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.
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.
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 + PaO
/FiO
ratio < 300 with a Positive End-Expiratory Pressure ≥ 5 cm H
O + 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.
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.
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.
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.
This is an open trial, so no masking of treatment assignment will be used.
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.
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.
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.
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.
Background
The criteria for the selection of COVID‐19 patients that could benefit most from ECMO organ support are yet to be defined. In this study, we evaluated the predictive performance of ECMO ...mortality predictive models in patients with COVID‐19. We also performed a cost–benefit analysis depending on the mortality predicted probability. We conducted a retrospective cohort study in COVID‐19 patients who received ECMO at two tertiary care hospitals between March 2020 to July 2021.
Materials and Methods
We evaluated the discrimination (C‐statistic), calibration (Cox calibration), and accuracy of the prediction of death due to severe ARDS in V‐V ECMO score (PRESERVE), the Respiratory Extracorporeal Membrane Oxygenation Survival Score (RESP) score, and the PREdiction of Survival on ECMO Therapy‐Score (PRESET) score. In addition, we compared the RESP score with Plateau pressure instead of Peak pressure.
Results
We included a total of 36 patients, 29 (80%) of them male and with a median (IQR) APACHE of 10 (8–15). The PRESET score had the highest discrimination (AUROCs 0.81 95%CI 0.67–0.94) and calibration (calibration‐in‐the‐large 0.5 95%CI −1.4 to 0.3; calibration slope 2.2 95%CI 0.7/3.7). The RESP score with Plateau pressure had higher discrimination than the conventional RESP score. The cost per QALY in the USA, adjusted to life expectancy, was higher than USD 100 000 in patients older than 45 years with a PRESET > 10.
Conclusion
The PRESET score had the highest predictive performance and could help in the selection of patients that benefit most from this resource‐demanding and highly invasive organ support.
Validation of five mortality predictive models in COVID‐19 patients under ECMO support.
Aim
There is limited evidence on the diagnostic accuracy of a quick Sequential Sepsis‐Related Organ Failure Assessment (qSOFA) sepsis screening (SS) tool in developing nation health settings. The aim ...of this study was to test the diagnostic accuracy of a qSOFA‐based SS tool, and the predictive validity of the qSOFA score in hospital ward patients from Argentina.
Methods
Prospective observational study. Patients (≥18 years, without sepsis) were recruited within 24‐48 hours of admission to a 169‐bed tertiary referral private hospital in Buenos Aires. The index test was the qSOFA‐based SS tool, and the reference standard sepsis diagnosed at discharge blindly evaluated with reference to the Sepsis‐3.
Results
In 1151 patients (median age 69.9 IQR, 29.0); 47 (4.1%) had sepsis, 413 (35.9%) had infection and 691 (60.0%) other diagnoses at discharge. The qSOFA‐based SS tool (index test) had moderate sensitivity (60%), good specificity (89%), a very low positive (19%) and very high negative (98%) predictive value for sepsis diagnosed at discharge according to the Sepsis‐3 criteria (reference standard). For the same outcome, the qSOFA score in isolation had a reasonable predictive validity area under receiver operating characteristics curve 0.77 (95% CI 0.70‐0.83) P < 0.001.
Conclusion
The qSOFA score could reasonably discriminate patients at risk of developing sepsis; qSOFA‐based screening may be valuable where no screening criteria are in place.
OBJECTIVESTo prospectively evaluate the performance of the Clinical Pulmonary Infection Score (CPIS) and its components to identify early in the hospital course of ventilator-associated pneumonia ...(VAP) which patients are responding to therapy.
DESIGNProspective, multicenter, in a cohort of mechanically ventilated patients.
SETTINGThe intensive care unit of six hospitals located in the metropolitan area of Buenos Aires, Argentina.
PATIENTSSixty-three patients, from a cohort of 472 mechanically ventilated patients hospitalized for >72 hrs, had clinical evidence of VAP and bacteriologic confirmation by bronchoalveolar lavage (BAL) or blood cultures.
INTERVENTIONSBronchoscopy with BAL fluid culture and blood cultures after establishing a clinical diagnosis of VAP. All patients received antibiotics, 46 before bronchoscopy and 17 immediately after bronchoscopy.
MEASUREMENTS AND RESULTSCPIS was measured at 3 days before VAP (VAP-3); at the onset of VAP (VAP); and at 3 (VAP+3), 5 (VAP+5), and 7 (VAP+7) days after onset. CPIS rose from VAP-3 to VAP and then fell progressively in the population as a whole (p < .001), and the fall in CPIS was significant in 31 survivors, but not in 32 nonsurvivors. From the individual components of the CPIS, only the Pao2/Fio2 ratio distinguished survivors from nonsurvivors, beginning at VAP+3. When CPIS was <6 at 3 or 5 days after VAP onset, mortality was lower than in the remaining patients (p = .018). These differences also related to the finding that those receiving adequate therapy had a slight fall in CPIS and a significant increase of Pao2/Fio2 at VAP+3, whereas those getting inadequate therapy did not.
CONCLUSIONSSerial measurements of CPIS can define the clinical course of VAP resolution, identifying those with good outcome as early as day 3, and could possibly be of help to define strategies to shorten the duration of therapy.
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
The objective was to evaluate the predictive value of the ROX index and describe the evolution of a population of patients admitted to intensive care for COVID-19 pneumonia who required high-flow ...oxygen therapy.
Retrospective cohort study in patients older than 18 years with a positive nasopharyngeal swab for SARS-COV-2 who were admitted to intensive care unit with acute respiratory failure and required high-flow oxygen therapy for > 2 hours.
Of a total of 97 patients, 42 (43.3%) responded satisfactorily to treatment with high-flow nasal cannula (HFNC) and 55 (56.7%) failed treatment, requiring orotracheal intubation and invasive ventilatory support. Of the 55 patients who failed, 11 (20%) survived and 44 (80%) died during intensive care admission (p < 0.001). No patient who responded satisfactorily to HFNC treatment died during hospitalization. The ROC analysis identified the 12-hour ROX index as the best predictor of failure with an area under the curve of 0.75 (0.64-0.85) and a cut-off point of 6.23 as the best predictor of intubation Sensitivity 0.85 (95% CI 0.70-0.94), Specificity 0.55 (95% CI 0.39-0.70).
In patients with acute respiratory failure secondary to COVID-19 pneumonia treated with highflow oxygen therapy, the ROX index was a good predictor of success.
Abstract
Objective
The aim of this study was to evaluate the outcomes of implementing a sepsis screening (SS) tool based on the quick Sequential Sepsis-Related Organ Failure Assessment (qSOFA) and ...the presence of confirmed/suspected infection. The implementation of the 6-h bundle was also evaluated.
Design
Interrupted times series with prospective data collection.
Setting
Five hospital wards in a developing nation, Argentina.
Participants
A total of 1151 patients (≥18 years) recruited within 24–48 h of hospital admission.
Intervention
The qSOFA-based SS tool and the 6-h bundle.
Main outcome measures
The primary outcome was the timing of implementation of the first 6-h bundle element. Secondary outcomes were related to the adherence to the screening procedures.
Results
Of 1151 patients, 145 (12.6%) met the qSOFA-based SS tool criteria, among them intervention (39/64) patients received the first 6-h bundle element earlier (median 8 h; 95% confidence interval (CI): 0.1–16) than baseline (48/81) patients (median 22 h; 95% CI: 3–41); these times, however, did not differ significantly (P = 0.525). Overall, 47 (4.1%) patients had sepsis; intervention patients (18/25) received the first 6-h bundle element sooner (median 5 h; 95% CI: 4–6) than baseline patients (15/22) did (median 12 h; 95% CI: 0–33); however, times were not significantly different (P = 0.470). While intervention patients were screened regularly, only one-third of patients who required sepsis alerts had them activated.
Conclusion
The implementation of the qSOFA-based SS tool resulted in early, but not significantly improved, provision of 6-h bundle care. Screening procedures were regularly conducted, but sepsis alerts rarely activated. Further research is needed to better understand the implementation of sepsis care in developing settings.
Extracorporeal membrane oxygenation is used in refractory hypoxemia in many clinical settings. Thoracic trauma patients usually develop acute respiratory distress syndrome. Due to high risk of ...bleeding, thrombotic complications present in this context are particularly difficult to manage and usually require insertion of an inferior vena cava filter to prevent embolism from the distal veins to the pulmonary circulation. Here, we present a case of a thoracic trauma patient with severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation via a right internal jugular double lumen cannula due to a previously inserted inferior vena cava filter caused by distal bilateral calf muscle vein deep vein thrombosis.
Evidence on sepsis screening and care in developing nations is insufficient to inform implementation practices in hospital wards. The aim of this multi‐method study was to describe and evaluate the ...implementation of a three‐step intervention (sepsis screening, alert activation, care) in five wards in Argentina in 2017. The implementation involved three stages: (1) context assessment, (2) development/participation in implementation strategies, and (3) evaluation of intervention adherence. Results were variable. The context assessment (Stage 1) demonstrated the value of education, proactivity towards care and team structures. Strategies developed (Stage 2) included sepsis screening and response guide, education, team rounding, posters, champions, audit/feedback and knowledge brokering. In Stage 3, staff screened 92% patients (506/547) for sepsis at ≥60% of set times; only 33% (21/64) patients had a sepsis alert activated when needed. A similar proportion of patients who had alerts activated (n = 16, 76%) or not (n = 32, 74%) received at least one element of care. The use of implementation strategies resulted in adherence to some aspects of the intervention. Future research is needed to improve sepsis screening and alert activation and care in this setting.
To determine the incidence, risk factors, and outcome of barotrauma in a cohort of mechanically ventilated patients where limited tidal volumes and airway pressures were used.
Prospective cohort of ...361 intensive care units from 20 countries.
A total of 5183 patients mechanically ventilated for more than 12 h.
Baseline demographic data, primary indication for mechanical ventilation, daily ventilator settings, multiple-organ failure over the course of mechanical ventilation and outcome were collected. Barotrauma was present in 154 patients (2.9%). The incidence varied according to the reason for mechanical ventilation: 2.9% of patients with chronic obstructive pulmonary disease; 6.3% of patients with asthma; 10.0% of patients with chronic interstitial lung disease (ILD); 6.5% of patients with acute respiratory distress syndrome (ARDS); and 4.2% of patients with pneumonia. Patients with and without barotrauma did not differ in any ventilator parameter. Logistic regression analysis identified as factors independently associated with barotrauma: asthma RR 2.58 (1.05-6.50), ILD RR 4.23 (95%CI 1.78-10.03); ARDS as primary reason for mechanical ventilation RR 2.70 (95%CI 1.55-4.70); and ARDS as a complication during the course of mechanical ventilation RR 2.53 (95%CI 1.40-4.57). Case-control analysis showed increased mortality in patients with barotrauma (51.4 vs 39.2%; p=0.04) and prolonged ICU stay.
In a cohort of patients in whom airway pressures and tidal volume are limited, barotrauma is more likely in patients ventilated due to underlying lung disease (acute or chronic). Barotrauma was also associated with a significant increase in the ICU length of stay and mortality.
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