Escenarios para el diagnóstico de encefalopatía hipóxico isquémica e inicio de tratamiento con hipotermia controlada en recién nacidos con asfixia perinatal

La hipoxia isquemia perinatal y su complicación más temida, la encefalopatía hipóxica isquémica, continúa siendo uno de los principales motivos de ingreso a las unidades de cuidados neonatales. En la actualidad la hipotermia controlada es el tratamiento recomendado para los pacientes con encefalopatía moderada a severa, dado su carácter de neuroprotección ante la injuria cerebral hipóxico isquémica. Si bien los criterios de inclusión en esta terapia han sido bien establecidos, aún hay dificultades tanto en la identificación precoz de aquellos que pueden verse beneficiados, como en la toma de decisiones ante situaciones de controversia entre la evidencia disponible y la que se está gestando en estudios en curso. Este artículo pretende aportar herramientas al clínico para abordar diferentes escenarios que surgen de la práctica diaria.

Summary: Perinatal hypoxic ischemia and its most feared complication, hypoxic ischemic encephalopathy, remain one of the main reasons for admission to neonatal care. Controlled hypothermia is currently the recommended treatment for patients with moderate to severe encephalopathy, given its neuroprotective nature against hypoxic-ischemic brain injury. Although the inclusion criteria for this therapy have been well established, there are still difficulties both in the early identification of those who may benefit, and in making decisions regarding situations of controversy between the available evidence and that being developing in ongoing studies. This paper aims at providing tools so that clinicians can address different scenarios that arise during their daily practice.

A hipóxia isquêmica perinatal e sua complicação mais temida, a encefalopatia hipóxico-isquêmica, continuam sendo um dos principais motivos de internação em unidades de cuidados neonatais. A hipotermia controlada é atualmente o tratamento recomendado para pacientes com encefalopatia moderada a grave, dada a sua natureza neuroprotetora contra lesão cerebral hipóxico-isquêmica. Embora os critérios de inclusão dessa terapia estejam bem estabelecidos, ainda há dificuldades tanto na identificação precoce daqueles que podem se beneficiar, quanto na tomada de decisões em situações de controvérsia entre as evidências disponíveis e aquelas que estão se desenvolvendo em estudos em andamento. Este paper tem como objetivo fornecer ferramentas aos clínicos para abordar diferentes cenários que surgem da prática diária.

Implementación de paquete de medidas de conductas perinatales en recién nacidos con gastrosquisis congénita

Introducción: la gastrosquisis congénita (GC) es una patología con creciente demanda asistencial. Atentos a esto, en el Centro Hospitalario Pereira Rossell (CHPR) se implementó un protocolo de cuidados llevado adelante por un equipo multidisciplinario. En este trabajo nos proponemos evaluar el impacto en la sobrevida y morbilidad a partir de su aplicación. Material y método: estudio comparativo tipo antes y después de pacientes portadores de GC (n = 47), 29 de una cohorte histórica (GH) y 18 de una cohorte posaplicación de protocolo (GP). Con edad gestacional ≥ 36 semanas y peso al nacer ≥ 2500 g, asistidos en el CHPR entre los años 2016 y 2021. Resultados: no se observaron diferencias perinatales entre ambos grupos, ni en la incidencia de GQ complicadas. En el GP se observó mayor incidencia de cierre abdominal precoz (p < 0,01), menor necesidad de realización de silo quirúrgico (p < 0,01), menor tiempo de administración de ventilación mecánica (p = 0,03), de uso total de opioides (p < 0,01), de administración de nutrición parenteral (p = 0,03), e inicio más temprano de la alimentación enteral (p = 0,03). Sin diferencias en la sobrevida al egreso hospitalario. Conclusiones: la aplicación de un protocolo estandarizado se asoció a una reducción significativa en el tiempo de cierre abdominal, de ventilación mecánica, nutrición parenteral y de opioides, con inicio más precoz de la nutrición enteral.

Summary: Introduction: congenital gastroschisis is an increasingly demanded pathology, therefore a care protocol was implemented at the Pereira Rossell Pediatric Hospital (CHPR), and it has been carried out by a multidisciplinary team. In this paper, we aim at assessing the morbidity and mortality impact of survival and morbidity of this application. Materials and Methods: comparative before and after study of a historical cohort (GH, n=29) versus a post-protocol application cohort (GP, n=18), in patients with a gestational age ≥36 weeks and birth weight ≥2500 grams assisted in CHPR between 2016-2021. Results: no perinatal differences were observed between both groups or in the incidence of complicated GQ. In the GP, a higher incidence of early abdominal closure was decreased (GH 3.4% vs GP 67%, p<0.01), less need to perform a surgical silo (GH 100% vs GP 33%, p<0.01 ), shorter mechanical ventilation administration time (GH 2 days vs GP 0.5 days, p=0.03), total use of opioids (GH 3.5 days vs GP 7 days, p<0.01) , of administration of parenteral nutrition (GH 24.5 days vs GP 20 days, p=0.03), and earlier start of enteral feeding (GH 11 days vs GP 7 days, p=0.03). No differences in survival after hospital discharge (93% vs 89%, p=0.63). Conclusions: the application of a standardized protocol was linked to a significant reduction in the time of abdominal closure, mechanical ventilation, parenteral nutrition, and opioids, with earlier initiation of enteral nutrition.

Introdução: a gastrosquise congênita (GC) é uma patologia com demanda crescente de atendimento e, porém, foi implementado um protocolo de atendimento por equipe multidisciplinar no Centro Hospitalar Pediátrico Pereira Rossell (CHPR). Neste trabalho propomos avaliar o impacto na mortalidade e morbidade depois de sua aplicação. Material e Métodos: estudo comparativo antes e depois de pacientes com CG (n=47), sendo 29 de uma coorte histórica (GH) e 18 de uma coorte pós-aplicação de protocolo (GP). Idade gestacional ≥ 36 semanas e peso ao nascer ≥ 2.500 gramas atendidos no CHPR entre os anos de 2016-2021. Resultados: não foram observadas diferenças perinatais entre os dois grupos ou na incidência de QG complicada. No GP observou-se maior incidência de fechamento abdominal precoce (p<0,01), menor necessidade de silos cirúrgicos (p<0,01), menor tempo de administração de ventilação mecânica (p=0,03) e uso total de opioides. (p<0,01), administração de nutrição parenteral (p=0,03) e início mais precoce da alimentação enteral (p=0,03). Não houve diferenças na sobrevivência até a alta hospitalar. Conclusões: a aplicação de protocolo padronizado foi associada à redução significativa do tempo de fechamento abdominal, ventilação mecânica, nutrição parenteral e opioides, com início mais precoce da nutrição enteral.

Sepsis neonatal precoz a Streptococcus pneumoniae: a propósito de un caso clínico / Early neonatal sepsis caused by Streptococcus pneumoniae: a case study / Sepse neonatal precoce por Streptococcus pneumoniae: relato de caso clínico

Resumen: Introducción: la sepsis causada por S. pneumoniae es infrecuente en neonatos, sin embargo, se asocia a una elevada morbimortalidad. Las vías de transmisión son transplacentaria o por vía ascendente, posterior a la colonización vaginal materna en la sepsis neonatal precoz, o a través de portadores de la comunidad en la sepsis neonatal tardía. La introducción de la vacuna neumocócica en la población pediátrica no ha logrado reducir en forma significativa los casos de sepsis neonatal, por lo que se proponen otras estrategias, como la vacunación materna. Caso clínico: se presenta un neonato con diagnóstico de sepsis precoz a S. pneumoniae serotipo 3 (vacunal) sensible a penicilina y madre con colonización vaginal por el germen. Se realizó un diagnóstico y tratamiento oportuno, logrando una buena evolución clínica. Conclusiones: S. pneumoniae, aunque infrecuente en el período neonatal, se asocia a importante mortalidad y morbilidad, lo que hace necesario la sospecha clínica y el tratamiento oportuno para asegurar un buen pronóstico sin secuelas. Se han propuesto diferentes estrategias para disminuir la incidencia de enfermedad neumocócica invasiva neonatal, entre ellas la vacunación materna. La evidencia científica actual no aporta suficientes datos para recomendar la vacunación a madres, teniendo en cuenta costo-beneficio y sostenibilidad de la medida en el tiempo de implementarse.

Summary: Introduction: sepsis caused by S. pneumoniae is infrequent in newborns, however, it is associated with high morbidity and mortality. Transmission routes are transplacental or ascending, after maternal vaginal colonization in early onset sepsis, or through community carriers in late onset sepsis. The introduction of the pneumococcal vaccine has not been able to reduce the cases of early neonatal sepsis, so other strategies, such as maternal vaccination are proposed. Clinical case: we present a newborn diagnosed with S. pneumoniae (serotype 3 (vaccine) early onset sepsis, sensitive to penicillin and his mother with vaginal colonization by the same bacteria. A timely diagnosis and treatment were made, achieving a good clinical evolution. Conclusions: S. pneumoniae has low incidence of sepsis in the neonatal period, but it is associated with high mortality and morbidity, making clinical suspicion and prompt treatment necessary to ensure good prognosis. Different strategies have been proposed to decrease the incidence of neonatal invasive pneumococcal disease, including maternal vaccination. Current scientific evidence does not provide enough data to recommend vaccination to mothers, considering its cost-effectiveness and sustainability over time.

Resumo: Introdução: a sepse por S. pneumoniae é rara em neonatos, porém está associada a alta morbimortalidade. As vias de transmissão são transplacentárias ou ascendentes, após a colonização vaginal materna na sepse neonatal precoce ou por meio de portadores comunitários na sepse neonatal tardia. A introdução da vacina pneumocócica na população pediátrica não tem conseguido reduzir significativamente os casos de sepse neonatal, por isso propõem-se outras estratégias como a vacinação materna. Caso clínico: apresenta-se um recém-nascido com diagnóstico de sepse precoce para S. pneumoniae sorotipo 3 (vacina) sensível à penicilina e mãe com colonização vaginal pelo germe. Realizou-se diagnóstico e tratamento oportunos, com boa evolução clínica. Conclusões: S. pneumoniae, embora infrequente no período neonatal, está associada a mortalidade e morbidade significativas, o que torna necessária a suspeita clínica e o tratamento oportuno para garantir um bom prognóstico sem sequelas. Diferentes estratégias têm sido propostas para reduzir a incidência de doença pneumocócica invasiva neonatal, incluindo a vacinação materna. As evidências científicas atuais não fornecem dados suficientes para recomendar a vacinação às mães, considerando o custo-benefício e a sustentabilidade da medida ao longo prazo, se for implementada.

Factors Associated with Survival and Survival without Major Morbidity in Very Preterm Infants in Two Neonatal Networks: SEN1500 and NEOCOSUR.

INTRODUCTION: Very low-birth weight (VLBW) infants represent a high-risk population for morbidity and mortality in the neonatal period. Variability in practices and outcomes between centers has been acknowledged. Multicenter benchmarking studies are useful to detect areas of improvement and constitute an interesting research tool. OBJECTIVES: The aim of the study was to determine the perinatal variables and interventions associated with survival and survival without major morbidity in VLBW infants and compare the performance of 2 large networks. METHODS: This is a prospective study analyzing data collected in 2 databases, the Spanish SEN1500 and the South American NEOCOSUR networks, from January 2013 to December 2016. Inborn patients, from 240 to 306 weeks of gestational age (GA) were included. Hazard ratios for survival and survival without major morbidity until the first hospital discharge or transfer to another facility were studied by using Cox proportional hazards regression. RESULTS: A total of 10,565 patients, 6,120 (57.9%) from SEN1500 and 4,445 (42.1%) from NEOCOSUR, respectively, were included. In addition to GA, birth weight, small for gestational age (SGA), female sex, and multiple gestation, less invasive resuscitation, and the network of origin were significant independent factors influencing survival (aHR [SEN1500 vs. NEOCOSUR]: 1.20 [95% CI: 1.15-1.26] and survival without major morbidity: 1.34 [95% CI: 1.26-1.43]). Great variability in outcomes between centers was also found within each network. CONCLUSIONS: After adjusting for covariates, GA, birth weight, SGA, female sex, multiple gestation, less invasive resuscitation, and the network of origin showed an independent effect on outcomes. Determining the causes of these differences deserves further study.

Hiperinsulinismo congénito por mutación del gen ABCC8 / Congenital hyperinsulinism due to the ABCC8 gene mutation / Hiperinsulinismo congênito causado por mutação do gen ABCC8

Resumen: El hiperinsulinismo congénito es la causa más común de hipoglucemia persistente en el recién nacido y la infancia, con un alto riesgo de daño neurológico irreversible. En los últimos años, gracias a los avances en el conocimiento de la genética molecular, se ha avanzado y profundizado en sus bases genéticas; sin embargo, el diagnóstico se sigue realizando en muchas ocasiones demasiado tarde, dada la heterogeneidad que presenta esta enfermedad. Se detalla a continuación el caso de una paciente con hipoglicemias de difícil control desde el nacimiento, secundaria a hiperinsulinismo congénito y en cuyo estudio genético se evidenció mutación del gen ABCC8.

Summary: Congenital hyperinsulinism (CH) is the most common cause of persistent hypoglycemia in newborns and children at a high risk of irreversible neurological damage. In spite of the recent progress made by the molecular genetics' genetic base, diagnosis is still often late, given the heterogeneity of this disease. We hereby report the case of a patient ranging from secondary and difficult to control hypoglycemia to congenital hyperinsulinemia. Her genetic test showed ABCC8 gene mutation.

Resumo: O hiperinsulinismo congênito (HC) é a causa mais comum de hipoglicemia persistente em recém-nascidos e crianças com alto risco de dano neurológico irreversível. Apesar dos recentes progressos realizados pela base genética da genética molecular, o diagnóstico ainda é frequentemente realizado tarde demais, dada a heterogeneidade dessa doença. Relatamos o caso duma paciente que varia de hipoglicemia secundária e de difícil controle a hiperinsulinemia congênita. Seu teste genético mostrou mutação no gene ABCC8.

Neonatal outcomes of antenatal corticosteroids in preterm multiple pregnancies compared to singletons.

BACKGROUND: Antenatal corticosteroids (ACS) during preterm labour reduce neonatal mortality and morbidity. Evidence on preterm multiple pregnancies is limited and contradictory. OBJECTIVE: Compare the effect of ACS on very low birth weight infant's (VLBW) mortality and morbidity among singleton and multiple pregnancies. STUDY DESIGN: Retrospective cohort study, employing prospectively collected data, of infants 23 to 34 weeks' gestation and 500 to 1500 g born at the Neocosur Neonatal Network centers during 2007-2016. Neonatal outcomes were compared among singleton and multiple pregnancies exposed to at least one dose of ACS to those not exposed using logistic regression analyses controlled for birthweight, gestational age, sex, small for gestational age (SGA) and mode of delivery. RESULTS: A total of 13,864 infants were studied; 2948 multiple (21.3%) and 10,904 singleton pregnancies (78.7%). Overall, 11,218 (81.4%) received at least one dose of ACS with a significant reduction in the risk of death, RDS and grade III or IV IVH compared to those not exposed. Both singleton and multiple pregnancies exposed to ACS showed similar reduced risk of death (aRR 0.41 [95% CI, 0.36-0.47] vs. aRR 0.46 [95% CI, 0.34-0.64]). However, ACS were not associated with reduced odds of RDS (aRR 0.89 [95% CI, 0.66-1.23]) or grade III or IV IVH (aRR 0.99 [95% CI, 0.67-1.48]) in multiple pregnancies. CONCLUSION: The benefit of administration of at least one dose of ACS in VLBW multiple and singleton pregnancies is comparable in terms of death. However, ACS showed no relevant impact in short-term morbidity in multiple pregnancies.

Efficacy and safety of a novel nitric oxide generator for the treatment of neonatal pulmonary hypertension: Experimental and clinical studies.

Persistent pulmonary hypertension of the newborn (PPHN) is a complex pathology resulting from a failure of the post-natal reduction in pulmonary vascular resistance leading to hypoxemia. The standard therapy is inhaled Nitric Oxide (NO) improving oxygenation but its availability is limited, especially in hospitals with restricted financial resources. We evaluated the efficacy and safety of a new device generating NO (TAS + PLUS), in three experimental piglet models of pulmonary hypertension (PH), and we later tested its application in a pilot study of newborn patients suffering from PPHN. Piglets with experimentally induced PH showed a decrease in pulmonary arterial pressure (PAP) after breathing NO. Both acute and chronic exposure of piglets and rats did not cause any adverse effect in blood gas levels and biological parameters. A pilot study including 32 patients suffering from PPHN showed an increase in oxygen saturation (SatO2) and partial pressure of oxygen in arterial blood (PaO2) leading to a decrease of Oxygenation Index (OI) after compassionate treatment with NO from TAS + PLUS device. The device showed effectiveness and safety both in experimental PH and in the clinical setting. Therefore, it represents an excellent alternative for PPHN management in conditions where commercial NO is unavailable.

TRALI neonatal. A propósito de un caso clínico / TRALI in newborns. Clinical case report / A TRALI em recém-nascidos. Relato de caso clínico

Resumen: Los recién nacidos, sobre todo los pretérminos, constituyen uno de los grupos que reciben más hemoderivados. Si bien se han disminuido los riesgos asociados a las transfusiones, aun así pueden presentarse complicaciones1,2. TRALI (Tranfusion Related Acute Lung Injury; en español: lesión pulmonar aguda asociada a transfusión) es una complicación poco frecuente pero potencialmente grave. Reconocida inicialmente en adultos, posteriormente se describieron casos en niños. En neonatos solamente existe un caso confirmado y publicado a nivel internacional. La incidencia real es incierta, dado el poco conocimiento de la patología y el subreporte. TRALI resultaría de un daño del endotelio vascular pulmonar, causando edema pulmonar y subsecuentemente hipoxemia. El tratamiento es de sostén3. La prevención se basa principalmente en la revisión permanente de las indicaciones de transfusión de hemoderivados y en la comunicación fluida con el equipo de hemoterapia para su diagnóstico oportuno. Se describe el caso clínico de un recién nacido prematuro que durante una transfusión de concentrado de glóbulos rojos presentó hipoxemia con necesidad de asistencia ventilatoria mecánica, alteraciones hemodinámicas y fiebre. Se descartaron procesos infecciosos. La radiografía de tórax mostró infiltrados compatibles con edema pulmonar. Se descartó la falla cardíaca. El tratamiento realizado fue de sostén de las funciones vitales. La evolución fue favorable en el correr de 72 horas. Se comunicó el caso al servicio de hemoterapia. A fin de prevenir transfusiones innecesarias es importante que cada servicio revise periódicamente sus guías de transfusión de hemoderivados.

Summary: Newborns, especially preterm newborns, are one of the age groups that receive the most hemoderivatives. Although the progress made in the field of hemotherapy have made it possible to reduce the risks associated with transfusions, in some cases there are still complications1,2. TRALI (transfusion related acute lung injury) is a rare but potentially serious complication. It was initially detected in adults, though cases were later described in children. In newborns, only one case has been confirmed and published globally. The actual incidence is uncertain, given the insufficient knowledge of the pathology and the fact that findings have been under reported. TRALI results from pulmonary vascular endothelial damage and causes pulmonary edema and subsequent hypoxemia. Treatment is observed with supportive treatment3. Prevention is mainly based on the permanent review of the hemoderivatives' transfusion directives and on the fluent communication among members of the hemotherapy medical team in order to ensure a timely diagnosis. The clinical case described below is that of a preterm newborn who, during a transfusion of red blood cell concentrate, showed hypoxemia, hemodynamic alterations and fever and required mechanical ventilatory support. Infectious processes were ruled out. Chest X-Rays showed infiltrates compatible with pulmonary edema. Heart failure was ruled out. The treatment was performed to support vital functions. The evolution was favorable in the course of 72 hours. The case was reported to the Hemotherapy Service. Blood component transfusion guidelines should be regularly reviewed in order to prevent the performance of unnecessary transfusions.

Resumo: Os recém-nascidos, especialmente os prematuros, são um dos grupos que recebem maior quantidade de hemoderivados. Embora os riscos associados tenham diminuído com o tempo, as transfusões ainda podem trazer complicações1,2. A TRALI (lesão pulmonar aguda relacionada à transfusão) é uma complicação rara, mas potencialmente grave. Inicialmente reconhecida em adultos, os casos foram posteriormente descritos em crianças. Em neonatos, há apenas um caso confirmado e publicado a nível internacional. A incidência real é incerta, dado que existe pouco conhecimento da patologia e é pouco relatada. A TRALI é provocada por danos no endotélio vascular pulmonar e causa edema pulmonar e subsequentemente hipoxemia. O tratamento é de suporte3. A prevenção baseia-se principalmente na revisão permanente das indicações de transfusão de hemoderivados e na comunicação fluida com a equipe de hemoterapia para o diagnóstico oportuno. Descrevemos o caso clínico de um recém-nascido prematuro que apresentou hipoxemia durante transfusão de concentrado de hemácias com necessidade de ventilação mecânica, alterações hemodinâmicas e febre. Descartamos processos infecciosos. A radiografia de tórax mostrou infiltrados compatíveis com edema pulmonar. Descartamos insuficiência cardíaca. Realizamos tratamento de suporte de funções vitais. A evolução foi favorável durante 72 horas. O caso foi relatado ao serviço de Hemoterapia. Para evitar transfusões desnecessárias, é importante que cada serviço revise periodicamente as diretrizes de transfusão de hemoderivados.

Shock neonatal como forma de presentación de panhipopituitarismo. A propósito de un caso clínico / Neonatal shock as the initial presentation of panhypopituitarism. A clinical case

Resumen: El panhipopituitarismo congénito es una enfermedad poco frecuente, de presentación clínica variable, dependiendo del déficit hormonal. La interrupción del tallo hipofisario, una de las etiologías, se diagnostica solo en un 23% de los casos en el período neonatal, causando hipogenesia de la hipófisis anterior y agenesia o ectopia de la hipófisis posterior. El diagnóstico temprano y el tratamiento oportuno condicionan la morbimortalidad. Se presenta el caso de un recién nacido de término, sexo femenino, pequeño para la edad gestacional, producto de embarazo y parto sin complicaciones. Sin dismorfias. Ingresó a la unidad neonatal a las 14 h de vida por hipotermia leve e hipoglicemias con elevados requerimientos de glucosa parenteral. En la evolución episodios reiterados de shock de etiología no clara, que responden al tratamiento instituido. Se descartó causa infecciosa, cardiovascular y metabólica. Agregó movimientos anormales, inestabilidad hemodinámica y anisocoria; por lo cual se solicitó resonancia nuclear magnética de cráneo que informo neurohipófisis ectópica asociado a tallo hipofisario y adenohipófisis hipoplásica. La determinación hormonal reveló: cortisol 0,2 (g/dl (normal >3 para recién nacidos de término), adenocorticotrofina (ACTH) 15,8 pg/ml (7,2-63,6), T4 0,78 ng/dl (1-1,6), TSH 3,83 (UI/ml (0,6-6) y hormona de crecimiento (GH) 2,45 ng/ml (0,05-6). Con diagnóstico de insuficiencia suprarrenal e hipotiroidismo secundario se inició tratamiento con hidrocortisona oral 20 mg/m2/día en dos dosis y T4 25 (g/día, con buena evolución posterior. Alta a domicilio a los 45 días de vida. El objetivo de esta presentación es exponer una etiología poco frecuente de un cuadro clínico habitual en la unidad neonatal, como lo es el shock.

Summary: Congenital panhypopituitarism is a rare disease which may have variable clinical presentations, depending on the hormonal deficit. Disruption of the hypophyseal stem, one of the etiologies, is diagnosed in only 23% of the cases in the neonatal period, causing hypogenesis of the anterior pituitary and agenesis or ectopia of the posterior pituitary. Early diagnosis and timely treatment have an impact on morbidity and mortality. We present the case of a term newborn, female, small for gestational age, product of pregnancy and childbirth without complications. No dysmorphism. She was admitted into the neonatal unit at 14 hours of life, due to mild hypothermia and hypoglycemia with high parenteral glucose requirements. In the evolution, repeated episodes of shock of unclear etiology occurred, which responded to the treatment applied. Infectious, cardiovascular and metabolic causes were ruled out. The patient added abnormal movements, hemodynamic instability and anisocoria. Thus, MRI of the skull was requested, and it revealed ectopic neurohypophysis associated with hypophyseal stem and hypoplastic adenohypophysis.

Uso de óxido nítrico inhalado en el tratamiento de la dificultad respiratoria temprana en el recién nacido pretérmino inmaduro y pretérmino tardío. Reporte de dos casos clínicos / Inhaled nitric oxide in the treatment of early respiratory failure in the late preterm and early term newborn. Report of two cases

La falla en la transición de la circulación fetal a la neonatal puede ser causada por la persistencia de resistencias vasculares elevadas, lo que induce al síndrome de hipertensión pulmonar (HPPN) que ocurre en aproximadamente 2 de cada 1.000 recién nacidos. La HPPN severa se asocia con recién nacidos de término o cercanos al término, si bien puede verse en recién nacidos prematuros. El tratamiento estándar de oro es el óxido nítrico inhalado (ONi) en neonatos con falla respiratoria hipóxica e HPPN. En el Departamento de Neonatología del Hospital de Clínicas de Montevideo se utilizó un generador in situ de óxido nítrico-NO- (TAS+plus®) portátil, capaz de producir continuamente el gas para ser entregado al recién nacido. Su bajo costo y accesibilidad han ampliado sus indicaciones en pacientes con asistencia ventilatoria mecánica (AVM), presión positiva continua en la vía aérea a través de cánula nasal (CPAP nasal) o bajo carpa cefálica. Presentamos dos pacientes con dificultad respiratoria, en los que una vez descartada cardiopatía congénita estructural y con evidencia ecocardiográfica de HPPN se administró ONi, concomitante al soporte respiratorio con CPAP nasal, con el objetivo de evitar la progresión de la enfermedad respiratoria y AVM. Dichos pacientes de 32 y 37 semanas, presentaron buena evolución de su dificultad respiratoria. La mejoría de la falla respiratoria hipóxica mediante la administración de ONi, sin necesidad de ventilación invasiva, fue posible, de bajo costo y fácil de aplicar a los pacientes, incorporando la utilización de un novel generador de ONi en la práctica clínica.

Failure in transition from fetal to neonatal circulation can be caused by the persistence of elevated vascular resistance, which can lead to pulmonary hypertension syndrome (HPPN), occuring in approximately 2 out of 1,000 live newborns. Severe HPPN is associated with term or near term newborns, although it may be seen in preterms. The gold standard treatment is inhaled nitric oxide (NOi) in neonates with hypoxic respiratory failure and HPPN. In the Department of Neonatology of the University Hospital in Montevideo, a portable, in situ generator of nitric oxide-NO- (TAS+plus®) was used, which is capable to continuously produce the gas to be delivered to the newborn. Its low cost and accessibility have expanded its indications to patients with mechanical ventilation (MVA), continuous positive airway pressure through nasal cannula (nasal CPAP) or cephalic carp. We present two patients with respiratory distress, in whom, once the structural congenital heart disease and echocardiographic evidence of HPPN were discarted, NOi was administered, concomitant with nasal CPAP, in order to avoid the progression of respiratory disease and AVM. These patients of 32 and 37 weeks presented good evolution of their respiratory difficulty. The improvement of hypoxic respiratory failure through the administration of NOi, without the need for invasive ventilation, was possible, low cost and easy to apply to patients, incorporating the use of a novel ONi generator in clinical practice.

Neuroprotección en pacientes con asfixia perinatal / Neuroprotection in patients with perinatal asphyxia

Introducción: la asfixia perinatal (APN) y su consecuencia, la encefalopatía hipóxico isquémica (EHI), son responsables de la elevada morbimortalidad neonatal e infantil. El desarrollo de una estrategia integral de neuroprotección que incluya hipotermia terapéutica busca mitigar sus efectos. Objetivo: evaluar la implementación de un protocolo global de neuroprotección en un servicio de recién nacidos. Metodología: estudio monocéntrico, retrospectivo y observacional de una cohorte de pacientes que recibieron hipotermia controlada entre 2011 y 2014 internados en el Centro Hospitalario Pereira Rossell (CHPR). El protocolo incluyó la formación del personal de enfermería y el equipo médico así como la adecuación tecnológica a tales efectos. Resultados: 20 pacientes cumplieron con criterios de inclusión, 2/20 no completaron las 72 horas necesarias de enfriamiento por alteración de la coagulación y sangrado activo refractario y 4/20 fallecieron. El enfriamiento activo se inició con una mediana de 60 minutos, y el objetivo de 33,5°C se alcanzó con una mediana de 2 horas. Se observó hiperoxia e hipocapnia en la asistencia inicial y acidosis metabólica, hiponatremia e hiperglicemia durante el período de mantenimiento así como sobre-diagnóstico de crisis convulsivas. Los trastornos de la coagulación fueron los efectos adversos más graves. Conclusión: la implementación de un protocolo de asistencia del paciente asfíctico con EHI moderada-severa permite la introducción de hipotermia controlada como estrategia para reducir la mortalidad, colocándola en los niveles observados para los países de altos ingresos. Muestra la necesidad de mejorar la asistencia inicial, de controlar alteraciones del metabolismo ácido-base, metabolismo glucídico, del sodio y sobre todo de las alteraciones de la coagulación como los fenómenos asociados de mayor gravedad.

Introduction: perinatal asphyxia and its consequence, the hypoxic-ischemic encephalopathy are responsible for the high level of morbidity (and mortality) in neonates and children. The development of a comprehensive neuroprotective strategy that includes therapeutic hypothermia, aims to mitigate its effects. Objective: our goal is to achieve the implementation of a global neuroprotection protocol in a newborn service. Methodology: monocentric, retrospective and observational study of a cohort of patients that received controlled hypothermia between 2011 and 2014 and were hospitalized in the Pereira Rossell Hospital Center (CHPR). The protocol included the training of the nursing staff and the medical team as well as the necessary technological adaptation. Results: 20 patients matched the inclusion criteria, 2/20 did not fulfill the 72 hours needed for the cooling by alteration of the coagulation and active refractory bleeding and 4/20 died. The active cooling started with a mean of 60 minutes, and the goal of 33,5°C was reached with a mean of 2 hours. Both hyperoxia and hypocapnia were observed in the initial assistance and metabolic acidosis, hyponatremia and hyperglicemia were also observed during the maintenance period, as well as over-diagnosis of convulsive crisis. Coagulation disorders were the most severe side effects. Conclusion: the implementation of a protocol of assistance of the asphyctic newborn with mild-severe HIE allows the introduction of controlled hypothermia as a strategy to reduce mortality, placing it on the levels observed in higher-income countries. It shows the need of improving the initial assistance, of controlling alterations in the acid-base metabolism, glucidic metabolism, sodium metabolism and above all, of the alterations of the coagulation as the associated phenomena of greatest severity.

Documentación filmográfica de la ventilación mecánica en un modelo animal / Filmed documentation of mechanical ventilation in an animal model

Introducción: el aprendizaje de la ventilación mecánica (VM) pediátrica requiere de tiempo y diversas estrategias educativas. En los últimos años se han utilizado los videopodcast para la educación médica. Objetivos: documentación filmográfica de los elementos básicos de la mecánica respiratoria durante la VM en un modelo animal. Creación de un videopodcast para la formación de recursos humanos especializados en VM pediátrica. Metodología: se prepararon diferentes secuencias de VM con ventilador y en forma manual. Se realizó exposición pulmonar mediante toracotomía y VM convencional en un cerdo. Se grabó simultáneamente lo monitorizado por el ventilador y la visualización in vivo del pulmón expuesto ante cada secuencia. Dos especialistas en cuidados intensivos pediátricos analizaron durante la edición las grabaciones y confeccionaron un guión explicativo de lo observado. Resultados: se editó un video con las diferentes secuencias previstas: VM basal, VM sin presión positiva teleespiratoria (PEEP), VM con niveles incrementales de PEEP, VM con bolsa autoinflable, aspiración de sonda endotraqueal con circuito cerrado y abierto durante VM con ventilador y manual con operador. Se editó un videopodcast con leyendas explicativas. Discusión: la utilización de recursos digitales para la enseñanza y divulgación de diversas especialidades médicas es cada vez más frecuente. El videopodcast se ha expandido como una nueva herramienta educativa. Se construyó un modelo para la capacitación de los recursos humanos en VM mediante este formato. La experiencia servirá para construir una videoteca universitaria dirigida a la enseñanza de cuidados críticos del niño y para la divulgación de experimentos biomédicos.

Introduction: learning about mechanical ventilation (MV) in pediatrics requires time and several educational strategies. In recent years, videopodcast has been used for medical training. Objectives: to prepare a filmed documentary of the basic elements in respiratory mechanics during MV in an animal model. To create a videopodcast to train human resources specialized in MV in pediatrics. Material: different sequences of MV with ventilator and manual ventilation were prepared. Lungs were accessed through thoracotomy and MV was started in a pig. Monitored data from the ventilator was simultaneously recorded, the same as the live visualization of the visible lung for each sequence. Two specialists in pediatrics intensive care analysed the recording while it was edited and composed a script explaining what was observed. Results: a video was edited with the different sequences expected: basal MV, MV with zero PEEP, increasing PEEP levels, MV with self-inflating bag, traqueal suction with open and closed traqueal suction systems and manual ventilation with an operator. A videopodcast with explanatory subtitles was edited. Discussion: digital resources are increasingly being used to train physicians and disseminate several medical techniques. Today, videopodcast constitutes a new educational tool. A model was designed to train human resources in MV under this format. This experience will be used to build up a new university video library to assist the training in pediatric critical care and to disseminate biomedical experiments.

Intravenous nanosomes of quercetin improve brain function and hemodynamic instability after severe hypoxia in newborn piglets.

Perinatal asphyxia is a major cause of death and neurological morbidity in newborns and oxidative stress is one of the critical mechanisms leading to permanent brain lesions in this pathology. In this context we have chosen quercetin, a natural antioxidant, known also by its brain protective effects to study its potential as a therapy for brain pathology provoked by severe hypoxia in the brain. To overcame the difficulties of quercetin to access the brain, we have developed lecithin/cholesterol/cyclodextrin nanosomes as a safe and protective vehicle. We have applied the nanosomal preparation intravenously to newborn piglets submitted to a severe hypoxic or ischemic/hypoxic episode and followed them for 8 or 72 h, respectively. Either towards the end of 8 h after hypoxia or up to 72 h after, electroencephalographic amplitude records in animals that received the nanosomes improved significantly. Animals receiving quercetin also stabilized blood pressure and recovered spontaneous breathing. In this experimental group mechanical ventilation assistance was withdrawn in the first 24 h while the hypoxic and vehicle groups required more than 24 h of mechanical ventilation. Three days after the hypoxia the suckling and walking capacity in the group that received quercetin recovered significantly compared with the hypoxic groups. Pathological studies did not show significant differences in the brain of newborn piglets treated with nanosomes compared with hypoxic groups. The beneficial effects of quercetin nanosomal preparation after experimental perinatal asphyxia show it as a promising putative treatment for the damaged brain in development.

Clampeo tardío de cordón umbilical: saturación de oxígeno en recién nacidos / Delayed umbilical cord clamping: oxygen saturation in newborn and value the presence of maternal and neonatal

Introducción: el retraso del clampeo de cordón umbilical tiene como beneficios la reducción del número de transfusiones de sangre y de la incidencia de hemorragia intraventricular en recién nacidos prematuros, además de la prevención de la anemia infantil. El objetivo de este trabajo es determinar los efectos del clampeo tardío sobre la saturación de oxígeno capilar y valorar la presencia de complicaciones maternas y neonatales en las primeras horas de adaptación a la vida extrauterina. Material y método: en 19 neonatos en los que se realizó el pinzamiento de cordón al cese de latidos umbilicales, se demostró el pasaje de sangre mediante el control continuo de la variación de peso. El tiempo promedio de cese del latido del cordón umbilical fue 2' 39" (±2' 27 "). Se controló de manera específica la saturación de oxígeno capilar, alcanzando 89% (± 4,6%), 94% (± 4,1%) y 96% (± 3,8%) a los 5, 10 y 15 minutos de vida respectivamente. La temperatura a los 10 minutos de vida fue de 36,6° ± 0,6°C. A las 48 horas de internación no se comprobó ictericia que requiriera fototerapia ni complicaciones cardiovasculares o respiratorias. Tampoco se comprobaron diferencias en los valores hematimétricos maternos, antes del parto y en el puerperio inmediato ni en el alumbramiento. Conclusiones: esperar el cese de latido de cordón umbilical no se asoció a complicaciones en las madres ni en la adaptación a la vida extrauterina de los recién nacidos en las primeras 48 horas de vida.

Introduction: delayed umbilical cord clamping has the benefit of reducing the number of blood transfusions and the incidence of intraventricular hemorrhage in pre-term infants, including the prevention of childhood anemia. The aim of this study is to determine the effects of late clamping on capillary oxygen saturation and value the presence of maternal and neonatal complications in the early hours of adaptation to extra-uterine life. Material and methods: in 19 infants who underwent the cord clamping the umbilical cessation of heartbeat, showed the passage of blood through the continuous monitoring of changes in weight. The average time of cessation of the heartbeat of the umbilical cord was 2'39" (±2' 27"). It is controlled specifically capillary oxygen saturation, reaching 89% (± 4,6%), 94% (± 4,1%) and 96% (± 3,8%) at 5, 10 and 15 minutes of life respectively. The temperature after 10 minutes of life was 36,6°C ± 0,6°C. After 48 hours of hospitalization were not found jaundice requiring phototherapy or cardiovascular or respiratory complications. Nor are differences found in maternal hematimetric values before delivery and the postpartum period or immediate delivery. Conclusions: waiting for the cessation of heartbeat umbilical cord was not associated with complications in mothers or in adapting to extra-uterine life of newborn babies within 48 hours of life.

Randomized trial of early bubble continuous positive airway pressure for very low birth weight infants.

OBJECTIVE: To determine whether very low birth weight infants (VLBWIs), initially supported with continuous positive airway pressure (CPAP) and then selectively treated with the INSURE (intubation, surfactant, and extubation to CPAP; CPAP/INSURE) protocol, need less mechanical ventilation than those supported with supplemental oxygen, surfactant, and mechanical ventilation if required (Oxygen/mechanical ventilation [MV]). STUDY DESIGN: In a multicenter randomized controlled trial, spontaneously breathing VLBWIs weighing 800-1500 g were allocated to receive either therapy. In the CPAP/INSURE group, if respiratory distress syndrome (RDS) did not occur, CPAP was discontinued after 3-6 hours. If RDS developed and the fraction of inspired oxygen (FiO(2)) was >0.35, the INSURE protocol was indicated. Failure criteria included FiO(2) >0.60, severe apnea or respiratory acidosis, and receipt of more than 2 doses of surfactant. In the Oxygen/MV group, in the presence of RDS, supplemental oxygen without CPAP was given, and if FiO(2) was >0.35, surfactant and mechanical ventilation were provided. RESULTS: A total of 256 patients were randomized to either the CPAP/INSURE group (n = 131) or the Oxygen/MV group (n = 125). The need for mechanical ventilation was lower in the CPAP/INSURE group (29.8% vs 50.4%; P = .001), as was the use of surfactant (27.5% vs 46.4%; P = .002). There were no differences in death, pneumothorax, bronchopulmonary dysplasia, and other complications of prematurity between the 2 groups. CONCLUSION: CPAP and early selective INSURE reduced the need for mechanical ventilation and surfactant in VLBWIs without increasing morbidity and death. These results may be particularly relevant for resource-limited regions.

Evaluación hemodinámica y respuesta al óxido nítrico inhalado ante hipoxia y acidosis en cerdos recién nacidos / Evaluate the effect of inhaled nitric oxide on hemodynamic response to hypoxia and acidosis in newborn pigs

La hipertensión pulmonar (HTP) es un trastorno de la adaptación a la vida extrauterina de muchos recién nacidos. La hipoxia y la acidosis son factores desencadenantes y perpetuadores de la misma. Objetivos: evaluar el efecto del óxido nítrico inhalado (ONi) a la respuesta vascular pulmonar a la hipoxia y acidosis en cerdos recién nacidos. Material y método: se diseñó una serie de intervenciones experimentales en cerdos recién nacidos, sedados, anestesiados y en asistencia ventilatoria mecánica. El protocolo experimental consistió en inducir hipoxia en forma controlada y progresiva (FiO2 desde 0,21 (basal) hasta 0,14; 0,10 o 0,08, mezclando nitrógeno con aire), entre 6 y 10 minutos, valorando la respuesta hemodinámica. Estabilizada la respuesta a la hipoxia con elevación en meseta de la presión arterial pulmonar (PAP) y sistémica, se administró ONi a 20 ppm. Mediante infusión de HCl 0,1 N i/v se estabilizó el pH en diferentes valores en los cuales se reiteraron esta serie de experimentos. Resultados: se encontró que el descenso de la FiO2 (debajo de 0,21) produce una caída de la saturación y un aumento inmediato de la PAP a diferentes pH y una efectividad del ONi para descender la PAP próximo a 70%. Sin embargo a pH más bajo la existencia de acidosis genera un nivel basal de PAP elevado con respecto a pH 7,4, que el ONi no desciende. En cuanto a la HTP desarrollada ante diferentes FiO2 se confirmó que la elevación de la PAP es gradualmente más elevada. Conclusión: en la investigación experimental en cerdos recién nacidos se observa que los eventos hipóxicos de breve duración generan HTP e inestabilidad sobre la hemodinamia sistémica. De igual modo la acidosis induce un incremento en la PAP basal en este modelo experimental. En estas condiciones la aplicación de ONi desciende la PAP eficazmente sin alterar la hemodinamia sistémica. Es más efectiva su acción a pH normal que en acidosis.

Pulmonary hypertension (HTP) is a frequently pathological situation of maladaptation to the extratuerine life in newborns. Hypoxia and acidosis are key factors capable of evoking the referred situation and can also act as a perpetuator factor of it. Objectives: To evaluate the effect of inhaled nitric oxide (iNO) on pulmonary vascular response to hypoxia and acidosis in newborn pigs. Material and methods: we performed a series of experimental interventions in newborn pigs, sedated, anesthetized and mechanical ventilation. The experimental protocol was to induce hypoxia in a controlled and progressive (FiO2 from 0.21 (baseline) to 0.14, 0.10 or 0.08, mixing nitrogen with air), between 6 and 10 minutes, evaluating the hemodynamic response. Stabilized response to hypoxia plateau elevation in pulmonary artery pressure (PAP) and systemic administered iNO at 20 ppm. By infusión of HC1 0.1 N i/v was stable at different pH valúes which were reiterated in this series of experiments. Results: we found that the decrease in FiO2 (below 0,21) produces a fall in saturation and an immediate increase in PAP at different pH and an ERA of iNO for the PAP down near 70%. However, at lower pH, the presence of acidosis produces a basal level of PAP high relative to pH 7.4, which does not descend iNO. As PH developed at different FiO2 was confirmed that the elevation of the PAP is gradually higher. Conclusion: experimental research in newborn pigs shows that the short-term hypoxic events genérate HTP and instability on systemic hemodynamics. Similarly acidosis induces an increase in baseline PAP in this experimental model. Under these conditions the application of iNO decreases the PAP effectively without altering systemic hemodynamics. Its action is more effective than normal pH in acidosis.

Evaluación hermodinámica y respuesta al óxido nítrico inhalado / Hemodynamic assessment and response to inhaled nitric oxide to hypoxia and acidosis un newborn pigs

La hipertensión pulmonar (HTP) es un trastorno de la adaptación a la vida extrauterina de muchos recién nacidos. La hipoxia y la acidosis son factores desencadenantes y perpetuadores de la misma. Objetivos: evaluar el efecto del óxido nítrico inhalado (ONi) a la respuesta vascular pulmonar a la hipoxia y acidosis en cerdos recién nacidos. Material y método: se diseñó una serie de intervenciones experimentales en cerdos recién nacidos, sedados, anestesiados y en asistencia ventilatoria mecánica. El protocolo experimental consistió en inducir hipoxia en forma controlada y progresiva (FiO2 desde 0,21 (basal) hasta 0,14; 0,10 o 0,08, mezclando nitrógeno con aire), entre 6 y 10 minutos, valorando la respuesta hemodinámica. Estabilizada la respuesta a la hipoxia con elevación en meseta de la presión arterial pulmonar (PAP) y sistémica, se administró ONi a 20 ppm. Mediante infusión de HCl 0,1 N i/v se estabilizó el pH en diferentes valores en los cuales se reiteraron esta serie de experimentos. Resultados: se encontró que el descenso de la FiO2 (debajo de 0,21) produce una caída de la saturación y un aumento inmediato de la PAP a diferentes pH y una efectividad del ONi para descender la PAP próximo a 70%. Sin embargo a pH más bajo la existencia de acidosis genera un nivel basal de PAP elevado con respecto a pH 7,4, que el ONi no desciende. En cuanto a la HTP desarrollada ante diferentes FiO2 se confirmó que la elevación de la PAP es gradualmente más elevada. Conclusión: en la investigación experimental en cerdos recién nacidos se observa que los eventos hipóxicos de breve duración generan HTP e inestabilidad sobre la hemodinamia sistémica. De igual modo la acidosis induce un incremento en la PAP basal en este modelo experimental. En estas condiciones la aplicación de ONi desciende la PAP eficazmente sin alterar la hemodinamia sistémica. Es más efectiva su acción a pH normal que en acidosis.

Pulmonary hypertension (HTP) is a frequently pathological situation of maladaptation to the extratuerine life in newborns. Hypoxia and acidosis are key factors capable of evoking the referred situation and can also act as a perpetuator factor of it. Objectives: To evaluate the effect of inhaled nitric oxide (iNO) on pulmonary vascular response to hypoxia and acidosis in newborn pigs. Material and methods: we performed a series of experimental interventions in newborn pigs, sedated, anesthetized and mechanical ventilation. The experimental protocol was to induce hypoxia in a controlled and progressive (FiO2 from 0.21 (baseline) to 0.14, 0.10 or 0.08, mixing nitrogen with air), between 6 and 10 minutes, evaluating the hemodynamic response. Stabilized response to hypoxia plateau elevation in pulmonary artery pressure (PAP) and systemic administered iNO at 20 ppm. By infusion of HCl 0.1 N i/v was stable at different pH values which were reiterated in this series of experiments. Results: we found that the decrease in FiO2 (below 0,21) produces a fall in saturation and an immediate increase in PAP at different pH and an ERA of iNO for the PAP down near 70%. However, at lower pH, the presence of acidosis produces a basal level of PAP high relative to pH 7.4, which does not descend iNO. As PH developed at different FiO2 was confirmed that the elevation of the PAP is gradually higher.Conclusion: experimental research in newborn pigs shows that the short-term hypoxic events generate HTP and instability on systemic hemodynamics. Similarly acidosis induces an increase in baseline PAP in this experimental model. Under these conditions the application of iNO decreases the PAP effectively without altering systemic hemodynamics...