Remote Monitoring for Seizures During Therapeutic Hypothermia in Neonates With Hypoxic-Ischemic Encephalopathy.

Importance: Neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently experience seizures, which are associated with adverse outcomes. Efforts to rapidly identify seizures and reduce seizure burden may positively change neurologic and neurodevelopmental outcomes. Objective: To describe the onset, treatment, and evolution of seizures in a large cohort of newborns with HIE during TH assisted by a telehealth model and remote neuromonitoring approach. Design, Setting, and Participants: This was a prospective, observational, multicenter cohort study performed between July 2017 and December 2021 in 32 hospitals in Brazil. Participants were newborns with HIE meeting eligibility criteria and receiving TH. Data were analyzed from November 2022 to April 2023. Exposure: Infants with HIE receiving TH were remotely monitored with 3-channel amplitude-integrated electroencephalography (aEEG) including raw tracing and video imaging, and bedside clinicians received assistance from trained neonatologists and neurologists. Main Outcomes and Measures: Data on modified Sarnat examination, presence, timing and seizure type, aEEG background activity, sleep-wake cycling, and antiepileptic drugs used were collected. Descriptive statistical analysis was used with independent t test, χ2, Mann-Whitney test, and post hoc analyses applied for associations. Results: A total of 872 cooled newborns were enrolled; the median (IQR) gestational age was 39 (38-40) weeks, 518 (59.4%) were male, and 59 (6.8%) were classified as having mild encephalopathy by modified Sarnat examination, 504 (57.8%) as moderate, and 180 (20.6%) as severe. Electrographic seizures were identified in 296 newborns (33.9%), being only electrographic in 213 (71.9%) and clinical followed by electroclinical uncoupling in 50 (16.9%). Early abnormal background activity had a significant association with seizures. Infants with flat trace had the highest rate of seizures (58 infants [68.2%]) and the greatest association with the incidence of seizures (odds ratio [OR], 12.90; 95% CI, 7.57-22.22) compared with continuous normal voltage. The absence of sleep-wake cycling was also associated with a higher occurrence of seizures (OR, 2.22; 95% CI, 1.67-2.96). Seizure onset was most frequent between 6 and 24 hours of life (181 infants [61.1%]); however, seizure occurred in 34 infants (11.5%) during rewarming. A single antiepileptic drug controlled seizures in 192 infants (64.9%). The first line antiepileptic drug was phenobarbital in 294 (99.3%). Conclusions and Relevance: In this cohort study of newborns with HIE treated with TH, electrographic seizure activity occurred in 296 infants (33.9%) and was predominantly electrographic. Seizure control was obtained with a single antiepileptic drug in 192 infants (64.9%). These findings suggest neonatal neurocritical care can be delivered at remote limited resource hospitals due to innovations in technology and telehealth.

Use of laryngeal mask for neonatal resuscitation in Brazil: A national survey.

Background: The International Liaison Committee on Resuscitation suggests using the laryngeal mask airway (LMA) as an alternative to the face mask for performing positive pressure ventilation (PPV) in the delivery room in newborns ≥34 weeks. Because not much is known about the health professionals' familiarity in using LMA in Brazil, this study aimed to describe the health professionals' knowledge and practice of using LMA, who provide neonatal care in the country. Methods: An online questionnaire containing 29 questions was sent to multi-healthcare professionals from different regions in the country through email and social media groups (WhatsApp®, Instagram®, Facebook®, and LinkedIn®). The participants anonymously answered the questions regarding their knowledge and expertise in using LMA to ventilate newborns in the delivery room. Results: We obtained 749 responses from all the regions in Brazil, with 80% from health professionals working in public hospitals. Most respondents were neonatologists (73%) having > 15 years of clinical practice. Among the respondents, 92% recognized the usefulness of LMA for performing PPV in newborns, 59% did not have specific training in LMA insertion, and only 8% reported that they have already used LMA in the delivery room. In 90% of the hospitals, no written protocol was available to use LMA; and in 68% of the hospitals, LMA was not available for immediate use. Conclusion: This nationwide survey showed that most professionals recognize the usefulness of LMA. However, the device is scarcely available and underused in the routine of ventilatory assistance for newborns in delivery rooms in Brazil.

Newborns at high risk for brain injury: the role of the amplitude-integrated electroencephalography

Abstract Objective: Amplitude-integrated electroencephalography (aEEG) is a simplified bedside neurophysiology tool that has been implemented in the neonatal intensive care unit and studied in an extensive range of clinical applications in the past decade. This critical review aimed to evaluate a variety of clinical applications of aEEG monitoring in diagnosis, clinical management, and prognosis assessment in critically ill neonates. Sources: The databases of Pubmed, SciELO, Lilacs, and Cochrane, books, and other online resources were consulted, as well as sources of professional experiences. Summary of findings: The clinical use of aEEG to access real-time brain function, background activity, and utility in seizures detection has been described. A critical review was realized considering the authors' professional experience. Newborns with hypoxic-ischemic encephalopathy and seizures screening represent the most common studied population. However, several studies have shown interesting applications on preterm infants, newborns with congenital heart disease, and other clinical situations of high risk of injury to the developing brain. Conclusion: The aEEG has shown to be a useful non-invasive bedside monitor that aids in evaluating brain function, background activity, and cyclicity. aEEG findings have also demonstrated good prognostic value in a group of critically ill neonates. The aEEG seizure diagnosis capability has limitations, which have been already well established. The use of neonatal brain monitoring such as aEEG was shown to give valuable information in several high-risk clinical situations.

Protecting brains and saving futures guidelines: A prospective, multicenter, and observational study on the use of telemedicine for neonatal neurocritical care in Brazil.

BACKGROUND: Management of high-risk newborns should involve the use of standardized protocols and training, continuous and specialized brain monitoring with electroencephalography (EEG), amplitude integrated EEG, Near Infrared Spectroscopy, and neuroimaging. Brazil is a large country with disparities in health care assessment and some neonatal intensive care units (NICUs) are not well structured with trained personnel able to provide adequate neurocritical care. To reduce this existing gap, an advanced telemedicine model of neurocritical care called Protecting Brains and Saving Futures (PBSF) Guidelines was developed and implemented in a group of Brazilian NICUs. METHODS: A prospective, multicenter, and observational study will be conducted in all 20 Brazilian NICUs using the PBSF Guidelines as standard-of-care. All infants treated accordingly to the guidelines during Dec 2021 to Nov 2024 will be eligible. Ethical approval was obtained from participating centers. The primary objective is to describe adherence to the PBSF Guidelines and clinical outcomes, by center and over a 3-year period. Adherence will be measured by quantification of neuromonitoring, neuroimaging exams, sub-specialties consultation, and clinical case discussions and videoconference meetings. Clinical outcomes of interest are detection of seizures during hospitalization, use of anticonvulsants, inotropes, and fluid resuscitation, death before hospital discharge, length of hospital stay, and referral of patients to specialized follow-up. DISCUSSION: The study will provide evaluation of PBSF Guidelines adherence and its impact on clinical outcomes. Thus, data from this large prospective, multicenter, and observational study will help determine whether neonatal neurocritical care via telemedicine can be effective. Ultimately, it may offer the necessary framework for larger scale implementation and development of research projects using remote neuromonitoring. TRIAL REGISTRATION: NCT03786497, Registered 26 December 2018, https://www.clinicaltrials.gov/ct2/show/NCT03786497?term=protecting+brains+and+saving+futures&draw=2&rank=1.

Newborns at high risk for brain injury: the role of the amplitude-integrated electroencephalography.

OBJECTIVE: Amplitude-integrated electroencephalography (aEEG) is a simplified bedside neurophysiology tool that has been implemented in the neonatal intensive care unit and studied in an extensive range of clinical applications in the past decade. This critical review aimed to evaluate a variety of clinical applications of aEEG monitoring in diagnosis, clinical management, and prognosis assessment in critically ill neonates. SOURCES: The databases of Pubmed, SciELO, Lilacs, and Cochrane, books, and other online resources were consulted, as well as sources of professional experiences. SUMMARY OF FINDINGS: The clinical use of aEEG to access real-time brain function, background activity, and utility in seizures detection has been described. A critical review was realized considering the authors' professional experience. Newborns with hypoxic-ischemic encephalopathy and seizures screening represent the most common studied population. However, several studies have shown interesting applications on preterm infants, newborns with congenital heart disease, and other clinical situations of high risk of injury to the developing brain. CONCLUSION: The aEEG has shown to be a useful non-invasive bedside monitor that aids in evaluating brain function, background activity, and cyclicity. aEEG findings have also demonstrated good prognostic value in a group of critically ill neonates. The aEEG seizure diagnosis capability has limitations, which have been already well established. The use of neonatal brain monitoring such as aEEG was shown to give valuable information in several high-risk clinical situations.

Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries: A call for action.

Although low- and middle-income countries (LMICs) shoulder 90 % of the neonatal encephalopathy (NE) burden, there is very little evidence base for prevention or management of this condition in these settings. A variety of antenatal factors including socio-economic deprivation, undernutrition and sub optimal antenatal and intrapartum care increase the risk of NE, although little is known about the underlying mechanisms. Implementing interventions based on the evidence from high-income countries to LMICs, may cause more harm than benefit as shown by the increased mortality and lack of neuroprotection with cooling therapy in the hypothermia for moderate or severe NE in low and middle-income countries (HELIX) trial. Pooled data from pilot trials suggest that erythropoietin monotherapy reduces death and disability in LMICs, but this needs further evaluation in clinical trials. Careful attention to supportive care, including avoiding hyperoxia, hypocarbia, hypoglycemia, and hyperthermia, are likely to improve outcomes until specific neuroprotective or neurorestorative therapies available.

Effectiveness of reaching and maintaining therapeutic hypothermia target temperature using low-cost devices in newborns with hypoxic-ischemic encephalopathy.

Therapeutic hypothermia (TH) using servo-controlled cooling devices has proved to be a safe and effective method to reduce mortality and sequelae in neonates with hypoxic-ischemic encephalopathy (HIE). However, such cooling devices can be expensive and have limited availability in low- and middle-income countries. To evaluate the feasibility and effectiveness of low-cost cooling devices (ice packs) to reach and maintain the target temperature in newborns with moderate or severe HIE. Descriptive retrospective cross-sectional study, including newborns with gestational age ≥35 weeks, weight ≥1800 g, with diagnosis of moderate or severe HIE, submitted to whole body hypothermia using ice packs for 72 hr. Data was obtained from medical records and databases. The thermal curves of each patient, time spent at the target temperature and rewarming time were evaluated. Complications directly related to therapeutic hypothermia, evolution, and early outcomes before hospital discharge were analyzed. Seventy-one newborns met the criteria for TH, and 61 completed the entire cooling period and were included in the final analysis. The average time to reach the target temperature was 1.50 ± 1.3 hr. The mean temperature during the cooling period was 33.5°C (±0.62). 82.32% of the measurements were within the target temperature range (from 33 to 34°C). The following adverse events were observed during TH: pulmonary hypertension 11.3%, arrhythmia 4.2%, and coagulopathy 26.7%. Whole body hypothermia using low-cost devices proved to be an effective method in the absence of availability of servo-controlled devices, representing a plausible option in restricted resource settings.

Current Status and Future Directions of Neuromonitoring With Emerging Technologies in Neonatal Care.

Neonatology has experienced a significant reduction in mortality rates of the preterm population and critically ill infants over the last few decades. Now, the emphasis is directed toward improving long-term neurodevelopmental outcomes and quality of life. Brain-focused care has emerged as a necessity. The creation of neonatal neurocritical care units, or Neuro-NICUs, provides strategies to reduce brain injury using standardized clinical protocols, methodologies, and provider education and training. Bedside neuromonitoring has dramatically improved our ability to provide assessment of newborns at high risk. Non-invasive tools, such as continuous electroencephalography (cEEG), amplitude-integrated electroencephalography (aEEG), and near-infrared spectroscopy (NIRS), allow screening for seizures and continuous evaluation of brain function and cerebral oxygenation at the bedside. Extended and combined uses of these techniques, also described as multimodal monitoring, may allow practitioners to better understand the physiology of critically ill neonates. Furthermore, the rapid growth of technology in the Neuro-NICU, along with the increasing use of telemedicine and artificial intelligence with improved data mining techniques and machine learning (ML), has the potential to vastly improve decision-making processes and positively impact outcomes. This article will cover the current applications of neuromonitoring in the Neuro-NICU, recent advances, potential pitfalls, and future perspectives in this field.

Simultaneous Near-Infrared Spectroscopy (NIRS) and Amplitude-Integrated Electroencephalography (aEEG): Dual Use of Brain Monitoring Techniques Improves Our Understanding of Physiology.

Continuous brain monitoring tools are increasingly being used in the neonatal intensive care unit (NICU) to assess brain function and cerebral oxygenation in neonates at high risk for brain injury. Near infrared spectroscopy (NIRS) is useful in critically ill neonates as a trend monitor to evaluate the balance between tissue oxygen delivery and consumption, providing cerebral and somatic oximetry values, and allowing earlier identification of abnormalities in hemodynamics and cerebral perfusion. Amplitude-integrated electroencephalography (aEEG) is a method for continuous monitoring of cerebral function at the bedside. Simultaneous use of both monitoring modalities may improve the understanding of alterations in hemodynamics and risk of cerebral injury. Several studies have described correlations between aEEG and NIRS monitoring, especially in infants with hypoxic-ischemic encephalopathy (HIE), but few describe the combined use of both monitoring techniques in a wider range of clinical scenarios. We review the use of NIRS and aEEG in neonates and describe four cases where abnormal NIRS values were immediately followed by changes in brain activity as seen on aEEG allowing the impact of a hemodynamic disturbance on the brain to be correlated with the changes in the aEEG background pattern. These four clinical scenarios demonstrate how simultaneous neuromonitoring with aEEG and NIRS provides important clinical information. We speculate that routine use of these combined monitoring modalities may become the future standard for neonatal neuromonitoring.

Early amplitude-integrated electroencephalography for monitoring neonates at high risk for brain injury / Eletroencefalograma de amplitude integrada precoce no monitoramento de neonatos com risco elevado de lesão cerebral

Abstract Objective: This study aimed to correlate amplitude-integrated electroencephalography findings with early outcomes, measured by mortality and neuroimaging findings, in a prospective cohort of infants at high risk for brain injury in this center in Brazil. Methods: This blinded prospective cohort study evaluated 23 preterm infants below 31 weeks of gestational age and 17 infants diagnosed with hypoxic-ischemic encephalopathy secondary to perinatal asphyxia, with gestational age greater than 36 weeks, monitored with amplitude-integrated electroencephalography in a public tertiary center from February 2014 to January 2015. Background activity (classified as continuous, discontinuous high-voltage, discontinuous low-voltage, burst-suppression, continuous low-voltage, or flat trace), presence of sleep-wake cycling, and presence of seizures were evaluated. Cranial ultrasonography in preterm infants and cranial magnetic resonance imaging in infants with hypoxic-ischemic encephalopathy were performed. Results: In the preterm group, pathological trace or discontinuous low-voltage pattern (p = 0.03) and absence of sleep-wake cycling (p = 0.019) were associated with mortality and brain injury assessed by cranial ultrasonography. In patients with hypoxic-ischemic encephalopathy, seizure patterns on amplitude-integrated electroencephalography traces were associated with mortality or brain lesion in cranial magnetic resonance imaging (p = 0.005). Conclusion: This study supports previous results and demonstrates the utility of amplitude-integrated electroencephalography for monitoring brain function and predicting early outcome in the studied groups of infants at high risk for brain injury.

Resumo Objetivo: Este estudo visou correlacionar os achados do eletroencefalograma de amplitude integrada (aEEG) com resultados precoces, medidos por mortalidade e achados de neuroimagem, em uma coorte prospectiva de neonatos com risco elevado de lesão cerebral em nosso centro no Brasil. Métodos: O estudo prospectivo de coorte cego avaliou 23 neonatos prematuros abaixo de 31 semanas de idade gestacional (IG) e 17 neonatos diagnosticados com encefalopatia hipóxico-isquêmica (EHI) secundária à asfixia perinatal, com IG superior a 36 semanas, monitorados com aEEG em um centro terciário público de fevereiro de 2014 a janeiro de 2015. Foram avaliadas a atividade de fundo (classificada como padrão contínuo, descontínuo de alta voltagem, descontínuo de baixa voltagem, supressão de explosão, contínuo de baixa voltagem ou traço plano), a presença de ciclo do sono-vigília e a presença de convulsões. Foram feitas a ultrassonografia craniana em prematuros e a ressonância magnética (RMI) craniana em neonatos com EHI. Resultados: No grupo de prematuros, o traço patológico ou padrão descontínuo de baixa voltagem (p = 0,03) e a ausência de ciclo do sono-vigília (p = 0,019) foram associados a mortalidade e lesão cerebral avaliada por ultrassonografia craniana. Em pacientes com EHI, os padrões de convulsão nos traços do aEEG foram associados a mortalidade ou lesão cerebral na RMI craniana (p = 0,005). Conclusão: Este estudo corrobora os resultados anteriores e demonstra a utilidade do aEEG no monitoramento da função cerebral e na predição de alterações precoces nos grupos de neonatos estudados com risco elevado de lesão cerebral.

Early amplitude-integrated electroencephalography for monitoring neonates at high risk for brain injury.

OBJECTIVE: This study aimed to correlate amplitude-integrated electroencephalography findings with early outcomes, measured by mortality and neuroimaging findings, in a prospective cohort of infants at high risk for brain injury in this center in Brazil. METHODS: This blinded prospective cohort study evaluated 23 preterm infants below 31 weeks of gestational age and 17 infants diagnosed with hypoxic-ischemic encephalopathy secondary to perinatal asphyxia, with gestational age greater than 36 weeks, monitored with amplitude-integrated electroencephalography in a public tertiary center from February 2014 to January 2015. Background activity (classified as continuous, discontinuous high-voltage, discontinuous low-voltage, burst-suppression, continuous low-voltage, or flat trace), presence of sleep-wake cycling, and presence of seizures were evaluated. Cranial ultrasonography in preterm infants and cranial magnetic resonance imaging in infants with hypoxic-ischemic encephalopathy were performed. RESULTS: In the preterm group, pathological trace or discontinuous low-voltage pattern (p=0.03) and absence of sleep-wake cycling (p=0.019) were associated with mortality and brain injury assessed by cranial ultrasonography. In patients with hypoxic-ischemic encephalopathy, seizure patterns on amplitude-integrated electroencephalography traces were associated with mortality or brain lesion in cranial magnetic resonance imaging (p=0.005). CONCLUSION: This study supports previous results and demonstrates the utility of amplitude-integrated electroencephalography for monitoring brain function and predicting early outcome in the studied groups of infants at high risk for brain injury.