BACKGROUNDPatients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao 2 ) would result in lower mortality than using a higher target. METHODSIn this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao 2 of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higheroxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days. RESULTSAt 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P = 0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P = 0.24). CONCLUSIONSAmong adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days.

BACKGROUNDIntravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODSIn this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTSWe enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], −4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, −1.7 percentage points; 99% CI, −7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONSAmong adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.

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Background Endotheliopathy is suggested as pivotal pathophysiology of sepsis and trauma-associated organ failure, but its role in acute respiratory failure is not yet determined. We investigated if endotheliopathy biomarkers at ICU admission are associated with illness severity and clinical outcomes in patients with acute respiratory failure requiring mechanical ventilation. Methods We conducted a prospective single-center cohort study including 459 mechanically ventilated adults at ICU admission. Plasma levels of three endotheliopathy biomarkers were measured at ICU admission: Syndecan-1, soluble Thrombomodulin (sTM), and Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1). The primary outcome was the rate of liberation from mechanical ventilation, which is presented together with the rate of the competing risk of death while still on mechanical ventilation. Secondary outcomes were PaO2/FiO2-ratios on admission and on last measurement in patients dying within five days, and 30-day all-cause mortality. The primary outcome and 30-day all-cause mortality were analyzed using Cox regression, controlled for gender, age, chronic obstructive pulmonary disease, septic shock, heart failure, PaO2/FiO2-ratio at admission, respiratory infection, acute kidney injury, and bilirubin. PaO2/FiO2-ratios were analyzed using linear regression, controlled for age, chronic obstructive pulmonary disease, respiratory infection, and shock. Results Patients with high sTM were liberated from mechanical ventilation at a lower rate (adjusted hazard ratio (HR) 0.71, for an increase from the 25th to the 75th percentile, 95% confidence interval (CI) 0.54–0.93, p = 0.01). Patients with high PECAM-1 were liberated from mechanical ventilation at a lower rate, but only during the first 5 days (adjusted HR 0.72, for an increase from the 25th to the 75th percentile, 95% CI 0.58–0.9, p < 0.01). High levels of Syndecan-1 and PECAM-1 were associated with a higher rate of death while still on mechanical ventilation. sTM and PECAM-1 were negatively associated with PaO2/FiO2-ratio at ICU admission and no biomarker was associated with last measured PaO2/FiO2-ratio. High levels of all biomarkers were associated with higher 30-day all-cause mortality. Conclusion In acute respiratory failure, endotheliopathy biomarkers are associated with lower rates of liberation from mechanical ventilation, hypoxemia at ICU admission, and 30-day all-cause mortality. Graphic Abstract