Background Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. Methods REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1–5, followed by dexamethasone 10 mg on days 6–10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. Discussion We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. Trial registration EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020

Despite increasing clinical experience with extracorporeal membrane oxygenation (ECMO), its optimal indications remain unclear. Here, we externally evaluated all currently available ECMO survival-predicting scoring systems and the APACHE II score in subjects undergoing veno-venous ECMO (VV ECMO) support due to acute respiratory distress syndrome (ARDS) with influenza (IVA) and non-influenza (n-IVA) etiologies. Our aim was to find the best scoring system for influenza A ARDS ECMO success prediction. Retrospective data were analyzed to assess the abilities of the PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores to predict patient outcome. Patients treated with veno-venous ECMO support for ARDS were divided into two groups: IVA and n-IVA etiologies. Parameters collected within 24 hours before ECMO initiation were used to calculate PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores. Compared to the IVA group, the n-IVA group exhibited significantly higher ICU, 28-day, and 6-month mortality (P = .043, .034, and .047, respectively). Regarding ECMO support success predictions, the area under the receiver operating characteristic curve (AUC) was 0.62 for PRESERVE, 0.44 for RESP, 0.57 for PRESET, and 0.67 for ECMOnet, and 0.62 for Roch calculated for all subjects according to the original papers. In the IVA group, APACHE II had the best predictive value for ICU, hospital, 28-day, and 6-month mortality (AUC values of 0.73, 0.73, 0.70, and 0.73, respectively). In the n-IVA group, APACHE II was the best predictor of survival in the ICU and hospital (AUC 0.54 and 0.57, respectively). From all possible ECMO survival scoring systems, the APACHE II score had the best predictive value for VV ECMO subjects with ARDS caused by influenza A-related pneumonia with a cut-off value of about 32 points.

The review article is focused on developments in optical devices, other than laryngoscopes, in airway management and tracheal intubation. It brings information on advantages and limitations in their use, compares different devices, and summarizes benefits in various clinical settings. Supraglottic airway devices may be used as a conduit for fiberscope-guided tracheal intubation mainly as a rescue plan in the scenario of difficult or failed laryngoscopy. Some of these devices offer the possibility of direct endotracheal tube placement. Hybrid devices combine the features of two different intubating tools. Rigid and semi-rigid optical stylets represent another option in airway management. They offer benefits in restricted mouth opening and may be used also for retromolar intubation. Awake flexible fiberoptic intubation has been a gold standard in predicted difficult laryngoscopy for decades. Modern flexible bronchoscopes used in anesthesia and intensive care are disposable devices and contain optical lenses instead of fibers. Endotracheal tubes with an incorporated optics are used mainly in thoracic anesthesia for lung separation. They are available in double-lumen and single-lumen versions. They offer a benefit of direct view to the carina and do not require flexible fiberscope for their correct placement.

Objectives The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. Trial design REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. Participants The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. Inclusion criteria Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria:  • Moderate – PaO2/FiO2 100–200 mmHg;  • Severe – PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. Exclusion criteria Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history:  a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days;  b) Systemic corticosteroid use before hospitalization;  c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment;  d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g.  • intractable hyperglycaemia;  • active gastrointestinal bleeding;  • adrenal gland disorders;  • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. Intervention and comparator Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1–5, followed by dexamethasone 10 mg intravenously once daily on day 6–10. Patients in the control group will receive dexamethasone 6 mg day 1–10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. Main outcomes Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. Secondary endpoints a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. Randomisation Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. Blinding (masking) This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. Numbers to be randomised (sample size) The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. Trial Status This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. Trial registration The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. Full protocol The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.