Post-pandemic acute respiratory distress syndrome: A New Global Definition with extension to lower-resource regions.

Acute respiratory distress syndrome (ARDS), first described in 1967, is characterized by acute respiratory failure causing profound hypoxemia, decreased pulmonary compliance, and bilateral CXR infiltrates. After several descriptions, the Berlin definition was adopted in 2012, which established three categories of severity according to hypoxemia (mild, moderate and severe), specified temporal aspects for diagnosis, and incorporated the use of non-invasive ventilation. The COVID-19 pandemic led to changes in ARDS management, focusing on continuous monitoring of oxygenation and on utilization of high-flow oxygen therapy and lung ultrasound. In 2021, a New Global Definition based on the Berlin definition of ARDS was proposed, which included a category for non-intubated patients, considered the use of SpO2, and established no particular requirement for oxygenation support in regions with limited resources. Although debates persist, the continuous evolution seeks to adapt to clinical and epidemiological needs, and to the search of personalized treatments.

Mortality Due to Acute Respiratory Distress Syndrome in Latin America.

OBJECTIVES: Mortality due to acute respiratory distress syndrome (ARDS) is a major global health problem. Knowledge of epidemiological data on ARDS is crucial to design management, treatment strategies, and optimize resources. There is ample data regarding mortality of ARDS from high-income countries; in this review, we evaluated mortality due to ARDS in Latin America. DATA SOURCES: We searched in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Science Literature databases from 1967 to March 2023. STUDY SELECTION: We searched prospective or retrospective observational studies and randomized controlled trials conducted in Latin American countries reporting ARDS mortality. DATA EXTRACTION: Three pairs of independent reviewers checked all studies for eligibility based on their titles and abstracts. We performed meta-analysis of proportions using a random-effects model. We performed sensitivity analyses including studies with low risk of bias and with diagnosis using the Berlin definition. Subgroup analysis comparing different study designs, time of publication (up to 2000 and from 2001 to present), and studies in which the diagnosis of ARDS was made using Pao2/Fio2 less than or equal to 200 and regional variations. Subsequently, we performed meta-regression analyses. Finally, we graded the certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation). DATA SYNTHESIS: Of 3315 articles identified, 32 were included (3627 patients). Mortality was 52% in the pooled group (low certainty of evidence). In the sensitivity analysis (according to the Berlin definition), mortality was 46% (moderate certainty of evidence). In the subgroup analysis mortality was 53% (randomized controlled trials), 51% (observational studies), 66% (studies published up to 2000), 50% (studies after 2000), 44% (studies with Pao2/Fio2 ≤ 200), 56% (studies from Argentina/Brazil), and 40% (others countries). No variables were associated with mortality in the meta-regression. CONCLUSIONS: ARDS mortality in Latin America remains high, as in other regions. These results should constitute the basis for action planning to improve the prognosis of patients with ARDS (PROSPERO [CRD42022354035]).

Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines.

Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.

Characteristics and risk factors associated with mortality during the first cycle of prone secondary to ARDS due to SARS-CoV-2 pneumonia / Características y factores de riesgo asociados a mortalidad durante el primer ciclo de prono por SDRA secundario a neumonía por SARS-CoV-2

Objective To analyze characteristics, changes in oxygenation, and pulmonary mechanics, in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position and evaluate the response to this maneuver.Design Cohort study including patients with PaO2/FiO2 <150mmHg requiring prone position over 18 months. We classified patients according to PaO2/FiO2 changes from basal to 24h after the first prone cycle as: 1) no increase 2) increase <25%, 3) 25%–50% increase 4) increase >50%. Setting 33-bed medical-surgical Intensive Care Unit (ICU) in Argentina. Patients 273 patients. Interventions None. Main variables of interest Epidemiological characteristics, respiratory mechanics and oxygenation were compared between survivors and non-survivors. Independent factors associated with in-hospital mortality were identified. Results Baseline PaO2/FiO2 was 116 [97–135]mmHg (115 [94–136] in survivors vs. 117 [98–134] in non-survivors; p=0.50). After prone positioning, 22 patients (8%) had similar PaO2/FiO2 values; 46(16%) increased PaO2/FiO2 ≤25%; 55 (21%) increased it 25%–50%; and 150 (55%), >50%. Mortality was 86%, 87%, 72% and 50% respectively (p<0.001). Baseline PaO2/FiO2, <100mmHg did not imply that patients were refractory to prone position. Factors independently associated with mortality were age, percentage increase in PaO2/FiO2 after 24h being in prone, and number of prone cycles. Conclusions Older patients unable to improve PaO2/FiO2 after 24h in prone position and who require >1 cycle might early receive additional treatments for refractory hypoxemia. After the first 24h in the prone position, a low percentage of PaO2/FiO2 increase over baseline, beyond the initial value, was independently associated with higher mortality. (AU)

Objetivo Analizar las características, cambios en la oxigenación y mecánica pulmonar, en pacientes ventilados mecánicamente con SDRA por SARS-CoV-2 tratados con posición prona, y evaluar la respuesta a esta maniobra. Diseño Estudio de cohorte que incluyó pacientes con PaO2/FiO2 <150mmHg que requirieron posición prona durante 18 meses. Se clasificaron los pacientes según los cambios de PaO2/FiO2 desde el basal y 24horas después del primer ciclo prono como: 1) Sin aumento 2) Aumento <25%, 3) 25–50% de aumento 4) Aumento >50%. Ambito Unidad de Cuidados Intensivos (UCI) médico-quirúrgica de 33 camas en Argentina. Pacientes 273 pacientes. Intervenciones Ninguna. Principales variables de interés Se compararon características epidemiológicas, mecánica respiratoria y oxigenación entre sobrevivientes y no sobrevivientes. Se identificaron factores independientes asociados a la mortalidad hospitalaria. Resultados La PaO2/FiO2 basal fue de 116 [97–135]mmHg (115 [94–136] en sobrevivientes vs. 117 [98–134] en no sobrevivientes; p=0,50). Después de la posición prona, 22 pacientes (8%) tenían valores similares de PaO2/FiO2; 46 (16%) aumentaron PaO2/FiO2 ≤25%; 55 (21%) lo aumentaron 25%–50%; y 150 (55%), >50%. La mortalidad fue de 86%, 87%, 72% y 50% respectivamente (p<0,001). La PaO2/FiO2 basal, <100mmHg no implicó que los pacientes fueran refractarios a la posición prona. Los factores asociados independientemente con la mortalidad fueron la edad, el aumento porcentual de PaO2/FiO2 después de 24horas en prona, y el número de ciclos prono. Conclusiones Los pacientes mayores que no pueden mejorar PaO2/FiO2 después de 24 horas en posición prona y que requieren más de 1 ciclo podrían recibir tratamientos adicionales para la hipoxemia refractaria. Después de las primeras 24horas en decúbito prono, un bajo porcentaje de aumento de PaO2/FiO2 sobre el valor basal, más allá del valor inicial, se asoció de forma independiente con una mayor mortalidad. (AU)

Characteristics and risk factors associated with mortality during the first cycle of prone secondary to ARDS due to SARS-CoV-2 pneumonia.

OBJECTIVE: To analyze characteristics, changes in oxygenation, and pulmonary mechanics, in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position and evaluate the response to this maneuver. DESIGN: Cohort study including patients with PaO2/FiO2 <150mmHg requiring prone position over 18 months. We classified patients according to PaO2/FiO2 changes from basal to 24h after the first prone cycle as: 1) no increase 2) increase <25%, 3) 25%-50% increase 4) increase >50%. SETTING: 33-bed medical-surgical Intensive Care Unit (ICU) in Argentina. PATIENTS: 273 patients. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiological characteristics, respiratory mechanics and oxygenation were compared between survivors and non-survivors. Independent factors associated with in-hospital mortality were identified. RESULTS: Baseline PaO2/FiO2 was 116 [97-135]mmHg (115 [94-136] in survivors vs. 117 [98-134] in non-survivors; p=0.50). After prone positioning, 22 patients (8%) had similar PaO2/FiO2 values; 46(16%) increased PaO2/FiO2 ≤25%; 55 (21%) increased it 25%-50%; and 150 (55%), >50%. Mortality was 86%, 87%, 72% and 50% respectively (p<0.001). Baseline PaO2/FiO2, <100mmHg did not imply that patients were refractory to prone position. Factors independently associated with mortality were age, percentage increase in PaO2/FiO2 after 24h being in prone, and number of prone cycles. CONCLUSIONS: Older patients unable to improve PaO2/FiO2 after 24h in prone position and who require >1 cycle might early receive additional treatments for refractory hypoxemia. After the first 24h in the prone position, a low percentage of PaO2/FiO2 increase over baseline, beyond the initial value, was independently associated with higher mortality.

Protection of homologous and heterologous boosters after primary schemes of rAd26-rAd5, ChAdOx1 nCoV-19 and BBIBP-CorV during the omicron outbreak in adults of 50 years and older in Argentina: a test-negative case-control study.

Background: After primary vaccination schemes with rAd26-rAd5 (Sputnik V), ChAdOx1 nCoV-19, BBIBP-CorV or heterologous combinations, the effectiveness of homologous or heterologous boosters (Sputnik V, ChAdOx, Pfizer-BioNTech, Moderna) against SARS-CoV-2 infections, hospitalisations and deaths has been scarcely studied. Methods: Test-negative, case-control study, conducted in Argentina during omicron BA.1 predominance, in adults ≥50 years old tested for SARS-CoV-2 who had received two or three doses of COVID-19 vaccines. Outcomes were COVID-associated infections, hospitalisations and deaths after administering mRNA and vectored boosters, < or ≥60 days from the last dose. Findings: Of 422,124 individuals tested for SARS-CoV-2, 221,993 (52.5%) tested positive; 190,884 (45.2%) and 231,260 (54.8%) had received 2-dose and 3-dose vaccination schemes, respectively. The 3-dose scheme reduced infections, hospitalisations and death (OR 0.81 [0.80-0.83]; 0.28 [0.25-0.32] and 0.25 [0.22-0.28] respectively), but protection dropped after 60 days to 1.04 [1.01-1.06]; 0.52 [0.44-0.61] and 0.38 [0.33-0.45]). Compared with 2-dose-schemes, homologous boosters after primary schemes with vectored-vaccines provided lower protection against infections < and ≥60 days (0.94 [0.92-0.97] and 1.05 [1.01-1.09], respectively) but protected against hospitalisations (0.30 [0.26-0.35]) and deaths (0.29 [0.25-0.33]), decreasing after 60 days (0.59 [0.47-0.74] and 0.51 [0.41-0.64], respectively). Heterologous boosters protected against infections (0.70 [0.68-0.71]) but decreased after 60 days (1.01 [0.98-1.04]) and against hospitalisations and deaths (0.26 [0.22-0.31] and 0.22 [0.18-0.25], respectively), which also decreased after 60 days (0.43 [0.35-0.53] and 0.33 [0.26-0.41], respectively). Heterologous boosters protected against infections when applied <60 days (0.70 [0.68-0.71], p < 0.001), against hospitalisations when applied ≥60 days (0.43 [0.35-0.53], p < 0.01), and against deaths < and ≥60 days (0.22 [0.18-0.25], p < 0.01 and 0.33 [0.26-0.41], p < 0.001). Interpretation: During omicron predominance, heterologous boosters such as viral vectored and mRNA vaccines, following Sputnik V, ChAdOx1, Sinopharm or heterologous primary schemes might provide better protection against death; this effect might last longer in individuals aged ≥50 than homologous boosters. Funding: None.

Efectividad de refuerzos homólogos y heterólogos luego de esquemas primarios con Sputnik V, Astra-Zeneca y Sinopharm durante el período omicron en adultos mayores de 50 años en la provincia de Buenos Aires / Effectiveness of homologous and heterologous boosters after primary regimens with Sputnik V, AstraZeneca, and Sinopharm during the omicron variant period in adults over 50 years old in the province of Buenos Aires

Objetivo: Evaluar la efectividad de esquemas primarios de Sputnik V, Astra-Zeneca, Sinopharm o combinaciones heterólogas seguidos de refuerzos a vector viral (Sputnik V, Astra-Zeneca) o ARNm (Pfizer-BioNTech, Moderna) frente a infecciones, hospitalizaciones y muertes por SARS-CoV-2. Material y métodos: Estudio de casos y controles con test negativo realizado en la provincia de Buenos Aires, durante el predominio de ómicron BA.1, que incluyó individuos ≥ 50 años con test positivo para SARS-CoV-2 que habían recibido 2 o 3 dosis de vacunas. Se registraron infecciones, hospitalizaciones y muertes después de administrar refuerzos con Sputnik V, Astra-Zeneca o ARNm. Resultados: De 422 124 personas analizadas para SARS-Cov-2, 221 993 (52.5%) presentaron test positivos; 190 884 (45.2%) y 231.260 (54.8%) recibieron esquemas de vacunación de 2 y 3 dosis, respectivamente. Los esquemas primarios con Astra-Zeneca, Sputnik V o vector viral, combinados con un refuerzo a vector viral, mostraron protección contra infecciones (OR: 0.94 [0.92 a 0.97]), hospitalizaciones (OR: 0.30 [0.26 a 0.35]) y muertes (OR: 0.29 [0.25 a 0.33]. Los esquemas primarios con Astra-Zeneca y Sputnik V más refuerzo de ARNm, o con Sinopharm más refuerzo de ARNm o vector viral otorgaron protección adicional contra infecciones (OR: 0.70 [0.68 a 0.71]). Hubo un efecto protector frente a hospitalizaciones y muertes (OR: 0.26 [0.22 a 0.31] y 0.22 [0.18 a 0.25]) en todos los casos. Conclusiones: Durante el predominio de ómicron, los refuerzos heterólogos con vacunas a vector viral y de ARNm, posteriores a los esquemas primarios de Sputnik V, Astra-Zeneca, Sinopharm o heterólogos, podrían proporcionar mejor protección y mayor duración del efecto contra la muerte en personas mayores de 50 años, en comparación con refuerzos homólogos

Objective: To evaluate the effectiveness of primary vaccination regimens involving Sputnik V, Astra-Zeneca, Sinopharm, or heterologous combinations followed by viral vector boosters (Sputnik V, As-traZeneca) or mRNA boosters (Pfizer-BioNTech, Moderna) against infections, hospitalizations and deaths caused by SARS-CoV-2. Material and methods: Case-control studies with negative tests conducted in the Buenos Aires province during the Omicron BA.1 predominance. The study included patients ≥ 50 years of age, who tested positive for SARS-CoV-2 and had received two or three doses of vaccines. Infections, hospitalizations, and deaths were registered following the administration of Sputnik V, AstraZeneca, or mRNA boosters. Findings: Out of 422 124 people tested for SARS-Cov-2, 221 993 (52.5%) had positive test results; 190,884 (45.2%) and 231 260 (54.8%) received two-dose and three-dose vaccination schemes, respectively. Primary regimens with AstraZeneca, Sputnik V, or viral vector, combined with a viral vector booster demonstrated protection against infections (OR 0.94 [0.92 to 0.97]), hospitalizations (OR 0.30 [0.26 to 0.35]) and deaths (OR 0.29 [0.25 to 0.33]. Primary regimens with AstraZeneca and Sputnik V combined with mRNA boosters, as well as pri-mary schemes with Sinopharm combined with mRNA or viral vectored boosters showed additional protection against infections (OR 0.70 [0.68 to 0.71]). There was a protective effect against hospi-talizations and deaths (OR 0.26 [0.22-0.31] and 0.22 [0.18 -0.25]) in all cases. Conclusions: During Omicron predominance, heterologous boosters with viral-vector and mRNA vaccines, administered after Sputnik V, AstraZeneca, Sinopharm, or heterologous primary regimens, could provide enhanced protection and prolonged effectiveness against mortality in individuals aged ≥ 50, compared to ho-mologous boosters

Epidemiology, patterns of care and prognosis of acute kidney injury in critically ill patients: A multicenter study in Argentina (The EPIRA study).

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality rates in the intensive care unit (ICU). In low- and middle-income countries (LMICs), epidemiological information about this condition is still scarce. Our main objective was to characterize its epidemiology, prognosis, and its treatment. METHODS: This multicenter prospective cohort study included 1466 patients from 35 ICUs during 6 months in Argentina in 2018. Risk factors and outcomes in patients with and without AKI, and between AKI on admission (AKIadm) and that developed during hospitalization (AKIhosp) were analyzed. RESULTS: AKI occurred in 61.3% of patients (900/1466); 72.6% were AKIadm and 27.3% AKIhosp. Risk factors were age, BMI, arterial hypertension, cardiovascular diseases, diabetes, SOFA, APACHE II, dehydration, sepsis, vasopressor use, radiocontrast, diuresis/h and mechanical ventilation. Independent predictors for AKI were sepsis, diabetes, dehydration, vasopressors on admission, APACHE II and radiocontrast use. Renal replacement therapies (RRT) requirement in AKI patients was 14.8%. Hospital mortality in AKI vs. non-AKI was 38.7% and 23.3% (p < 0.001); and in AKIadm vs. AKIhosp, 41.2% and 37.8% (p = 0.53). CONCLUSIONS: ICU-acquired AKI has high incidence, complications and mortality. Risk factors for AKI and RRT utilization were similar to those described in other epidemiological studies. AKIadm was more frequent than AKIhosp, but had equal prognosis.

Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires / Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study

Resumen Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes >18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró adminis tración temprana o tardía a la infusión de TCZ ≤ ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no inva siva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

Abstract Introduction: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. Methods: Multicenter, retrospective cohort study in cluding patients>18 years hospitalized between 7/1/2021- 8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. Results: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Com pared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). Discussion: This study supports the early use of TCZ in patients with severe or critical COVID-19.

[Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study]. / Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires.

INTRODUCTION: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. METHODS: Multicenter, retrospective cohort study including patients >18 years hospitalized between 7/1/2021-8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were 28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. RESULTS: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Compared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). DISCUSSION: This study supports the early use of TCZ in patients with severe or critical COVID-19.

Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes > 18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró administración temprana o tardía a la infusión de TCZ = ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no invasiva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

Effectiveness of BBIBP-CorV, BNT162b2 and mRNA-1273 vaccines against hospitalisations among children and adolescents during the Omicron outbreak in Argentina: A retrospective cohort study.

Background: Although paediatric clinical presentations of COVID-19 are usually less severe than in adults, serious illness and death have occurred. Many countries started the vaccination rollout of children in 2021; still, information about effectiveness in the real-world setting is scarce. The aim of our study was to evaluate vaccine effectiveness (VE) against COVID-19-associated-hospitalisations in the 3-17-year population during the Omicron outbreak. Methods: We conducted a retrospective cohort study including individuals aged 3-17 registered in the online vaccination system of the Buenos Aires Province, Argentina. mRNA-1273 and BNT162b2 were administered to 12-17-year subjects; and BBIBP-CorV to 3-11-year subjects. Vaccinated group had received a two-dose scheme by 12/1/2021. Unvaccinated group did not receive any COVID-19 vaccine between 12/14/2021 and 3/9/2022, which was the entire monitoring period. Vaccine effectiveness (VE) against COVID-19-associated hospitalisations was calculated as (1-OR)x100. Findings: By 12/1/2021, 1,536,435 individuals aged 3-17 who had received zero or two doses of SARS-CoV-2 vaccines were included in this study. Of the latter, 1,440,389 were vaccinated and 96,046 not vaccinated. VE were 78.0%[68.7-84.2], 76.4%[62.9-84.5] and 80.0%[64.3-88.0] for the entire cohort, 3-11-year (BBIBP-CorV) subgroup and 12-17 (mRNA vaccines) subgroup, respectively. VE for the entire population was 82.7% during the period of Delta and Omicron overlapping circulation and decreased to 67.7% when Omicron was the only variant present. Interpretation: This report provides evidence of high vaccine protection against associated hospitalisations in the paediatric population during the Omicron outbreak but suggests a decrease of protection when Omicron became predominant. Application of a booster dose in children aged 3-11-year warrants further consideration. Funding: None.

Hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial study protocol. / Ressuscitação direcionada ao tempo de enchimento capilar baseada em fenótipo hemodinâmico no choque séptico precoce: protocolo de estudo do ensaio clínico randomizado ANDROMEDA-SHOCK-2.

BACKGROUND: Early reversion of sepsis-induced tissue hypoperfusion is essential for survival in septic shock. However, consensus regarding the best initial resuscitation strategy is lacking given that interventions designed for the entire population with septic shock might produce unnecessary fluid administration. This article reports the rationale, study design and analysis plan of the ANDROMEDA-2 study, which aims to determine whether a peripheral perfusion-guided strategy consisting of capillary refill time-targeted resuscitation based on clinical and hemodynamic phenotypes is associated with a decrease in a composite outcome of mortality, time to organ support cessation, and hospital length of stay compared to standard care in patients with early (< 4 hours of diagnosis) septic shock. METHODS: The ANDROMEDA-2 study is a multicenter, multinational randomized controlled trial. In the intervention group, capillary refill time will be measured hourly for 6 hours. If abnormal, patients will enter an algorithm starting with pulse pressure assessment. Patients with pulse pressure less than 40mmHg will be tested for fluid responsiveness and receive fluids accordingly. In patients with pulse pressure > 40mmHg, norepinephrine will be titrated to maintain diastolic arterial pressure > 50mmHg. Patients who fail to normalize capillary refill time after the previous steps will be subjected to critical care echocardiography for cardiac dysfunction evaluation and subsequent management. Finally, vasopressor and inodilator tests will be performed to further optimize perfusion. A sample size of 1,500 patients will provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy. CONCLUSIONS: If hemodynamic phenotype-based, capillary refill time-targeted resuscitation demonstrates to be a superior strategy, care processes in septic shock resuscitation can be optimized with bedside tools.

INTRODUçÃO: A reversão precoce da hipoperfusão tecidual induzida é essencial para a sobrevida no choque séptico. No entanto, falta consenso sobre a melhor estratégia de ressuscitação inicial, uma vez que intervenções destinadas a toda a população com choque séptico podem produzir administração desnecessária de líquidos. Este artigo relata a justificativa, o delineamento e o plano de análise do estudo ANDROMEDA-2, que visa determinar se uma estratégia guiada por perfusão periférica, que consiste na ressuscitação guiada pelo tempo de enchimento capilar com base em fenótipos clínicos e hemodinâmicos, está associada a uma diminuição no desfecho composto de mortalidade, tempo até a interrupção ao suporte de órgãos e tempo de internação em comparação com o atendimento padrão em pacientes com choque séptico precoce (< 4 horas do diagnóstico). METÓDOS: O estudo ANDROMEDA-2 é um ensaio clínico randomizado controlado multinacional e multicêntrico. No grupo de intervenção, o tempo de enchimento capilar será medido a cada hora, durante 6 horas. Se estiver anormal, os pacientes serão alocados em um algoritmo, começando com a avaliação da pressão de pulso. Pacientes com pressão de pulso inferior a 40mmHg serão testados quanto à capacidade de resposta a líquidos e receberão líquidos de acordo. Em pacientes com pressão de pulso > 40mmHg, norepinefrina será titulada para manter a pressão arterial diastólica > 50mmHg. Os pacientes que não normalizarem o tempo de enchimento capilar após as etapas anteriores serão submetidos à ecocardiografia de cuidados intensivos para avaliação da disfunção cardíaca e posterior manejo. Por fim, serão realizados testes com vasopressores e inodilatadores para otimizar ainda mais a perfusão. Um tamanho de amostra de 1.500 pacientes fornecerá 88% de poder para demonstrar a superioridade da estratégia direcionada ao tempo de enchimento capilar. CONCLUSÃO: Se for demonstrado que o direcionamento ao tempo de enchimento capilar é uma estratégia melhor, os processos de atendimento na ressuscitação do choque séptico podem ser otimizados com ferramentas usadas à beira do leito.

Incidence and determinats of augmented renal clearance in traumatic brain injury: A prospective observational study.

PURPOSE: To characterize the incidence, timing, and predictors of augmented renal clearance (ARC) in patients with traumatic brain injury (TBI). MATERIALS AND METHODS: In 61 patients with TBI, creatinine clearance (CrCl) was prospectively measured from urine samples, over seven days. ARC was defined as a CrCl >130 mL/min/1.73 m2 in at least one day. We compared patients with and without ARC. RESULTS: We performed 295 determinations of CrCl. ARC was present in 82% of the patients and arose in the first 2 days in 86% of them. ARC was more frequent in patients with associated injuries (100 vs. 75%, P = 0.02). There was a trend to a more aggressive resuscitation in patients with ARC but young age was the only independent predictor. Hospital length of stay was higher in ARC (15 [8-25] vs. 6 [3-19] days, P < 0.05). CONCLUSIONS: ARC is very common and has an early appearance in patients with TBI. Young age is its main determinant.

Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-Covid-19 study: A prospective, multicenter, multinational, cohort study.

PURPOSE: The COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19. MATERIAL AND METHODS: This was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19. RESULTS: A total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], p<0.001). The risk factors independently associated with progression to ICU admission were age, shortness of breath, and obesity. In-hospital mortality was 24.1%, whereas the ICU mortality rate was 35.1%. Most patients had equal self-care ability at discharge 43.8%; however, ICU patients had worse self-care ability at hospital discharge (25.7% [497/1934] vs. 3.7% [40/1074], p<0.001). CONCLUSIONS: This study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

Clinical characteristics, respiratory management, and determinants of oxygenation in COVID-19 ARDS: A prospective cohort study.

PURPOSE: To identify determinants of oxygenation over time in patients with COVID-19 acute respiratory distress syndrome (ARDS); and to analyze their characteristics according to Berlin definition categories. MATERIALS AND METHODS: Prospective cohort study including consecutive mechanically ventilated patients admitted between 3/20/2020-10/31/2020 with ARDS. Epidemiological and clinical data on admission; outcomes; ventilation, respiratory mechanics and oxygenation variables were registered on days 1, 3 and 7 for the entire population and for ARDS categories. RESULTS: 1525 patients aged 61 ± 13, 69% male, met ARDS criteria; most frequent comorbidities were obesity, hypertension, diabetes and respiratory disease. On admission, 331(21%), 849(56%) and 345(23%) patients had mild, moderate and severe ARDS; all received lung-protective ventilation (mean tidal volumes between 6.3 and 6.7 mL/kg PBW) and intermediate PEEP levels (10-11 cmH2O). PaO2/FiO2, plateau pressure, static compliance, driving pressure, ventilation ratio, pH and D-dimer >2 mg/L remained significantly different among the ARDS categories over time. In-hospital mortality was, respectively, 55%, 58% and 70% (p < 0.000). Independent predictors of changes of PaO2/FiO2 over time were BMI; preexistent respiratory disease; D-dimer >2 mg/L; day 1-PEEP, and day 1-ventilatory ratio. CONCLUSION: Hypoxemia in patients with COVID-19-related ARDS is associated with comorbidities, deadspace and activated coagulation markers, and disease severity-reflected by the PEEP level required.

Ressuscitação direcionada ao tempo de enchimento capilar baseada em fenótipo hemodinâmico no choque séptico precoce: protocolo de estudo do ensaio clínico randomizado ANDROMEDA-SHOCK-2 / Hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial study protocol

RESUMO Introdução: A reversão precoce da hipoperfusão tecidual induzida é essencial para a sobrevida no choque séptico. No entanto, falta consenso sobre a melhor estratégia de ressuscitação inicial, uma vez que intervenções destinadas a toda a população com choque séptico podem produzir administração desnecessária de líquidos. Este artigo relata a justificativa, o delineamento e o plano de análise do estudo ANDROMEDA-2, que visa determinar se uma estratégia guiada por perfusão periférica, que consiste na ressuscitação guiada pelo tempo de enchimento capilar com base em fenótipos clínicos e hemodinâmicos, está associada a uma diminuição no desfecho composto de mortalidade, tempo até a interrupção ao suporte de órgãos e tempo de internação em comparação com o atendimento padrão em pacientes com choque séptico precoce (< 4 horas do diagnóstico). Metódos: O estudo ANDROMEDA-2 é um ensaio clínico randomizado controlado multinacional e multicêntrico. No grupo de intervenção, o tempo de enchimento capilar será medido a cada hora, durante 6 horas. Se estiver anormal, os pacientes serão alocados em um algoritmo, começando com a avaliação da pressão de pulso. Pacientes com pressão de pulso inferior a 40mmHg serão testados quanto à capacidade de resposta a líquidos e receberão líquidos de acordo. Em pacientes com pressão de pulso > 40mmHg, norepinefrina será titulada para manter a pressão arterial diastólica > 50mmHg. Os pacientes que não normalizarem o tempo de enchimento capilar após as etapas anteriores serão submetidos à ecocardiografia de cuidados intensivos para avaliação da disfunção cardíaca e posterior manejo. Por fim, serão realizados testes com vasopressores e inodilatadores para otimizar ainda mais a perfusão. Um tamanho de amostra de 1.500 pacientes fornecerá 88% de poder para demonstrar a superioridade da estratégia direcionada ao tempo de enchimento capilar. Conclusão: Se for demonstrado que o direcionamento ao tempo de enchimento capilar é uma estratégia melhor, os processos de atendimento na ressuscitação do choque séptico podem ser otimizados com ferramentas usadas à beira do leito.

ABSTRACT Background: Early reversion of sepsis-induced tissue hypoperfusion is essential for survival in septic shock. However, consensus regarding the best initial resuscitation strategy is lacking given that interventions designed for the entire population with septic shock might produce unnecessary fluid administration. This article reports the rationale, study design and analysis plan of the ANDROMEDA-2 study, which aims to determine whether a peripheral perfusion-guided strategy consisting of capillary refill time-targeted resuscitation based on clinical and hemodynamic phenotypes is associated with a decrease in a composite outcome of mortality, time to organ support cessation, and hospital length of stay compared to standard care in patients with early (< 4 hours of diagnosis) septic shock. Methods: The ANDROMEDA-2 study is a multicenter, multinational randomized controlled trial. In the intervention group, capillary refill time will be measured hourly for 6 hours. If abnormal, patients will enter an algorithm starting with pulse pressure assessment. Patients with pulse pressure less than 40mmHg will be tested for fluid responsiveness and receive fluids accordingly. In patients with pulse pressure > 40mmHg, norepinephrine will be titrated to maintain diastolic arterial pressure > 50mmHg. Patients who fail to normalize capillary refill time after the previous steps will be subjected to critical care echocardiography for cardiac dysfunction evaluation and subsequent management. Finally, vasopressor and inodilator tests will be performed to further optimize perfusion. A sample size of 1,500 patients will provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy. Conclusions: If hemodynamic phenotype-based, capillary refill time-targeted resuscitation demonstrates to be a superior strategy, care processes in septic shock resuscitation can be optimized with bedside tools.

Timing of convalescent plasma administration and 28-day mortality in COVID-19 pneumonia.

This is a multicenter cohort study including consecutive, hospitalized patients ≥18 years, with moderate to severe COVID-19, carried out to evaluate the relationship between the timing of convalescent plasma administration and 28-day mortality. Data were prospectively collected between May 14, 2020 and October 31, 2020. Patients were grouped according to the timing of administration of convalescent plasma as <3 days, between 3 and 7 days, and >7 days. The main outcome variable was 28-day mortality. Independent predictors of mortality were identified by logistic regression. Of 4719 patients receiving convalescent plasma, 3036 (64.3%) were in the general ward, 1171 (24.8%) in the intensive care unit (ICU), and 512 (10.8%) in the ICU on mechanical ventilation. Convalescent plasma was administered to 3113 (66%) patients within the first 3 days of hospital admission, to 1380 (29.2%) between 3 and 7 days, and to 226 after 7 days; 28-day mortality was, respectively, 18.1%, 30.4% and 38.9% (p<0.001). In the regression model, convalescent plasma administration within the first 3 days of admission was associated with reduced 28-day mortality, compared with the administration after 7 days (OR 0.40, 95% CI 0.30 to 0.53). Early convalescent plasma administration was associated to a significant decreased mortality in patients in the general ward (OR 0.45, 95% CI 0.29 to 0.69) and in the ICU (OR 0.35, 95% CI 0.19 to 0.64), but not in those requiring mechanical ventilation (OR 0.52, 95% CI 0.27 to 1.01). In conclusion, this study suggests that early administration of convalescent plasma to patients with COVID-19 pneumonia is critical to obtain therapeutic benefit.

Capacidad estructural, recursos humanos tecnológicos y requerimientos de ventilación mecánica en 58 unidades de cuidados intensivos en argentina durante la pandemia por SARS-CoV-2. Estudio SATICOVID-19 / Structural capacity, technological human resources and mechanical ventilation requirements in 58 intensive care units in Argentina during the SARS-CoV-2 pandemic. A SATICOVID-19 Study

Resumen Durante la pandemia por SARS-CoV-2 hubo un marcado requerimiento de camas de cuidados críticos, insumos y profesionales entrenados para asistir a pacientes con insuficiencia respiratoria grave. La Sociedad Argentina de Terapia Intensiva (SATI) diseñó un estudio para caracterizar estos aspectos en las Unidades de Cuidados Intensivos (UCIs). Estudio multicéntrico, de cohorte prospectiva; las UCIs participantes completaron un formulario al final del estudio (31/10/2020) sobre características hospitalarias, número de camas de áreas críticas pre- e intra-pandemia, incorporación de profesionales, insumos y recursos tecnológicos, y carga de trabajo. Participaron 58 UCIs; 28(48%) de Provincia de Buenos Aires, 22(38%) de Ciudad Autónoma de Bue nos Aires, 10(17%) de otras; 31(53%) UCIs pertenecían al sector público; 23(47%) al privado-seguridad social. En 35/58(60%) hospitales las camas de cuidados críticos aumentaron de 902 a 1575(75%); 37% en UCI y 63% principalmente en Unidad Coronaria y Emergencias-shock room. En 41/55(75%) UCIs se incorporó personal: 27(49%) médicos/as (70% intensivistas), 36(65%) enfermeros/as, 28(51%) kinesiólogos/as, 20(36%) personal de limpieza, y 1(2%) otros/as; 96% de las UCIS reportaron disponer de respiradores suficientes, y 95%, insumos y EPP suficientes. De todos los pacientes en ventilación mecánica invasiva, 55% [43-64] presentaron COVID-19. Se requirió oxigenoterapia como soporte no invasivo en 14% [8-24] de los ingresos por COVID-19. Se registró una importante expansión de las áreas críticas operativas, secundariamente al aumento de camas, personal, y adecuada disponibilidad de respiradores e insumos esenciales. La carga de la enfermedad crítica por COVID-19 fue intensa, constituyendo más de la mitad de los pacientes en ventilación mecánica.

Abstract During the SARS-CoV-2 pandemic, there was a marked requirement for critical care beds, supplies and trained professionals to assist patients with severe respiratory failure. The Argentine Society of Intensive Care (SATI) designed a study to characterize these aspects in intensive care units (ICUs). Multicenter, prospective cohort study; the participating ICUs completed a form at the end of the study (31/10/2020) on hospital characteristics, number of beds in pre- and intra-pandemic critical areas, incorporation of professionals, technological resources, and workload. Fifty-eight ICUs participated; 28(48%) were located in Buenos Aires Province, 22(38%) in Buenos Aires Autonomous City and 10 (17%) in other provinces; 31 (53%) of UCIs belonged to the public sector; 23 (47%) to the private-social security. In 35/58 (60%) of the hospitals critical care beds increased from 902 to 1575 (75%), 37% in ICU and 63% mainly in Coronary Care Unit and Emergency-shock room. In 41/55 (75%) UCIs, staff were incorporated: 27(49%) physicians (70% intensivists), 36 (65%) nurses, 28 (51%) respiratory therapists, 20(36%) cleaning staff, and 1(2%) others. A 96% of the ICUS reported having sufficient ventilators and 95% enough sup plies and PPE. Of all patients on invasive mechanical ventilation, 55% [43-64] had COVID-19. Oxygen therapy was required as noninvasive support in 14% [8-24] of COVID-19 admissions. There was a significant expansion of critical operational areas, secondary to the increase in beds, staff, and adequate availability of ventilators and essential supplies. The burden of critical illness from COVID-19 was intense, with more than half of patients on mechanical ventilation.

[Structural capacity, technological human resources and mechanical ventilation requirements in 58 intensive care units in Argentina during the SARS-CoV-2 pandemic. A SATICOVID-19 Study]. / Capacidad estructural, recursos humanos tecnológicos y requerimientos de ventilación mecánica en 58 unidades de cuidados intensivos en Argentina durante la pandemia por SARS-CoV-2. Estudio SATICOVID-19.

During the SARS-CoV-2 pandemic, there was a marked requirement for critical care beds, supplies and trained professionals to assist patients with severe respiratory failure. The Argentine Society of Intensive Care (SATI) designed a study to characterize these aspects in intensive care units (ICUs). Multicenter, prospective cohort study; the participating ICUs completed a form at the end of the study (31/10/2020) on hospital characteristics, number of beds in pre- and intra-pandemic critical areas, incorporation of professionals, technological resources, and workload. Fifty-eight ICUs participated; 28(48%) were located in Buenos Aires Province, 22(38%) in Buenos Aires Autonomous City and 10 (17%) in other provinces; 31 (53%) of UCIs belonged to the public sector; 23 (47%) to the private-social security. In 35/58 (60%) of the hospitals critical care beds increased from 902 to 1575 (75%), 37% in ICU and 63% mainly in Coronary Care Unit and Emergency-shock room. In 41/55 (75%) UCIs, staff were incorporated: 27(49%) physicians (70% intensivists), 36 (65%) nurses, 28 (51%) respiratory therapists, 20(36%) cleaning staff, and 1(2%) others. A 96% of the ICUS reported having sufficient ventilators and 95% enough supplies and PPE. Of all patients on invasive mechanical ventilation, 55% [43-64] had COVID-19. Oxygen therapy was required as noninvasive support in 14% [8-24] of COVID-19 admissions. There was a significant expansion of critical operational areas, secondary to the increase in beds, staff, and adequate availability of ventilators and essential supplies. The burden of critical illness from COVID-19 was intense, with more than half of patients on mechanical ventilation.

Durante la pandemia por SARS-CoV-2 hubo un marcado requerimiento de camas de cuidados críticos, insumos y profesionales entrenados para asistir a pacientes con insuficiencia respiratoria grave. La Sociedad Argentina de Terapia Intensiva (SATI) diseñó un estudio para caracterizar estos aspectos en las Unidades de Cuidados Intensivos (UCIs). Estudio multicéntrico, de cohorte prospectiva; las UCIs participantes completaron un formulario al final del estudio (31/10/2020) sobre características hospitalarias, número de camas de áreas críticas pre- e intra-pandemia, incorporación de profesionales, insumos y recursos tecnológicos, y carga de trabajo. Participaron 58 UCIs; 28(48%) de Provincia de Buenos Aires, 22(38%) de Ciudad Autónoma de Buenos Aires, 10(17%) de otras; 31(53%) UCIs pertenecían al sector público; 23(47%) al privado-seguridad social. En 35/58(60%) hospitales las camas de cuidados críticos aumentaron de 902 a 1575(75%); 37% en UCI y 63% principalmente en Unidad Coronaria y Emergencias-shock room. En 41/55(75%) UCIs se incorporó personal: 27(49%) médicos/as (70% intensivistas), 36(65%) enfermeros/as, 28(51%) kinesiólogos/as, 20(36%) personal de limpieza, y 1(2%) otros/as; 96% de las UCIS reportaron disponer de respiradores suficientes, y 95%, insumos y EPP suficientes. De todos los pacientes en ventilación mecánica invasiva, 55% [43-64] presentaron COVID-19. Se requirió oxigenoterapia como soporte no invasivo en 14% [8-24] de los ingresos por COVID-19. Se registró una importante expansión de las áreas críticas operativas, secundariamente al aumento de camas, personal, y adecuada disponibilidad de respiradores e insumos esenciales. La carga de la enfermedad crítica por COVID-19 fue intensa, constituyendo más de la mitad de los pacientes en ventilación mecánica.