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Overcooling During Therapeutic Hypothermia and Temperature Instability after Rewarming are associated with a Poorer Neurodevelopmental Outcome

Presented at the Neonatal Society 2015 Spring Meeting.

Lee-Kelland R1,2, Chakkarapani E1,2, Jarry S1, Liu X1, Smolicz I1, Scull-Brown E1, Thoresen M1,2

1 University of Bristol
2 St Michael’s Hospital, University Hospitals Bristol

Background: Therapeutic hypothermia at rectal temperature 33.5ºC is now standard of care for babies with neonatal encephalopathy (NE). Infants receiving hypothermia have been noted to overshoot the target temperature during both passive (1) and active cooling (2). This may reflect a dysfunction in autonomic regulation secondary to cerebral damage. Our hypothesis is that excessive hypothermia during cooling and temperature instability post therapeutic hypothermia are associated with a poorer neurodevelopmental outcome. 

Methods: A case note review of 145 neonates treated with therapeutic hypothermia under the TOBY protocol was undertaken. We recorded hourly rectal temperature measurements during passive cooling, active (servo controlled) cooling, rewarming and for 24h post rewarming. The target temperature during cooling was 33.5ºC. overcooling during passive/active cooling was defined as a temperature <33.0ºC. After rewarming, Temperature instability was defined as hypothermia <36.0ºC and hyperthermia ≥38ºC. Temperature was maintained by using a heated bed, overhead heating or the servo controlled device set at 36.5 ºC. Outcomes were assessed by neurodevelopmental assessment at 18 months using converted Bayley II scores (3). Poorer neurodevelopmental outcome was defined as Bayley II MDI/PDI <70 (<2SD from the mean) or presence or cerebral palsy at 2 years. 

Results: Excessive hypothermia occurred in 31% of infants during the passive or active cooling phase. The Absence of overcooling was associated with better neurodevelopmental outcome RR = 0.69, 95% CI (0.488-0.982), P = 0.039. Following rewarming only one infant at one time point became hyperthermic. However 56% of infants became hypothermic, despite being cared for in an incubator or with other external heating. Being able to maintain normothermia after rewarming was associated with a better neurodevelopmental outcome RR = 0.718, 95% CI (0.531 -0.970), P = 0.031. Measures of severity of injury at initial presentation including: APGAR score, Sarnat score, cord blood pH, cord blood base excess or aEEG reading did not predict the presence of overcooling or hypothermia after rewarming.

Conclusion: Overcooling during active cooling and temperature instability leading to hypothermia after rewarming are associated with a poorer neurodevelopmental outcome. We do not know whether optimising therapeutic hypothermia to prevent excessive hypothermia will improve neurodevelopmental outcome. Hyperthermia is negligible following therapeutic hypothermia using current practise.

Corresponding author: richardleekelland@gmail.com

1. Fairchild, K., Sokora, D., Scott, J., & Zanelli, S. (2010). Therapeutic hypothermia on neonatal transport: 4-year experience in a single NICU. Journal of Perinatology, 30(5), 324–329.
2. Massaro AN et al. Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children’s Hospitals Neonatal Consortium HIE focus group. (2014) Journal of Perinatology 13, 1-7
3. Jary, S., Whitelaw, A., Walløe, L., & Thoresen, M. (2013). Comparison of Bayley-2 and Bayley-3 scores at 18 months in term infants following neonatal encephalopathy and therapeutic hypothermia. Developmental Medicine and Child Neurology, 55(11)

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