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.

Background Previous studies suggested that the prevalence of chronic respiratory disease in patients hospitalised with COVID-19 was lower than its prevalence in the general population. The aim of this study was to assess whether chronic lung disease or use of inhaled corticosteroids (ICS) affects the risk of contracting severe COVID-19. MethodsIn this population cohort study, records from 1205 general practices in England that contribute to the QResearch database were linked to Public Health England's database of SARS-CoV-2 testing and English hospital admissions, intensive care unit (ICU) admissions, and deaths for COVID-19. All patients aged 20 years and older who were registered with one of the 1205 general practices on Jan 24, 2020, were included in this study. With Cox regression, we examined the risks of COVID-19-related hospitalisation, admission to ICU, and death in relation to respiratory disease and use of ICS, adjusting for demographic and socioeconomic status and comorbidities associated with severe COVID-19. Findings Between Jan 24 and April 30, 2020, 8 256 161 people were included in the cohort and observed, of whom 14 479 (0•2%) were admitted to hospital with COVID-19, 1542 (<0•1%) were admitted to ICU, and 5956 (0•1%) died. People with some respiratory diseases were at an increased risk of hospitalisation (chronic obstructive pulmonary disease [COPD] hazard ratio [HR] 1•54 [95% CI 1•45-1•63], asthma 1•18 [1•13-1•24], severe asthma 1•29 [1•22-1•37; people on three or more current asthma medications], bronchiectasis 1•34 [1•20-1•50], sarcoidosis 1•36 [1•10-1•68], extrinsic allergic alveolitis 1•35 [0•82-2•21], idiopathic pulmonary fibrosis 1•59 [1•30-1•95], other interstitial lung disease 1•66 [1•30-2•12], and lung cancer 2•24 [1•89-2•65]) and death (COPD 1•54 [1•42-1•67], asthma 0•99 [0•91-1•07], severe asthma 1•08 [0•98-1•19], bronchiectasis 1•12 [0•94-1•33], sarcoidosis 1•41 [0•99-1•99), extrinsic allergic alveolitis 1•56 [0•78-3•13], idiopathic pulmonary fibrosis 1•47 [1•12-1•92], other interstitial lung disease 2•05 [1•49-2•81], and lung cancer 1•77 [1•37-2•29]) due to COVID-19 compared with those without these diseases. Admission to ICU was rare, but the HR for people with asthma was 1•08 (0•93-1•25) and severe asthma was 1•30 (1•08-1•58). In a post-hoc analysis, relative risks of severe COVID-19 in people with respiratory disease were similar before and after shielding was introduced on March 23, 2020. In another post-hoc analysis, people with two or more prescriptions for ICS in the 150 days before study start were at a slightly higher risk of severe COVID-19 compared with all other individuals (ie, no or one ICS prescription): HR 1•13 (1•03-1•23) for hospitalisation, 1•63 (1•18-2•24) for ICU admission, and 1•15 (1•01-1•31) for death.Interpretation The risk of severe COVID-19 in people with asthma is relatively small. People with COPD and interstitial lung disease appear to have a modestly increased risk of severe disease, but their risk of death from COVID-19 at the height of the epidemic w...

Supplemental Digital Content is available in the text.

No abstract