Lesión cerebral post paro cardiaco: aspectos médicos, éticos y legales / Brain injury after cardiac arrest: Medical, ethical and legal issues disorder

RESUMEN Los sobrevivientes de la reanimación cardiopulmonar posterior a un paro cardiaco pueden tener un amplio rango de desenlaces y van desde recuperación neurológica completa, estado de vigilia sin respuesta, compromiso cognoscitivo diverso o la muerte. La lesión del tejido cerebral se presenta inmediatamente después del paro cardíaco, durante la reanimación y al retornar la circulación espontánea. La severidad y duración de la noxa isquémica determinarán el devenir neurológico. El examen clínico es el punto de partida en el abordaje multimodal del neuropronóstico. Se debe complementar con electroencefalograma, potenciales evocados somatosensoriales, neuroimágenes y biomar-cadores séricos. Entre un 10 a 15% de los pacientes con lesión cerebral posterior al paro cardiaco evolucionan hacia muerte por criterios neurológicos y son potenciales candidatos a la donación de órganos. Un retiro temprano de las terapias de sostenimiento de vida puede malograr la posibilidad de un potencial donante de órganos. Se puede estimar de manera temprana qué pacientes tienen mayor riesgo de evolucionar a muerte por criterios neurológicos. El neurólogo tiene un papel protagónico en el manejo de pacientes con lesión cerebral post paro cardiaco y sus decisiones tienen implicaciones éticas y legales.

ABSTRACT People who survive cardiopulmonary resuscitation (CPR) after cardiac arrest, have a wide range of outcomes including complete neurological recovery, coma, compromised cognitive function and death. Injury of the brain parenchyma starts immediately after a cardiac arrest, during CPR and return of spontaneous circulation. The severity of the ischemic injury will define the neurological outcome. The first step needed to determine a neurological prognosis is the clinical exam, with the help of electroencephalography, somatosensory evoked potentials, neuroimaging, and serum biomarkers. Between 10 and 15% of patients with brain injury after a cardiac arrest, develop brain death and become potential candidates for organ donation. A premature withdrawal of vital support can hamper the possibility of organ donation. The patients with higher risk of developing brain death can be identified early based on neurological criteria. The neurologist has a major role in the approach of patients with brain injury after cardiac arrest and the decision making with legal and ethical consequences.

Evaluación renal y multiorgánica en el paciente con encefalopatía hipóxico-isquémica / Renal and multiorgan evaluation in infants with post-asphyxial hypoxic-ischaemic encephalopathy

Resumen Introducción: La encefalopatía hipóxico-isquémica (EHI) moderada-grave secundaria a asfixia perinatal puede afectar a cualquier órgano, empeorando el pronóstico. Objetivo: Evaluar la afectación renal y multiorgánica de estos pacientes. Material y método: Se incluyó a recién nacidos > 35 semanas con EHI moderada-grave tratados con hipotermia activa entre 2010 y 2020. Se evaluó la creatinina en tres periodos: 48-72 horas de vida, entre el 3.o y 7.o día de vida y del 7.o al 28.o día de vida. Resultados: Se incluyeron 135 pacientes: 112 con EHI moderada y 23 con EHI grave. Al comparar ambos grupos, se obtuvieron diferencias significativas a las 48-72 horas y entre 3.o-7.o día de vida. No hubo diferencias al comparar el método de hipotermia. Los pacientes con EHI grave presentaron mayor afectación hemodinámica, respiratoria y hepática. Conclusiones: Neonatos con EHI grave presentan aumento de los niveles de creatinina sérica y mayor afectación multiorgánica respecto a aquellos con EHI moderada.

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia can affect any organ, worsening the prognosis. Objective: To describe renal and multiorgan involvement in moderate-severe HIE. Material and method: Newborns > 35 weeks diagnosed with moderate-severe HIE who required active hypothermia between 2010-2020 were included. To assess renal involvement, serum creatinine was measured in three different periods: at 48-72 hours, between the 3rd and the 7th day, and from the 7th to the 28th day. Results: A total of 135 patients were included, 112 (83%) with moderate and 23 (17%) with severe HIE. Significant differences were obtained when comparing median creatinine levels at 48-72 hours and between 3-7 days in both groups. There were no differences in creatinine according to the hypothermia method. Patients with severe HIE presented greater hemodynamic, respiratory, and hepatic involvement. Conclusions: Neonates with severe HIE present increased serum creatinine levels and greater multi-organ involvement than those with moderate HIE.

Application status of generalized periodic discharges in continuous electroencephalography monitoring in hypoxic-ischemic encephalopathy / 中华神经科杂志

In the electroencephalography (EEG) monitoring of patients with hypoxic-ischemic encephalopathy, generalized periodic discharges are often monitored abnormal waveforms. When there are some features of generalized periodic discharges (e.g., frequency≥1.5 Hz or plus), it indicates that the patient is at high risk for seizures or has a poor prognosis. Compared with conventional EEG, the time of continuous EEG monitoring is longer, so the detection rate of these waveforms is higher. At present, scholars at home and abroad have studied these waveforms, but there is controversy about the significance of these waveforms. In this paper, the definition and characteristics of these waveforms and their significance in determining prognosis and guiding treatment in patients with hypoxic-ischemic encephalopathy are reviewed.

The role of SUMOylation in the protective mechanisms of therapeutic hypothermia on neonatal hypoxic-ischemic encephalopathy / 中国新生儿科杂志

Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.

Early enteral feeding guided by intestinal ultrasound during therapeutic hypothermia for hypoxic-ischemic encephalopathy in neonates / 中国新生儿科杂志

Objective:To study the safety and feasibility of early enteral feeding during therapeutic hypothermia guided by intestinal ultrasound in neonates with hypoxic-ischemic encephalopathy (HIE).Methods:From January 2019 to December 2021, neonates with HIE who received therapeutic hypothermia in the neonatology department of our hospital were retrospectively selected. They were assigned into the ultrasound-guided observation group (admitted from May 2020 to December 2021) and the control group (admitted from January 2019 to April 2020). In the ultrasound-guided observation group, intestinal ultrasound was performed during therapeutic hypothermia. Based on clinical manifestations and ultrasound results, a small amount of enteral feeding [20 ml/(kg·d)] was initiated and gradually increased to total enteral feeding after rewarming. In the control group, 5 ml (once every 3 h) of glucose and sodium chloride solution was given during 72 h of therapeutic hypothermia. After rewarming, enteral feeding was started and gradually increased to total enteral feeding without intestinal ultrasound. The time to start enteral feeding, the time to achieve total enteral feeding, the incidences of feeding intolerance, necrotizing enterocolitis (NEC) and late-onset sepsis were compared between the two groups.Results:A total of 17 cases were in the ultrasound-guided observation group and 18 cases in the control group. The median time to start enteral feeding and to achieve total enteral feeding in the ultrasound-guided observation group were earlier than the control group [36.0 (33.5, 39.0) h vs. 77.0 (74.0, 79.3) h, 6.0 (5.5, 6.5) d vs. 8.0 (7.0, 9.0) d, P<0.001]. No significant difference existed in the incidence of feeding intolerance between the two groups. Neither groups had NEC or late-onset sepsis. Conclusions:Early enteral feeding during therapeutic hypothermia in neonates with HIE is safe and feasible. Intestinal ultrasound helps implementing feeding plan and achieving early total enteral feeding.

Progress of bedside monitoring tools in neonate with hypoxic-ischemic encephalopathy / 国际儿科学杂志

Neonatal hypoxic-ischemic encephalopathy (HIE) is a perinatal hypoxic ischemic injury caused by hypoxia, which is one of the common neurological disorders in neonatal period, and the untimely treatment can lead to serious complications and sequelae, including poor neurodevelopmental outcome and death.Currently, no specific therapeutic drugs have been found for this disease, so early clinical intervention is very important.This article reviews the advantages and disadvantages of cranial ultrasound, amplitude-integrated electroencephalography, and near-infrared spectroscopy for the diagnosis of neonatal HIE and the monitoring of brain function, as well as the outlook for the use of portable magnetic resonance.The aim is to provide cerebral function monitoring and early diagnosis and treatment for children with HIE, and to better predict their immediate and long-term outcomes.

A novel method for electroencephalography background analysis in neonates with hypoxic-ischemic encephalopathy / 中国当代儿科杂志

OBJECTIVES@#To explore a new method for electroencephalography (EEG) background analysis in neonates with hypoxic-ischemic encephalopathy (HIE) and its relationship with clinical grading and head magnetic resonance imaging (MRI) grading.@*METHODS@#A retrospective analysis was performed for the video electroencephalography (vEEG) and amplitude-integrated electroencephalography (aEEG) monitoring data within 24 hours after birth of neonates diagnosed with HIE from January 2016 to August 2022. All items of EEG background analysis were enrolled into an assessment system and were scored according to severity to obtain the total EEG score. The correlations of total EEG score with total MRI score and total Sarnat score (TSS, used to evaluate clinical gradings) were analyzed by Spearman correlation analysis. The total EEG score was compared among the neonates with different clinical gradings and among the neonates with different head MRI gradings. The receiver operating characteristic (ROC) curve and the area under thecurve (AUC) were used to evaluate the value of total EEG score in diagnosing moderate/severe head MRI abnormalities and clinical moderate/severe HIE, which was then compared with the aEEG grading method.@*RESULTS@#A total of 50 neonates with HIE were included. The total EEG score was positively correlated with the total head MRI score and TSS (rs=0.840 and 0.611 respectively, P<0.001). There were significant differences in the total EEG score between different clinical grading groups and different head MRI grading groups (P<0.05). The total EEG score and the aEEG grading method had an AUC of 0.936 and 0.617 respectively in judging moderate/severe head MRI abnormalities (P<0.01) and an AUC of 0.887 and 0.796 respectively in judging clinical moderate/severe HIE (P>0.05). The total EEG scores of ≤6 points, 7-13 points, and ≥14 points were defined as mild, moderate, and severe EEG abnormalities respectively, which had the best consistency with clinical grading and head MRI grading (P<0.05).@*CONCLUSIONS@#The new EEG background scoring method can quantitatively reflect the severity of brain injury and can be used for the judgment of brain function in neonates with HIE.

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.

Effect of ligustrazine on hypoxic-ischemic encephalopathy in neonatal rats by regulating autophagy through the PINK1/Parkin pathway / 中国当代儿科杂志

OBJECTIVES@#To study the effect of ligustrazine injection on mitophagy in neonatal rats with hypoxic-ischemic encephalopathy (HIE) and its molecular mechanism.@*METHODS@#Neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group with 8 rats, a model group with 12 rats, and a ligustrazine group with 12 rats. The rats in the model group and the ligustrazine group were used to establish a neonatal rat model of HIE by ligation of the left common carotid artery followed by hypoxia treatment, and blood vessels were exposed without any other treatment for the rats in the sham-operation group. The rats in the ligustrazine group were intraperitoneally injected with ligustrazine (20 mg/kg) daily after hypoxia-ischemia, and those in the sham-operation group and the model group were intraperitoneally injected with an equal volume of normal saline daily. Samples were collected after 7 days of treatment. Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of neurons in brain tissue; immunohistochemical staining was used to observe the positive expression of PINK1 and Parkin in the hippocampus and cortex; TUNEL staining was used to measure neuronal apoptosis; Western blotting was used to measure the expression levels of the mitophagy pathway proteins PINK1 and Parkin and the autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (P62).@*RESULTS@#Compared with the sham-operation group, the model group had a significant reduction in the number of neurons, an increase in intercellular space, loose arrangement, lipid vacuolization, and a reduction in Nissl bodies. The increased positive expression of PINK1 and Parkin, apoptosis rate of neurons, and protein expression levels of PINK1, Parkin, Beclin1 and LC3 (P<0.05) and the decreased protein expression level of P62 in the hippocampus were also observed in the model group (P<0.05). Compared with the model group, the ligustrazine group had a significant increase in the number of neurons with ordered arrangement and an increase in Nissl bodies, significant reductions in the positive expression of PINK1 and Parkin, the apoptosis rate of neurons, and the protein expression levels of PINK1, Parkin, Beclin1, and LC3 (P<0.05), and a significant increase in the protein expression level of P62 (P<0.05).@*CONCLUSIONS@#Ligustrazine can alleviate hypoxic-ischemic brain damage and inhibit neuronal apoptosis in neonatal rats to a certain extent, possibly by inhibiting PINK1/Parkin-mediated autophagy.

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.

Correlation of Clinical Profile and Electroencephalographic Finding in Hypoxic-Ischemic Encephalopathy in a Tertiary Care Hospital: A Single-Center Experience from Bangladesh

Background: Perinatal asphyxia and resultant hypoxic-ischemic encephalopathy (HIE) is not an uncommon phenomenon in a developing country, like Bangladesh. Electroencephalogram (EEG) is regarded as an effective prognostic tool. Correlation of clinical profiles and EEG findings of HIE patients arenot commonly observed in Bangladesh. The aim of the study was to observe the clinical profile and EEG changes in different stages of hypoxic-ischemic encephalopathy and compare them in a tertiary care hospital.Material & Methods:This is a cross-sectional observational study conducted for a period of six months in Dhaka Medical College Hospital, Dhaka. Sarnat and Sarnat score was used to classify HIE. 20 asphyxiated neonates without HIE were selected as the control group (group II) while 30asphyxiated neonates with HIE, were selected as the case group (group I) by purposive sampling. Clinical profiles, EEG findings, and immediate outcomes were observed and compared between the two groups.Results:73.3% patients were delivered at term and 30% patients were delivered at home in group I. 70% patients’ delivery were conducted by doctor in group I and 75% in group II. 63.3% patients had meconium stain in group I and 25% in group II, which was found significant. 46.7% had prolong labor in group I and 20% in group II, 40% had premature ruptured membrane (PROM) in group I and 40% in group II. Hypothermia, weak primitive reflexes, hypotonia, lethargy and seizure were significantly higher in group I. Changes in EEG correlated between the two groups and was found significant. Also, patients in group I, needed prolong hospital stay.Conclusions:The clinical profiles and EEG changes in patients with hypoxic ischemic encephalopathy was concluded that there is significant association with meconium stain, seizure, hypothermia, weak primitive reflexes, lethargic, miosis, hypotonia, poor APGAR score, burst suppression & SET findings in EEG and prolonged hospital stay in prenatal asphyxia with hypoxic ischemic encephalopathy.

Adición de melatonina a terapia con hipotermia para encefalopatía hipóxico-isquémica neonatal / Addition of melatonin to hypothermia therapy for neonatal hypoxic-ischemic encephalopathy

Introducción La encefalopatía hipóxico-isquémica neonatal es una patología caracterizada por una disfunción neurológica aguda, de severidad variable, causada por un episodio asfíctico perinatal. Se presenta en uno a seis de cada 1000 recién nacidos de término, asociándose a una alta morbimortalidad neonatal y a desenlaces neurológicos adversos. El uso de hipotermia es considerado como la terapia estándar para esta condición. Sin embargo, debido a su limitada eficacia clínica, se han propuesto diferentes opciones terapéuticas adyuvantes, incluyendo el uso de fármacos como la melatonina. Existe controversia sobre si la terapia combinada con melatonina es superior a la monoterapia con hipotermia. Métodos Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta-análisis y preparamos una tabla de resumen de los resultados utilizando el método Grading of Recommendations Assessment, Development and Evaluation, GRADE Resultados Identificamos dos revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, ambos ensayos aleatorizados. Se incluyeron los dos ensayos aleatorizados en el análisis del presente trabajo. Conclusiones No es posible establecer con claridad si la adición de melatonina disminuye la mortalidad o la probabilidad de presentar alteraciones reflejadas en la resonancia magnética cerebral, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja. Por otro lado, adicionar melatonina a la terapia con hipotermia, comparado con la monoterapia con hipotermia, podría aumentar la probabilidad de que el examen neurológico sea normal a los seis meses, y que la cognición sea normal a los 18 meses. Finalmente, la adición de melatonina a la terapia con hipotermia probablemente disminuya la probabilidad de presentar convulsiones.

Introduction Neonatal hypoxic-ischemic encephalopathy is caused by perinatal asphyxia, resulting in an acute neurological dysfunction of variable severity. It occurs in one to six of every 1000 full-term newborns and is associated with high neonatal morbimortality and adverse neurological outcomes. The use of hypothermia is considered the standard therapy for this condition. However, different adjuvant therapeutic options have been proposed due to limited clinical efficacy, including drugs like melatonin. There is controversy about whether combined therapy with melatonin is superior to monotherapy with hypothermia. Methods We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, and Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of the findings table using the GRADE approach. Results We identified two systematic reviews that included two primary studies, both randomized trials. The two randomized trials were included in the analysis of the present work. Conclusion It is not possible to establish whether the addition of melatonin decreases mortality or the probability of alterations in brain magnetic resonance imaging because the certainty of the existing evidence has been assessed as very low. On the other hand, the addition of melatonin to hypothermia therapy, compared to hypothermia monotherapy, may increase the probability of normal neurological examination at six months and the probability of normal cognition at 18 months. Finally, adding melatonin to hypothermia therapy likely reduces the probability of seizures.

Effect of pediatric Tuina combined with nerve growth factor therapy on neural function of children with acute ischemic hypoxic encephalopathy / 国际中医中药杂志

Objective:To explore the effect of pediatric massage combined with nerve growth factor treatment on the neurological function of children with acute ischemic hypoxic encephalopathy (HIS).Methods:A total of 96 children with HIS who were treated in Hubei Maternal and Child Health Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from February 2017 to October 2019 were selected for the study. The children were divided into 2 groups using a random number table method, with 48 cases in each group. The control group was treated with nerve growth factor on the basis of conventional treatment, and the observation group was treated with pediatric massage on the basis of the control group. The clinical efficacy, neurobehavior, intelligence index, EEG index, cerebral blood flow and hematology index were compared between the two groups.Results:The total effective rate of the observation group was 95.84%, which was higher than 81.25% of the control group, and the difference between the two groups was statistically significant ( χ2=5.03, P=0.025). The 28-day NBNA score ( t=-2.55, P=0.012) and three-month MDI and PDI of the observation group were significantly higher than those of the control group ( t values were -3.43, -2.65, all Ps<0.01). After treatment, the EEG spike wave amplitude of the two groups of children decreased significantly, and the decrease was greater in the observation group[(35.02 ± 4.16) mV vs. (46.92±5.81)mV, t=11.54]. After treatment, the cerebral blood flow of the two groups of children increased significantly, and the increase was more significant in the observation group [(179.36 ± 22.25) ml/(100 g?min) vs. (158.30±14.92) ml/(100 g?min), t=-5.45]. After treatment, the levels of MBP, NSE and VEGF in the two groups of children decreased significantly, but the decrease in the observation group was greater ( t values were 3.29, 4.07, 8.17, all Ps<0.01). Conclusion:Pediatric massage combined with nerve growth factor alone can improve the curative effect of children with HIS, improve neurobehavioral and intelligent indicators, increase cerebral blood flow, and reduce EEG spike wave amplitude and MBP, NSE and VEGF levels.

Progress on controversial treatment of mild hypothermia for neonatal hypoxic-ischemic encephalopathy / 国际儿科学杂志

Hypoxic-ischemic encephalopathy (HIE) is one of the main causes of neonatal morbidity, mortality and disability.Randomized clinical trials have confirmed the safety and effectiveness of mild hypothermia in the treatment of neonatal HIE, and it can significantly reduce the mortality and disability rate of the disease.Although mild hypothermia can improve the prognosis of some neonates with HIE, there is still some controversy about the selection of treatment subjects, the time window and whether it is effective in the resource-limited countries.This article reviews the research progress on controversial parts of mild hypothermia treatment in recent years, so as to provide the corresponding reference basis for clinical decision-making.

The impact of therapeutic hypothermia on peripheral blood cell in newborns with hypoxic ischemic encephalopathy

Abstract The effect of hypothermia treatment on white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) values as an indicator of inflammation was evaluated in newborns with hypoxic ischemic encephalopathy (HIE). The study was performed that the before-therapeutic hypothermia (TH) and after-TH WBC, lymphocytes, neutrophils, monocytes and NLR, LMR and PLR values of the complete blood cell count were retrospectively evaluated. The results of the patient group were compared with the results of healthy newborns. A total of 78 patients who underwent TH were evaluated in our study. Mean values before and after TH were NLR3.8/2.7, LMR 5.6/8.6, and PLR 60.3/67.1 respectively. A statistical significance was present for NLR values before and after TH in those with seizure in our study (4.15±2.95/3.01±2.54) but no statistical significance was found for LMR or PLR. In neonates with HIE, effect of TH on complete blood cell count and inflammatory mechanisms (mediated neutrophil and lymphocyte) may be minimal.

Changes of brain functional network in neonates with different degrees of hypoxic-ischemic encephalopathy / 中华行为医学与脑科学杂志

Objective:To explore the changes of brain network functional connection in neonates with different degrees of hypoxic-ischemic encephalopathy(HIE), and to understand its influence on brain function.Methods:Clinical data of full-term HIE children hospitalized in Neonatology Department of Changzhou Children's Hospital from January 2017 to May 2020 were collected by convenient sampling method. A total of 44 cases were scanned by conventional and functional magnetic resonance image.Twenty-four of them met the inclusion criteria, including 11 mild patients (PT1 group) and 13 moderate and severe patients (PT2 group). The amplitude of low frequency fluctuation (ALFF) was used to compare the differences of ALFF values between PT1 group and PT2 group, and the differences of functional connectivity (FC) between PT1 group and PT2 group were compared by the method of brain network connectivity analysis.Results:In the edge analysis, compared with the PT1 group, the FC of the right supplementary motor area and the right precentral gyrus ( Z1=0.39, Z2 =-0.08), the right lingual gyrus and the right hippocampus ( Z1=0.61, Z2=0.20), the left calcarine cortex and the right amygdala ( Z1=0.30, Z2=-0.02), the right pallidus and the right posterior cingulate cortex ( Z1=0.33, Z2=0.05) were decreased in the PT2 group (all P<0.001, uncorrected). In ALFF analysis, there was no significant difference between PT1 group and PT2 group ( P>0.05, FDR adjusted). Conclusion:There are changes in functional connections in some brain regions in children with moderate and severe HIE.These functional connections are related to motor function, emotional processing, language development, cognitive function, learning and memory, etcetera.

Urinary uric acid or urinary creatinine ratio as a non-invasive marker for perinatal asphyxia

Background: Perinatal asphyxia is amongst the common problem of neonates and there exists a significant contribution to the neonatal morbidity and mortality. It is observed as a common and a vital cause of the preventable cerebral injury. The prediction of the perinatal asphyxial outcome is very important but dreadful. There is a limited role for APGAR score to predict the immediate outcome, like HIE and the long-term neurological sequelae observational error may happen in APGAR. But the biochemical parameters can truly be relied upon. This study was done to assess urinary uric acid/urinary creatinine ratio (UA/Cr) as a non-invasive marker for perinatal asphyxia and co-relate its absolute value to the degree of the perinatal asphyxia.Methods: In this prospective case control study conducted in the Pediatrics Department of Shri Ram Murti Smarak Institute of Medical Sciences between Nov 2017 to May 2019, 42 asphyxiated and 42 non-asphyxiated newborns were included. Detailed history and assessment were for all the enrolled newborns. Spot urine samples were sent for the uric acid and creatinine estimation. Results were documented, and statistical analysis was performed.Results: Urinary uric acid to creatinine ratio used as additional non-invasive, early and easy biochemical marker of the birth asphyxia that biochemically supports severity grading and clinical diagnosis of the asphyxia by APGAR score.Conclusions: The ratio of the urinary uric acid and creatinine enables rapid and early recognition of asphyxial injury and also the evaluation of its severity and potential for short-term morbidity or death.

N-terminal pro brain natriuretic peptide as a marker of myocardial dysfunction in newborns with perinatal asphyxia

Background: Perinatal asphyxia refers to a condition during first and second stage of labour in which impaired gas exchange leads to foetal hypoxemia. Perinatal asphyxia causes cardiac dysfunction in 24 to 60 percent of the cases. The reduced cardiovascular reserve is associated with hypoxic brain damage and has high impact on neonatal mortality and adverse neurological outcomes. It has been challenging to diagnose myocardial dysfunction in resource constraint setting. Aim and objective of this study was to Determine N-Terminal Pro BNP concentrations in perinatal asphyxia and correlate with modified Sarnat stages of hypoxic ischemic encephalopathy.Methods: Among 120 Neonates admitted in neonatal intensive care unit with diagnosis of perinatal asphyxia were considered for the study. 2mL of venous blood drawn within 48hours of life was analyzed for quantitative N-Terminal Pro BNP and was correlated with modified Sarnat stages of hypoxic ischemic encephalopathy.Results: A Total of 120 cases of perinatal asphyxia were considered for the study, among which 44 cases had HIE stage 1, 48 had HIE stage 2 and rest 28 had HIE stage 3. The mean and standard deviation of N-Terminal Pro BNP concentrations in stage 1 was 1,502.86'3,581.170 pg/mL, stage 2 was 4,916.31'8,001.674 pg/mL and stage 3 was 8,912.41'13,927.152 pg/mL with significant p value of 0.003.Conclusions: Early N-Terminal Pro BNP concentrations may provide a useful marker for the anticipated severity of myocardial dysfunction.

Características clínicas y del electroencefalograma de amplitud integrada en recién nacidos con encefalopatía hipóxico-isquémica bajo protocolo de hipotermia corporal total / Clinical and integrated amplitude electroencephalogram characteristics of newborns with hypoxic-ischemic encephalopathy under the protocol of total body hypothermia

RESUMEN La encefalopatía hipóxico-isquémica (EHI) es causa importante de mortalidad y discapacidad neurológica en neonatos. La evidencia sugiere que la terapia de hipotermia es capaz de impactar estos desenlaces. Este estudio se realizó con el objetivo de describir las características clínicas y las ayudas diagnósticas realizadas a recién nacidos con EHI sometidos a terapia de hipotermia corporal total con el uso de criterios preestablecidos de ingreso a la terapia, en una muestra de dos instituciones de la ciudad de Medellín. MÉTODOS: Se realizó un estudio descriptivo en el periodo 2017-2018, incluyendo la totalidad de pacientes con EHI ingresados a terapia de hipotermia. RESULTADOS: Se obtuvieron datos de 256 pacientes, con predominio masculino (182; 71,1%). Se evidenciaron fallas en el registro y subjetividad en la aplicación de los criterios de ingreso al protocolo de hipotermia en ambas instituciones. En 197 pacientes (77 %) no hubo reporte de evento centinela, y el expulsivo prolongado fue considerado por los clínicos un hallazgo significativo a la hora de definir el ingreso a la terapia. Hubo, además, pacientes ingresados que no cumplieron con el criterio de APGAR ≤ 5 a los 10 minutos (n = 136). Los resultados sugieren la necesidad de mejorar la adherencia al protocolo de ingreso a la terapia, pero al mismo tiempo señalan la importancia del concepto del clínico a la hora de abordar cada paciente de manera individual.

SUMMARY Hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality in the neonatal population and neurological disability. The evidence shows that hypothermia therapy is capable of impacting these outcomes. This study was carried out with the objective of describing the clinical characteristics and the diagnostic aids made to newborns with HIE undergoing total body hypothermia therapy and the use of criteria for admission to therapy in a sample of two institutions in the city of Medellin. METHODS: A descriptive retrospective study was conducted, including all patients with HIE admitted to hypothermia therapy during 2017 and 2018. RESULTS: The data of 256 patients (males 182; 71.1 %) were obtained. There were flaws in the registry and subjectivity in the application of the entry criteria to the hypothermia protocol in both institutions. In 197 (77 %) patients there was no report of sentinel event and the prolonged labour was considered by the clinicians as a significant finding when defining the entrance to the therapy. There were also admitted patients who did not meet the criterion of APGAR ≤ 5 at 10 minutes (n = 136). The results suggest the need to improve adherence to the protocol for admission to therapy; but at the same time, it points out the importance of the clinician's concept when dealing with each patient individually.

A prospective observational study to describe magnetic resonance imaging findings in perinatal asphyxia in terms of severity, outcome and neurological sequel in term and preterm babies

Background: Perinatal asphyxia is a significant cause of neonatal mortality and morbidity. MRI is useful for assessing the severity and pattern of brain injuries. There is less data of MRI findings of perinatal asphyxia from India and the subcontinents. This prospective observational study was done to describe MRI brain findings in neonates with perinatal asphyxia with respect to various determinants.Methods:' Initial MRI brain was done when babies were stable after fulfilling inclusion criteria. Immediate outcome was assessed at the end of hospital stay. They were followed up for presence of any sequel up to 1 year. Repeat MRI brain was done in few selected babies. Data was collected and statistically analyzed.Results: Total 55 babies were included in the study (term 27, preterm 28). There were 9 babies in stage 1, 17 babies in stage II and 22 babies in stage III. MRI brain findings were normal in 8 and abnormal in 47 patients. There were Deep gray matter injury (DG) in 22, Para Sagittal subcortical white matter injury (PS) in 6, Germinal matrix haemorrage (GMH), intraventricular haemorrage (IVH) and Periventricular leucomalacia (PVL) in 12 and Mixed pattern of injury in 7 babies. Findings among 9 expired babies were: 4 (44.4%) DG, 2 (22.2%) GMH+IVH and 3 (33.3%) mixed. There was neurological sequel in 13 babies (48.1%).' Babies with normal MRI initially had no sequel.Conclusion: Brain injury due to perinatal asphyxia follows several patterns according to gestational age and severity. Early and accurate recognition of these patterns with the help of MRI brain helps in managing the baby and predicting the prognosis.