there is little data on whether the physiological effects of prone positioning differ between the two conditions. We aimed to compare the physiological effect of prone positioning between patients with COVID-19 ARDS and those with non-COVID ARDS. METHODS: We retrospectively compared 23 patients with COVID-19 ARDS and 145 patients with non-COVID ARDS treated using prone positioning while on mechanical ventilation. Changes in PaO2/FiO2 ratio and static respiratory system compliance (Crs) after the first session of prone positioning were compared between the two groups: first, using all patients with non-COVID ARDS, and second, using subgroups of patients with non-COVID ARDS matched 1:1 with patients with COVID-19 ARDS for baseline PaO2/FiO2 ratio and static Crs. We also evaluated whether the response to the first prone positioning session was associated with the clinical outcome. RESULTS: When compared with the entire group of patients with non-COVID ARDS, patients with COVID-19 ARDS showed more pronounced improvement in PaO2/FiO2 ratio [adjusted difference 39.3 (95% CI 5.2-73.5) mmHg] and static Crs [adjusted difference 3.4 (95% CI 1.1-5.6) mL/cmH2O]. However, these between-group differences were not significant when the matched samples (either PaO2/FiO2-matched or compliance-matched) were analyzed. Patients who successfully discontinued mechanical ventilation showed more remarkable improvement in PaO2/FiO2 ratio [median 112 (IQR 85-144) vs. 35 (IQR 6-52) mmHg, P = 0.003] and static compliance [median 5.7 (IQR 3.3-7.7) vs. - 1.0 (IQR - 3.7-3.0) mL/cmH2O, P = 0.006] after prone positioning compared with patients who did not. The association between oxygenation and Crs responses to prone positioning and clinical outcome was also evident in the adjusted competing risk regression. CONCLUSIONS: In patients with COVID-19 ARDS, prone positioning was as effective in improving respiratory physiology as in patients with non-COVID ARDS. Thus, it should be actively considered as a therapeutic option. The physiological response to the first session of prone positioning was predictive of the clinical outcome of patients with COVID-19 ARDS.

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS.

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

Compliance Phenotypes in Early Acute Respiratory Distress Syndrome before the COVID-19 Pandemic.

Rationale: A novel model of phenotypes based on set thresholds of respiratory system compliance (Crs) was recently postulated in context of coronavirus disease (COVID-19) acute respiratory distress syndrome (ARDS). In particular, the dissociation between the degree of hypoxemia and Crs was characterized as a distinct ARDS phenotype.Objectives: To determine whether such Crs-based phenotypes existed among patients with ARDS before the COVID-19 pandemic and to closely examine the Crs-mortality relationship.Methods: We undertook a secondary analysis of patients with ARDS, who were invasively ventilated on controlled modes and enrolled in a large, multinational, epidemiological study. We assessed Crs, degree of hypoxemia, and associated Crs-based phenotypic patterns with their characteristics and outcomes.Measurements and Main Results: Among 1,117 patients with ARDS who met inclusion criteria, the median Crs was 30 (interquartile range, 23-40) ml/cm H2O. One hundred thirty-six (12%) patients had preserved Crs (≥50 ml/cm H2O; phenotype with low elastance ["phenotype L"]), and 827 (74%) patients had poor Crs (<40 ml/cm H2O; phenotype with high elastance ["phenotype H"]). Compared with those with phenotype L, patients with phenotype H were sicker and had more comorbidities and higher hospital mortality (32% vs. 45%; P < 0.05). A near complete dissociation between PaO2/FiO2 and Crs was observed. Of 136 patients with phenotype L, 58 (43%) had a PaO2/FiO2 < 150. In a multivariable-adjusted analysis, the Crs was independently associated with hospital mortality (adjusted odds ratio per ml/cm H2O increase, 0.988; 95% confidence interval, 0.979-0.996; P = 0.005).Conclusions: A wide range of Crs was observed in non-COVID-19 ARDS. Approximately one in eight patients had preserved Crs. PaO2/FiO2 and Crs were dissociated. Lower Crs was independently associated with higher mortality. The Crs-mortality relationship lacked a clear transition threshold.