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 * mortalita komplikace MeSH
- dexamethason * aplikace a dávkování terapeutické užití MeSH
- farmakoterapie COVID-19 * MeSH
- lidé středního věku MeSH
- lidé MeSH
- SARS-CoV-2 MeSH
- senioři MeSH
- syndrom dechové tísně * farmakoterapie mortalita MeSH
- umělé dýchání * MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Česká republika MeSH
AIM: This study aimed to analyze the influence of the hospital admitting department on adherence to the Guidelines of European Society of Cardiology for management of acute coronary syndromes in patients after out-of-hospital cardiac arrest (OHCA) of coronary etiology. METHODS: We studied retrospective-prospective register of 102 consecutive patients with OHCA as a manifestation of acute coronary syndrome (ACS). Patients were admitted to the coronary care unit (CCU) 52, general intensive care unit (GICU) 21, or GICU after initial Cath lab treatment (CAG-GICU) 29. This study compared the differences in the management of ACS in patients with OHCA of coronary etiology based on the admitting department in a tertiary care institution. RESULTS: Twelve of the 21 (57.1%) patients admitted to the GICU were evaluated as having ACS on-site where they experienced OHCA. In the CCU group, 50 out of 52 (96.2%) and 28 of 29 (100%) patients in the CAG-GICU group (P<0.001). Coronary angiography was performed in 10 of 21 patients (48%) admitted to the GICU. It was performed in 49 out of 52 (94%) CCU patients and, in the CAG-GICU group, 28 out of 29 patients. The mean time to CAG differed significantly across groups (that is, GICU 200.7 min., CCU 71.2 min., and CAG-GICU 7.5 min. (P<0.001)). Aspirin was used in 48% of GICU, 96% of CCU, and 79% of CAG-GICU patients (P<0.001), while in the pre-hospital phase, aspirin was used in 9.5% of GICU, 71.2% of CCU, and 50% of CAG-GICU patients (P<0.001). P2Y12 inhibitor prescriptions were lower in patients admitted to the GICU (33% vs. 89% CCU and 57% CAG-GICU, P<0.001). The department's choice significantly affected the time to initiation of antithrombotics, which was the longest in the GICU. CONCLUSION: The choice of admission department for patients with OHCA caused by ACS was found to affect the extent to which the recommended treatments were used. An examination of OHCA patients by a cardiologist upon admission to the hospital increased the likelihood of an early diagnosis of ACS as the cause of OHCA.
- MeSH
- akutní koronární syndrom * komplikace terapie MeSH
- Aspirin terapeutické užití MeSH
- koronární angiografie škodlivé účinky MeSH
- koronární angioplastika * škodlivé účinky MeSH
- lidé MeSH
- přijímací oddělení nemocnice * MeSH
- retrospektivní studie MeSH
- zástava srdce mimo nemocnici * etiologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Diabetes is a well-known risk factor in pregnancy. Because maternal diabetes involves oxidative stress that is also induced by chronic hypoxia and can alter vascular function, we sought to determine the effects of chronic maternal hyperglycemia on the fetoplacental vasculature in rats and to compare it with the effects of chronic hypoxia. METHODS: Diabetes was induced in female rats by a streptozotocin injection at a neonatal age. When these animals reached adulthood, their hyperglycemia was confirmed and they were inseminated. Half of them were exposed to hypoxia (10% O2) for the last week before the delivery. One day before the expected date of delivery, one of their placentae was isolated and perfused. RESULTS: Fetoplacental vascular resistance was increased equally by experimental diabetes, chronic hypoxia, and their combination. Fetoplacental perfusion pressure-flow analysis suggested increased resistance in the small vessels in chronic hypoxia and in larger vessels in diabetes. Fetal plasma nitrotyrosine levels, measured as a marker of peroxynitrite (reaction product of superoxide and nitric oxide), mirrored the differences in fetoplacental resistance, suggesting a causative role. Fetoplacental vasoconstrictor reactivity to acute hypoxic stimuli was reduced similarly in all groups. Fasudil, a strong vasodilator agent, reduced fetoplacental vascular resistance similarly in all groups, suggesting that for the observed differences among the groups, the changes in vascular morphology were more important than variances in vascular tone. DISCUSSION: Maternal diabetes increases fetoplacental vascular resistance to a similar extent as chronic hypoxia. These stimuli are not additive. Changes in vascular tone are not responsible for these effects.
- MeSH
- cévní rezistence fyziologie MeSH
- experimentální diabetes mellitus metabolismus patofyziologie MeSH
- gestační diabetes metabolismus patofyziologie MeSH
- hypoxie metabolismus patofyziologie MeSH
- krysa rodu rattus MeSH
- oxidační stres fyziologie MeSH
- placenta krevní zásobení MeSH
- placentární oběh fyziologie MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- chronická nemoc MeSH
- hypoxie * patofyziologie MeSH
- maternofetální výměna látek fyziologie MeSH
- modely nemocí na zvířatech MeSH
- perfuze metody MeSH
- placenta krevní zásobení MeSH
- potkani Wistar * MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The vessels on the fetal side of the placenta differ from most other vascular beds except the lungs in that they respond to acute hypoxia by vasoconstriction. An essential role of calcium influx in the mechanism of this hypoxic fetoplacental vasoconstriction (HFPV) has been shown previously. That finding does not, however, exclude the possible involvement of other mechanisms of vascular tone regulation. In this study we tested the hypothesis that Rho-kinase-mediated calcium sensitization is involved in HFPV. We used a model of isolated rat placenta dually perfused (from both the maternal and fetal side) with Krebs salt solution saturated with normoxic and hypoxic gas mixture respectively at constant flow rate. Rho-kinase pathway was inhibited by fasudil (10 μM). We found that fasudil reduced basal normoxic fetoplacental vascular resistance and completely prevented HFPV. This suggests that the activity of Rho-kinase signaling pathway is essential for HFPV.
- MeSH
- cévní rezistence fyziologie MeSH
- hypoxie metabolismus patofyziologie MeSH
- kinázy asociované s rho antagonisté a inhibitory metabolismus MeSH
- placenta * krevní zásobení MeSH
- placentární oběh * fyziologie MeSH
- těhotenství MeSH
- vápník MeSH
- vazokonstrikce fyziologie MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
