Comparison between selective head cooling and whole-body cooling in neonatal therapeutic hypothermia / Comparação entre resfriamento seletivo da cabeça e resfriamento de corpo inteiro na hipotermia terapêutica neonatal

INTRODUCTION: Experimental evidence, as well as improved clinical studies of the reduction of brain injury and, improves the neurological outcome, in newborns with hypoxic-ischemic encephalopathy (HIE) occurring in therapeutic hypothermia (TH). OBJECTIVE: To verify the potential of hypothermic hypoxic-ischemic encephalopathy (HIE) therapy in neonatal asphyxia, based on literature data, comparing the benefits between selective head cooling (SHC) and whole-body cooling (WBC), see that the use of TH as a standard treatment in newborns with moderate or severe HIE has been adopted. METHODS: A search was performed in the PubMed and SciELO databases of human studies, using the keywords "Therapeutic Hypothermia", "Induced Hypothermia", and "Hypoxic-Ischemic Encephalopathy", "Selective cooling of the head", "Total body cooling" and its variables. RESULTS: Eleven articles were selected to compose the review, after detailed reading. There is a consensus, that the reduction of the risk of death or disability at 18 months of life in neonates with moderate to severe HIE, occurs to TH through the techniques of WBC or SHC. It was found in the studies that there is no difference in terms of adverse effects between the two methods. As for radiological changes, such as hypoxic-ischemic injuries and the incidence of seizures after cooling, they are more frequent with SHC. CONCLUSION: Both WBC and SHC demonstrated neuroprotective properties, although WBC provides a broader area of brain protection. However, no significant differences were found between the methods in terms of adverse effects and beneficial short or long-term results.

INTRODUÇÃO: Evidências experimentais, assim como estudos clínicos, sugerem a redução da lesão cerebral e melhora do desfecho neurológico, em recém-nascidos com encefalopatia isquêmica hipóxica (EHI) submetidos à hipotermia terapêutica (HT). OBJETIVO: Verificar a potencialidade da terapia hipotérmica de encefalopatia hipóxico-isquêmica (EHI) na asfixia neonatal, com base em dados da literatura, comparando os benefícios entre o resfriamento seletivo da cabeça (RSC) e o resfriamento de corpo inteiro (RCI), visto que o uso de hipotermia terapêutica (HT) como tratamento padrão em recém-nascidos com EHI moderada ou grave tem sido amplamente adotada. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed e SciELO de estudos em humanos, utilizando-se as palavras-chave "Therapeutic Hypothermia", "Induced Hypothermia", "Hypoxic-Ischemic Encephalopathy", "selective head cooling", "whole body cooling" e suas respectivas variáveis. RESULTADOS: Foram selecionados 11 artigos para compor a revisão, após leitura detalhada. É consenso, a redução do risco de morte ou incapacidade aos 18 meses de vida nos neonatos com EHI moderado a grave, submetidos à HT através das técnicas de RCI ou RSC. Constatou-se diante dos estudos que não há diferença em termos de efeitos adversos entre os dois métodos. Quanto às alterações radiológicas, as lesões hipóxico-isquêmicas e incidência de convulsões após o resfriamento são mais frequentes com o RSC. CONCLUSÃO: Tanto RCI quanto o RSC demonstraram propriedades neuroprotetoras, embora o RCI proporcione uma área de proteção cerebral mais ampla. No entanto, não foram constatadas diferenças significativas entre os métodos quanto a efeitos adversos e a resultados benéficos em curto e longo prazo.

Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical efficacy of mild therapeutic hypothermia (MTH) with different rewarming time on neonatal hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital, Xiamen University, from January 2018 to January 2022. These neonates were randomly divided into two groups: MTH1 group (n=50; rewarming for 10 hours at a rate of 0.25°C/h) and MTH2 group (n=51; rewarming for 25 hours at a rate of 0.10°C/h). The clinical features and the clinical efficacy were compared between the two groups. A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle (SWC) on amplitude-integrated electroencephalogram (aEEG) at 25 hours of rewarming.@*RESULTS@#There were no significant differences between the MTH1 and MTH2 groups in gestational age, 5-minute Apgar score, and proportion of neonates with moderate/severe HIE (P>0.05). Compared with the MTH2 group, the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming, a significantly shorter duration of oxygen dependence, a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming, and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5, 12, and 28 after birth (P<0.05), while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups (P>0.05). There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age (P>0.05). The binary logistic regression analysis showed that prolonged rewarming time (25 hours) was not conducive to the occurrence of normal SWC (OR=3.423, 95%CI: 1.237-9.469, P=0.018).@*CONCLUSIONS@#Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours. Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC, and therefore, it is not recommended as a routine treatment method.

A neonatal intelligent regulation system based on the combination of mild hypothermia mattress and hyperbaric oxygen chamber: introduction to a patent / 中国当代儿科杂志

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.

Impact of mild hypothermia therapy on hemodynamics during the induction stage in neonates with moderate to severe hypoxic-ischemic encephalopathy / 中国当代儿科杂志

OBJECTIVE@#To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously.@*RESULTS@#The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI (@*CONCLUSIONS@#The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.

Hipotermia terapêutica na encefalopatia hipóxico-isquêmica neonatal: revisão integrativa / Therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: integrative review / Hipotermia terapéutica em la encefalopatía hipóxico-isquémica neonatal: revisión integrativa

Objetivo: identificar evidências acerca do uso seguro da hipotermia terapêutica em recém-nascidos. Método: revisão integrativa realizada entre junho e julho de 2018, em fontes eletrônicas da Biblioteca Virtual de Saúde e PubMed, por meio da pergunta:"Que evidências podem subsidiar o cuidado de enfermagem voltado para a redução de sequelas em recém-nascidos submetidos à hipotermia terapêutica?".Foram eleitos nove artigos para análise, sendo oito internacionais e um nacional. Resultados:o resfriamento deve acontecer por 72 horas, com hipotermia leve. As indicações para inclusão no protocolo foram: primeiras seis horas de vida, idade gestacional maior que 35 semanas e acidose na primeira hora de vida.São cuidados essenciais: monitoração hemodinâmica, observação da pele, controle térmico retal, vigilância do Eletroencefalograma de Amplitude Integrada. Conclusão: a terapêutica apresenta benefícios, porém sua aplicação depende de protocolo institucional e treinamento das equipes com foco nas potenciais complicações.

Objective: to identify the evidence on safe use of therapeutic hypothermia in newborns. Method: integrative review of the literature, conducted between June and July of 2018, in electronic sources from the Virtual Health Library and PubMed, through the question: "What evidence can support nursing care aimed at reducing sequelae in newborns undergoing therapeutic hypothermia?". Analysis was conducted for nine selected article, being eight from international literature and one from Brazilian national literature. Results: cooling should occur for 72 hours with mild hypothermia. Indications for inclusion in the protocol were: first six hours of life, gestational age greater than 35 weeks and acidosis in the first hour of life. Essential care includes hemodynamic monitoring, skin observation, rectal thermal control, Integrated Amplitude Electroencephalogram surveillance. Conclusion: the therapy has benefits, but its application depends on institutional protocol and team training focusing on potential complications.

Objetivo: identificar la evidencia sobre el uso seguro de la hipotermia terapéutica en recién nacidos. Método: revisión integradora de la literatura, realizada entre junio y julio de 2018, en fuentes electrónicas de la Biblioteca Virtual de Salud y PubMed, a través de la pregunta: "¿Qué evidencia puede apoyar la atención de enfermería dirigida a reducir las secuelas en los recién nacidos que sufren hipotermia terapéutica?". Se realizaron análisis para nueve artículos seleccionados, ocho de literatura internacional y uno de literatura nacional brasileña. Resultados: el enfriamiento debe ocurrir durante 72 horas con hipotermia leve. Las indicaciones para la inclusión en el protocolo fueron: primeras seis horas de vida, edad gestacional mayor de 35 semanas y acidosis en la primera hora de vida. El cuidado esencial incluye monitoreo hemodinámico, observación de la piel, control térmico rectal, vigilancia integrada de electroencefalograma de amplitud. Conclusión: la terapia tiene beneficios, pero su aplicación depende del protocolo institucional y del entrenamiento del equipo, enfocándose en posibles complicaciones.

Hipomagnesemia en recién nacidos con encefalopatía hipóxico isquémica en hipotermia corporal total / Hypomagnesemia in newborns with hypoxic ischemic encephalopathy and whole-body hypothermia

Resumen: Introducción: En recién nacidos (RN) con encefalopatía hipóxico isquémica (EHI) en hipotermia se describen alte raciones metabólicas que se asocian a pronóstico neurológico. La hipomagnesemia ha sido reportada en la literatura, pero no es medida ni corregida en todos los centros de atención neonatal. Objeti vo: Evaluar la frecuencia de hipomagnesemia e hipocalcemia en RN con EHI en tratamiento con hipotermia corporal total y evaluar la respuesta al aporte de sulfato de magnesio. Pacientes y Méto do: Estudio prospectivo, observational y descriptivo en RN con EHI sometidos a hipotermia corporal total, hospitalizados entre los años 2016-2017. Se realizó medición seriada en sangre de magnesemia (Mg) y calcemia (Ca). Con Mg menor o igual de 1,8 mg/dl se administró suplemento como sulfato de Mg para mantener niveles entre 1,9 y 2,8 mg/dl. Se describió la frecuencia de hipomagnesemia e hipocalcemia y su presentación en el tiempo. Se realizó registro prospectivo de evolución clínica. Se hizo un análisis estadístico descriptivo, con medidas de tendencia central. Resultados: Se incluyeron 16 pacientes. Presentaron hipomagnesemia 13/16 (81,3%), la que fue precoz (6-36 h de vida), nor malizándose con aporte de sulfato de magnesio, requiriendo 2a dosis 4 de ellos. Presentaron hipo- calcemia 6/16 (37,5%). Conclusiones: La hipomagnesemia es frecuente (80%), similar a lo descrito en la literatura. Dado su importancia fisiológica debe controlarse y corregirse, de igual manera que el calcio.

Abstract: Introduction: In newborns with the diagnosis of hypoxic-ischemic encephalopathy (HIE) treated with hypother mia, metabolic alterations are observed, which are associated with neurological prognosis. Hypo magnesemia has been reported frequently in the literature in these patients, but it is not measured or corrected in all neonatal healthcare centers. Objective: To evaluate the frequency of hypomag nesemia and hypocalcemia in newborns with HIE treated with whole-body hypothermia and to evaluate the response to the magnesium sulfate administration. Patients and Method: Prospective, observational and descriptive study in hospitalized newborns with the diagnosis of HIE and trea ted with whole-body hypothermia between the years 2016 and 2017. Serial blood measurement of magnesemia (Mg) and calcemia (Ca) was performed. When presenting an Mg level < 1.8 mg/dl, supplementation with magnesium sulfate was administered to maintain levels between 1.9 and 2.8 mg/dl. The frecuency of hypomagnesemia, hypocalcemia and clinical evolution was registered. A descriptive statistical analysis was performed, with central tendency measures. Results: Sixteen ca ses were included, 13 of them presented hypomagnesemia (81.3%), with early-onset (6-36 hours of life), which was normalized with magnesium sulfate treatment, receiving a second dose 4 patients. Six of 16 patients presented hypocalcemia (37.5 %). Conclusions: Hypomagnesemia is frequent (80%), similar to that described in the literature, and should be controlled and corrected early, given its physiological role, in the same way that calcium is controlled.

Factores predominantes de encefalopatía neonatal: hipoxia e isquemia, un problema global / Predominant factors of neonatal encephalopathy: hypoxic and ischemia, a global problem

Si una dificultad sobreviene durante el nacimiento de un niño, por una anomalía materna o fetal, aguda o crónica, la asfixia del cerebro fetal constituye un riesgo mayor, porque ella podría dar como resultado la destrucción de las neuronas y la posibilidad de evolucionar hacia una encefalopatía hipóxico isquémica con secuelas a largo plazo. En esta revisión se resaltan los aspectos científicos más recientes pero a la vez se ofrece un margen de conocimiento imprescindible en cuanto a la patofisiología, diagnóstico y tratamiento, así como también se ofrece una perspectiva sobre el futuro de la atención clínica de la encefalopatía hipóxico isquémica.

If a difficulty arises during birth, due to a maternal or fetal anomaly, acute or chronic, asphyxia of the fetal brain constitutes a greater risk, because it could result in the destruction of neurons and the possibility of evolving towards a Ischemic Hypoxic Encephalopathy with long -term sequelae. This review highlights the most recent scientific aspects but at the same time it offers an essential margin of knowledge regarding pathophysiology, diagnosis and treatment, as well as offering a perspective on the future of clinical care of ischemic hypoxic encephalopathy.

Encefalopatía hipóxica-isquémica neonatal / Neonatal hypoxic-ischemic encephalopathy

La encefalopatía hipóxica-isquémica es un síndrome bien definido que afecta a los recién nacidos a término debido a asfixia fetal al nacer. La incidencia es 1-8 de cada 1000 nacidos en países desarrollados y asciende hasta 25 cada 1000 nacidos en países en desarrollo. Las causas más frecuentes son desprendimiento de la placenta, prolapso del cordón umbilical y rotura uterina. El criterio diagnóstico incluye incapacidad parcial o total del recién nacido para llorar y respirar al ser estimulado que requiere ventilación asistida en la sala de partos, Apgar < 5 en 5 y 10 minutos, acidemia (pH ≤ 7 y/o déficit de bases ≥ 12 mmol/l), alteraciones del estado de vigilia/sueño, de los reflejos primitivos y estiramiento muscular y tono muscular. En la forma leve la recuperación es total en tres días y sin (o con mínimas) secuelas de neurodesarrollo. En las formas moderadas y graves existen déficits neurológicos permanentes y alteraciones del neurodesarrollo (48%), 27% mueren y 25% son normales. El EEG regular o amplitud integrada y la resonancia magnética y espectroscópica realizados entre las 24 y las 96 horas y los 7 y 21 días de nacido respectivamente tienen un gran valor diagnóstico y pronóstico. Se recomienda hipotermia corporal (33.5 °C por 72 horas) antes de las 6 horas de nacido en las formas moderadas y graves. El resultado es una disminución de la mortalidad (de 35% a 27%) y de la morbilidad (de 48% a 27%).

Hypoxic-ischemic encephalopathy is a clearly recognizable clinical syndrome of in term newborns due to fetal asphyxia at birth. The incidence is 1.5 (95% CI 1.3 to 1.7) but it ranges from 1-8 and 25 out of every 1000 born in developed and developing countries, respectively. The most frequent causes are detachment of the placenta, prolapse of the umbilical cord and uterine rupture. The diagnostic criteria include partial or total incapacity for the newborn to cry and breath at birth even when stimulated, requiring assisted ventilation in the delivery room, Apgar < 5 in 5 and 10 minutes, acidemia (pH ≤ 7 and / or bases deficit ≥ 12 mmol/l), alterations of the conscience and the reflexes of Moro, grasping and suction, muscular stretching and muscle tone. The clinical forms are mild, moderate and severe. In the mild forms, the recovery is total in three days without, or with minimal, neurodevelopmental alterations. The moderate and severe forms cause permanent neurological deficits and neurodevelopmental alterations (48%) or death (27%). The regular or amplitude integrated EEG and the magnetic and spectroscopic magnetic resonance imaging performed between 24 and 96 hours and 7 and 21 days after birth, respectively, have a high diagnostic and prognostic value. Induced hypothermia (33.5° C for 72 hours) is recommended before 6 hours old. The result is a decrease in mortality (from 35% to 27%) and morbidity (from 48% to 27%).

Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy / Eficácia da hipotermia passiva e eventos adversos durante o transporte de recém-nascidos asfixiados de acordo com a gravidade da encefalopatia hipóxico-isquêmica

Abstract Objective To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. Methods This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Results Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4 ± 1.4 °C and mean transfer time was 3.3 ± 2.0 h. Mean age at arrival was 5.6 ± 2.5 h. Temperature at arrival was between 33 and 35 °C in 41 (61%) infants, between 35 °C and 36.5 °C in 15 (22%) and <33 °C in 11 (16%). Infants with severe hypoxic-ischemic encephalopathy had greater risk of having an admission temperature < 33 °C (OR: 4.5; 95% CI: 1.1-19.3). The severity of hypoxic-ischemic encephalopathy and the umbilical artery pH were independent risk factors for a low temperature on admission (p < 0.05). Adverse events during transfer, mainly hypotension and bleeding from the endotracheal tube, occurred in 14 infants (21%), with no differences between infants with moderate or severe hypoxic-ischemic encephalopathy. Conclusion The risk of overcooling during transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport.

Resumo Objetivo Determinar se a eficácia da hipotermia passiva e eventos adversos durante o transporte estão relacionados à gravidade da encefalopatia hipóxico-isquêmica neonatal. Métodos Estudo retrospectivo de 67 neonatos com encefalopatia hipóxico-isquêmica (nascidos entre abril de 2009 e dezembro de 2013) transferidos para hipotermia terapêutica e resfriados durante o transporte. Resultados Foram transportados 56 recém-nascidos (84%) sem fontes externas de calor e 11 (16%) precisaram de uma fonte externa de calor. A temperatura média na saída foi de 34,4 ± 1,4 °C e o tempo médio de transporte foi de 3,3 ± 2,0 horas. A idade média na chegada foi de 5,6 ± 2,5 horas. A temperatura na chegada ficou entre 33-35 °C em 41 (61%) neonatos, entre 35°-36,5 °C em 15 (22%) e < 33 °C em 11 (16%). Neonatos com encefalopatia hipóxico-isquêmica grave apresentaram maior risco de temperatura < 33 °C na internação (RC 4,5; IC de 95% 1,1-19,3). A gravidade da encefalopatia hipóxico-isquêmica e o pH da artéria umbilical foram fatores de risco independentes para uma baixa temperatura na internação (p < 0,05). Eventos adversos durante o transporte, principalmente hipotensão e sangramento do tubo endotraqueal, ocorreram em 14 neonatos (21%), sem diferenças entre neonatos com encefalopatia hipóxico-isquêmica moderada ou grave. Conclusão O risco de super-resfriamento durante o transporte é maior em recém-nascidos com encefalopatia hipóxico-isquêmica grave e naqueles com acidose mais grave no nascimento. Os eventos adversos mais comuns durante o transporte estão relacionados a deterioração fisiológica e sangramento do tubo endotraqueal. Essa observação fornece informações úteis para identificar neonatos asfixiados que exigem maior vigilância clínica durante o transporte.

Síndrome posterior do tronco cerebral e o uso de ventilação assistida ajustada neuralmente (nava) em lactente / Dorsal brainstem syndrome and the use of neurally adjusted ventilatory assist (nava) in an infant

RESUMO Objetivo: Relatar um caso raro de síndrome posterior do tronco cerebral em um lactente após um episódio hipóxico-isquêmico devido a sepse grave, e o uso da ventilação assistida ajustada neuralmente no auxílio diagnóstico e no desmame da ventilação mecânica. Descrição do caso: Lactente masculino de 2 meses de idade, previamente hígido, apresentou sepse grave que evoluiu para síndrome posterior do tronco encefálico, entidade que pode ocorrer após lesão hipóxico-isquêmica em neonatos e lactentes e que apresenta imagens de ressonância magnética muito particulares. Devido à lesão neurológica, permaneceu em ventilação mecânica. Optou-se por iniciar ventilação assistida ajustada neuralmente para verificar a patência da condução do nervo frênico ao diafragma e auxiliar no desmame da ventilação mecânica. Comentários: A síndrome posterior do tronco cerebral é uma entidade rara que deve ser considerada em lactentes após evento hipóxico-isquêmico.

ABSTRACT Objective: To report a rare case of dorsal brainstem syndrome in an infant after hypoxic-ischemic episode due to severe sepsis and the use of neurally adjusted ventilatory assist (NAVA) to aid in diagnosis and in the removal of mechanical ventilation. Case description: A 2-month-old male infant, previously healthy, presented with severe sepsis that evolved to dorsal brainstem syndrome, which usually occurs after hypoxic-ischemic injury in neonates and infants, and is related to very specific magnetic resonance images. Due to neurological lesions, thei nfant remained in mechanical ventilation. A NAVA module was installed to keep track of phrenic nerve conduction to the diaphragm, having successfully showed neural conduction and helped removing mechanical ventilation. Comments: Dorsal brainstem syndrome is a rare condition that should be considered after hypoxic-ischemic episode in infants.

Mechanical Ventilation of Neonates at the University Hospital of the West Indies 1987-2015 / Ventilación Mecánica de Neonatos en el Hospital Universitario de West Indies 1987-2015

ABSTRACT Aim: To compare present trends in utilization of the neonatal intensive care unit (NICU) with trends seen during the period when neonates were ventilated in the main intensive care unit of the University Hospital of the West Indies. Methods: Data from previously published studies on outcome of neonates ventilated at the main intensive care unit 1987-2001, the neonatal intensive care unit 2002-2004 and the annual perinatal statistics (2006-2010, 2015) were reviewed to detect trends in mechanical ventilation, utilization and outcome. Descriptive analyses were performed. Results: The number of neonates mechanically ventilated per thousand admissions increased from 10/1000 in the 1990s to 73/1000 in 2015. Percentage mortality for ventilated neonates increased from 51% between 1987-1991 to 62 % in 2015. The proportion of extremely low birthweight infants (< 1000 g) mechanically ventilated increased from 29% in 1987-1991 to 50% in 2015. The percentage mortality for extremely low birthweight infants increased from 17.5% in 1987-1991 to 40.6% in 2015. The percentage mortality for all other birthweight categories decreased over time. Respiratory distress syndrome remains the major reason for neonates requiring mechanical ventilation. Fifty per cent of neonates < 1500 g ventilated for respiratory distress syndrome received surfactant replacement therapy. Conclusion: Access to mechanical ventilation by neonates has increased tremendously at the University Hospital of the West Indies. The present challenge, however, is decreasing mortality in these neonates who access this technology.

RESUMEN Objetivo: Comparar las tendencias actuales en la utilización de la Unidad de Cuidados Intensivos Neonatales (UCIN) con las tendencias observadas durante el período en que los neonatos eran ventilados en la Unidad Principal de Cuidados Intensivos del Hospital Universitario de West Indies. Métodos: Se revisaron los datos de estudios publicados anteriormente sobre el resultado clínico de los neonatos ventilados en la Unidad Principal de Cuidados Intensivos en 1987-2001, La Unidad de Cuidados Intensivos Neonatales en 2002-2004 y las y las Esta-dísticas Perinatales Anuales (2006-2010, 2015) con el propósito de detectar las tendencias en la utilización y los resultados de la ventilación mecánica. Se realizaron análisis descriptivos. Resultados: El número de neonatos ventilados mecánicamente por cada mil ingresos aumentó de 10/1000 en la década de 1990 a 73/1000 en 2015. El porcentaje de mortalidad de neonatos ventilados aumentó de 51% entre 1987-1991 a 62% en 2015. La proporción de neonatos de peso extremadamente bajo al nacer (< 1000 g) ventilados mecánicamente aumentó de 29% en 1987-1991 a 50% en 2015. El porcentaje de mortalidad de recién nacidos de peso extremadamente bajo al nacer aumentó de 17.5% en 1987-1991 a 40.6% en 2015. La mortalidad porcentual para todas las otras categorías de peso al nacer disminuyó con el tiempo. El síndrome de dificultad respiratoria sigue siendo la razón principal por la que los neonatos requieren ventilación mecánica. El cincuenta por ciento de los neonatos < 1500 g ventilados por el síndrome de dificultad respiratoria recibió terapia de reemplazo de surfactantes. Conclusión: El acceso a la ventilación mecánica por los neonatos ha aumentado enormemente en el Hospital Universitario de West Indies. No obstante, el reto actual es disminuir la mortalidad de los neonatos que acceden a esta tecnología.

Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage

Abstract Purpose: To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). Methods: The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. Results: The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (p<0.01) and longer than that of sham-operated group. The piercing indexes of 3 treated groups were higher than that of HIBD control group (p<0.01). Conclusion: Hyperbaric oxygen and nerve growth factor treatments may improve learning and memory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.

Clinical hypoxic-ischemic encephalopathy score of the Iberoamerican Society of Neonatology (Siben): A new proposal for diagnosis and management / Escore clínico de encefalopatia hipóxico-isquêmica da Sociedad Iberoamericana de Neonatología (Siben): uma nova proposta para seu diagnóstico e manejo perinatal

Summary Hypoxic ischemic encephalopathy is a major complication of perinatal asphyxia, with high morbidity, mortality and neurologic sequelae as cerebral palsy, mostly in poor or developing countries. The difficulty in the diagnosis and management of newborns in these countries is astonishing, thus resulting in unreliable data on this pathology and bad outcomes regarding mortality and incidence of neurologic sequelae. The objective of this article is to present a new clinical diagnostic score to be started in the delivery room and to guide the therapeutic approach, in order to improve these results.

Resumo A encefalopatia hipóxico-isquêmica é a principal complicação da asfixia perinatal, com alta morbidade, mortalidade e incidência de sequelas neurológicas, como a paralisia cerebral, principalmente em países pobres e/ou em desenvolvimento. Nessas regiões, as dificuldades no diagnóstico e no manejo desses recém-nascidos é surpreendente, o que resulta em dados pouco confiáveis e em péssimos desfechos tanto no que se refere à mortalidade como à incidência de sequelas neurológicas. O objetivo deste artigo é apresentar um novo escore para o diagnóstico clínico ser iniciado na sala de parto e uma abordagem terapêutica com o intuito de melhorar esses resultados.

Hipotermia terapéutica: programa para prevención del daño neurológico de la encefalopatía hipóxico isquémica en Buenos Aires / THERAPEUTIC HYPOTHERMIA: A MODEL TO PREVENT NEUROLOGIC DAMAGE BY ISCHEMIC HIPOXIC ENCEPHALOPATHY

Introducción: La hipotermia terapéutica (HT) es el estándar de cuidado para la encefalopatía hipóxico-isquémica (EHI). El servicio de neonatología implemento el programa de HT en el marco de la red perinatal de la Ciudad de Buenos Aires (RPCABA). Objetivos: Describir la implementación del programa de hipotermia en RPCABA. Reportar la mortalidad, complicaciones y efectos adversos asociados al tratamiento. Métodos: La implementación del programa se realizó en etapas: 1) 2009- 2010 Capacitación y entrenamiento en el uso del equipamiento. 2) 2010 hasta la actualidad: Tratamiento y seguimiento para los pacientes con EHI moderada o grave. Resultados: Hasta Marzo de 2017, 65 neonatos recibieron HT (7 con hipotermia corporal total y los 58 restantes hipotermia activa selectiva), 49 paciente fueron clasificados según la Escala Sarnat & Sarnat como EHI moderada y 16 como EHI grave. Conclusiones: Fue factible implementar el programa en nuestra unidad, auditarlo para mejorarlo y sostenerlo en el tiempo. El sistema de traslado pudo responder ante la activación del "código de hipotermia", cumpliendo tiempos, sosteniendo el tratamiento y el monitoreo adecuado. Creemos necesario mejorar la identificación de neonatos con diagnóstico de EHI en RPCABA. Se necesita nueva capacitación para evitar el subdiagnóstico de esta patología en los centros de nivel 2

Therapeutic hypothermia (TH) is nowadays the gold standard of care for the treatment of hypoxic- ischemic encephalopathy (HIE) in developed countries. The term encephalopathy refers to a diffuse disturbance of brain function, resulting in behavioral changes, altered consciousness or seizures. The brain is particularly vulnerable to even brief interruptions of blood flow or oxygen supply. If the brain´s oxygen supply is insufficient, consciousness is lost rapidly. If oxygenation is restored immediately, consciousness returns without sequelae. However, if oxygen deprivation lasts longer than 1 or 2 minutes, signs of an encephalopathy may persists for hours or permanently. Total ischemic anoxia lasting longer than about 4 minutes usually results in severe irreversible brain damage. The aim of the present report was to describe the implementation of the hypothermia program in a model for the perinatal system at the City of Buenos Aires, with the equipment Cool Cap® for selective hypothermia, and the equipment CFM Olympic 6000® and CFM OMB from Medix® by Natus®, these two to monitoreate the cerebral function. The results obtained are referred, with special consideration to mortality, complications and adverse effects associated with the treatment.

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.

Influência da hipotermia terapêutica no desenvolvimento motor de recém-nascidos com encefalopatia hipóxico-isquêmica / Therapeutic hypothermia influence on the motor development of infants with hypoxic-ischemic encephalopathy

OBJETIVO: Avaliar a influência da hipotermia no desenvolvimento motor de recém-nascidos com encefalopatia hipóxico--isquêmica. MÉTODOS: Foi realizada pesquisa nas bases de dados LILACS, MEDLINE, SciELO, Bireme e PubMed, em português, inglês e espanhol. RESULTADOS: A encefalopatia hipóxico-isquêmica é uma das principais causas de morte neonatal e de deficiência a longo prazo. Todos os estudos utilizaram a hipotermia leve, e os critérios para inclusão de recém-nascidos com encefalopatia hipóxico-isquêmica não se diferenciaram entre si. A redução de taxa de mortalidade foi de 15%, e houve redução de deficiências a longo prazo. CONCLUSÃO: A técnica foi eficaz e segura, quando iniciada no prazo de 6 horas após o nascimento em crianças a termo. Ela reduziu a taxas de mortalidade e melhorou da gravidade neurológica, reduzindo a presença de deficiência motora e cognitiva na infância. São de grande importância a intervenção precoce e o acompanhamento do desenvolvimento.

OBJECTIVE: To evaluate the influence of hypothermia on motor development of infants with hypoxic-ischemic encephalopathy. METHODS: Research was conducted in the databases LILACS, MEDLINE, SciELO, Bireme and PubMed, in Portuguese, English and Spanish. RESULTS: Hypoxic-ischemic encephalopathy is a major cause of neonatal death and the presence of long-term disability. All studies used mild hypothermia, and the criteria for inclusion of newborns with hypoxic-ischemic encephalopathy did not differ among themselves. The reduction of mortality rate was 15%, and decreased long-term disabilities. CONCLUSION: The technique was safe and effective when started within 6 hours after birth in full-term infants. She has reduced mortality rates and improved neurological severity of, reducing the presence of motor and cognitive impairment in children. They are of great importance to early intervention and monitoring of development

Necrosis grasa subcutánea con hipercalcemia persistente en un neonato tratado con hipotermia terapéutica: Reporte de un caso / Subcutaneous fat necrosis and persistent hypercalcaemia in a newborn treated with therapeutic neonatal hypothermia: A case report

La hipotermia terapéutica constituye el tratamiento de elección para los recién nacidos con encefalopatía hipóxico-isquémica moderada-grave, que cambia el pronóstico de estos niños y se acepta como una técnica segura y con escasas complicaciones secundarias considerando su beneficio. Un posible efecto adverso es la necrosis grasa subcutánea, una paniculitis transitoria aguda de presentación durante las primeras semanas de vida. Se presenta un caso de un recién nacido a término afecto de encefalopatía hipóxico-isquémica con lesiones cutáneas en forma de eritema multiforme generalizado y placas eritematosas firmes e induradas en la espalda, los glúteos y las extremidades a los 12 días de vida, tras el tratamiento con hipotermia. El estudio histopatológico, tras la biopsia cutánea, confirmó la sospecha de necrosis grasa subcutánea. Al mes de vida, presentó cifras elevadas de calcio sérico, que precisaron tratamiento con hidratación intravenosa y diuréticos. La calcemia descendió hasta normalizarse a los 3 meses, con desaparición progresiva de las lesiones cutáneas.

Therapeutic hypothermia is the current standard treatment in newborns with moderate to severe hypoxic-ischemic encephalopathy, changing the outcome of these children. It is considered a safe technique with almost no side effects. A possible adverse side event is subcutaneous fat necrosis, which is an acute self-limiting panniculitis that develops during the first weeks of life. We report a case of a newborn at term suffering hypoxic-ischemic encephalopathy with a generalized multiform erythematous rash and firm and indurated plaques over the back, buttocks and extremities on his 12th day of life after being treated with therapeutic hypothermia. Histopathological study after skin punchbiopsy confirmed the suspicion of subcutaneous fat necrosis. The infant developed asymptomatic moderate hypercalcaemia within the first month of life, which was treated with intravenous fluids and diuretics. Serum calcium levels decreased and normalized in 3 months, with progressive disappearance of skin lesions.