Systemic effects of whole-body cooling to 35°C, 33.5°C, and 30°C in a piglet model of perinatal asphyxia: Implications for therapeutic hypothermia

Introduction: The precise temperature for optimal neuroprotection in infants with neonatal encephalopathy is unclear. Our aim was to assess systemic effects of whole-body cooling to 35°C, 33.5°C, and 30°C in a piglet model of perinatal asphyxia. Methods: Twenty-eight anesthetized male piglets aged 24 h underwent hypoxia-ischemia (HI) and were randomized to normothermia or cooling to rectal temperature (Trec) 35 °C, 33.5 °C, or 30 °C during 2-26 h after insult (n = 7 in each group). HR, MABP, and Trec were recorded continuously. Results: Five animals cooled to 30°C had fatal cardiac arrests. During 30°C cooling, heart rate (HR) was lower vs. normothermia (P < 0.001). Although mean arterial blood pressure (MABP) did not vary between groups, more fluid boluses were needed at 30°C than at normothermia (P < 0.02); dopamine use was higher at 30°C than at normothermia or 35°C (P = 0.005 and P = 0.02, respectively). Base deficit was increased at 30°C at 12, 24, and 36h vs. all other groups (P < 0.05), pH was acidotic at 36h vs. normothermia (P = 0.04), and blood glucose was higher for the 30°C group at 12h vs. the normothermia and 35°C groups (P < 0.05). Potassium was lower at 12h in the 30°C group vs. the 33.5°C and 35°C groups. There was no difference in cortisol level between groups. Discussion: Cooling to 30°C led to metabolic derangement and more cardiac arrests and deaths than cooling to 33.5°C or 35°C. Inadvertent overcooling should be avoided.