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Abstract Background Previous retrospective research has shown that maintaining prone positioning (PP) for an average of 40 h is associated with an increase of survival rates in intubated patients with COVID-19-related acute respiratory distress syndrome (ARDS). This study aims to determine whether a cumulative PP duration of more than 32 h during the first 2 days of intensive care unit (ICU) admission is associated with increased survival compared to a cumulative PP duration of 32 h or less. Methods This study is an ancillary analysis from a previous large international observational study involving intubated patients placed in PP in the first 48 h of ICU admission in 149 ICUs across France, Belgium and Switzerland. Given that PP is recommended for a 16-h daily duration, intensive PP was defined as a cumulated duration of more than 32 h during the first 48 h, whereas standard PP was defined as a duration equal to or less than 32 h. Patients were followed-up for 90 days. The primary outcome was mortality at day 60. An Inverse Probability Censoring Weighting (IPCW) Cox model including a target emulation trial method was used to analyze the data. Results Out of 2137 intubated patients, 753 were placed in PP during the first 48 h of ICU admission. The intensive PP group (n = 79) had a median PP duration of 36 h, while standard PP group (n = 674) had a median of 16 h during the first 48 h. Sixty-day mortality rate in the intensive PP group was 39.2% compared to 38.7% in the standard PP group (p = 0.93). Twenty-eight-day and 90-day mortality as well as the ventilator-free days until day 28 were similar in both groups. After IPCW, there was no significant difference in mortality at day 60 between the two-study groups (HR 0.95 [0.52–1.74], p = 0.87 and HR 1.1 [0.77–1.57], p = 0.61 in complete case analysis or in multiple imputation analysis, respectively). Conclusions This secondary analysis of a large multicenter European cohort of intubated patients with ARDS due to COVID-19 found that intensive PP during the first 48 h did not provide a survival benefit compared to standard PP.

Abstract Background Inhaled sedation during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) has received increasing attention. However, inhaled sedation devices increase dead-space ventilation and an undesirable effect is the increase in minute ventilation needed to maintain CO2 removal. A consequence of raising minute ventilation is an increase in mechanical power (MP) that can promote lung injury. However, the effect of inhaled sedation devices on MP remains unknown. Methods We conducted a bench study to assess and compare the effects of three devices delivering inhaled sevoflurane currently available in ICU (AnaConDa-50 mL (ANA-50), AnaConDa-100 mL (ANA-100), and MIRUS) on MP by using a test lung model set with three compliances (20, 40, and 60 mL/cmH2O). We simulated lung-protective ventilation using a low tidal volume and two levels of positive end-expiratory pressure (5 and 15 cmH2O) under ambient temperature and dry conditions. Following the insertion of the devices, either the respiratory rate or tidal volume was increased in 15%-steps until end-tidal CO2 (EtCO2) returned to the baseline value. MP was calculated at baseline and after EtCO2 correction using a simplified equation. Results Following device insertion, the EtCO2 increase was significantly greater with MIRUS (+ 78 ± 13%) and ANA-100 (+ 100 ± 11%) than with ANA-50 (+ 49 ± 7%). After normalizing EtCO2 by adjusting minute ventilation, MP significantly increased by more than 50% with all inhaled sedation devices compared to controls. The lowest increase in MP was observed with ANA-50 (p 50% with all devices after normalizing EtCO2 by adjusting minute ventilation. Conclusion Inhaled sedation devices substantially increased MP in this bench model of protective ventilation, which might limit their benefits in ARDS.

Abstract Background Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. Methods This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for

Abstract Acute brain injury (ABI) covers various clinical entities that may require invasive mechanical ventilation (MV) in the intensive care unit (ICU). The goal of MV, which is to protect the lung and the brain from further injury, may be difficult to achieve in the most severe forms of lung or brain injury. This narrative review aims to address the respiratory issues and ventilator management, specific to ABI patients in the ICU.

No major trial evaluating prone positioning for acute respiratory distress syndrome (ARDS) has incorporated a high-positive end-expiratory pressure (high-PEEP) strategy despite complementary physiological rationales. We evaluated generalizability of three recent proning trials to patients receiving a high-PEEP strategy. All trials employed a relatively low-PEEP strategy. After protocol ventilator settings were initiated and the patient was positioned per treatment assignment, post-intervention PEEP was not more than 5 cm H2O in 16.7 % and not more than 10 cm H2O in 66.0 % of patients. Post-intervention PEEP would have been nearly twice the set PEEP had a high-PEEP strategy been employed. Use of either proning or high-PEEP likely improves survival in moderate-severe ARDS; the role for both concomitantly remains unknown.

During mechanical ventilation for acute respiratory distress syndrome, tidal volume (VT) must be reduced. Once switched to pressure-support ventilation, there is a risk that uncontrolled large VT may be delivered. A 63-year-old man with community-acquired pneumonia required tracheal intubation and mechanical ventilation, with a VT of 6 mL/kg predicted body weight, PEEP of 10 cm H2O, a respiratory rate of 30 breaths/min, and FIO2 of 0.60. Plateau pressure was 22 cm H2O. He improved and received pressure-support. Twelve days later a chest radiograph showed suspected air leaks, confirmed via computed tomogram (CT), which showed anterior pneumomediastinum. VT received over the previous 3 days had averaged 14 mL/kg predicted body weight. The patient was put back onto volume-controlled mode, and 2 days later there were no air leaks. In pressure-support ventilation, VT must be closely monitored to ensure lung-protective mechanical ventilation. [ABSTRACT FROM AUTHOR]

BACKGROUND: In patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), the use of alveolar-recruitment maneuvers to improve oxygenation is controversial. There is lack of standardization and lack of clinical studies to compare various recruitment maneuvers. Recruitment maneuvers are closely linked to the selection of positive end-expiratory pressure (PEEP), which is also a subject of debate. METHODS: With 12 intubated and mechanically ventilated patients with early ALI/ARDS we conducted a recruitment maneuver (sustained inflation at 40 cm H2O for 30 s), then set PEEP at 24 cm H2O, and then we reduced PEEP stepwise, by 4 cm H2O every 10 min. We kept the fraction of inspired oxygen (FIO2 ) at 0.8. After each PEEP decrement step we measured Pao2 . We defined the "optimal" PEEP as the PEEP step above which Pao2 decreased by ≥ 20%. All the patients then underwent a period of ventilation on the same settings: tidal volume 6 mL/kg, PEEP at the level set by the physician before the experiment, plateau pressure < 30 cm H2O. Then each patient underwent 3 ventilation strategies, each applied for one hour: optimal PEEP alone; optimal PEEP plus one sustained inflation (40 cm H2O for 30 s); and optimal PEEP plus sigh breaths (ie, twice the baseline tidal volume, plateau pressure < 40 cm H2O) every 25 breaths. After the application of each PEEP strategy we measured arterial blood gas values and the static compliance of the respiratory system. RESULTS: The mean ± SD optimal PEEP was 12 ± 4 cmH2O. The measurements from the standardization periods were comparable between the 3 PEEP groups. In the optimal-PEEP-plus-sighs group the changes in Pao2 (85 ± 96%) and static compliance (14 ± 20%) were significantly greater than in the 2 other groups. CONCLUSIONS: Sighs superimposed on lung-protective mechanical ventilation with optimal PEEP improved oxygenation and static compliance in patients with early ALI/ARDS. [ABSTRACT FROM AUTHOR]

Abstract Background Delaying time to prone positioning (PP) may be associated with higher mortality in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). We evaluated the use and the impact of early PP on clinical outcomes in intubated patients hospitalized in intensive care units (ICUs) for COVID-19. Methods All intubated patients with ARDS due to COVID-19 were involved in a secondary analysis from a prospective multicenter cohort study of COVID-ICU network including 149 ICUs across France, Belgium and Switzerland. Patients were followed-up until Day-90. The primary outcome was survival at Day-60. Analysis used a Cox proportional hazard model including a propensity score. Results Among 2137 intubated patients, 1504 (70.4%) were placed in PP during their ICU stay and 491 (23%) during the first 24 h following ICU admission. One hundred and eighty-one patients (36.9%) of the early PP group had a PaO2/FiO2 ratio > 150 mmHg when prone positioning was initiated. Among non-early PP group patients, 1013 (47.4%) patients had finally been placed in PP within a median delay of 3 days after ICU admission. Day-60 mortality in non-early PP group was 34.2% versus 39.3% in the early PP group (p = 0.038). Day-28 and Day-90 mortality as well as the need for adjunctive therapies was more important in patients with early PP. After propensity score adjustment, no significant difference in survival at Day-60 was found between the two study groups (HR 1.34 [0.96–1.68], p = 0.09 and HR 1.19 [0.998–1.412], p = 0.053 in complete case analysis or in multiple imputation analysis, respectively). Conclusions In a large multicentric international cohort of intubated ICU patients with ARDS due to COVID-19, PP has been used frequently as a main treatment. In this study, our data failed to show a survival benefit associated with early PP started within 24 h after ICU admission compared to PP after day-1 for all COVID-19 patients requiring invasive mechanical ventilation regardless of their severity.

Acute respiratory distress syndrome (ARDS) is mostly characterized by the loss of aerated lung volume associated with an increase in lung tissue and intense and complex lung inflammation. ARDS has long been associated with the histological pattern of diffuse alveolar damage (DAD). However, DAD is not the unique pathological figure in ARDS and it can also be observed in settings other than ARDS. In the coronavirus disease 2019 (COVID-19) related ARDS, the impairment of lung microvasculature has been pointed out. The airways, and of notice the small peripheral airways, may contribute to the loss of aeration observed in ARDS. High-resolution lung imaging techniques found that in specific experimental conditions small airway closure was a reality. Furthermore, low-volume ventilator-induced lung injury, also called as atelectrauma, should involve the airways. Atelectrauma is one of the basic tenet subtending the use of positive end-expiratory pressure (PEEP) set at the ventilator in ARDS. Recent data revisited the role of airways in humans with ARDS and provided findings consistent with the expiratory flow limitation and airway closure in a substantial number of patients with ARDS. We discussed the pattern of airway opening pressure disclosed in the inspiratory volume-pressure curves in COVID-19 and in non-COVID-19 related ARDS. In addition, we discussed the functional interplay between airway opening pressure and expiratory flow limitation displayed in the flow-volume curves. We discussed the individualization of the PEEP setting based on these findings.

Prone position can reduce mortality in acute respiratory distress syndrome (ARDS), but several studies found variable effects on oxygenation and lung mechanics. It is unclear whether different positive end-expiratory pressure (PEEP) titration techniques modify the effect of prone position. We tested, in an animal model of ARDS, if the PEEP titration method may influence the effect of prone position on oxygenation and lung protection. In a crossover study in 10 piglets with a two-hit injury ARDS model, we set the “best PEEP” according to the ARDS Network low-PEEP table (BPARDS) or targeting the lowest transpulmonary driving pressure (BPDPL). We measured gas exchange, lung mechanics, aeration, ventilation, and perfusion with computed tomography (CT) and electrical impedance tomography in each position with both PEEP titration techniques. The primary endpoint was the PaO2/FiO2 ratio. Secondary outcomes were lung mechanics, regional distribution of ventilation, regional distribution of perfusion, and homogeneity of strain derived by CT scan. The PaO2/FiO2 ratio increased in prone position when PEEP was set with BPARDS [difference 54 (19–106) mmHg, p = 0.04] but not with BPDPL [difference 17 (−24 to 68) mmHg, p = 0.99]. The transpulmonary driving pressure significantly decreased during prone position with both BPARDS [difference −0.9 (−1.5 to −0.9) cmH2O, p = 0.009] and BPDPL [difference −0.55 (−1.6 to −0.4) cmH2O, p = 0.04]. Pronation homogenized lung regional strain and ventilation and redistributed the ventilation/perfusion ratio along the sternal-to-vertebral gradient. The PEEP titration technique influences the oxygenation response to prone position. However, the lung-protective effects of prone position could be independent of the PEEP titration strategy.

Abstract Background In acute respiratory distress syndrome (ARDS) patients, it has recently been proposed to set positive end-expiratory pressure (PEEP) by targeting end-expiratory transpulmonary pressure. This approach, which relies on the measurement of absolute esophageal pressure (Pes), has been used in supine position (SP) and has not been investigated in prone position (PP). Our purposes were to assess Pes-guided strategy to set PEEP in SP and in PP as compared with a PEEP/FIO2 table and to explore the early (1 h) and late (16 h) effects of PP on lung and chest wall mechanics. Results We performed a prospective, physiologic study in two ICUs in university hospitals on ARDS patients with PaO2/FIO2

Abstract Background Predicting fluid responsiveness may help to avoid unnecessary fluid administration during acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the diagnostic performance of the following methods to predict fluid responsiveness in ARDS patients under protective ventilation in the prone position: cardiac index variation during a Trendelenburg maneuver, cardiac index variation during an end-expiratory occlusion test, and both pulse pressure variation and change in pulse pressure variation from baseline during a tidal volume challenge by increasing tidal volume (VT) to 8 ml.kg-1. Methods This study is a prospective single-center study, performed in a medical intensive care unit, on ARDS patients with acute circulatory failure in the prone position. Patients were studied at baseline, during a 1-min shift to the Trendelenburg position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed present if cardiac index assessed by transpulmonary thermodilution increased by at least 15% after fluid administration. Results There were 33 patients included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15 (45%) were deemed fluid-responsive. The area under the receiver operating characteristic (ROC) curve of the pulse contour-derived cardiac index change during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90 (95% CI, 0.80–1.00) and 0.65 (95% CI, 0.46–0.84), respectively. An increase in cardiac index ≥ 8% during the Trendelenburg maneuver enabled diagnosis of fluid responsiveness with sensitivity of 87% (95% CI, 67–100), and specificity of 89% (95% CI, 72–100). The area under the ROC curve of pulse pressure variation and change in pulse pressure variation during the tidal volume challenge were 0.52 (95% CI, 0.24–0.80) and 0.59 (95% CI, 0.31–0.88), respectively. Conclusions Change in cardiac index during a Trendelenburg maneuver is a reliable test to predict fluid responsiveness in ARDS patients in the prone position, while neither change in cardiac index during end-expiratory occlusion, nor pulse pressure variation during a VT challenge reached acceptable predictive performance to predict fluid responsiveness in this setting. Trial registration ClinicalTrials.gov, NCT01965574 . Registered on 16 October 2013. The trial was registered 6 days after inclusion of the first patient.