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Rationale: We wished to determine the influence of sex on the management and outcomes in acute respiratory distress syndrome (ARDS) patients in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE)., Methods: We assessed the effect of sex on mortality, intensive care unit and hospital length of stay, and duration of invasive mechanical ventilation (IMV) in patients with ARDS who underwent IMV, adjusting for plausible clinical and geographic confounders., Findings: Of 2377 patients with ARDS, 905 (38%) were female and 1472 (62%) were male. There were no sex differences in clinician recognition of ARDS or critical illness severity profile. Females received higher tidal volumes (8.2±2.1 versus 7.2±1.6 mL·kg -1 ; p<0.0001) and higher plateau and driving pressures compared with males. Lower tidal volume ventilation was received by 50% of females compared with 74% of males (p<0.0001). In shorter patients (height ≤1.69 m), females were significantly less likely to receive lower tidal volumes. Surviving females had a shorter duration of IMV and reduced length of stay compared with males. Overall hospital mortality was similar in females (40.2%) versus males (40.2%). However, female sex was associated with higher mortality in patients with severe confirmed ARDS (OR for sex (male versus female) 0.35, 95% CI 0.14-0.83)., Conclusions: Shorter females with ARDS are less likely to receive lower tidal volume ventilation, while females with severe confirmed ARDS have a higher mortality risk. These data highlight the need for better ventilatory management in females to improve their outcomes from ARDS., Competing Interests: Conflict of interest: B.A. McNicholas has nothing to disclose. Conflict of interest: F. Madotto has nothing to disclose. Conflict of interest: T. Pham has nothing to disclose. Conflict of interest: E. Rezoagli has nothing to disclose. Conflict of interest: C.H. Masterson has nothing to disclose. Conflict of interest: S. Horie has nothing to disclose. Conflict of interest: G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Hamilton, Getinge and Dimar SRL, outside the submitted work. Conflict of interest: L. Brochard reports grants from Covidien, grants and nonfinancial support from Fisher Paykel, Air Liquide and General Electric, nonfinancial support from Philips and Sentec, outside the submitted work. Conflict of interest: J.G. Laffey has nothing to disclose., (Copyright ©ERS 2019.)

Objectives: To understand the impact of mild-moderate and severe acute kidney injury in patients with acute respiratory distress syndrome., Design: Secondary analysis of the "Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure", an international prospective cohort study of patients with severe respiratory failure., Setting: Four-hundred fifty-nine ICUs from 50 countries across five continents., Subjects: Patients with a glomerular filtration rate greater than 60 mL/min/1.73 m prior to admission who fulfilled criteria of acute respiratory distress syndrome on day 1 and day 2 of acute hypoxemic respiratory failure., Interventions: Patients were categorized based on worst serum creatinine or urine output into: 1) no acute kidney injury (serum creatinine < 132 µmol/L or urine output ≥ 0.5 mL/kg/hr), 2) mild-moderate acute kidney injury (serum creatinine 132-354 µmol/L or minimum urine output between 0.3 and 0.5mL/kg/hr), or 3) severe acute kidney injury (serum creatinine > 354 µmol/L or renal replacement therapy or minimum urine output < 0.3 mL/kg/hr)., Measurements and Main Results: The primary outcome was hospital mortality, whereas secondary outcomes included prevalence of acute kidney injury and characterization of acute respiratory distress syndrome risk factors and illness severity patterns, in patients with acute kidney injury versus no acute kidney injury. One-thousand nine-hundred seventy-four patients met inclusion criteria: 1,209 (61%) with no acute kidney injury, 468 (24%) with mild-moderate acute kidney injury, and 297 (15%) with severe acute kidney injury. The impact of acute kidney injury on the ventilatory management of patients with acute respiratory distress syndrome was relatively limited, with no differences in arterial CO2 tension or in tidal or minute ventilation between the groups. Hospital mortality increased from 31% in acute respiratory distress syndrome patients with no acute kidney injury to 50% in mild-moderate acute kidney injury (p ≤ 0.001 vs no acute kidney injury) and 58% in severe acute kidney injury (p ≤ 0.001 vs no acute kidney injury and mild-moderate acute kidney injury). In multivariate analyses, both mild-moderate (odds ratio, 1.61; 95% CI, 1.24-2.09; p < 0.001) and severe (odds ratio, 2.13; 95% CI, 1.55-2.94; p < 0.001) acute kidney injury were independently associated with mortality., Conclusions: The development of acute kidney injury, even when mild-moderate in severity, is associated with a substantial increase in mortality in patients with acute respiratory distress syndrome.