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

BACKGROUND: The dominant feature of COVID-19-associated ARDS is gas exchange impairment. Extravascular lung water index is a surrogate for lung edema and reflects the level of alveolocapillary disruption. The primary aim was the prediction of extravascular lung water index by the alveolar-arterial oxygen difference. The secondary aims were in determining the relationship between the extravascular lung water index and other oxygenation parameters, the [Formula: see text], end-tidal oxygen concentration, pulmonary oxygen gradient ([Formula: see text] minus end-tidal oxygen concentration), and [Formula: see text]. METHODS: This observational prospective single-center study was performed at the Department of Anaesthesiology and Intensive Care, The University Hospital in Ostrava, The Czech Republic, during the COVID-19 pandemic, from March 20, 2020, until May 24, 2021. RESULTS: The relationship between the extravascular lung water index and alveolar-arterial oxygen difference showed only a mild-to-moderate correlation (r = 0.33, P < .001). Other extravascular lung water index correlations were as follows: [Formula: see text] (r = 0.33, P < .001), end-tidal oxygen concentration (r = 0.26, P = .0032), [Formula: see text] minus end-tidal oxygen concentration (r = 0.15, P = .0624), and [Formula: see text] (r = -0.15, P = .01). CONCLUSIONS: The alveolar-arterial oxygen difference does not reliably correlate with the extravascular lung water index and the degree of lung edema in COVID-19-associated ARDS.

• MeSH
• COVID-19 * komplikace   patofyziologie   MeSH
• dospělí MeSH
• extravaskulární plicní voda * metabolismus   MeSH
• kyslík * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní alveoly * metabolismus   patofyziologie   MeSH
• plicní edém etiologie   patofyziologie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• syndrom dechové tísně * patofyziologie   etiologie   MeSH
• výměna plynů v plicích MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions ́ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.

• MeSH
• epidurální analgezie * MeSH
• kolorektální nádory * chirurgie   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• morfin MeSH
• multicentrické studie jako téma MeSH
• nádorové cirkulující buňky * MeSH
• opioidní analgetika terapeutické užití   MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH

• MeSH
• akutní bolest farmakoterapie   komplikace   MeSH
• analgezie metody   MeSH
• antidepresiva terapeutické užití   MeSH
• bolest farmakoterapie   MeSH
• chronická bolest farmakoterapie   MeSH
• deprese farmakoterapie   MeSH
• imunomodulace účinky léků   MeSH
• ketamin * farmakologie   škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• urgentní zdravotnické služby MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH