Brain Hypothermia Therapy and Targeted Temperature Management for Acute Encephalopathy in Children: Status and Prospects

Abstract

In adult intensive care, brain hypothermia therapy (BHT) was reported to be effective in neuroprotection after resuscitation and cardiac arrest. By contrast, in neonatal intensive care, the pathophysiology of brain damage caused by hypoxic–ischemic encephalopathy (HIE) is attributed to circulatory disturbances resulting from ischemia/reperfusion, for which neonatal brain cryotherapy is used. The International Liaison Committee on Resuscitation, 2010, recommends cerebral cryotherapy for HIE associated with severe neonatal pseudoparenchyma death. The usefulness of BHT for neuroprotection in infants and children, especially in pediatric acute encephalopathy, is expected. Theoretically, BHT could be useful in basic medical science and animal experiments. However, there are limitations in clinical planning for treating pediatric acute encephalopathy. No international collaborative study has been conducted, and no clinical evidence exists for neuroprotection using BHT. In this review, we will discuss the pathogenesis of neuronal damage in hypoxic and hypoperfused brains; the history of BHT, its effects, and mechanisms of action; the success of BHT; cooling and monitoring methods of BHT; adverse reactions to BHT; literature on BHT. We will review the latest literature on targeted temperature management, which is used for maintaining and controlling body temperature in adults in intensive care. Finally, we will discuss the development of BHT and targeted temperature management as treatments for pediatric acute encephalopathy.

Coiling ruptured aneurysms arising from the posterior genu of the cavernous internal carotid artery: A report of two cases

“…It was suggested to her family that she undergo decompressive craniotomy, but they refused. Conservative treatment with mannitol dehydration (250 ml, q6h) and temperature control (34.5 °C–37 °C) with intubation and continuous use of anticonvulsants and muscle relaxants were given [ 6 ]. However, she died on the 11th postoperative day.…”

Current status and controversies in the treatment of neonatal hypoxic-ischemic encephalopathy: A review

“…The start time of subcooling treatment for neonatal HIE is within 6 hours after brain tissue hypoxia and ischemia, and it is generally accepted in current research that there are 2 stages of energy failure in the development of neonatal HIE. [ 14 – 16 ] The first stage is the reduction of blood flow and oxygen supply to the brain tissue, which causes a decrease in adenosine triphosphate, followed by Na+-K+-ATP pump failure, depolarization of neuronal cells, intracellular water and sodium retention, cellular edema, ischemia, and ultimately, neuronal cell death. The second stage is the secondary energy failure caused by early excessive energy expenditure a few hours after the occurrence of moderate and severe injury, in which a cascade response of ischemic injury to nerve cells can be triggered, and continuous ischemia produces the excitatory neurotransmitter glutamate, which in turn stimulates calcium influx through activation of the N-methyl-D-aspartate receptor, and calcium influx aggravates the neuronal injury.…”

Ginkgolide B promotes spontaneous recovery and enhances endogenous netrin‐1 after neonatal hypoxic–ischemic brain damage

“…Perinatal hypoxic–ischemic encephalopathy (HIE), which can be caused by birth asphyxia, can cause long‐term cognitive, motor, or behavioral impairments in newborns (Ferriero, 2004; Imataka et al, 2023). Brain hypothermia therapy (BHT) is currently the safest and most effective therapeutic intervention for neuroprotection and improving the prognosis of neonatal HIE (Grass et al, 2020).…”

“…Brain hypothermia therapy (BHT) is currently the safest and most effective therapeutic intervention for neuroprotection and improving the prognosis of neonatal HIE (Grass et al, 2020). However, it is important to note that BHT does not provide complete neuroprotection (Imataka et al, 2023). The efficacy of BHT is influenced by factors such as gestational age, timing, and available resources (Hutchison et al, 2008; Rao et al, 2017).…”