Later cooling within 6 h and temperatures outside 33-34 °C are not associated with dysfunctional autoregulation during hypothermia for neonatal encephalopathy

Abstract

Background: Cooling delays, temperature outside 33-34 °C, and blood pressure below the mean arterial blood pressure with optimal cerebral autoregulation (MAP_OPT) might diminish neuroprotection from therapeutic hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized that longer time to reach temperature <34 °C and having temperature outside 33-34 °C would be associated with worse autoregulation and greater brain injury.

Methods: Neonates with HIE had rectal temperature and near-infrared spectroscopy autoregulation monitoring during hypothermia (n = 63) and rewarming (n = 58). All underwent brain MRI, and a subset received diffusion tensor imaging MRI before day 10 (n = 41).

Results: Most neonates reached <34 °C at 3-6 h of life. MAP_OPT was identified in 54/63 (86%) during hypothermia and in 53/58 (91%) during rewarming. Cooling time was not related to blood pressure deviation from MAP_OPT. Later cooling was associated with lower ADC scalar in unilateral posterior centrum semiovale but not in other regions. Temperatures >34 °C were associated with blood pressure above MAP_OPT but not with brain injury.

Conclusions: In neonates who were predominantly cooled after 3 h, cooling time was not associated with autoregulation or overall brain injury. Blood pressure deviation above MAP_OPT was associated with temperature >34 °C. Additional studies are needed in a more heterogeneous population.

Impact: Cooling time to reach target hypothermia temperature within 6 h of birth did not affect cerebral autoregulation measured by NIRS in neonates with hypoxic-ischemic encephalopathy (HIE). Temperature fluctuations >33-34 °C were associated with blood pressures that exceeded the range of optimal autoregulatory vasoreactivity. Cooling time within 6 h of birth and temperatures >33-34 °C were not associated with qualitative brain injury on MRI. Regional apparent diffusion coefficient scalars on diffusion tensor imaging MRI were not appreciably affected by cooling time or temperature >33-34 °C. Additional research in a larger and more heterogeneous population is needed to determine how delayed cooling and temperatures beyond the target hypothermia range affect autoregulation and brain injury.

Figure 1.

Flow chart of study enrollment.

Figure 2.

Inborn neonates reached the goal core temperature faster than did outborn neonates (*p<0.001). Though cooling began within 6 h of birth for all neonates, outborn neonates were passively cooled during transport whereas inborn neonates received early active cooling. Medians with interquartile ranges are shown. Each circle represents one neonate.