Active cooling temperature required to achieve therapeutic hypothermia correlates with short‐term outcome in neonatal hypoxic‐ischaemic encephalopathy

Abstract

Key points Hypoxic‐ischaemic encephalopathy (HIE) affects 2–4/1000 live term births. Treatment with therapeutic hypothermia (TH) improves the long‐term neurodevelopmental outcome of neonates with moderate to severe HIE. However, early prediction of outcome still remains challenging, and no reliable and easily obtainable biomarker has been identified to date. Neonates with HIE display impaired thermoregulation, resulting in spontaneous hypothermia. The degree of cooling required to achieve TH may therefore act as a biomarker of injury severity. The present study demonstrates a correlation between servo‐controlled mattress temperature during TH and short‐term outcome. Neonates with an unfavourable outcome require less cooling to maintain a core temperature between 33 and 34°C during TH compared to neonates with a favourable outcome. The degree of impaired temperature regulation was strongly associated with a high magnetic resonance imaging injury score and death. Cooling device output temperature is a potential and easily obtainable early physiological biomarker of outcome in infants with HIE undergoing TH. Abstract Neonatal hypoxic‐ischaemic encephalopathy (HIE) is a leading cause of death and disability in children. Therapeutic hypothermia (TH) at 33.5°C for 72 h is the only therapy to date shown to improve outcome in moderate to severe HIE; however, assessment of severity and prediction of outcome remains challenging. Infants with HIE display significant physiological perturbations, including spontaneous hypothermia. We hypothesized that neonates with more severe brain injury on magnetic resonance imaging (MRI) would exhibit a greater degree of spontaneous hypothermia, and thus require less active cooling to attain TH. Twenty‐eight neonates with moderate or severe HIE treated with TH were included in the present study. MRI images obtained on day of life 4–7 were scored according to standardized injury criteria. Unfavourable outcome was defined as death or significant grey matter injury on MRI according to a previously validated scoring system. A significantly higher cooling device output temperature was seen in infants with an unfavourable outcome. All neonates who required the mattress to provide a temperature ≥32°C to maintain their core body temperature at 33.5°C had a high likelihood of unfavourable outcome (likelihood ratio = 14.4). By contrast, infants who never required a device output temperature ≥32°C had a low likelihood of an unfavourable outcome (likelihood ratio = 0.07, P < 0.001). Infants with significant grey matter injury on MRI require less active cooling to maintain target temperature during TH. The cooling device output temperature has the potential to be an easily accessible physiological biomarker and predictor of injury and mortality in neonates with moderate or severe HIE.

Theoretical basis for the use of non-invasive thermal measurements to assess the brain injury in newborns undergoing therapeutic hypothermia

“…It has been shown that heat production estimated in this way correlates with HIE severity in adult patients after cardiac arrest 27,28 . Similar results were obtained in the study of neonates with PA 29 . It should, however, be underlined that considering only the water-cooling process, some other heat transfer mechanisms have been ignored.…”

“…Mietzsch 29 also noted that in newborns with PA treated by TH, temperature of the active cooling medium correlates with severity of brain injury diagnosed with Magnetic Resonance Imaging (MRI). Namely, the temperature of the cooling medium required to keep patients' at target temperature of 33.5 °C was found and proposed to be a prognostic factor for neurological injuries in neonates with HIE.…”

Время Начала Лечебной Гипотермии И Течение Гипоксически-Ишемической Энцефалопатии У Доношенных Новорожденных

“…Спонтанну гіпотермію вважають проявом порушень чи зміни схеми терморегуляції у дітей із постгіпоксичними ураженнями ЦНС. У новонароджених із помірною та тяжкою ГIE спонтанно виникає гіпотермія, причому в дітей із тяжкою ГІЕ температура тіла була нижча порівняно з немовлятами з помірною ГІЕ [7,19]. Доведено, що при проведенні активного охолодження новонароджені з короткостроковим несприятливим прогнозом ГІЕ (значним ураженням сірої речовини на МРТ) потребували меншої інтенсивності охолодження (вищої температури пристрою для охолодження) для підтримки центральної температури (температури ядра, ректальної температури) в межах 33,0-34,0 °C протягом 72 годин [7].…”

“…Як короткотермінові критерії несприятливого прогнозу розглядали смерть внаслідок поліорганної недостатності та постішемічного набряку мозку, діагностику деструктивних гіпоксично-ішемічних уражень мозку при нейросонографічному обстеженні. Як додаткові критерії сприятливого короткотермінового прогнозу (у разі відсутності деструктивних гіпоксично-ішемічних уражень мозкової тканини) розглядались відсутність електроенцефалографічних елементів судом, наявність повноцінного перорального харчування [7,20].…”

Thermal Index for Early Non-invasive Assessment of Brain Injury in Newborns Treated With Therapeutic Hypothermia – Preliminary Report of Non-invasive Thermal Measurements

“…The relationship between disturbances in thermoregulation and prognosis in patients with traumatic brain injury and after cardiac arrest has been proven [18][19][20][21][22][23][24][25][26][27] . Even some simple methods of assessing brain damage in adult patients after cardiac arrest and in newborns after PA have been proposed [28][29][30] . However, these methods result in a Heat Index (HI) 28 and utilize temperature of the cooling water only.…”