Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Factores pronósticos de mortalidad a 30 días en neumonía por SARS-CoV-2 / Prognostic Factors for 30-day Mortality in SARS-CoV-2 Pneumonia

Introducción: SARS-CoV-2 ha causado millones de muertes a nivel global desde su primer caso reportado en China. En Guatemala existen pocos estudios que describan los factores pronósticos. Nuestro objetivo fue determinar los factores asociados de mortalidad a 30 días en pacientes con neumonía (Nm) por SARS-CoV-2 y construir un modelo predictor. Material y Métodos: Estudio retrospectivo en 144 sujetos en el Hospital Roosevelt de marzo a diciembre 2020 con criterios de Nm por SARS-CoV-2. Se revisó el expediente médico para datos clínicos y de laboratorio desde ingreso hasta alta hospitalaria o muerte. Resultados: Se evaluaron 105 hombres y 39 mujeres con media de edad 53 años. El 47% tenía comorbilidades como diabetes mellitus 2 e hipertensión arterial sistémica. Promedio de días de hospitalización: 13. Cuadros leves a moderados de Síndrome de Distrés Respiratorio Agudo (SDRA): 92%. Se indicó ventilación mecánica invasiva (VMI) a 46 pacientes. La mortalidad general fue 35%. Factores asociados a mortalidad a 30 días: edad ≥50 años, inicio de síntomas ≥7 días, SDRA severo, radio NL >4,4, recibir VMI, alteración en LDH y procalcitonina. Nuestro modelo mostró que los mejores predictores de mortalidad eran alteración en procalcitonina (OR: 4,45), recibir VMI (OR: 112) y días de estancia hospitalaria (OR: 1,12) con precisión de 91,5% y área bajo la curva de 94,4%. Conclusiones: Los factores pronósticos de mortalidad en pacientes guatemaltecos con Nm por SARS-CoV-2 son múltiples e incluyen rasgos demográficos, clínicos y serológicos; identificarlos y contar con un modelo pronóstico ayudará a brindar atención médica de precisión.

Introduction: SARS-CoV-2 has caused millions of deaths globally since its first case was reported in China. In Guatemala, few studies describe prognostic factors. Our objective was to determine the factors associated with 30 day mortality in patients with Pneumonia (Nm) due to SARS-CoV-2 and to build a predictor model. Material and Methods: Retrospective study in 144 subjects at Roosevelt Hospital from March to December 2020 with Nm criteria for SARS-CoV-2. The medical record was rviewed, obtaining clinical and laboratory data from admission to hospital discharge or death. Results: 105 men and 39 women with an average age of 53 years were evaluated. 47% had comorbidities, with type 2 diabetes mellitus and systemic arterial hypertension being common. The average number of days of hospitalization was 13. 92% had mild to moderate acute respiratory distress syndrome (ARDS). Invasive mechanical ventila-tion (IMV) was indicated for 46 patients. Overall mortality was 35%. The factors asso-ciated with 30-day mortality were age ≥50 years, the onset of symptoms ≥7 days, severe ARDS, N/L ratio >4.4, receiving IMV, alterations in LDH, and procalcitonin. Our model showed that the best predictors of mortality were altered procalcitonin (OR: 4.45), receiving IMV (OR: 112), and days of hospital stay (OR: 1.12) with precision of 91.5% and area under the curve of 94.4%. Conclusions: The prognostic factors of mortality in Guatemalan patients with Nm due to SARS-CoV-2 are multiple and include demographic, clinical and serological features; identifying them and having a prognostic model will help provide precision medical care.

Risk factors for mortality in culture-negative neonatal sepsis in Malawi: a propensity score-matched analysis.

We conducted a propensity score-matched multivariable regression analysis of 1050 culture-negative neonatal sepsis cases in Malawi, where 160 (15.2%) died. Mortality among neonates with culture-negative sepsis was associated with very low birth weight (adjusted OR (AOR) 12.82, 95% CI 1.23 to 137.49), respiratory distress syndrome (AOR 13.20, 95% CI 2.58 to 83.66), a low Apgar score at 1 min (AOR 3.50, 95% CI 1.21 to 10.72) and at 5 min (AOR 4.77, 95% CI 1.94 to 12.50). Addressing maternal and perinatal factors around health and delivery of care is key to improving outcomes in the context of culture-negative sepsis in neonates from low-income country settings like Malawi.

Non-invasive high-frequency ventilation in newborn infants with respiratory distress.

BACKGROUND: Respiratory distress occurs in up to 7% of newborns, with respiratory support (RS) provided invasively via an endotracheal (ET) tube or non-invasively via a nasal interface. Invasive ventilation increases the risk of lung injury and chronic lung disease (CLD). Using non-invasive strategies, with or without minimally invasive surfactant, may reduce the need for mechanical ventilation and the risk of lung damage in newborn infants with respiratory distress. OBJECTIVES: To evaluate the benefits and harms of nasal high-frequency ventilation (nHFV) compared to invasive ventilation via an ET tube or other non-invasive ventilation methods on morbidity and mortality in preterm and term infants with or at risk of respiratory distress. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and three trial registries in April 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster- or quasi-RCTs of nHFV in newborn infants with respiratory distress compared to invasive or non-invasive ventilation. DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials for inclusion, extracted data, assessed the risk of bias, and undertook GRADE assessment. MAIN RESULTS: We identified 33 studies, mostly in low- to middle-income settings, that investigated this therapy in 5068 preterm and 46 term infants. nHFV compared to invasive respiratory therapy for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 0.67, 95% CI 0.20 to 2.18; 1 study, 80 infants) or the incidence of CLD (RR 0.38, 95% CI 0.09 to 1.59; 2 studies, 180 infants), both very low-certainty. ET intubation, death or CLD, severe intraventricular haemorrhage (IVH) and neurodevelopmental disability (ND) were not reported. nHFV vs nasal continuous positive airway pressure (nCPAP) used for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 1.00, 95% CI 0.41 to 2.41; 4 studies, 531 infants; very low-certainty). nHFV may reduce ET intubation (RR 0.52, 95% CI 0.33 to 0.82; 5 studies, 571 infants), but there may be little or no difference in CLD (RR 1.35, 95% CI 0.80 to 2.27; 4 studies, 481 infants); death or CLD (RR 2.50, 95% CI 0.52 to 12.01; 1 study, 68 participants); or severe IVH (RR 1.17, 95% CI 0.36 to 3.78; 4 studies, 531 infants), all low-certainty evidence. ND was not reported. nHFV vs nasal intermittent positive-pressure ventilation (nIPPV) used for initial RS nHFV may result in little to no difference in mortality before hospital discharge (RR 1.86, 95% CI 0.90 to 3.83; 2 studies, 84 infants; low-certainty). nHFV may have little or no effect in reducing ET intubation (RR 1.33, 95% CI 0.76 to 2.34; 5 studies, 228 infants; low-certainty). There may be a reduction in CLD (RR 0.63, 95% CI 0.42 to 0.95; 5 studies, 307 infants; low-certainty). A single study (36 infants) reported no events for severe IVH. Death or CLD and ND were not reported. nHFV vs high-flow nasal cannula (HFNC) used for initial RS We are very uncertain whether nHFV reduces ET intubation (RR 2.94, 95% CI 0.65 to 13.27; 1 study, 37 infants) or reduces CLD (RR 1.18, 95% CI 0.46 to 2.98; 1 study, 37 participants), both very low-certainty. There were no mortality events before hospital discharge or severe IVH. Other deaths, CLD and ND, were not reported. nHFV vs nCPAP used for RS following planned extubation nHFV probably results in little or no difference in mortality before hospital discharge (RR 0.92, 95% CI 0.52 to 1.64; 6 studies, 1472 infants; moderate-certainty). nHFV may result in a reduction in ET reintubation (RR 0.42, 95% CI 0.35 to 0.51; 11 studies, 1897 infants) and CLD (RR 0.78, 95% CI 0.67 to 0.91; 10 studies, 1829 infants), both low-certainty. nHFV probably has little or no effect on death or CLD (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 966 infants) and severe IVH (RR 0.80, 95% CI 0.57 to 1.13; 3 studies, 1117 infants), both moderate-certainty. We are very uncertain whether nHFV reduces ND (RR 0.92, 95% CI 0.37 to 2.29; 1 study, 74 infants; very low-certainty). nHFV versus nIPPV used for RS following planned extubation nHFV may have little or no effect on mortality before hospital discharge (RR 1.83, 95% CI 0.70 to 4.79; 2 studies, 984 infants; low-certainty). There is probably a reduction in ET reintubation (RR 0.69, 95% CI 0.54 to 0.89; 6 studies, 1364 infants), but little or no effect on CLD (RR 0.88, 95% CI 0.75 to 1.04; 4 studies, 1236 infants); death or CLD (RR 0.92, 95% CI 0.79 to 1.08; 3 studies, 1070 infants); or severe IVH (RR 0.78, 95% CI 0.55 to 1.10; 4 studies, 1162 infants), all moderate-certainty. One study reported there might be no difference in ND (RR 0.88, 95% CI 0.35 to 2.16; 1 study, 72 infants; low-certainty). nHFV versus nIPPV following initial non-invasive RS failure nHFV may have little or no effect on mortality before hospital discharge (RR 1.44, 95% CI 0.10 to 21.33); or ET intubation (RR 1.23, 95% CI 0.51 to 2.98); or CLD (RR 1.01, 95% CI 0.70 to 1.47); or severe IVH (RR 0.47, 95% CI 0.02 to 10.87); 1 study, 39 participants, all low- or very low-certainty. Other deaths or CLD and ND were not reported. AUTHORS' CONCLUSIONS: For initial RS, we are very uncertain if using nHFV compared to invasive respiratory therapy affects clinical outcomes. However, nHFV may reduce intubation when compared to nCPAP. For planned extubation, nHFV may reduce the risk of reintubation compared to nCPAP and nIPPV. nHFV may reduce the risk of CLD when compared to nCPAP. Following initial non-invasive respiratory support failure, nHFV when compared to nIPPV may result in little to no difference in intubation. Large trials, particularly in high-income settings, are needed to determine the role of nHFV in initial RS and following the failure of other non-invasive respiratory support. Also, the optimal settings of nHVF require further investigation.

Puntaje APP como predictor de mortalidad en pacientes con síndrome de dificultad respiratoria agudo grave por COVID-19 en un hospital referencial del norte del Perú / APP score as a predictor of mortality in patients with severe acute respiratory distress syndrome due to COVID-19 in a reference hospital in northern of Peru

INTRODUCCIÓN: La mortalidad por pacientes por COVID-19 grave que desarrollaban neumonía grave y síndrome de dificultad respiratoria agudo (SDRA) grave ha sido significativa a pesar del tratamiento oportuno. Es importante determinar predictores tempranos de enfermedad que nos ayuden a estratificar aquellos pacientes con mayor riesgo de fallecer. Se pretende estudiar el comportamiento del puntaje APP (APPS) como predictor de ello, basados en algunos reportes de uso y utilidad en el SDRA. no COVID-19. OBJETIVO: Determinar si el APPS es útil como predictor de mortalidad en SDRA. por COVID-19 grave. PACIENTES Y MÉTODO: Se realizó un estudio tipo cohorte retrospectivo, incluyendo pacientes de la Unidad de Cuidados Intensivos (UCI), con SDRA. por COVID-19 grave, que ingresaron a la UCI del Hospital Regional Docente de Trujillo (HRDT) en el período abril 2020- abril 2021. Se evalúo la utilidad del APPS como predictor de mortalidad em dicha población. RESULTADOS: El APPS demostró ser un factor asociado a mortalidad en pacientes con SDRA. y COVID-19 grave (RPa 1,34; IC 95% 1,16 a 1,56; p < 0,001). Además, encontramos que, al realizar un modelo de predicción ajustado por edad, sexo, SOFA, APPS, shock, Indice de Charlson (ICh), se comportan como factores asociados a mortalidad el APPS, el sexo masculino (RPa: 1,48; IC 95% 1,09 a 2,049; p < 0,05) y el ICh (RPa: 1,11; IC 95% 1,02 a 1,21; p < 0,05). CONCLUSIÓN: El APPS, el sexo masculino y el ICh son predictores de mortalidad en SDRA. por COVID-19 grave.

BACKGROUND: Mortality in patients with severe COVID-19 who developed severe pneumonia and severe Acute Respiratory Distress Syndrome (ARDS) has been significant despite timely treatment. It is important to determine early predictors of disease that help us to stratify those patients with a higher risk of death. It is intended to study the behavior of the APPS score as a predictor of this, based on some reports of use and usefulness in non-COVID-19 ARDS. AIM: To determine if the APP score is useful as a predictor of mortality in ARDS due to severe COVID-19. METHOD: A retrospective cohort study was carried out, including patients from the Intensive Care Unit (ICU) with ARDS due to severe COVID-19 who were admitted to the ICU of the Trujillo Regional Teaching Hospital (HRDT) in the period March 2020 to March 2021. The usefulness of the APP score as a predictor of mortality in mentioned population was evaluated. RESULTS: The APP score proved to be a factor associated with mortality in patients with ARDS and severe COVID-19 (APR 1.34; 95% CI 1.16 to 1.56; p < 0.001). We also found that when performing a prediction model adjusted for age, sex, SOFA, APP score, shock and Charlson Index (ICh) we found that the APP score, male sex (APR: 1.48; 95% CI 1.09 to 2.049; p < 0.05) and the ICh behave as factors associated with mortality (RPa: 1.11; 95% CI 1.02 to 1.21; p < 0.05). CONCLUSION: The APP score, male sex, and ICh are predictors of mortality in ARDS due to severe COVID-19.

Presión de distensión alveolar: su asociación a la mortalidad y protección pulmonar en pacientes ventilados / Alveolar distension pressure: association to mortality and pulmonary protection in ventilated patients

Introducción: La ventilación mecánica artificial es una medida terapéutica de soporte vital aplicada en contextos clínicos como el síndrome de distrés respiratorio agudo. Por eso es necesario establecer parámetros de seguridad. La presión de distensión alveolar es una variable de interés en la protección pulmonar. Se usa para optimizar el volumen tidal de acuerdo con el tamaño del pulmón disponible durante el intercambio gaseoso. Refleja el grado de estiramiento pulmonar en cada ciclo respiratorio. Objetivo: Actualizar contenidos referentes a la presión de distensión alveolar en pacientes ventilados con distrés respiratorio agudo. Método: Se realizó una pesquisa en Google Scholar, Pubmed/Medline, SciELO regional entre otros, bajo los términos: ventilación de protección pulmonar/variables, presión de distensión alveolar durante la ventilación/medición, relación de la presión de distensión alveolar y mortalidad en SDRA/resultados. Se seleccionaron 65 referencias que cumplieron los criterios de inclusión. Resultados: La evidencia actual asocia el hecho de mantener una excesiva presión de distención alveolar, a la mortalidad en pacientes ventilados con síndrome de distrés respiratorio. Permite identificar el riesgo de daño inducido por la ventilación y complicaciones pulmonares en otros escenarios clínicos. Se logra así mejoría en los objetivos y metas en la ventilación mecánica artificial. Conclusiones: La presión de distensión alveolar está asociada con cambios en la supervivencia y ha demostrado ser el mediador clave en los efectos de la ventilación mecánica sobre los resultados del síndrome de distrés respiratorio agudo(AU)

Introduction: Artificial mechanical ventilation is a life support therapeutic measure applied in clinical scenarios such as acute respiratory distress syndrome (ARDS). Therefore, to establish safety parameters is necessary. Alveolar distending pressure is a variable of interest in lung protection. It is used to optimize tidal volume according to the size of the lung available during gas exchange. It reflects the degree of lung stretch in each respiratory cycle. Objective: To update contents concerning alveolar distending pressure in ventilated patients with acute respiratory distress. Methods: A search was carried out in Google Scholar, Pubmed/Medline, regional SciELO, among others, under the terms ventilación de protección pulmonar/variables [lung-protective ventilation/variables], presión de distensión alveolar durante la ventilación/medición [alveolar distending pressure during ventilation/measurement], relación de la presión de distensión alveolar [relationship between alveolar distending pressure] and mortalidad en SDRA/resultados [ARDS mortality/results]. Sixty-five references that met the inclusion criteria were selected. Results: Current evidence associates the maintenance of excessive alveolar distending pressure with mortality in ventilated patients with respiratory distress syndrome. It allows to identify the risk of ventilator-induced damage and pulmonary complications in other clinical scenarios. It thus achieves improved goals and objectives in artificial mechanical ventilation. Conclusions: Alveolar distending pressure is associated with changes in survival and has been shown to be the key mediator in the effects of mechanical ventilation on acute respiratory distress syndrome outcomes(AU)

Poder mecánico como predictor de mortalidad en pacientes críticos con síndrome de distrés respiratorias agudo por Covid-19 en la unidad de cuidados intensivos / Mechanical power as a predictor of mortality in critical ill patients with acute respiratory distress syndrome by Covid-19 in the intensive care unit

La ventilación mecánica invasiva como estrategia terapéutica no está exenta de complicaciones. Es imperativo tener parámetros de ventilación protectiva en aquellos pacientes que están sometidos a ello. Se pretende demostrar si la potencia mecánica como parámetro ventilatorio tiene validez pronóstica de mortalidad en pacientes críticos con ventilación mecánica invasiva prolongada. Material y Métodos: Se realizó un estudio transversal analítico de pacientes críticos en ventilación mecánica invasiva prolongada debido a Síndrome de Distrés Respiratorio Agudo por COVID-19 que ingresaron a la Unidad de Cuidados Intensivos del Hospital Regional Docente de Trujillo durante el periodo de marzo 2020 a marzo del 2021. Resultados: La potencia mecánica, como parámetro ventilatorio, se asocia a mortalidad (RPa 1.061; IC 95% 1.037-1.085; p=0.00) al igual que la presión plateau y siendo la driving pressure y compliance estática factores protectores para mortalidad. La potencia mecánica como parámetro ventilatorio tiene validez pronóstica para mortalidad severa por COVID-19(AU)

Invasive mechanical ventilation as a therapeutic strategy is not without complications. It is imperative to have protective ventilation parameters in those patients who are subjected to it. We aim to demonstrate whether mechanical power as a ventilatory parameter has prognostic validity for mortality in critically ill patients with prolonged invasive mechanical ventilation. Material and Methods: An analytical cross-sectional study was carried out of critically ill patients on prolonged invasive mechanical ventilation due to Acute Respiratory Distress Syndrome due to COVID-19 who were admitted to the Intensive Care Unit of the Hospital Regional de Trujillo during the March 2020 to March 2021 period. Results: Mechanical power, as a ventilatory parameter, is associated with mortality (RPa 1.061; 95% CI 1.037-1.085; p = 0.00) as well as plateau pressure, and driving pressure and static compliance are protective factors for mortality. Mechanical power as a ventilatory parameter has prognostic validity for mortality in critically ill patients with invasive mechanical ventilation due to severe acute respiratory distress syndrome due to COVID-19(AU)

Mortalidad en pacientes críticos con síndrome de distrés respiratorio agudo por Covid-19 en la unidad de cuidados intensivos de un hospital público del norte de Perú / Mortality in critical patients with acute respiratory distress syndrome by Covid-19 in the intensive care unit of a public hospital in northern Peru

La enfermedad COVID-19 tiene como complicación el de Síndrome Agudo Respiratorio Severo (SDRA), que es considerada la principal causa de mortalidad dentro de las unidades de cuidados intensivos, a pesar de brindar soporte ventilatorio precoz y óptimo. Sin embargo, es necesario identificar los factores que se asocian a mortalidad en estos pacientes. Objetivo: Determinar cuáles son los factores asociados a mortalidad en pacientes críticos con Síndrome de distrés respiratorio agudo severo por COVID-19 en unidad de cuidados intensivos. Material y métodos: Estudio transversal analítico. Se usó una base de datos obtenida de 176 historias clínicas de los pacientes con distrés respiratorio agudo severo por COVID-19 en un hospital público de Trujillo desde marzo 2020 a junio 2021. Se dividieron un grupo de pacientes que sobreviven y otro grupo de los que fallecen, subdividiéndose según presentaron o no factores de mortalidad asociados. Se realizó un análisis bivariado y con los factores que resultaron estadísticamente significativos se realizó un análisis multivariado para determinar variables asociadas a mortalidad. Resultados: Se halló una mortalidad de 57% del total de pacientes, al realizar el análisis multivariado se encontró asociación estadística significativa en la presencia de comorbilidades medidas con el Índice de Charlson (RPa=1,348; IC 95%: 1,01-1,79; p=0,040) y dentro de los parámetros ventilatorios a la presión pico (RPa=1,261 IC; 95%: 1,13-1,40; p<=0,000). Es necesario identificar aquellas variables de riesgo de mortalidad para estratificar a pacientes y optimizar la terapéutica(AU)

The COVID-19 disease is complicated by severe acute respiratory syndrome (ARDS), which is considered the main cause of mortality within intensive care units, despite providing early and optimal ventilatory support. However, it is necessary to identify the factors associated with mortality in these patients. Objective: To determine the factors associated with mortality in critically ill patients with severe acute respiratory distress syndrome due to COVID-19 in the intensive care unit. Material and methods: Analytical cross-sectional study. A database obtained from 176 medical records of patients with severe acute respiratory distress due to COVID-19 was used in a public hospital in Trujillo from March 2020 to June 2021. A group of patients who survived and another group of those who died were divided, being subdivided according to whether or not they present associated mortality factors. A bivariate analysis was performed and with the factors that were statistically significant, a multivariate analysis was performed to determine variables associated with mortality. Results: A mortality of 57% of the total number of patients was found, when performing the multivariate analysis, a significant statistical association was found in the presence of comorbidities measured with the Charlson Index (RPa = 1.348; 95% CI: 1.01-1.79; p = 0.040) and within the ventilatory parameters at peak pressure (RPa = 1.261 CI; 95%: 1.13-1.40; p <= 0.000). It is necessary to identify those mortality risk variables to stratify patients and optimize therapy(AU)

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Ventilación en posición prona en el manejo de pacientes con síndrome de dificultad respiratoria aguda / Prone ventilation in the management of patients with acute respiratory distress syndrome

INTRODUCCIÓN. El posicionamiento prono es una de las estrategias ventilatorias más estudiadas y difundidas de la medicina intensiva, forma parte del manejo de ventilación protectiva con impacto en disminución de la mortalidad en pacientes con síndrome de dificultad respiratoria aguda. OBJETIVO. Revisar la evidencia disponible acerca de ventilación en posición prona en pacientes con síndrome de dificultad respiratoria aguda, enfocada en el análisis fisiopatológico y clínico. MATERIALES Y MÉTODOS. Se realizó una revisión bibliográfica en la base de datos de buscadores académicos como PubMed, Google Scholar y Elsevier, en los idiomas español e inglés, en el período comprendido entre los años 1970-2020; se seleccionaron 16 publicaciones en texto completo: 3 metaanálisis, 10 estudios randomizado, 3 revisiones sistemáticas. CONCLUSIÓN. En base a la evidencia y percepción recopilada de la experiencia de los autores, la ventilación en posición prona es una estrategia de manejo de primera línea, fiable, que no requiere para su empleo equipamiento costoso ni complejo y ha demostrado mejoría en desenlaces relevantes en el tratamiento del paciente crítico respiratorio como disminución en la mortalidad y optimización de los parámetros ventilatorios y de oxigenación.

INTRODUCTION. Prone positioning is one of the most studied and widespread ventilatory strategies in intensive medicine, it is part of protective ventilation management with an impact on mortality reduction in patients with acute respiratory distress syndrome. OBJECTIVE. To review the available evidence about ventilation in the prone position in patients with acute respiratory distress syndrome, focused on the pathophysiological and clinical analysis. MATERIALS AND METHODS. A bibliographic review was carried out in the databases of academic search engines such as PubMed, Google Scholar and Elsevier, in the Spanish and English languages, in the period between the years 1970-2020, 16 full text publications were selected: 3 meta-analyses, 10 randomized studies, 3 systematic reviews. CONCLUSION. Based on the evidence and perception gathered from the authors' experience, prone ventilation is a reliable first-line management strategy that does not require costly or complex equipment for its use and has demonstrated improvements in relevant outcomes in the treatment of the critically ill respiratory patient, such as decreased mortality and optimization of ventilatory and oxygenation parameters.

Increased circulating cytokeratin 19 fragment levels in preterm neonates receiving mechanical ventilation are associated with poor outcome.

Invasive mechanical ventilation and oxygen toxicity are postnatal contributors to chronic lung disease of prematurity, also known as bronchopulmonary dysplasia (BPD). Cyfra 21-1 is a soluble fragment of cytokeratin 19, which belongs to the cytoskeleton stabilizing epithelial intermediate filaments. As a biomarker of structural integrity, Cyfra 21-1 might be associated with airway injury and lung hypoplasia in neonates. Serum Cyfra 21-1 concentrations for 80 preterm and 80 healthy term newborns were measured within 48 h after birth. Preterm infants with the combined endpoint BPD/mortality had significantly higher Cyfra 21-1 levels compared with those without fulfilling BPD/mortality criteria (P = 0.01). Also, severe RDS (>grade III) was associated with higher Cyfra levels (P = 0.01). Total duration of oxygen therapy was more than five times longer in neonates with high Cyfra 21-1 levels (P = 0.01). Infants with higher Cyfra 21-1 values were more likely to receive mechanical ventilation (50% vs. 17.5%). However, the duration of mechanical ventilation was similar between groups. The median Cyfra value was 1.93 ng/mL (IQR: 1.68-2.53 ng/mL) in healthy term neonates and 8.5 ng/mL (IQR: 3.6-16.0 ng/mL) in preterm infants. Using ROC analysis, we calculated a Cyfra cutoff > 8.5 ng/mL to predict BPD/death with an AUC of 0.795 (P = 0.004), a sensitivity of 88.9%, and a specificity of 55%. Mortality was predicted with a cutoff > 17.4 ng/mL (AUC: 0.94; P = 0.001), a sensitivity of 100%, and a specificity of 84%. These findings suggest that Cyfra 21-1 concentration might be useful to predict poor outcome in premature infants.

Evolución del síndrome de distrés respiratorio agudo en los neonatos del área de cuidados intensivos del hospital "Delfina Torres de Concha" / Evolution of the acute respiratory distress syndrome in neonates in the intensive care area of ​​the "Delfina Torres de Concha" hospital

Analizar la evolución del síndrome de distrés respiratorio agudo (SDRA) en neonatos pretérminos del área de cuidados intensivos del Hospital General Delfina Torres de Concha. Materiales y Métodos: La investigación es un estudio cuantitativo, de corte transversal y alcance descriptivo. La muestra probabilística quedó conformada por 49 madres de neonatos prematuros. Las técnicas utilizadas son el estudio documental y la encuesta. Los criterios de inclusión incluyeron ambos sexos, que nacieron entre las 26 y las 35 semanas de gestación, durante los meses de julio, agosto y septiembre de 2020. Las variables fueron los factores sociodemográficos de las madres, los factores de riesgo maternos, el género, vía del parto, peso al nacer, complicaciones de los neonatos y la mortalidad infantil. Resultados: Los resultados muestran que la etnia prevalente fue la mestiza (65,3%), el estado civil más representado fue el de unión libre (51,0%) y el nivel de escolaridad es muy bajo, así como el per cápita económico familiar. Los factores de riesgo maternos fueron la hipertensión (21,5%), la edad y la preeclamsia (18,5%, respectivamente). En los recién nacidos prevaleció el sexo masculino (46,9%) sobre el femenino (53.06%), al igual que las cesáreas (55,1%). Las complicaciones más importantes fueron la hemorragia intraventricular (23,8%), la hipertensión pulmonar persistente (20,6%) y la displasia broncopulmonar (15,9%). La tasa de mortalidad infantil se situó en el 32,7%. Conclusiones: Existe una correlación entre las complicaciones severas de los recién nacidos y la mortalidad neonatal. Por la trascendencia familiar y social del fallecimiento de neonatos y la frecuencia de trastornos respiratorios en la morbimortalidad de los recién nacidos en dicho Hospital, se hace necesario realizar estudios que estimulen la prevención y diagnóstico oportuno, especialmente en contextos como el nuestro

To analyze the evolution of acute respiratory distress syndrome (ARDS) in preterm neonates in the intensive care area of the Hospital General Delfina Torres de Concha. Materials and Methods: The research is a quantitative, cross-sectional, descriptive study. The probabilistic sample consisted of 49 mothers of preterm infants. The techniques used were documentary study and survey. The inclusion criteria included both sexes, born between 26 and 35 weeks of gestation, during the months of July, August and September 2020. The variables were sociodemographic factors of the mothers, maternal risk factors, gender, and route of delivery, birth weight, neonatal complications and infant mortality. The results: The results show that the most prevalent ethnic group was mestizo (65.3%), the most represented marital status was a union (51.0%) and the level of schooling was very low, as well as the family economic per capita. Maternal risk factors were hypertension (21.5%), age and preeclamsia (18.5%, respectively). Among the newborns, the male sex (46.9%) prevailed over the female (53.06%), as did cesarean sections (55.1%). The most important complications were intraventricular hemorrhage (23.8%), persistent pulmonary hypertension (20.6%) and bronchopulmonary dysplasia (15.9%). The infant mortality rate was 32.7%. Conclusions: There is a correlation between severe newborn complications and neonatal mortality. Due to the family and social importance of neonatal deaths and the frequency of respiratory disorders in the morbidity and mortality of newborns in this Hospital, it is necessary to carry out studies to stimulate prevention and timely diagnosis, especially in contexts such as ours

Association between antenatal corticosteroid use and perinatal mortality among preterm births in hospitals in Tanzania.

OBJECTIVES: The primary aims of this study were to investigate if exposure to antenatal corticosteroids (ACS) was associated with lower rates of perinatal mortality (primary outcome) and other adverse perinatal outcomes (i.e., stillbirth, early neonatal mortality, APGAR score of < 7 at 5 mins, neonatal sepsis and respiratory distress syndrome) in preterm infants in hospitals in Tanzania. We also examine factors associated with administration of ACS among women at risk of preterm delivery. METHODS: A hospital-based prospective chart review study was undertaken in four hospitals located in Nyamagana and Sengerema districts, Tanzania. The study population included all stillborn and live born preterm infants delivered between 24 to 34 weeks of gestation between July 2019 to February 2020. A total 1125 preterm infants were delivered by 1008 women (895 singletons, 230 multiple). Sociodemographic and medical data were recorded from participants' medical records. RESULTS: Three hundred and fifty-six (35.3%) women were administered at least one dose of ACS between 24 to 34 weeks' gestation and 385 (34.2%) infants were exposed to ACS. Infants exposed to ACS had a lower rate of perinatal mortality (13.77%) compared to those who were not exposed (28.38%). Multivariate analysis indicated that infants exposed to ACS were less likely to die during perinatal period, aRR 0.34 (95%CI 0.26-0.44). Only one-third of the sample was provided with ACS. Administration of ACS was associated with maternal education, attending antenatal care more than 3 times, method used to assess gestational age, maternal infection, exposure to maternal antibiotics, delivery mode and level of health facility. CONCLUSION: ACS significantly reduced the risk in perinatal mortality among infants born preterm in a limited resource setting. However, only about one-third of eligible women were provided with ACS, indicating low usage of ACS. Numerous factors were associated with low usage of ACS in this setting.

Causes of preterm and low birth weight neonatal mortality in a rural community in Kenya: evidence from verbal and social autopsy.

BACKGROUND: Under-five mortality in Kenya has declined over the past two decades. However, the reduction in the neonatal mortality rate has remained stagnant. In a country with weak civil registration and vital statistics systems, there is an evident gap in documentation of mortality and its causes among low birth weight (LBW) and preterm neonates. We aimed to establish causes of neonatal LBW and preterm mortality in Migori County, among participants of the PTBI-K (Preterm Birth Initiative-Kenya) study. METHODS: Verbal and social autopsy (VASA) interviews were conducted with caregivers of deceased LBW and preterm neonates delivered within selected 17 health facilities in Migori County, Kenya. The probable cause of death was assigned using the WHO International Classification of Diseases (ICD-10). RESULTS: Between January 2017 to December 2018, 3175 babies were born preterm or LBW, and 164 (5.1%) died in the first 28 days of life. VASA was conducted among 88 (53.7%) of the neonatal deaths. Almost half (38, 43.2%) of the deaths occurred within the first 24 h of life. Birth asphyxia (45.5%), neonatal sepsis (26.1%), respiratory distress syndrome (12.5%) and hypothermia (11.0%) were the leading causes of death. In the early neonatal period, majority (54.3%) of the neonates succumbed to asphyxia while in the late neonatal period majority (66.7%) succumbed to sepsis. Delay in seeking medical care was reported for 4 (5.8%) of the neonatal deaths. CONCLUSION: Deaths among LBW and preterm neonates occur early in life due to preventable causes. This calls for enhanced implementation of existing facility-based intrapartum and immediate postpartum care interventions, targeting asphyxia, sepsis, respiratory distress syndrome and hypothermia.

Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth.

OBJECTIVE: To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. STUDY DESIGN: EPT infants (240/7-276/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks of PMA and follow-up outcomes at 18-22 months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. RESULTS: Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32 weeks PMA, and 32-36 weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score <85 at 18-22 months corrected age (P = .002). CONCLUSIONS: EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation.

Factors associated with neonatal mortality in a tertiary hospital in Phnom Penh, Cambodia.

This study aimed to identify hospital neonatal mortality rate (NMR) and the causes of neonatal deaths, and to understand risk factors associated with neonatal mortality in a national tertiary hospital in Cambodia. The study included all newborn infants, aged 0-28 days old, hospitalized in the Pediatrics department of Khmer-Soviet Friendship Hospital between January 2016 and December 2017. In total, 925 infants were included in the study. The mean gestational age was 35.9 weeks (range, 24-42 weeks). Preterm infants and low birth weight accounted for 47.5% and 56.7%, respectively. With respect to payment methods, the government (53.5%) and non-governmental organizations (NGO) (13.7%) paid the fees as the families were not in a financial position to do so. The hospital NMR at the Pediatrics department was 9.3%. Respiratory distress syndrome (37.2%) was the main cause of deaths followed by hypoxic-ischemic encephalopathy (31.4%) and neonatal infection (21.0%). Factors associated with neonatal mortality were Apgar score at 5th minute <7 (adjusted odds ratio (AOR) = 3.57), payment by the government or NGO (AOR = 11.32), admission due to respiratory distress (AOR = 11.94), and hypothermia on admission (AOR = 9.41). The hospital NMR in the Pediatrics department was 9.3% (95% confidence interval 7.50-11.35) at Khmer-Soviet Friendship Hospital; prematurity and respiratory distress syndrome were the major causes of neonatal mortality. Introducing continuous positive airway pressure machine for respiratory distress syndrome and creating neonatal resuscitation guidelines and preventing hypothermia in delivery rooms are required to reduce the high NMR.

Face mask versus nasal prong or nasopharyngeal tube for neonatal resuscitation in the delivery room: a systematic review and meta-analysis.

IMPORTANCE: The current neonatal resuscitation guidelines recommend positive pressure ventilation via face mask or nasal prongs at birth. Using a nasal interface may have the potential to improve outcomes for newborn infants. OBJECTIVE: To determine whether nasal prong/nasopharyngeal tube versus face mask during positive pressure ventilation of infants born <37 weeks' gestation in the delivery room reduces in-hospital mortality and morbidity. DATA SOURCES: MEDLINE (through PubMed), Google Scholar and EMBASE, Clinical Trials.gov and the Cochrane Central Register of Controlled Trials through August 2019. STUDY SELECTION: Randomised controlled trials comparing nasal prong/nasopharyngeal tube versus face mask during positive pressure ventilation of infants born <37 weeks' gestation in the delivery room. DATA ANALYSIS: Risk of bias was assessed using the Covidence Collaboration Tool, results were pooled into a meta-analysis using a random effects model. MAIN OUTCOME: In-hospital mortality. RESULTS: Five RCTs enrolling 873 infants were combined into a meta-analysis. There was no statistical difference in in-hospital mortality (risk ratio (RR 0.98, 95% CI 0.63 to 1.52, p=0.92, I2=11%), rate of chest compressions in the delivery room (RR 0.37, 95% CI 0.10 to 1.33, p=0.13, I2=28%), rate of intraventricular haemorrhage (RR 1.54, 95% CI 0.88 to 2.70, p=0.13, I2=0%) or delivery room intubations in infants ventilated with a nasal prong/tube (RR 0.63, 95% CI 0.39,1.02, p=0.06, I2=52%). CONCLUSION: In infants born <37 weeks' gestation, in-hospital mortality and morbidity were similar following positive pressure ventilation during initial stabilisation with a nasal prong/tube or a face mask.