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.

Gas exchange and lung mechanics in patients with acute respiratory distress syndrome: comparison of three different strategies of positive end expiratory pressure selection.

PURPOSE: The purpose of the study was to compare gas exchange and lung mechanics between different strategies to select positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). METHODS: In 20 consecutive ARDS patients, 3 PEEP selection strategies were evaluated. One strategy was based on oxygenation using the ARDS network PEEP/fraction of inspired oxygen (Fio2) table; and two were based on lung mechanics, either PEEP titrated to reach a plateau pressure of 28 to 30 cm H2O as in the ExPress trial or best respiratory compliance method during a derecruitment maneuver. Gas exchange, airway pressures, stress index (SI), and end-expiratory transpulmonary pressure (P(tpe)) and end-inspiratory transpulmonary pressure (P(tpi)) values were assessed. Data are expressed as median (interquartile range [IQR]). RESULTS: Lower total PEEP levels were observed with the use of the PEEP/Fio2 table (8.7 [6-10] cm H2O); intermediate PEEP levels, with the Best Compliance approach (13.0 [10.2-13.8] cm H2O); and higher PEEP levels, with the ExPress strategy (16.5 [15.0-18.5] cm H2O) (P < .01). Pao2/Fio2 ratio was lower with the PEEP/Fio2 table. Oxygenation with Best Compliance approach and ExPress strategy was not different with lower plateau pressure in the former (23 [20-25] vs 30 [29-30] cm H2O; P < .01). Paco2 was slightly higher with the ExPress method than the others 2 strategies. Negative P(tpe) was observed in 35% of the patients with the PEEP/Fio2 table, in 15% applying the Best Compliance, and in only 1 case with the ExPress method. Higher SI and P(tpi), with lower lung compliance, were obtained with ExPress strategy. CONCLUSIONS: Using a best respiratory compliance approach resulted in better oxygenation levels without risk of overdistension according to SI and P(tpi), achieving a mild risk of lung collapse according to P(tpe).

Transpulmonary pressure and gas exchange during decremental PEEP titration in pulmonary ARDS patients.

BACKGROUND: Selection of the PEEP associated with the best compliance of the respiratory system during decremental PEEP titration can be used for the treatment of patients suffering from ARDS. We describe changes in transpulmonary pressure (Ptp) and gas exchange during a decremental PEEP titration maneuver in subjects with pulmonary ARDS. METHODS: Eleven subjects with early ARDS were included. After a recruitment maneuver they were ventilated in volume-controlled ventilation and PEEP was decreased from 30 to 0 cm H2O by steps of 3 cm H2O. Static airway pressure (Paw), esophageal pressure (Pes), Ptp (Paw - Pes), the ratio of dead space to tidal volume (VD/VT), and PaO2 were recorded at each step. RESULTS: A linear correlation was found between Paw and Ptp. Expiratory Ptp became negative in all subjects when PEEP decreased below 8.9 ± 5.2 cm H2O. VD/VT was 0.67 ± 0.06 with 30 cm H2O of PEEP, and decreased 15.4 ± 8.5% during the maneuver, when PEEP and expiratory Ptp were 10.6 ± 4.1 cm H2O and 1.2 ± 2.8 cm H2O, respectively. VD/VT was significantly higher during ventilation at high (> 18 cm H2O), compared to low, inspiratory Ptp values (P < .001). PaO2 decreased when expiratory Ptp became negative (P < .001). CONCLUSIONS: During decremental PEEP titration we sequentially observed high inspiratory Ptp that stressed lung tissue and increased VD/VT, and negative Ptp, indicating high risk of alveolar collapse, explaining worse oxygenation. PEEP selection based on Ptp and VD/VT in ARDS may help to avoid these situations.

Muscle weakness in septic patients requiring mechanical ventilation: protective effect of transcutaneous neuromuscular electrical stimulation.

PURPOSE: The aim of this study was to evaluate the effect of transcutaneous neuromuscular electrical stimulation (NMES) on muscle strength in septic patients requiring mechanical ventilation (MV). METHODS: Sixteen septic patients requiring MV and having 1 or more organ failure other than respiratory dysfunction were enrolled within 48 hours from admission to the intensive care unit. Neuromuscular electrical stimulation was administered twice a day on brachial biceps and vastus medialis (quadriceps) of 1 side of the body until MV withdrawal. Blinded investigators measured arm and thigh circumferences, biceps thickness by ultrasonography, and muscle strength after awakening with Medical Research Council scale. RESULTS: Two patients died before strength evaluation and were excluded from the analysis. Neuromuscular electrical stimulation was applied for 13 days (interquartile range, 7-30 days). Biceps (P = .005) and quadriceps (P = .034) strengths were significantly higher on the stimulated side at the last day of NMES. Improvement was mainly observed in more severe and weaker patients. Circumference of the nonstimulated arm decreased at the last day of NMES (P = .015), whereas no other significant differences in limb circumferences or biceps thickness were observed. CONCLUSION: Neuromuscular electrical stimulation was associated with an increase in strength of the stimulated muscle in septic patients requiring MV. Neuromuscular electrical stimulation may be useful to prevent muscle weakness in this population.

[Severe respiratory disease in an intensive care unit during influenza A(H1N1) 2009 pandemia]. / Enfermedad respiratoria grave en terapia intensiva durante la pandemia por el virus de influenza A (H1N1) 2009.

We describe characteristics of patients admitted to our intensive care unit with severe acute respiratory illness and influenza-like syndrome during the first months of the pandemic influenza A(H1N1) 2009 in Argentina. We analyzed clinical data, severity scores, laboratory tests, microbiological and radiological findings at admission, clinical outcomes and in-hospital mortality. H1N1 was confirmed by RT-PCR. Data from positive and negative PCR patients were compared. We admitted 31 adult patients between June and July 2009; median age: 54 years (IQR 33-66). A 54% (17) had positive PCR; 16 patients presented underlying medical conditions. Bilateral interstitial opacities were observed in chest radiography in 20 cases; 5 had unilateral lobar consolidation. Bacterial co-infection (isolation or IgM antibodies for bacterial infections) was found in 21 patients. Mechanical ventilation was required in 23 patients and 18 developed ARDS. Lymphopenia and increased creatine kinase levels were frequently observed (83% and 65% among PCR+ and PCR- respectively). Six patients died (19%); they were all over 75 years old, had cancer or immune-suppression. Early antiviral treatment (≤ 48 hours from symptoms onset) was associated with less frequency of mechanical ventilation (54% vs. 89%, p: 0.043). There were no differences in analyzed variables when comparing H1N1 positive and H1N1 negative patients; which suggests this approach as a most correct in future epidemic outbreaks. H1N1 infection was associated with severe respiratory illness and ARDS. Fatal outcome was observed in very old patients, or in those with major co-morbidities.

Enfermedad respiratoria grave en terapia intensiva durante la pandemia por el virus de influenza A (H1N1) 2009 / Severe respiratory disease in an intensive care unit during influenza A(H1N1)2009 pandemia

Se describen pacientes hospitalizados en una unidad de terapia intensiva por enfermedad respiratoria aguda grave con características de influenza durante los primeros meses de la pandemia por influenza A(H1N1) 2009 en la Argentina. Evaluamos datos clínicos, scores de gravedad, pruebas de laboratorio, microbiología y radiología torácica al ingreso, evolución y mortalidad hospitalaria, comparando pacientes con y sin confirmación de H1N1 por test de reacción de polimerasa en cadena, transcriptasa reversa (RT-PCR). Entre junio y julio de 2009 se internaron 31 pacientes adultos con una mediana de edad de 54 años (percentilo 25-75: 33-66). Presentaron test positivo para H1N1, 17 pacientes. Tenían al menos una condición concurrente 16 pacientes. La expresión radiográfica más frecuente fue infiltrados intersticio-alveolares bilaterales en 20 casos; 5 tenían consolidación lobar unilateral. La coinfección bacteriana (aislamiento de bacterias o IgM positiva para infecciones bacterianas), se demostró en 21 pacientes. Requirieron ventilación mecánica 23 pacientes y 18 desarrollaron síndrome de distrés respiratorio agudo (SDRA). La linfopenia y elevación de creatinina-fosfoquinasa fue frecuente (83% y 65%, respectivamente). Los 6 pacientes que murieron (19%) eran mayores de 75 años o tenían cáncer o inmunodepresión. El tratamiento antiviral temprano (≤ 48 horas) se asoció a menor necesidad de ventilación mecánica (54% vs. 89%; p: 0.043). No hubo diferencia significativa en las variables analizadas entre el grupo H1N1 positivo y el negativo, lo que sugiere tener igual enfoque terapéutico frente a una epidemia. La infección por H1N1 determinó falla respiratoria aguda y SDRA. La mortalidad ocurrió en pacientes añosos o con co-morbilidades graves.

We describe characteristics of patients admitted to our intensive care unit with severe acute respiratory illness and influenza-like syndrome during the first months of the pandemic influenza A(H1N1) 2009 in Argentina. We analyzed clinical data, severity scores, laboratory tests, microbiological and radiological findings at admission, clinical outcomes and in-hospital mortality. H1N1 was confirmed by RT-PCR. Data from positive and negative PCR patients were compared. We admitted 31 adult patients between June and July 2009; median age: 54 years (IQR 33-66). A 54% (17) had positive PCR; 16 patients presented underlying medical conditions. Bilateral interstitial opacities were observed in chest radiography in 20 cases; 5 had unilateral lobar consolidation. Bacterial co-infection (isolation or IgM antibodies for bacterial infections) was found in 21 patients. Mechanical ventilation was required in 23 patients and 18 developed ARDS. Lymphopenia and increased creatine kinase levels were frequently observed (83% and 65% among PCR+ and PCR- respectively). Six patients died (19%); they were all over 75 years old, had cancer or immune-suppression. Early antiviral treatment (≤ 48 hours from symptoms onset) was associated with less frequency of mechanical ventilation (54% vs. 89%, p: 0.043). There were no differences in analyzed variables when comparing H1N1 positive and H1N1 negative patients; which suggests this approach as a most correct in future epidemic outbreaks. H1N1 infection was associated with severe respiratory illness and ARDS. Fatal outcome was observed in very old patients, or in those with major co-morbidities.

Eficacia de la tinción de gram de muestras respiratorias para la predicción de la neumonía asociada al respirador, y su utilidad en la selección de la terapéutica antibiótica empírica / Effectiveness of the tinción of gram of respiratory samples for the prediction of the pneumonia associated to the respirator, and its utility in the selection of the therapeutic empirical antibiotic

Introducción. La neumonía asociada a la ventilación (NAV) es una complicación frecuente de la (VM) y se asocia a alta mortalidad. Su adecuado manejo se basa en detección precoz y terapia con antibióticos (ATB) empirica eficaz, siendo esenciales los métodos que permitan predecir la NAV y ayuden a seleccionar los ATB. Objetivo. Valorar la eficacia del exámen directo por tinción de Gram de muestras obtenidas del tracto respiratorio en la detección de NAV y como ayuda a la selección ATB. Material y Métodos. Se incluyeron prospectivamente 95 episodios de sospecha de NAV en 69 pacientes, considerando sólo los casos sin modificación ATB por más de 48hs o sin ATB. Las muestras fueron obtenidas por medio de lavado bronquioloalveolar a través de Fibrobroncoscopia (BAL) o miniBal por catéter envainado, a ciegas (miniBal). La confirmación se efectuó por el análisis bacteriológico cuantitativo (>10(4) y > 10(3) para el Bal y miniBal). Se calculó la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y negativo (VPN) de la técnica de tinción directa de Gram, considerando como referencia el resultado microbiológico del cultivo del BAL o miniBal. Se comparó además la concordancia entre el tipo de germen observado en la tinción directa de Gram, bacilo Gram negativo (BGN) o coco Gram positivo (CGP) y el tipo de bacteria aislada en el cultivo. Se analizaron tambien las variables predictivas específicas o cualitativas, esto es la eficacia del Gram en predecir VAP po CGP o por BGN. Resultados. Se diagnosticó NAV en 52 casos. La S de la tinción de Gram fue de 60%, E: 100%, VPP Positivo: 100%, VPN: 67%. En cuanto a la eficacia para predecir NAV por BGN se observó: S: 52%, E: 100%, VPP: 100%, VPN: 72%. Para CGP: S: 91%, E: 100%, VPP 100% y VPN: 99%. Conclusión. Si bien un examen bacteriológico directo con tinción de Gram predice presencia de NAV, su VPN es bajo por lo que un directo negativo no implica ausencia de NAV. Sin embargo si ese examen....

Eficacia de la tinción de gram de muestras respiratorias para la predicción de la neumonía asociada al respirador, y su utilidad en la selección de la terapéutica antibiótica empírica / Effectiveness of the tinción of gram of respiratory samples for the prediction of the pneumonia associated to the respirator, and its utility in the selection of the therapeutic empirical antibiotic

Introducción. La neumonía asociada a la ventilación (NAV) es una complicación frecuente de la (VM) y se asocia a alta mortalidad. Su adecuado manejo se basa en detección precoz y terapia con antibióticos (ATB) empirica eficaz, siendo esenciales los métodos que permitan predecir la NAV y ayuden a seleccionar los ATB. Objetivo. Valorar la eficacia del exámen directo por tinción de Gram de muestras obtenidas del tracto respiratorio en la detección de NAV y como ayuda a la selección ATB. Material y Métodos. Se incluyeron prospectivamente 95 episodios de sospecha de NAV en 69 pacientes, considerando sólo los casos sin modificación ATB por más de 48hs o sin ATB. Las muestras fueron obtenidas por medio de lavado bronquioloalveolar a través de Fibrobroncoscopia (BAL) o miniBal por catéter envainado, a ciegas (miniBal). La confirmación se efectuó por el análisis bacteriológico cuantitativo (>10(4) y > 10(3) para el Bal y miniBal). Se calculó la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y negativo (VPN) de la técnica de tinción directa de Gram, considerando como referencia el resultado microbiológico del cultivo del BAL o miniBal. Se comparó además la concordancia entre el tipo de germen observado en la tinción directa de Gram, bacilo Gram negativo (BGN) o coco Gram positivo (CGP) y el tipo de bacteria aislada en el cultivo. Se analizaron tambien las variables predictivas específicas o cualitativas, esto es la eficacia del Gram en predecir VAP po CGP o por BGN. Resultados. Se diagnosticó NAV en 52 casos. La S de la tinción de Gram fue de 60%, E: 100%, VPP Positivo: 100%, VPN: 67%. En cuanto a la eficacia para predecir NAV por BGN se observó: S: 52%, E: 100%, VPP: 100%, VPN: 72%. Para CGP: S: 91%, E: 100%, VPP 100% y VPN: 99%. Conclusión. Si bien un examen bacteriológico directo con tinción de Gram predice presencia de NAV, su VPN es bajo por lo que un directo negativo no implica ausencia de NAV. Sin embargo si ese examen...(AU).

Eficacia de la tinción de Gram de muestras respiratorias para la predicción de la neumonía asociada al respirador y su utilidad en la selección de la terapéutica antibiótica empírica / Efficacy of the Gram stain in respiratory samples for the prediction of ventilation associated pneumonia and its utility in the selection of the initial empiric antibiotic therapy

Introducción: La neumonía asociada a la ventilación (NAV) es una complicación frecuente de la ventilación mecánica (VM) y se asocia a alta mortalidad. Su adecuado manejo se basa en detección precoz y terapia con antibióticos (ATB) empírica eficaz, siendo esenciales los métodos que permitan predecir la NAV y ayuden a seleccionar los ATB. Objetivo: valorar la eficacia del examen directo por tinción de Gram de muestras obtenidas del tracto respiratorio en la detección de NAV y como ayuda a la selección de ATB. Materiales y Métodos: Se incluyeron prospectivamente 95 episodios de sospecha de NAV en 69 pacientes, considerando sólo los casos sin modificación de los ATB por más de 48 hs o sin ATB. Las muestras fueron obtenidas por medio de Lavado bronquioloalveolar a través de Fibro- broncoscopia (BAL) o minibal por catéter envainado a ciegas (miniBal). La confirmación se efectuó por el análisis bacteriológico cuantitativo (> 10 elevado a la cuarta y > 10³ para el BAL y minibal respectivamente). Se calculó la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y negativo (VPN) de la técnica de tinción directa de Gram, considerando como referencia el resultado microbiológico del cultivo del BAL o mini-BAL. Se comparó además la concordancia entre el tipo de germen observado en la tinción directa de Gram, bacilo Gram negativo (BGN) o coco Gram positivo (CGP) y el tipo de bacteria aislada en el cultivo. Se analizaron también las variables predictivas específicas o cualitativas, esto es la eficacia del Gram en predecir VAP por CGP o por BGN. Resultados: Se diagnosticó NAV en 52 casos. La S de la tinción de Gram fue de 60%, E: 100%, VPP Positivo: 100%, VPN: 67%. En cuanto a la eficacia para predecir VAP por BGN se observó: S: 52%, E: 100%, VPP: 100%, VPN: 72%. Para CGP: s: 91 %, E: 100%, VPP 100% y VPN: 99%. Conclusión: Si bien un examen bacteriológico directo por tinción de Gram predice presencia de VAP, su VPN es bajo por lo que un directo negativo...

Introduction: Ventilator Associated Pneumonia (VAP) is a frequent complication in mechanically ventilated patients, and is associated with a high mortality. Early diagnosis and appropriate use of empiric antibiotic therapy (ATB) is essential to its treatment. Tests that help to make an early diagnosis and select the initial ATB are useful. Objective: to evaluate the accuracy of the Gram stain examination of respiratory tract samples in the prediction of VAP and its potential role in the selection of empiric ATB. Materials and methods: prospective evaluation of 95 episodes in 69 patients with clinical suspicion of VAP who had not had any changes in the ATB for more than 48 hours or had not been treated with ATB. Samples were taken by bronchoalveolar lavage (BAL) through flexible bronchoscopy or blind mini bronchoalveolar lavage with protected catheter. VAP was confirmed when the quantitative cultures showed =10 to the fourth ufc/ml for BAL and =10³ ufc/ml for mini BAL. A comparison was made between the type of bacteria observed by the direct Gram staining (Gram negative bacteria or Gram positive bacteria) and the type of bacteria isolated by culture. Specific or qualitative predictive variables were analyzed to determine the value of Gram staining to predict a Gram-negative VAP or Gram-positive VAP. Results: VAP was confirmed in 52 cases. The sensitivity of the Gram stain for VAP was 60%, specificity 100%; positive predictive value: 100% and negative predictive value: 67%. The sensitivity of Gram negative bacteria for VAP was: 52%; specificity: 100%; positive predictive value: 100%; negative predictive value: 72%. The sensitivity of Gram positive bacteria for VAP was: 91 %; specificity: 100%; positive predictive value: 100%; negative predictive value: 99%. Conclusions: A positive finding in the Gram staining examination of respiratory tract samples was highly predictive of VAP but a negative result did not mean absence of VAP, because the negative...