BACKGROUND: Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs. 6 mg dexamethasone intravenously in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19. METHODS: In a multicenter, open-label, randomized trial conducted in nine hospitals in the Czech Republic, we randomized adult patients with ARDS and COVID-19 requiring high-flow oxygen, noninvasive or invasive mechanical ventilation to receive either intravenous high-dose dexamethasone (20 mg/day on days 1-5, 10 mg/day on days 6-10) or standard-dose dexamethasone (6 mg/d, days 1-10). The primary outcome was 28-day ventilator-free days. The five secondary outcomes were 60-day mortality, C-reactive protein dynamics, 14-day WHO (World Health Organization) Clinical Progression Scale score, adverse events and 90-day Barthel index. The long-term outcomes were 180- and 360-day mortality and the Barthel index. The planned sample size was 300, with interim analysis after enrollment of 150 patients. RESULTS: The trial was stopped due to a lack of recruitment, and the follow-up was completed in February 2023. Among 234 randomized patients of 300 planned patients, the primary outcome was available for 224 patients (110 high-dose and 114 standard-dose dexamethasone; median [interquartile range (IQR)] age, 59.0 [48.5-66.0] years; 130 [58.0%] were receiving noninvasive or invasive mechanical ventilation at baseline). The mean number of 28-day ventilator-free days was 8.9 (± 11.5) days for high-dose dexamethasone and 8.0 (± 10.7) days for standard-dose dexamethasone, with an absolute difference of + 0.81 days (95% CI - 2.12-3.73 days). None of the prespecified secondary outcomes, including adverse events, differed between the groups. CONCLUSIONS: Despite not reaching its prespecified enrollment, there was no signal to either benefit or harm high-dose dexamethasone over standard-dose dexamethasone in patients with COVID-19 and moderate-to-severe ARDS. Trial registration Trial registration: ClinicalTrials.gov Identifier: NCT04663555. Registered 10 December 2020, https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 and EudraCT: 2020-005887-70.

• MeSH
• COVID-19 * mortality   complications   MeSH
• Dexamethasone * administration & dosage   therapeutic use   MeSH
• COVID-19 Drug Treatment * MeSH
• Middle Aged MeSH
• Humans MeSH
• SARS-CoV-2 MeSH
• Aged MeSH
• Respiratory Distress Syndrome * drug therapy   mortality   MeSH
• Respiration, Artificial * MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Czech Republic MeSH

Úvod: Těžká sepse je stále spojena s významnou morbiditou a mortalitou, která se nicméně liší, stejně jako její management, v závislosti na regionu. Jaká je situace v ČR a jaký mají charakter pacienti s těžkou sepsí v současné době, není známo. Cílem projektu je popsat procesy péče, výsledek léčby a charakteristiku pacientů s těžkou sepsí přijímaných na pracoviště intenzivní péče v ČR. Metodika: Jedná se o multicentrický a observační projekt s retrospektivním zařazováním pacientů, kteří splní kritéria těžké sepse před nebo do 24 hod od přijetí na vybrané jednotky intenzivní péče (EPOSS‐ICU). Výsledky: Analyzováno bylo 394 pacientů. Medián věku při přijetí byl 66 (56–76) let, převažovali muži (58,9 %) a medián APACHE II skóre při příjmu byl 25 (19–32). Příjímaní pacienti byli převážně interního charakteru (56,9 %) a nejvíce příjmů bylo sekundárních z jiných ICU (53,6 %). Splnění kritérií těžké sepse bylo nejčastěji v období (? 4 hod) od příjmu na EPOSS‐ICU (77,6 %). Medián celkového příjmu tekutin během prvních 24 hod byl 6 680 (4 840–9 450) ml. Většina nemocných vyžadovala umělou plicní ventilaci (58,4 %). Splnění tzv. resuscitačních balíčků pro těžkou sepsi bylo v našem souboru velmi dobré a bylo spojeno s nižší mortalitou pacientů. Nejčastěji byla délka pobytu na EPOSS‐ICU 7 (3–15) dnů a medián celkové doby hospitalizace v nemocnici byl 13 (8–28) dnů. Celková nemocniční mortalita souboru byla 35,8 %. Závěr: Představujeme projekt, který ve své první fázi získal cenná a mezinárodně srovnatelná data o pacientech s těžkou sepsí přijímaných na zapojená pracoviště intenzivní péče v ČR.

Introduction: Severe sepsis is still associated with significant morbidity and mortality, which is however different, as well as its management, depending on the region. What is the situation in the Czech Republic and what is the character of patients with severe sepsis is currently not known. The aim of the project is to describe the processes of care, outcome and characteristics of patients with severe sepsis admitted to the intensive care department of the Czech Republic. Methods: This is a multicentre and observational project with retrospective enrollment of patients who meet the criteria for severe sepsis before or within 24 hours after admission to selected intensive care units (ICU‐EPOSS). Results: 394 patients were analyzed. Median age at admission was 66 (56–76) years, males predominated (58.9%) and the median APACHE II score on admission was 25 (19–32). Patients were predominantly medical (56.9%) and most were secondary admitted from other ICU (53.6%). Meeting the criteria of severe sepsis was most frequently within the period (? 4 hours) of admission the EPOSS‐ICU (77.6%). Median total fluid intake during the first 24 hours was 6,680 (4,840–9,450) ml. Most patients required mechanical ventilation (58.4%). Compliance with the resuscitation bundle of severe sepsis in our group was very good and was associated with lower mortality of patients. Most frequently, the EPOSS‐ICU length of stay (LOS) was 7 (3–15) days and median hospital LOS was 13 (8–28) days. Hospital mortality in our cohort was 35.8%. Conclusion: Introducing the project, which in its first stage obtained valuable and internationally comparable data about patients with severe sepsis admitted to the involved ICU in the Czech Republic.

• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• APACHE MeSH
• Length of Stay statistics & numerical data   MeSH
• Guideline Adherence MeSH
• Outcome Assessment, Health Care * statistics & numerical data   MeSH
• Intensive Care Units * standards   MeSH
• Middle Aged MeSH
• Humans MeSH
• Hospital Mortality MeSH
• Pilot Projects MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Sepsis * epidemiology   mortality   therapy   MeSH
• Statistics as Topic MeSH
• Fluid Therapy statistics & numerical data   MeSH
• Respiration, Artificial statistics & numerical data   MeSH
• Organ Dysfunction Scores MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH