Severe ARDS Patients Research Articles

Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury

Acute lung injury (ALI) is characterized by severe inflammation in lung tissue, excessive immune response and impaired lung function. In hospitalized high-risk patients and cases of secondary infection due to surgical contamination, it can lead to higher mortality rates and require immediate intervention. Currently, clinical treatments are limited in symptomatic therapy as mechanical ventilation and corticosteroids, having insufficient efficacy in mitigating the cause of progression to severe illness. Here we report a pulmonary targeting lung-homing nanoliposome (LHN) designed to attenuate excessive Neutrophil Extracellular Trap formation (NETosis) through sivelestat and DNase-1, coupled with an anti-inflammatory effect mediated by 25-hydroxycholesterol (25-HC), offering a promising intervention for the acute phase of ALI. Through intratracheal delivery, we intend prompt and constant action within the lungs to effectively prevent excessive NETosis. Isolated neutrophils from blood samples of severe ARDS patients demonstrated significant anti-NETosis effects, as well as reduced proinflammatory cytokine secretion. Furthermore, in a murine model of LPS-induced ALI, we confirmed improvements in lung histopathology, and early respiratory function. Also, attenuation of systemic inflammatory response syndrome (SIRS), with notable reductions in NETosis and neutrophil trafficking was investigated. This presents a targeted therapeutic approach that can be applied in early stages of high-risk patients to prevent severe pulmonary disease progression.

Recurrent ventilator-associated pneumonia in severe Covid-19 ARDS patients requiring ECMO support

ObjectiveTo describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence.MethodsAdult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence.ResultsAmong the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7–13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [< 8 days, median (IQR) duration 6 (5–7) days] and 52 (25%) received a prolonged course of antibiotics [≥ 8 days, median (IQR) duration 9 (8–10) days]. Estimated cumulative incidence of VAP recurrence, taking into account death and extubation as competing risks, was not different in patients with short– and prolonged–antimicrobial treatment.ConclusionsIn patients with severe Covid-19–ARDS requiring ECMO support, VAP recurrence occurs frequently, with Enterobacteriaceae and Pseudomonas aeruginosa as predominant causative microorganisms. An antimicrobial treatment of ≥ 8 days for the treatment of first VAP episode did not reduce the risk of VAP recurrence, as compared to shorter duration.

Effects of the prone position on gas exchange and ventilatory mechanics and their correlations with mechanical power in burn patients with ARDS

Background Prone position has many documented benefits on severe ARDS patients especially on mortality. The benefits in ARDS secondary to severe burns have not been fully documented. Aim To quantify the effects of prone positioning on gas exchange, ventilatory mechanics and their correlations with mechanical power in burn subjects with ARDS. Methods Cross-sectional observational analytical study that took place between January 2023 and October 2023 in Burns ICU in Brazil on subjects with moderate to severe ARDS ventilated with the volume controlled mode. Data were collected in the first prone positioning lasting 24 hours in the first 30 minutes after changing position and 30 minutes before returning to the supine position. The parameters of the components of mechanical ventilation and mechanical power calculated by the Gatinoni’s formula (respiratory rate, tidal volume, driving pressure, PEEP, peak and plateau pressures) were collected to evaluate ventilatory mechanics, and the values of the FiO2, PaO2, PaO2/FiO2 ratio, SpO2, EtCO2, PaCO2, PaCO2 - EtCO2 gradient to assess gas exchange. Mean, minimum and maximum values, 1st and 3rd quartiles, median and standard deviation are calculated. To compare the results obtained at the two evaluation moments, the student’s t-test for dependent samples and non-parametric Wilcoxon tests were considered. To evaluate the association between the variation between the two moments of each variable, and the variation in mechanical power, the Pearson correlation coefficient was calculated. The normality of the variables was assessed using the Jarque-Béra test. P values &lt;0.05 indicated statistical significance. Results Except for EtCO2 (P 0.939) and PaCO2 (P 0.391) all other variables presented statistical significance in relation to their variations with reduction in FiO2 (P &lt;0.001), reduction in PaCO2 - EtCO2 gradient (P 0.011), and increases in PaO2 (P 0.008), PaO2/FiO2 (P &lt;0.001), SpO2 (P 0.004). In the analysis of variables, reduction in respiratory rate (P 0.142), VT (P 0.385), peak pressure (P 0.085), plateau pressure (P 0.009), PEEP (P 0.032), driving pressure (P 0.083), elastance (P 0.180), mechanical power (P &lt; 0.001) with increase static compliance (P 0.414) and resistance pressure (P 0.443). Among the ventilatory mechanics variables, only the reductions in plateau pressure, PEEP, and mechanical power showed statistical significance. Conclusion The prone position in burns induced ARDS improved oxygenation and reduced arterial partial pressure to end tidal CO2 gradient, furthermore, reducing plateau pressures and PEEP, which in turn reduced mechanical power. Keywords: mechanical power, burns, ARDS, prone position

Incidence and Determinants of Acute Kidney Injury after Prone Positioning in Severe COVID-19 Acute Respiratory Distress Syndrome

(1) Background: Acute kidney injury (AKI) is common among critically ill COVID-19 patients, but its temporal association with prone positioning (PP) is still unknown, and no data exist on the possibility of predicting PP-associated AKI from bedside clinical variables. (2) Methods: We analyzed data from 93 COVID-19-related ARDS patients who underwent invasive mechanical ventilation (IMV) and at least one PP cycle. We collected hemodynamic variables, respiratory mechanics, and circulating biomarkers before, during, and after the first PP cycle. PP-associated AKI (PP-AKI) was defined as AKI diagnosed any time from the start of PP to 48 h after returning to the supine position. A t-test for independent samples was used to test for the differences between groups, while binomial logistical regression was performed to assess variables independently associated with PP-associated AKI. (3) Results: A total of 48/93 (52%) patients developed PP-AKI, with a median onset at 24 [13.5–44.5] hours after starting PP. No significant differences in demographic characteristics between groups were found. Before starting the first PP cycle, patients who developed PP-AKI had a significantly lower cumulative fluid balance (CFB), even when normalized for body weight (p = 0.006). Central venous pressure (CVP) values, measured before the first PP (OR 0.803, 95% CI [0.684–0.942], p = 0.007), as well as BMI (OR 1.153, 95% CI = [1.013–1.313], p = 0.031), were independently associated with the development of PP-AKI. In the multivariable regression analysis, a lower CVP before the first PP cycle was independently associated with ventilator-free days (OR 0.271, 95% CI [0.123–0.936], p = 0.011) and with ICU mortality (OR:0.831, 95% CI [0.699–0.989], p = 0.037). (4) Conclusions: Acute kidney injury occurs frequently in invasively ventilated severe COVID-19 ARDS patients undergoing their first prone positioning cycle. Higher BMI and lower CVP before PP are independently associated with the occurrence of AKI during prone positioning.

Tidal lung hysteresis to interpret PEEP-induced changes in compliance in ARDS patients

BackgroundIn ARDS, the PEEP level associated with the best respiratory system compliance is often selected; however, intra-tidal recruitment can increase compliance, falsely suggesting improvement in baseline mechanics. Tidal lung hysteresis increases with intra-tidal recruitment and can help interpreting changes in compliance. This study aims to assess tidal recruitment in ARDS patients and to test a combined approach, based on tidal hysteresis and compliance, to interpret decremental PEEP trials.MethodsA decremental PEEP trial was performed in 38 COVID-19 moderate to severe ARDS patients. At each step, we performed a low-flow inflation-deflation manoeuvre between PEEP and a constant plateau pressure, to measure tidal hysteresis and compliance.ResultsAccording to changes of tidal hysteresis, three typical patterns were observed: 10 (26%) patients showed consistently high tidal-recruitment, 12 (32%) consistently low tidal-recruitment and 16 (42%) displayed a biphasic pattern moving from low to high tidal-recruitment below a certain PEEP. Compliance increased after 82% of PEEP step decreases and this was associated to a large increase of tidal hysteresis in 44% of cases. Agreement between best compliance and combined approaches was accordingly poor (K = 0.024). The combined approach suggested to increase PEEP in high tidal-recruiters, mainly to keep PEEP constant in biphasic pattern and to decrease PEEP in low tidal-recruiters. PEEP based on the combined approach was associated with lower tidal hysteresis (92.7 ± 20.9 vs. 204.7 ± 110.0 mL; p < 0.001) and lower dissipated energy per breath (0.1 ± 0.1 vs. 0.4 ± 0.2 J; p < 0.001) compared to the best compliance approach. Tidal hysteresis ≥ 100 mL was highly predictive of tidal recruitment at next PEEP step reduction (AUC 0.97; p < 0.001).ConclusionsAssessment of tidal hysteresis improves the interpretation of decremental PEEP trials and may help limiting tidal recruitment and energy dissipated into the respiratory system during mechanical ventilation of ARDS patients.

Effect of EIT-guided PEEP titration on prognosis of patients with moderate to severe ARDS: study protocol for a multicenter randomized controlled trial

BackgroundAcute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table.MethodsThis is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA).DiscussionAs a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date.Trial registrationClinicalTrial.gov NCT05207202. First published on January 26, 2022.

The effect of therapeutic plasma exchange therapy on veno-venous ECMO weaning success in severe COVID-19 ARDS patients.

Primarily, this study aimed to investigate the effect of TPE (therapeutic plasma exchange) treatment on successful ECMO weaning in severe COVID-19 ARDS patients treated with V-V ECMO. The study was applied retrospectively on patients over the age of 18 who were hospitalized in the ICU between January 1, 2020 and March 1, 2022. The study was performed on 33 patients, 36.3% (n: 12) of whom received TPE treatment. The rate of successful ECMO weaning was statistically higher in the TPE treatment group (without TPE: 14.3% [n: 3], with TPE: 50% [n: 6], p=0.044). The 1-month mortality was also statistically lower in the TPE treatment group (p=0.044). In the logistic analysis, It was found that the risk of unsuccessful ECMO weaning increased 6 times in those who did not receive TPE treatment (OR; 6.0, 95% CI; 1.134-31.735, p=0.035). TPE treatment may increase the success rate of V-V ECMO weaning in severe COVID-19 ARDS patients treated with V-V ECMO.

No: 6348 Flow-controlled ventilation among severe ARDS patients with COVID-19 in ICU

No: 6348 Flow-controlled ventilation among severe ARDS patients with COVID-19 in ICU

Response to PEEP in COVID-19 ARDS patients with and without extracorporeal membrane oxygenation. A multicenter case–control computed tomography study

BackgroundPEEP selection in severe COVID-19 patients under extracorporeal membrane oxygenation (ECMO) is challenging as no study has assessed the alveolar recruitability in this setting. The aim of the study was to compare lung recruitability and the impact of PEEP on lung aeration in moderate and severe ARDS patients with or without ECMO, using computed tomography (CT).MethodsWe conducted a two-center prospective observational case–control study in adult COVID-19-related patients who had an indication for CT within 72 h of ARDS onset in non-ECMO patients or within 72 h after ECMO onset. Ninety-nine patients were included, of whom 24 had severe ARDS under ECMO, 59 severe ARDS without ECMO and 16 moderate ARDS.ResultsNon-inflated lung at PEEP 5 cmH2O was significantly greater in ECMO than in non-ECMO patients. Recruitment induced by increasing PEEP from 5 to 15 cmH2O was not significantly different between ECMO and non-ECMO patients, while PEEP-induced hyperinflation was significantly lower in the ECMO group and virtually nonexistent. The median [IQR] fraction of recruitable lung mass between PEEP 5 and 15 cmH2O was 6 [4–10]%. Total superimposed pressure at PEEP 5 cmH2O was significantly higher in ECMO patients and amounted to 12 [11–13] cmH2O. The hyperinflation-to-recruitment ratio (i.e., a trade-off index of the adverse effects and benefits of PEEP) was significantly lower in ECMO patients and was lower than one in 23 (96%) ECMO patients, 41 (69%) severe non-ECMO patients and 8 (50%) moderate ARDS patients. Compliance of the aerated lung at PEEP 5 cmH2O corrected for PEEP-induced recruitment (CBABY LUNG) was significantly lower in ECMO patients than in non-ECMO patients and was linearly related to the logarithm of the hyperinflation-to-recruitment ratio.ConclusionsLung recruitability of COVID-19 pneumonia is not significantly different between ECMO and non-ECMO patients, with substantial interindividual variations. The balance between hyperinflation and recruitment induced by PEEP increase from 5 to 15 cmH2O appears favorable in virtually all ECMO patients, while this PEEP level is required to counteract compressive forces leading to lung collapse. CBABY LUNG is significantly lower in ECMO patients, independently of lung recruitability.

Early assessment of the efficacy of noninvasive ventilation tested by HACOR score to avoid delayed intubation in patients with moderate to severe ARDS.

Background:Use of noninvasive ventilation (NIV) in patients with moderate to severe ARDS is controversial. We aimed to use HACOR (combination of heart rate, acidosis, consciousness, oxygenation and respiratory rate) score to comprehensively assess the efficacy of NIV in ARDS patients with PaO2/FiO2 ⩽ 150 mmHg.Methods:Secondary analysis was performed using the data collected from two databases. We screened the ARDS patients who used NIV as a first-line therapy. Patients with PaO2/FiO2 ⩽ 150 mmHg were enrolled. NIV failure was defined as requirement of intubation.Results:A total of 224 moderate to severe ARDS patients who used NIV as a first-line therapy were enrolled. Of them, 125 patients (56%) experienced NIV failure and received intubation. Among the intubated patients, the survivor had shorter time from initiation of NIV to intubation than nonsurvivors (median 10 vs 22 h, p < 0.01). The median differences of HACOR score before and 1–2 h of NIV were 1 point (interquartile range: 0–3). We defined the patients with △HACOR >1 as responders (n = 102) and the rest to non-responders (n = 122). Compared to non-responders, the responders had higher HACOR score before NIV. However, the HACOR score was lower in the responders than non-responders after 1–2 h, 12 h, and 24 h of NIV. The responders also had lower NIV failure rate (36% vs 72%, p < 0.01) and lower 28-day mortality (32% vs 47%, p = 0.04) than non-responders.Conclusions:NIV failure was high among patients with moderate to severe ARDS. Delayed intubation is associated with increased mortality. The reduction of HACOR score after 1–2 h of NIV can identify the patients who respond well to NIV.

Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19.

ECMO management of severe ARDS patients with COVID-19, who are not responding to lung protective ventilation and salvage strategies like prone positioning or inhaled nitric oxide, is safe if performed in a dedicated referral centre. https://bit.ly/3p5HOEN

Plasma Insulin-like Growth Factor Binding Protein 7 Contributes Causally to ARDS 28-Day Mortality: Evidence From Multistage Mendelian Randomization

ARDS is a devastating syndrome with heterogeneous subtypes, but few causal biomarkers have been identified. Would multistage Mendelian randomization identify new causal protein biomarkers for ARDS 28-day mortality? Three hundred moderate to severe ARDS patients were selected randomly from the Molecular Epidemiology of ARDS cohort for proteomics analysis. Orthogonal projections to latent structures discriminant analysis was applied to detect the association between proteins and ARDS 28-day mortality. Candidate proteins were analyzed using generalized summary data-based Mendelian randomization (GSMR). Protein quantitative trait summary statistics were retrieved from the Efficiency and safety of varying the frequency of whole blood donation (INTERVAL) study (n= 2,504), and a genome-wide association study for ARDS was conducted from the Identification of SNPs Predisposing to Altered Acute Lung Injury Risk (iSPAAR) consortium study (n= 534). Causal mediation analysis detected the role of platelet count in mediating the effect of protein on ARDS prognosis. Plasma insulin-like growth factor binding protein 7 (IGFBP7) moderately increased ARDS 28-day mortality (OR, 1.11; 95%CI, 1.04-1.19; P= .002) per log2 increase. GSMR analysis coupled with four other Mendelian randomization methods revealed IGFBP7 as a causal biomarker for ARDS 28-day mortality (OR, 2.61; 95%CI, 1.33-5.13; P= .005). Causal mediation analysis indicated that the association between IGFBP7 and ARDS 28-day mortality is mediated by platelet count (OR, 1.03; 95%CI, 1.02-1.04; P= .01). We identified plasma IGFBP7 as a novel causal protein involved in the pathogenesis of ARDS 28-day mortality and platelet function in ARDS, a topic for further experimental and clinical investigation.

Prone Positioning during Venovenous Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome. A Multicenter Cohort Study and Propensity-matched Analysis

Rationale: Prone positioning reduces mortality in patients with severe acute respiratory distress syndrome (ARDS). To date, no evidence supports the use of prone positioning (PP) during venovenous extracorporeal oxygenation (ECMO).Objectives: The aim of the study was to assess the feasibility, safety, and effect on oxygenation and lung mechanics of PP during ECMO. As a secondary exploratory aim, we assessed the association between PP and hospital mortality.Methods: We performed a multicenter retrospective cohort study in six Italian ECMO centers, including patients managed with PP during ECMO support (prone group; four centers) and patients managed in the supine position (control group; two centers). Physiological variables were analyzed at four time points (supine before PP, start of PP, end of PP, and supine after PP). The association between PP and hospital mortality was assessed by multivariate analysis and propensity score-matching.Results: A total of 240 patients were included, with 107 in the prone group and 133 in the supine group. The median duration of the 326 pronation cycles was 15 (12-18) hours. Minor reversible complications were reported in 6% of PP maneuvers. PP improved oxygenation and reduced intrapulmonary shunt. Unadjusted hospital mortality was lower in the prone group (34 vs. 50%; P = 0.017). After adjusting for covariates, PP remained significantly associated with a reduction of hospital mortality (odds ratio, 0.50; 95% confidence interval, 0.29-0.87). Sixty-six propensity score-matched patients were identified in each group. In this matched sample, patients who underwent pronation had higher ECMO duration (16 vs. 10 d; P = 0.0344) but lower hospital mortality (30% vs. 53%; P = 0.0241).Conclusions: PP during ECMO improved oxygenation and was associated with a reduction of hospital mortality.

Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study

RationaleCOVID-19 ARDS could differ from typical forms of the syndrome.ObjectivePulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics.MethodsBetween March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1–4] day after intubation (median [IQR]).Measurements and main resultsThirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1–44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721–2434] mL. Gas exchanges were characterized by hypercapnia 55 [44–62] mmHg, high physiological dead-space (VD/VT): 75 [69–85.5] % and ventilatory ratio (VR): 2.9 [2.2–3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12–46] cells per mL and 1483 [999–2217] ng/mL, respectively.ConclusionsWe observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

Prone positioning monitored by electrical impedance tomography in patients with severe acute respiratory distress syndrome on veno-venous ECMO

BackgroundProne positioning (PP) during veno-venous ECMO is feasible, but its physiological effects have never been thoroughly evaluated. Our objectives were to describe, through electrical impedance tomography (EIT), the impact of PP on global and regional ventilation, and optimal PEEP level.MethodsA monocentric study conducted on ECMO-supported severe ARDS patients, ventilated in pressure-controlled mode, with 14-cmH2O driving pressure and EIT-based “optimal PEEP”. Before, during and after a 16-h PP session, EIT-based distribution and variation of tidal impedance, VTdorsal/VTglobal ratio, end-expiratory lung impedance (EELI) and static compliance were collected. Subgroup analyses were performed in patients who increased their static compliance by ≥ 3 mL/cmH2O after 16 h of PP.ResultsFor all patients (n = 21), tidal volume and EELI were redistributed from ventral to dorsal regions during PP. EIT-based optimal PEEP was significantly lower in PP than in supine position. Median (IQR) optimal PEEP decreased from 14 (12–16) to 10 (8–14) cmH2O. Thirteen (62%) patients increased their static compliance by ≥ 3 mL/cmH2O after PP on ECMO. This subgroup had higher body mass index, more frequent viral pneumonia, shorter ECMO duration, and lower baseline VTdorsal/VTglobal ratio than patients with compliance ≤ 3 mL/cmH2O (P < 0.01).ConclusionAlthough baseline tidal volume distribution on EIT may predict static compliance improvement after PP on ECMO, our results support physiological benefits of PP in all ECMO patients, by modifying lung mechanics and potentially reducing VILI. Further studies, including a randomized–controlled trial, are now warranted to confirm potential PP benefits during ECMO.

Feasibility and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ARDS patients.

Mechanical ventilation with ultra-low tidal volume (VT) during ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury, with the main drawback of worsening respiratory acidosis. We hypothesized that VT could be reduced down to 4ml/kg, with clinically significant decrease in driving pressure, without the need for extracorporeal CO2 removal, while maintaining pH > 7.20. We conducted a non-experimental before-and-after multicenter study on 35 ARDS patients with PaO2/FiO2 ≤ 150mmHg, within 24h of ARDS diagnosis. After inclusion, VT was reduced to 4ml/kg and further adjusted to maintain pH ≥ 7.20, respiratory rate was increased up to 40min-1 and PEEP was set using a PEEP-FiO2 table. The primary judgment criterion was driving pressure on day 2 of the study, as compared to inclusion. From inclusion to day 2, driving pressure decreased significantly from 12 [9-15] to 8 [6-11] cmH2O, while VT decreased from 6.0 [5.9-6.1] to 4.1 [4.0-4.7] ml/kg. On day 2, VT was below 4.2ml/kg in 65% [CI95% 48%-79%], and below 5.25ml/kg in 88% [CI95% 74%-95%] of the patients. 2 patients (6%) developed acute cor pulmonale after inclusion. Eleven patients (32%) developed transient severe acidosis with pH < 7.15. Fourteen patients (41%) died before day 90. Ultra-low tidal volume ventilation may be applied in approximately 2/3 of moderately severe-to-severe ARDS patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients.

A 2-year multicenter, observational, prospective, cohort study on extracorporeal CO2 removal in a large metropolis area

BackgroundExtracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis.MethodsTo assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period.ResultsSeventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median VT was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3–8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related.ConclusionsBased on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices.Trial registrationClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079

Long-term neurocognitive outcome is not worsened by of the use of venovenous ECMO in severe ARDS patients

BackgroundVenovenous extracorporeal membrane oxygenation (VV-ECMO) is associated with a significant morbidity. There is the need to investigate long-term cognitive outcome among ARDS survivors treated with VV-ECMO. We aimed to compare the prevalence of long-term cognitive dysfunction and neuropsychological impairment using a highly specific test in severe ARDS survivors treated or not treated with VV-ECMO.MethodsSevere ARDS survivors treated between 2011 and 2017 in an ECMO Regional Referral Center were prospectively evaluated 2 years after their ICU discharge. Patients underwent an in-person interview and examination. The primary outcome was cognitive function, assessed by the Wechsler Adult Intelligence Scale 4th edition (WAIS-IV). Secondary outcomes included anxiety, depression, post-traumatic stress disorder (PTSD) and quality-of-life.ResultsWe investigated 40 consecutive patients surviving from severe ARDS treated (N = 22) or not (N = 18) with VV-ECMO at a median [interquartile range] of 20 [17–22] and 22 [18–23] months after ICU discharge, respectively. Regarding the main outcome, cognitive function was below normal ranges in 12 (55%) ECMO patients and 10 (56%) non-ECMO patients (p = 0.95). Eight (36%) ECMO patients had moderate-to-severe depressive symptoms as compared with 7 (39%) non-ECMO patients (p = 0.87). Twelve (55%) ECMO patients and eight (44%) non-ECMO patients had moderate-to-severe anxiety symptoms (p = 0.53). Seven (33%) ECMO patients and eight (44%) non-ECMO patients presented a PTSD (p = 0.48). Health-related quality of life did not differ between the two groups.ConclusionsUsing the WAIS-IV, VV-ECMO treatment does not appear to worsen long-term cognitive and neuropsychological outcomes in severe ARDS patients.

A novel risk score for severe ARDS patients undergoing ECMO after retrieval from peripheral hospitals.

Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to conventional protective ventilation is associated with elevated costs, resource and complications, and appropriate risk stratification of candidate patients could be useful to recognize those more likely to benefit from ECMO. We aimed to derive a new outcome prediction score for patientsretrieved by our ECMO team from peripheral centers, including systematic echocardiographic evaluation before ECMO start. Sixty-nine consecutive patients with refractory ARDS requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO referral center), from 1 October 2009 to 31 December 2015, were assessed. All patients were transported on ECMO (distance, median 77, range 4-456km) The mortality rate was 41% (28/69). Our new risk score included age ≥42years, BMI <31kg/m2 , RV dilatation, and pH <7.35. The proposed cut off (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30% (AUC-ROC: 0.85, 95% CI: 0.76-0.94, P<0.001). When assessing the discriminatory ability of our risk score in the population of local patients, survivors had a mean value of 15.4±8.6, whereas non-survivors showed a mean value of 20.1±7.4 (P<0.001). Our new risk score shows good discriminatory ability both in patients retrieved from peripheral centers and in those implanted at our center. This score includes variables easily available at bedside, and, for the first time, a pathophysiologic element, RV dilatation.

Ventilator-associated pneumonia in ARDS patients: the impact of prone positioning. A secondary analysis of the PROSEVA trial

The goal of this study was to assess the impact of prone positioning on the incidence of ventilator-associated pneumonia (VAP) and the role of VAP in mortality in a recent multicenter trial performed on patients with severe ARDS. An ancillary study of a prospective multicenter randomized controlled trial on early prone positioning in patients with severe ARDS. In suspected cases of VAP the diagnosis was based on positive quantitative cultures of bronchoalveolar lavage fluid or tracheal aspirate at the 10(4) and 10(7)CFU/ml thresholds, respectively. The VAP cases were then subject to central, independent adjudication. The cumulative probabilities of VAP were estimated in each position group using the Aalen-Johansen estimator and compared using Gray's test. A univariate and a multivariate Cox model was performed to assess the impact of VAP, used as a time-dependent covariate for mortality hazard during the ICU stay. In the supine and prone position groups, the incidence rate for VAP was 1.18 (0.86-1.60) and 1.54 (1.15-2.02) per 100days of invasive mechanical ventilation (p=0.10), respectively. The cumulative probability of VAP at 90days was estimated at 46.5% (27-66) in the prone group and at 33.5% (23-44) in the supine group. The difference between the two cumulative probability curves was not statistically significant (p=0.11). In the univariate Cox model, VAP was associated with an increase in the mortality rate during the ICU stay [HR 1.65 (1.05-2.61), p=0.03]. HR increased to 2.2 (1.39-3.52) (p<0.001) after adjustment for position group, age, SOFA score, McCabe score, and immunodeficiency. In severe ARDS patients prone positioning did not reduce the incidence of VAP and VAP was associated with higher mortality.