High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-Related Acute Respiratory Distress Syndrome: A Multicenter, Randomized Open-Label Clinical Trial.

OBJECTIVE: To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome (ARDS) caused by COVID-19. DESIGN: Multicenter, randomized, open-label, clinical trial. PARTICIPANTS: Consecutive patients with confirmed COVID-19-related ARDS were enrolled from June 17, 2020, to March 27, 2021, in four intensive care units (ICUs) in Argentina. INTERVENTION: 16 mg of dexamethasone intravenously daily for five days followed by 8 mg of dexamethasone daily for five days or 6 mg of dexamethasone intravenously daily for 10 days. MAIN OUTCOME AND MEASURES: The primary outcome was ventilator-free days during the first 28 days. The secondary outcomes were all-cause mortality at 28 and 90 days, infection rate, muscle weakness, and glycemic control in the first 28 days. RESULTS: Data from 98 patients who received at least one dose of dexamethasone were analyzed. The trial was prematurely terminated due to low enrollment rate. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 [interquartile range [IQR] 0-14] vs. 0 [IQR 0-1] days; P = .231), or in the mean duration of mechanical ventilation (19 ± 18 vs. 25 ± 22 days; P = .078). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P < .001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms. CONCLUSIONS: Among patients with ARDS due to COVID-19, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilator.

A 31-Year-Old Man With Seizures, Brain Lesion, and Lung Nodules.

CASE PRESENTATION: A 31-year-old man was admitted to our hospital with a recent history of generalized seizures. Three months earlier, he started with intermittent hemoptysis. CT scan showed a cavitary lung lesion in the upper segment of the right inferior lobe (RIL). Because of his job as a social worker in a high-risk population, he started treatment for Mycobacterium TB; however, the BAL culture result was negative. At the time of his current admission, he has continued taking rifampicin, isoniazid, pyrazinamide, and levofloxacin. He denied the use of any illicit drugs or alcohol. He had no history of smoking. One year earlier, he visited Southeast Asia, Oceania, and South Africa for several months. He reported a weight loss of 7 kg since then. Except for a recurrent oral candidiasis, he did not have a relevant medical history. His family history was notable for mother with lupus, and brother with sarcoidosis.

High dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to COVID-19: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this study is to explore the effectiveness and safety of high dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to SARS-Cov-2 pneumonia. TRIAL DESIGN: Multicentre, randomized clinical trial, controlled, open label, parallel group, to evaluate the effectiveness and safety of high dose dexamethasone in adult patients with confirmed COVID-19, with Acute Respiratory Distress Syndrome. PARTICIPANTS: We will include patients with SARS-Cov-2 pneumonia who develop acute respiratory distress syndrome, in several intensive care units (ICU) in Buenos Aires, Argentina (CEMIC, Clinica Bazterrica, Sanatorio Sagrado Corazon) Inclusion criteria: Men and women, age ≥ 18 years old. Confirmed diagnosis of SARS-CoV-2 infection, by RT-PCR. Diagnosis of Acute Respiratory Distress Syndrome (hypoxemic respiratory failure not explained by cardiac disease + PaO2/FiO2 ratio < 300 with a Positive End-Expiratory Pressure ≥ 5 cm H2O + bilateral pulmonary infiltrates) Length of mechanical ventilation of at least 72 hours Informed consent (next of kin / legal guardian) Exclusion criteria: Pregnant or breast-feeding women. Terminal disease (advanced cancer; under palliative care; cardiovascular, respiratory, or renal disease with a life expectancy less ≤ 1 year). Therapeutic limitation (advance directives or do not resuscitate order) Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents, active cancer). Patients under chronic treatment with glucocorticoids for other diseases (≥ 8 mg prednisone, or equivalent) Participation in another randomized clinical trial. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard ICU patient care (group 1) or standard ICU patient care plus high dose dexamethasone (group 2). Group 1: dexamethasone up to 6 mg/24 hours for up to 10 days + ventilatory, hemodynamic, nutritional, and antimicrobial support according to international guidelines. Group 2: dexamethasone 16 mg/24 hours for 5 days followed by dexamethasone 8 mg/24 hours for 5 days + ventilatory, hemodynamic, nutritional, and antimicrobial support according to international guidelines. MAIN OUTCOME: The main result is ventilator-free days at 28 days (Days without ventilator support in the first 28 days following randomization). Secondary outcomes are 28-days and 90-days mortality, frequency of nosocomial infections in the first 28 days after randomization, Sequential Organ Failure Assessment (SOFA) score variation and prone position in the first 10-days, viral shedding 28-days after randomization, and delirium and muscle weakness at ICU discharge. RANDOMISATION: Treatment will be assigned according to site stratified randomization by permuted random blocks sequence 1:1 generated with a table in R language concealed in a randomization tool in REDCap (Research Electronic Data CAPture) platform. BLINDING (MASKING): This is an open trial, so no masking of treatment assignment will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Assuming a 3 days difference in ventilator-free days between treatment groups, with a mean of 9 days, and a standard deviation of 9 days; the necessary sample size would be 284 subjects (142 per group), with a power of 80% and a two-tailed alpha error of 0.05. TRIAL STATUS: The protocol with code 1264, version 3.0 on date: May 13, 2020 is approved by the local Ethics Committee. The trial is in the recruitment phase. Recruitment began May 22, 2020 and is anticipated to be complete by the end of December 2021. TRIAL REGISTRATION: The trial was registered under the title "Dexamethasone for COVID-19 Related ARDS: a Multicenter, Randomized Clinical Trial" with ClinicalTrials number NCT04395105, https://clinicaltrials.gov/ct2/show/NCT04395105 , registered on 20 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Sizing the lung in dogs: the inspiratory capacity defines the tidal volume. / Avaliação do tamanho do pulmão em cães: a capacidade inspiratória define o volume corrente.

OBJECTIVE: To evaluate a novel physiological approach for setting the tidal volume in mechanical ventilation according to inspiratory capacity, and to determine if it results in an appropriate mechanical and gas exchange measurements in healthy and critically ill dogs. METHODS: Twenty healthy animals were included in the study to assess the tidal volume expressed as a percentage of inspiratory capacity. For inspiratory capacity measurement, the mechanical ventilator was set as follows: pressure control mode with 35cmH2O of inspired pressure and zero end-expiratory pressure for 5 seconds. Subsequently, the animals were randomized into four groups and ventilated with a tidal volume corresponding to the different percentages of inspiratory capacity. Subsequently, ten critically ill dogs were studied. RESULTS: Healthy dogs ventilated with a tidal volume of 17% of the inspiratory capacity showed normal respiratory mechanics and presented expected PaCO2 values more frequently than the other groups. The respiratory system and transpulmonary driving pressure were significantly higher among the critically ill dogs but below 15 cmH2O in all cases. CONCLUSIONS: The tidal volume based on the inspiratory capacity of each animal has proven to be a useful and simple tool when setting ventilator parameters. A similar approach should also be evaluated in other species, including human beings, if we consider the potential limitations of tidal volume titration based on the calculated ideal body weight.

OBJETIVO: Avaliar uma nova abordagem fisiológica para a determinação do volume corrente em ventilação mecânica, de acordo com a capacidade inspiratória, e determinar se isso resulta em medidas mecânicas e de troca gasosa adequadas em cães saudáveis e em estado crítico. MÉTODOS: Incluíram-se, neste estudo, 24 animais para avaliar o volume corrente expresso como porcentagem da capacidade inspiratória. Para mensuração da capacidade inspiratória, o ventilador mecânico foi regulado como segue: modo controle de pressão, com 35cmH2O de pressão de inspiração e pressão expiratória final de zero, por 5 segundos. Subsequentemente, estudaram-se dez cães em condições clínicas críticas. RESULTADOS: Cães saudáveis ventilados com volume corrente que correspondia a 17% da capacidade inspiratória demonstraram mecânica respiratória normal e apresentaram os valores previstos de PaCO2 mais frequentemente do que os animais nos demais grupos. A pressão no sistema respiratório e a pressão transpulmonar foram significantemente mais elevadas nos cães em condição crítica, porém em todos os casos, estiveram abaixo de 15cmH2O. CONCLUSÕES: O volume corrente calculado com base na capacidade inspiratória de cada animal comprovou ser uma ferramenta útil e simples para o estabelecimento dos parâmetros do ventilador. Convém também realizar abordagem semelhante em outras espécies, inclusive no ser humano, quando se consideram as potenciais limitações da titulação do volume corrente, com base no peso corpóreo ideal calculado.

Avaliação do tamanho do pulmão em cães: a capacidade inspiratória define o volume corrente / Sizing the lung in dogs: the inspiratory capacity defines the tidal volume

RESUMO Objetivo: Avaliar uma nova abordagem fisiológica para a determinação do volume corrente em ventilação mecânica, de acordo com a capacidade inspiratória, e determinar se isso resulta em medidas mecânicas e de troca gasosa adequadas em cães saudáveis e em estado crítico. Métodos: Incluíram-se, neste estudo, 24 animais para avaliar o volume corrente expresso como porcentagem da capacidade inspiratória. Para mensuração da capacidade inspiratória, o ventilador mecânico foi regulado como segue: modo controle de pressão, com 35cmH2O de pressão de inspiração e pressão expiratória final de zero, por 5 segundos. Subsequentemente, estudaram-se dez cães em condições clínicas críticas. Resultados: Cães saudáveis ventilados com volume corrente que correspondia a 17% da capacidade inspiratória demonstraram mecânica respiratória normal e apresentaram os valores previstos de PaCO2 mais frequentemente do que os animais nos demais grupos. A pressão no sistema respiratório e a pressão transpulmonar foram significantemente mais elevadas nos cães em condição crítica, porém em todos os casos, estiveram abaixo de 15cmH2O. Conclusões: O volume corrente calculado com base na capacidade inspiratória de cada animal comprovou ser uma ferramenta útil e simples para o estabelecimento dos parâmetros do ventilador. Convém também realizar abordagem semelhante em outras espécies, inclusive no ser humano, quando se consideram as potenciais limitações da titulação do volume corrente, com base no peso corpóreo ideal calculado.

ABSTRACT Objective: To evaluate a novel physiological approach for setting the tidal volume in mechanical ventilation according to inspiratory capacity, and to determine if it results in an appropriate mechanical and gas exchange measurements in healthy and critically ill dogs. Methods: Twenty healthy animals were included in the study to assess the tidal volume expressed as a percentage of inspiratory capacity. For inspiratory capacity measurement, the mechanical ventilator was set as follows: pressure control mode with 35cmH2O of inspired pressure and zero end-expiratory pressure for 5 seconds. Subsequently, the animals were randomized into four groups and ventilated with a tidal volume corresponding to the different percentages of inspiratory capacity. Subsequently, ten critically ill dogs were studied. Results: Healthy dogs ventilated with a tidal volume of 17% of the inspiratory capacity showed normal respiratory mechanics and presented expected PaCO2 values more frequently than the other groups. The respiratory system and transpulmonary driving pressure were significantly higher among the critically ill dogs but below 15 cmH2O in all cases. Conclusions: The tidal volume based on the inspiratory capacity of each animal has proven to be a useful and simple tool when setting ventilator parameters. A similar approach should also be evaluated in other species, including human beings, if we consider the potential limitations of tidal volume titration based on the calculated ideal body weight.