Nutrition of Newborns with Hypoxic-Ischaemic Encephalopathy during Therapeutic Hypothermia - A Survey of Practice in Polish Neonatal Care Units.

BACKGROUND: The nutritional practice for newborns with hypoxic-ischaemic encephalopathy during therapeutic hypothermia differs among Polish neonatal care units, as no guidelines are provided. We assessed the prevailing procedures. MATERIAL AND METHODS: Data was collected through an anonymous, web-based questionnaire. We surveyed aspects of the current nutritional practices and the reasoning behind the choice of the feeding strategy. RESULTS: Thirty-one responses were obtained (31/33, 94%). Based on participants' estimations, 342 newborns are diagnosed with hypoxic-ischaemic encephalopathy and qualified for therapeutic hypothermia annually. Among them, almost ⅓ is fed exclusively parenterally, while 71% both ways-parenterally and enterally. In the vast majority of units, the introduction of enteral nutrition takes place during the first 48 hours of therapeutic hypothermia, and breast milk is primarily provided, although with substantial first feeding volume differentiation (an average of 2,9 ml/kg (0,3 - 10ml/kg)). Adverse events, such as necrotising enterocolitis, sepsis, and glycemia level disturbances that derive from the initiation of enteral nutrition, are difficult to estimate as no official statistics are provided. CONCLUSIONS: The majority of newborns after hypoxic-ischaemic encephalopathy treated with therapeutic hypothermia are fed both parenterally and enterally during the procedure, predominantly with expressed or donor breast milk. However, due to the lack of nutritional guidelines, significant variability of nutritional strategies concerning initiation time, type and volume of enteral feeds given is noted. Therefore, further studies are required to clarify feeding recommendations.

Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however, additional neuroprotective agents are required to improve prognosis. The authors searched for all drugs in combination with HT and compared their effects using a network meta-analysis. METHODS: The authors searched PubMed, Embase, and Cochrane Library until September 24, 2022 for articles assessing mortality, NDI, seizures, and abnormal brain imaging findings in neonates with hypoxic-ischemic encephalopathy. Direct pairwise comparisons and a network meta-analysis was performed under random effects. RESULTS: Thirteen randomized clinical trials enroled 902 newborns treated with six combination therapies: erythropoietin magnesium sulfate, melatonin (MT), topiramate, xenon, and darbepoetin alfa. The results of all comparisons were not statistically significant, except for NDI, HT vs. MT+HT: odds ratio = 6.67, 95% confidence interval = 1.14-38.83; however, the overall evidence quality was low for the small sample size. CONCLUSIONS: Currently, no combination therapy can reduce mortality, seizures, or abnormal brain imaging findings in neonatal hypoxic-ischemic encephalopathy. According to low quality evidence, HT combined with MT may reduce NDI.

Acupuncture on intrauterine growth restriction associated brain injury: case study including use of magnetic resonance imaging.

Brain injury due to intrauterine growth restriction (IUGR) is a thorny clinical problem that often leads to permanent neurological deficits such as cerebral palsy. Few practical therapies can treat an IUGR-associated brain injury. We employed acupuncture to treat a 6-month-old male patient with severe hypoxic-ischemic encephalopathy (HIE) due to IUGR, as confirmed by magnetic resonance imaging (MRI). Three courses of acupuncture treatment significantly improved some of the patient's clinical characteristics, such as his insensitive responsiveness and motor deficits, with remarkably reversed HIE features on MRI at 1-year of age. This case suggests that acupuncture is a potential treatment option for an IUGR-associated brain injury and warrants further investigation.

[A neonatal intelligent regulation system based on the combination of mild hypothermia mattress and hyperbaric oxygen chamber: introduction to a patent]. / 基于亚低温床垫与高压氧舱结合的新生儿智能调控系统.

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.

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.

Early versus delayed enteral nutrition for neonatal hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: a randomized controlled trial.

BACKGROUND: The practice of therapeutic hypothermia (TH) is widely used for neonatal hypoxic-ischemic encephalopathy (HIE) despite its corresponding feeding strategies are still controversial. This randomized controlled trial (RCT) demonstrated to evaluate the effect of early vs. delayed enteral nutrition on the incidence of feeding intolerance (FI) and other association during TH. METHODS: This single center, parallel-group, and no-blinded RCT was processed in a level III, and academic neonatal intensive care unit. Infants who were diagnosed with HIE and undertaken TH from September 2020 to August 2021 were enrolled. Participants were randomized to receive enteral nutrition either during TH/rewarming (early enteral nutrition, EEN) or after TH (delayed enteral nutrition, DEN) according to a recommend enteral feeding protocol. All data were analyzed using SPSS 26.0 software with a p-value< 0.05 was considered statistically significant. RESULTS: Ninety-two infants were enrolled after randomization, but 12 (13.04%) cases including 3 (3.26%) deaths were excluded from eventually analyzed, who did not initiate or discontinue the intervention. 80 cases (42 and 38 in the EEN and DEN group, respectively) who completed the interventions were eventually analyzed. Besides initial time of enteral feeds, two groups had processed the same feeding method. Total 23 (25.0%) cases developed FI, and no difference of morbidity was found between two groups (23.4% vs 26.7%, p = 0.595; Log Rank, p = 0.803). There was no case died or developed late-onset bloodstream and no difference of the incidence of hypoglycemia or weight gain was found (p > 0.05). The percentage of infants who had not reaching the goal of full enteral feeding volume between the two groups was similar (21.43% vs 23.68%, p = 0.809). The average time of parenteral nutrition, reaching full enteral feeds and hospital stay were shorter in the EEN group compared with the DEN group with significant differences (8.81 ± 1.67 vs 10.61 ± 2.06 days, p < 0.001; 9.91 ± 1.88 vs 12.24 ± 2.50 days, p < 0.001; 12.55 ± 4.57 vs 16.47 ± 5.27 days, p = 0.001 respectively). CONCLUSIONS: Compared with delayed enteral nutrition, introduction of early enteral nutrition according to a recommend feeding strategy for neonatal HIE undergoing TH may be feasible and safe.FI is frequent in this high-risk group of infants which should not be ignored during feeding process. TRIAL REGISTRATION: The Chinese Clinical Trial Registry,ChiCTR2000038193, 2020-9-13, https://www.chictr.org.cn .

The efficacy and safety of massage therapy as an adjuvant in the treatment of hypoxic ischemic encephalopathy in neonates: A protocol for systematic review and meta-analysis.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) has become a major problem that endangers the life and health of newborns. It is the most serious complication after neonatal asphyxia with a high mortality rate. Even survivors of HIE would suffer permanent neurological developmental impairment that seriously affects the growth and development in the future. Previous studies have shown that massage therapy can improve the prognosis of neonatal HIE. However, the efficacy of massage therapy on the growth, development, and sleep in neonates with HIE reported by various studies is inconsistent, which will be thoroughly assessed in this meta-analysis. METHODS: Randomized controlled trials of massage therapy on the growth, development, and sleep neonates with HIE published before February 2022 will be retrieved from the PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Database, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, and Clinical Trial Register. Literature selection, data extraction, risk of bias assessment, and meta-analyses will be independently completed by 2 researchers. Meta-analysis will be performed by using RevMan5.4. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This systematic review provides a high-quality synthesis to assess the effect of massage therapy on growth, development, and sleep in neonates with HIE. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/G9WXN.

[Therapeutic effects of moxibustion on neonatal mice with hypoxia-ischemia brain injury].

Objective: To investigate the effects of moxibustion on the behavioral performance, brain morphological structure of mice with hypoxia-ischemia brain injury and to explore its mechanisms. Methods: One hundred and six ICR mice were randomly divided into three groups, sham group (n=23), model group (n=46) and moxibustion-treated group (n=37). Neonatal hypoxic-ischemia brain injury was induced by ligation of common carotid artery followed by hypoxia (8% oxygen, 100 min), and pups in the moxibustion-treated group were administered suspended moxibustion on the Dazhui points (GV14) at a height of approximately 2 cm over a hairless area of the skin once a day for 4 days (i.e. at 2, 24, 48 and 72 hours after hypoxia-ischemia procedure). Behavioral tests were used to evaluate behavioral performance. HE staining was used to observe brain morphological structure. Western blot was used to detect the expression of SOD2 protein, and spectrophotometry was used to determine the content of MDA in the ipsilateral brain. Results: Mouse pups in sham group showed that the behavioral performance was normal, the brain tissue cells were densely and neatly arranged, the expression of SOD2 and the level of MDA in the brain tissues were normal. Compared with sham group, mouse pups in the HI model group exhibited a significant longer latency to complete the righting reflex, geotaxis reflex, cliff avoidance (P＜0.05) and a marked shorter latency to complete the grip test (P＜0.05); and the HI model group had dramatic brain morphological changes showing missing regions, decreased expression of SOD2 protein (P＜0.05) and increased level of MDA in the brain. Compared with HI model group, mouse pups in the moxibustion-treated group exhibited a significant shorter latency to complete the righting reflex, geotaxis reflex, cliff avoidance test (P＜0.05) and a marked longer latency to complete the grip test (P＜0.05); and the moxibustion-treated group had less brain morphological changes, increased expression of SOD2 protein (P＜0.05) and decreased level of MDA in the brain (P＜0.05) . Conclusion: Moxibustion could improve behavioral performance and attenuate hypoxia-ischemia brain injury, which might be related to increasing the expression of SOD2 protein and decreasing the content of MDA, thus enhancing the anti-oxidative ability.

Dose-Dependent Neuroprotective Effects of Bovine Lactoferrin Following Neonatal Hypoxia-Ischemia in the Immature Rat Brain.

Injuries to the developing brain due to hypoxia-ischemia (HI) are common causes of neurological disabilities in preterm babies. HI, with oxygen deprivation to the brain or reduced cerebral blood perfusion due to birth asphyxia, often leads to severe brain damage and sequelae. Injury mechanisms include glutamate excitotoxicity, oxidative stress, blood-brain barrier dysfunction, and exacerbated inflammation. Nutritional intervention is emerging as a therapeutic alternative to prevent and rescue brain from HI injury. Lactoferrin (Lf) is an iron-binding protein present in saliva, tears, and breast milk, which has been shown to have antioxidant, anti-inflammatory and anti-apoptotic properties when administered to mothers as a dietary supplement during pregnancy and/or lactation in preclinical studies of developmental brain injuries. However, despite Lf's promising neuroprotective effects, there is no established dose. Here, we tested three different doses of dietary maternal Lf supplementation using the postnatal day 3 HI model and evaluated the acute neurochemical damage profile using 1H Magnetic Resonance Spectroscopy (MRS) and long-term microstructure alterations using advanced diffusion imaging (DTI/NODDI) allied to protein expression and histological analysis. Pregnant Wistar rats were fed either control diet or bovine Lf supplemented chow at 0.1, 1, or 10 g/kg/body weight concentration from the last day of pregnancy (embryonic day 21-E21) to weaning. At postnatal day 3 (P3), pups from both sexes had their right common carotid artery permanently occluded and were exposed to 6% oxygen for 30 min. Sham rats had the incision but neither surgery nor hypoxia episode. At P4, MRS was performed on a 9.4 T scanner to obtain the neurochemical profile in the cortex. At P4 and P25, histological analysis and protein expression were assessed in the cortex and hippocampus. Brain volumes and ex vivo microstructural analysis using DTI/NODDI parameters were performed at P25. Acute metabolic disturbance induced in cortical tissue by HIP3 was reversed with all three doses of Lf. However, data obtained from MRS show that Lf neuroprotective effects were modulated by the dose. Through western blotting analysis, we observed that HI pups supplemented with Lf at 0.1 and 1 g/kg were able to counteract glutamatergic excitotoxicity and prevent metabolic failure. When 10 g/kg was administered, we observed reduced brain volumes, increased astrogliosis, and hypomyelination, pointing to detrimental effects of high Lf dose. In conclusion, Lf supplementation attenuates, in a dose-dependent manner, the acute and long-term cerebral injury caused by HI. Lf reached its optimal effects at a dose of 1 g/kg, which pinpoints the need to better understand effects of Lf, the pathways involved and possible harmful effects. These new data reinforce our knowledge regarding neuroprotection in developmental brain injury using Lf through lactation and provide new insights into lactoferrin's neuroprotection capacities and limitation for immature brains.

NIR Laser Photobiomodulation Induces Neuroprotection in an In Vitro Model of Cerebral Hypoxia/Ischemia.

Brain photobiomodulation (PBM) is an innovative treatment for a variety of neurological conditions, including cerebral ischemia. However, the capability of PBM for ischemic stroke needs to be further explored and its mechanisms of action remain currently unclear. The aim of the present research was to identify a treatment protocol capable of inducing neuroprotection and to investigate the molecular mechanisms activated by a dual-wavelength near infrared (NIR) laser source in an organotypic hippocampal slice model of hypoxia/ischemia. Hippocampal slices were exposed to oxygen and glucose deprivation (OGD) for 30 min followed by NIR laser light (fluence 3.71, 7.42, or 14.84 J/cm2; wavelengths 808 nm and 905 nm) delivered immediately or 30 min or 60 min after OGD, in order to establish a therapeutic window. Neuronal injury was assessed by propidium iodide fluorescence 24 h later. Our results show that NIR laser irradiation attenuates OGD neurotoxicity once applied immediately or 30 min after OGD. Western blot analysis of proteins involved in neuroinflammation (iNOS, COX-2, NFkB subunit p65, and Bcl-2) and in glutamatergic-mediated synaptic activity (vGluT1, EAAT2, GluN1, and PSD95) showed that the protein modifications induced by OGD were reverted by NIR laser application. Moreover, CA1 confocal microscopy revealed that the profound morphological changes induced by OGD were reverted by NIR laser radiation. In conclusion, NIR laser radiation attenuates OGD neurotoxicity in organotypic hippocampal slices through attenuation of inflammatory mechanisms. These findings shed light on molecular definition of NIR neuroprotective mechanisms, thus underlining the potential benefit of this technique for the treatment of cerebral ischemia.

Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury.

In term and near-term neonates with neonatal encephalopathy, therapeutic hypothermia protocols are well established. The current focus is on how to improve outcomes further and the challenge is to find safe and complementary therapies that confer additional protection, regeneration or repair in addition to cooling. Following hypoxia-ischemia, brain injury evolves over three main phases (latent, secondary and tertiary), each with a different brain energy, perfusion, neurochemical and inflammatory milieu. While therapeutic hypothermia has targeted the latent and secondary phase, we now need therapies that cover the continuum of brain injury that spans hours, days, weeks and months after the initial event. Most agents have several therapeutic actions but can be broadly classified under a predominant action (e.g., free radical scavenging, anti-apoptotic, anti-inflammatory, neuroregeneration, and vascular effects). Promising early/secondary phase therapies include Allopurinol, Azithromycin, Exendin-4, Magnesium, Melatonin, Noble gases and Sildenafil. Tertiary phase agents include Erythropoietin, Stem cells and others. We review a selection of promising therapeutic agents on the translational pipeline and suggest a framework for neuroprotection and neurorestoration that targets the evolving injury.

Neurological symptoms improved by hyperbaric oxygen therapy in a post-cardiac arrest patient due to carbon monoxide poisoning: a case report.

Background: Carbon monoxide (CO) poisoning and cardiac arrest can cause neurological complications such as mental deterioration and movement disorders through ischemic brain injury. We report a case in which neurological sequelae after cardiac arrest caused by CO poisoning improved after hyperbaric oxygen (HBO2) therapy. Case report: A 43-year-old male visited the hospital with cardiac arrest due to CO poisoning. He developed neurological sequelae including mental deterioration and myoclonus after recovering spontaneous circulation. Anticonvulsant therapy was used after target temperature management but did not have a positive effect on neurological symptoms. However, after HBO2 therapy the patient's neurological symptoms improved, and he was discharged a month later. Conclusion: HBO2 therapy may be considered when neurological sequelae persist after cardiac arrest due to CO poisoning.

[Effect of moxibustion on learning and memory in neonatal hypoxic-ischemia encephalopathy mice].

OBJECTIVE: To observe the effect of moxibustion on the expression of phosphorylated calcium/calmodulin-dependent protein kinase Ⅱα(pCaMKⅡα) and neuronal nuclei (NeuN) and the ability of learning and memory in the neonatal mice model of hypoxic-ischemia encephalopathy(HIE), so as to explore its mechanism underlying improvement of learning and memory. METHODS: ICR mice (aged 7 days) were randomly divided into sham operation, model and moxibustion groups. HIE model was induced by ligation of the right common carotid artery combined with hypoxia in a closed transparent chamber. Mice in the moxibustion group were treated with gentle moxibustion at "Dazhui"(GV14) for 35 min，once daily for 3 consecutive days. The pathological changes of brain tissues were observed with the naked eyes and under microscope after H.E. staining, respectively. The expressions of pCaMKⅡα and NeuN in the ischemic penumbra were examined by immunofluorescent staining, and the learning and memory ablility was tested with Morris maze. RESULTS: No infarcts were found in the brain tissue of the mice in the sham operation group. Compared with the sham operation group, mice in the model group had infarcts and the expression of pCaMKⅡα and NeuN in the ischemic penumbra was significantly reduced (P<0.01), and the latency to find a platform was significantly prolonged in Morris maze test (P<0.01). After moxibustion, in comparison with the model group showed that, small areas of infarction were seen in the right hemisphere of the moxibustion group, and the expressions of pCaMKⅡα, NeuN increased significantly (P<0.01), and the latency to find a platform was significantly shortened (P<0.01). CONCLUSION: Moxibustion can improve the ability of learning and memory in the neonatal mice with HIE, which might be related to alleviating brain injury and increasing the expression of pCaMKⅡα in neurons of ischemic brain tissues.

Objective and Clinically Feasible Analysis of Diffusion MRI Data can Help Predict Dystonia After Neonatal Brain Injury.

BACKGROUND: Dystonia in cerebral palsy is debilitating but underdiagnosed precluding targeted treatment that is most effective if instituted early. Deep gray matter injury is associated with dystonic cerebral palsy but is difficult to quantify. Objective and clinically feasible identification of injury preceding dystonia could help determine the children at the highest risk for developing dystonia and thus facilitate early dystonia detection. METHODS: We examined brain magnetic resonance images from four- to five-day-old neonates after therapeutic hypothermia for hypoxic-ischemic encephalopathy at a tertiary care center. Apparent diffusion coefficient values in the striatum and thalamus were determined using a web-based viewer integrated with the electronic medical record (IBM iConnect Access). The notes of specialists in neonatal neurology, pediatric movement disorders, and pediatric cerebral palsy (physicians most familiar with motor phenotyping after neonatal brain injury) were screened for all subjects through age of five years for motor phenotype documentation. RESULTS: Striatal and thalamic apparent diffusion coefficient values significantly predicted dystonia with receiver operator characteristic areas under the curve of 0.862 (P = 0.0004) and 0.838 (P = 0.001), respectively (n = 50 subjects). Striatal apparent diffusion coefficient values less than 1.014 × 10-3 mm2/s provided 100% specificity and 70% sensitivity for dystonia. Thalamic apparent diffusion coefficient values less than 0.973 × 10-3 mm2/s provided 100% specificity and 80% sensitivity for dystonia. CONCLUSIONS: Lower striatal and thalamic apparent diffusion coefficient values predicted dystonia in four- to five-day-old neonates who underwent therapeutic hypothermia for hypoxic ischemic encephalopathy. Objective and clinically feasible neonatal brain imaging assessment could help increase vigilance for dystonia in cerebral palsy.

Hyperbaric oxygen therapy for hypoxic-ischemic encephalopathy in non-fatal drowning.

Paroxysmal autonomic instability syndrome with dystonia (PAISD) is a possible complication that worsens the prognosis of hypoxic-ischemic encephalopathy related to non-fatal drowning. There are case reports of hyperbaric oxygen (HBO2) therapy enhancing recovery in such cases. We report a case of a 5-year-old boy admitted to the Pediatric Intensive Care Unit after a non-fatal drowning. He was transferred under mechanical ventilation and sedation, with hemodynamic instability and hypothermia. On admission he had a Glasgow Coma Score of 6. On the fifth day of admission he presented episodes of dystonia with decerebration posture, diaphoresis, tachycardia and hypertension, sometimes with identified triggers, suggesting PAISD. The episodes were difficult to control; multiple drugs were needed. Electroencephalography showed diffuse slow wave activity, and cranioencephalic magnetic resonance imaging showed hypoxia-related lesions, suggesting hypoxic-ischemic encephalopathy. Early after admission the patient started physiotherapy combined with normobaric oxygen therapy. Subsequently he started HBO2 therapy at 2 atmospheres, with a total of 66 sessions. Dystonia progressively subsided, with gradual discontinuation of therapy. He also showed improvement in spasticity, non-verbal communication and cephalic control. This case highlights the diagnostic and therapeutic challenges of PAISD and the potential benefit of HBO2 therapy, even in the subacute phase, in recovery of hypoxic-ischemic encephalopathy.

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.

The prognosis of brain magnetic resonance imaging injury pattern for outcomes of hypothermia-treated infants.

Magnetic resonance imaging (MRI) can be a tool that allows the observation of structural injury patterns after cooling. The aim of this study was to determine the early pattern of brain injury in the MRIs of infants with hypoxic ischemic encephalopathy (HIE) after cooling and to search for any clinical factors related to abnormal MRI findings.The study retrospectively recruited 118 infants who were treated with therapeutic hypothermia (TH) between 2013 and 2016.Forty-three patients had normal brain MRI, and 75 had abnormal brain MRI findings. The TH-treated infants with abnormal brain MRI readings showed significantly more clinical seizures and the use of additional antiepileptic drugs (AEDs) than the normal MRI group. As a long-term outcome, more lesions in the basal ganglia and thalamus, posterior limb of internal capsule, or severe white matter lesions were associated with abnormal neurodevelopmental outcomes at 18 to 24 months of age.A higher frequency of clinical seizures and AED use were related to abnormal brain injury on MRI. A significant risk for poor long-term outcomes was found in the abnormal brain MRI group.

Inhaled H2 or CO2 Do Not Augment the Neuroprotective Effect of Therapeutic Hypothermia in a Severe Neonatal Hypoxic-Ischemic Encephalopathy Piglet Model.

Hypoxic-ischemic encephalopathy (HIE) is still a major cause of neonatal death and disability as therapeutic hypothermia (TH) alone cannot afford sufficient neuroprotection. The present study investigated whether ventilation with molecular hydrogen (2.1% H2) or graded restoration of normocapnia with CO2 for 4 h after asphyxia would augment the neuroprotective effect of TH in a subacute (48 h) HIE piglet model. Piglets were randomized to untreated naïve, control-normothermia, asphyxia-normothermia (20-min 4%O2-20%CO2 ventilation; Tcore = 38.5 °C), asphyxia-hypothermia (A-HT, Tcore = 33.5 °C, 2-36 h post-asphyxia), A-HT + H2, or A-HT + CO2 treatment groups. Asphyxia elicited severe hypoxia (pO2 = 19 ± 5 mmHg) and mixed acidosis (pH = 6.79 ± 0.10). HIE development was confirmed by altered cerebral electrical activity and neuropathology. TH was significantly neuroprotective in the caudate nucleus but demonstrated virtually no such effect in the hippocampus. The mRNA levels of apoptosis-inducing factor and caspase-3 showed a ~10-fold increase in the A-HT group compared to naïve animals in the hippocampus but not in the caudate nucleus coinciding with the region-specific neuroprotective effect of TH. H2 or CO2 did not augment TH-induced neuroprotection in any brain areas; rather, CO2 even abolished the neuroprotective effect of TH in the caudate nucleus. In conclusion, the present findings do not support the use of these medical gases to supplement TH in HIE management.