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

Abstract

ImportanceNeonates 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.ObjectiveTo 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 ParticipantsThis 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.ExposureInfants 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 MeasuresData 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.ResultsA 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 RelevanceIn 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.

Crecimiento y desarrollo en infantes con antecedentes de encefalopatía hipóxico-isquémica

“…La encefalopatía hipóxico-isquémica (EHI) es un síndrome clínico de lesión neural, de severidad y evolución variable, resultado de la interrupción del flujo sanguíneo y transporte de oxígeno en el recién nacido (Korf et al, 2023). Representa una de las principales causas de mortalidad y discapacidad infantil con una incidencia de 1 a 6/1000 nacimientos en países desarrollados y aumentando hasta en 40/1000 nacidos vivos en países de recursos limitados (Ritovska et al, 2022;Variane et al, 2023). La hipotermia terapéutica (HT) es considerada como un estándar de neuro protección efectiva cuando se inicia dentro de las primeras seis horas posteriores a la agresión por hipoxia (periodo de ventana terapéutica) en niños con EHI moderada a grave, reduciendo el riesgo de muerte o discapacidad mayor, al permitir reducir el daño, favoreciendo la reorganización cerebral y con ello un mejor pronóstico del neuro desarrollo (Brossard-Racine et al, 2023;Edwards et al, 2010;Fasce et al, 2021;Garfinkle et al, 2013;Groenendaal et al, 2013;Juul et al, 2023;Lemyre & Chau, 2018;Martínez-Hernández et al, 2020;Mathew et al, 2022;Medina-Alva et al, 2015;Packer et al, 2022;Simbruner et al, 2010;Variane et al, 2023;Vega-Del-Val et al, 2021;Zhou et al, 2010;Zubcevic et al, 2015).…”

“…Representa una de las principales causas de mortalidad y discapacidad infantil con una incidencia de 1 a 6/1000 nacimientos en países desarrollados y aumentando hasta en 40/1000 nacidos vivos en países de recursos limitados (Ritovska et al, 2022;Variane et al, 2023). La hipotermia terapéutica (HT) es considerada como un estándar de neuro protección efectiva cuando se inicia dentro de las primeras seis horas posteriores a la agresión por hipoxia (periodo de ventana terapéutica) en niños con EHI moderada a grave, reduciendo el riesgo de muerte o discapacidad mayor, al permitir reducir el daño, favoreciendo la reorganización cerebral y con ello un mejor pronóstico del neuro desarrollo (Brossard-Racine et al, 2023;Edwards et al, 2010;Fasce et al, 2021;Garfinkle et al, 2013;Groenendaal et al, 2013;Juul et al, 2023;Lemyre & Chau, 2018;Martínez-Hernández et al, 2020;Mathew et al, 2022;Medina-Alva et al, 2015;Packer et al, 2022;Simbruner et al, 2010;Variane et al, 2023;Vega-Del-Val et al, 2021;Zhou et al, 2010;Zubcevic et al, 2015). En la literatura se ha propuesto que entre los mecanismos por los cuales la HT (enfriamiento del cuerpo o sólo la cabeza del recién nacido) proporciona neuro protección se encuentran: la inhibición de la liberación de radicales libres, glutamato y de la actividad citotóxica de los aminoácidos; disminución de la tasa metabólica de oxígeno y consumo de energía del tejido cerebral; reducción de la respuesta inflamatoria; disminución del daño a la barrera hematoencefálica, acidosis y edema cerebral; promoción de la síntesis de proteínas, entre otros (Andrade, 2023;Walas et al, 2020;Wang et al, 2019).…”