What has changed over 10 years in neonatal therapeutic hypothermia? Part 1: Hypothermia in paediatric brain injury – a literature review

Abstract

It is estimated that brain injury, broadly understood, is the most common cause of death and severe neurological complications in the paediatric population under 18 years of age. A number of preclinical studies have demonstrated the effectiveness of moderate cooling in terms of neuroprotection. In paediatrics, mild therapeutic hypothermia is a well-established procedure in the treatment of term or near-term newborns with deep asphyxia. Since 2015, in accordance with the guidelines of the American Academy of Pediatrics, mild therapeutic hypothermia is no longer an experimental method and it is widely recognised as a factor that improves survival and long-term neurological prognosis compared to traditional treatments. Thus, it is not surprising that, based on strong preclinical data from animal studies and the acceptance of mild therapeutic hypothermia in neonatology, opportunities to extend the range of patients benefiting from it beyond neonates in the first 6 hours of life as well as its new applications beyond the neonatal period are still being sought. In adults who underwent successful resuscitation due to sudden cardiac arrest in shockable rhythms, therapeutic cooling was recommended as a treatment method in post-resuscitation management almost a decade earlier than in newborns; however, a simple extrapolation of data from the adult population to the neonate population or from adults to neonates did not prove effective. The variation in terms of mechanisms leading to cardiac arrest (i.e. respiratory cause in children vs. cardiac cause in adults) entails differences in neurohormonal modulation between these two groups, which affects the results. This paper presents aspects of the use of mild therapeutic hypothermia over the last decade and discusses the mechanisms of encephalopathy development in the paediatric population, the conditions for its effective application as well as its place in the treatment of brain injury unrelated to perinatal asphyxia.