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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.

Abstract Introduction Lung protective ventilation (LPV) comprising low tidal volume (VT) and high positive end-expiratory pressure (PEEP) may compromise cerebral perfusion in acute brain injury (ABI). In patients with ABI, we investigated whether LPV is associated with increased intracranial pressure (ICP) and/or deranged cerebral autoregulation (CA), brain compensatory reserve and oxygenation. Methods In a prospective, crossover study, 30 intubated ABI patients with normal ICP and no lung injury were randomly assigned to receive low VT [6 ml/kg/predicted (pbw)]/at either low (5 cmH2O) or high PEEP (12 cmH2O). Between each intervention, baseline ventilation (VT 9 ml/kg/pbw and PEEP 5 cmH2O) were resumed. The safety limit for interruption of the intervention was ICP above 22 mmHg for more than 5 min. Airway and transpulmonary pressures were continuously monitored to assess respiratory mechanics. We recorded ICP by using external ventricular drainage or a parenchymal probe. CA and brain compensatory reserve were derived from ICP waveform analysis. Results We included 27 patients (intracerebral haemorrhage, traumatic brain injury, subarachnoid haemorrhage), of whom 6 reached the safety limit, which required interruption of at least one intervention. For those without intervention interruption, the ICP change from baseline to “low VT/low PEEP” and “low VT/high PEEP” were 2.2 mmHg and 2.3 mmHg, respectively, and considered clinically non-relevant. None of the interventions affected CA or oxygenation significantly. Interrupted events were associated with high baseline ICP (p

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.

Abstract Venous return is the flow of blood from the systemic venous network towards the right heart. At steady state, venous return equals cardiac output, as the venous and arterial systems operate in series. However, unlike the arterial one, the venous network is a capacitive system with a high compliance. It includes a part of unstressed blood, which is a reservoir that can be recruited via sympathetic endogenous or exogenous stimulation. Guyton’s model describes the three determinants of venous return: the mean systemic filling pressure, the right atrial pressure and the resistance to venous return. Recently, new methods have been developed to explore such determinants at the bedside. In this narrative review, after a reminder about Guyton’s model and current methods used to investigate it, we emphasize how Guyton’s physiology helps understand the effects on cardiac output of common treatments used in critically ill patients.

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.

Abstract Background Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Methods Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ 2) test (p

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.

Abstract Background Pneumonia is a dreaded complication of varicella-zoster virus (VZV) infection in adults; however, the data are limited. Our objective was to investigate the clinical features, management, and outcomes of critically ill patients with VZV-related community-acquired pneumonia (VZV-CAP). Methods This was an observational study of patients with VZV-CAP admitted to 29 intensive care units (ICUs) from January 1996 to January 2015. Results One hundred and two patients with VZV-CAP were included. Patients were young (age 39 years (interquartile range 32–51)) and 53 (52%) were immunocompromised. Time since respiratory symptom onset was 2 (1–3) days. There was a seasonal distribution of the disease, with more cases during spring and winter time. All but four patients presented with typical skin rash on ICU admission. Half the patients received mechanical ventilation within 1 (1–2) day following ICU admission (the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) = 150 (80–284), 80% with acute respiratory distress syndrome (ARDS)). Sequential Organ Failure Assessment (SOFA) score on day 1 (odds ratio (OR) 1.90 (1.33–2.70); p