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.

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.

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.

Preclinical investigation of the cardiovascular actions induced by aqueous extract of Pimpinella anisum L. seeds in rats.

ETHNOPHARMACOLOGY RELEVANCE: Pimpinella anisum is used in traditional medicine because of its pharmacological properties which include cardiovascular action. However, no scientific information supports this use. AIM OF THE STUDY: This study investigated the effects of Pimpinella on arterial blood pressure (BP) and its pharmacological mechanism of action. MATERIAL AND METHODS: Pimpinella seeds were extracted with water, concentrated and freeze-dried yielding the aqueous extract (AE). A non-invasive BP assessment method was used (via the caudal artery) on Wistar, Wistar Kyoto, SHRs and rats that were submitted to high intake of dietary salt. Direct BP and heart rate were evaluated in Wistar rats in the absence or presence of atropine, L-NAME and angiotensin II. Spontaneous diuresis and the effect of AE on depolarized portal vein of Wistar rats was also examined. RESULTS: The data revealed that AE reduced BP in all groups evaluated and its effects were not due to diuretic, sympatholytic or parasympathomimetic actions. Additionally, it was shown that AE does not act as an angiotensin receptor blocker and does not induce hypotension by reducing vascular resistance induced by oxide nitric. In the depolarized portal vein, AE inhibited calcium influx, which indicates that AE acts as calcium channel blocker. CONCLUSION: This study validates the cardiovascular actions of Pimpinella and characterizes the hypotensive effects of Pimpinella that are related to the blockade of calcium channels.