Abstract
Background
Cooling delays, temperature outside 33–34 °C, and blood pressure below the mean arterial blood pressure with optimal cerebral autoregulation (MAPOPT) 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. MAPOPT 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 MAPOPT. 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 MAPOPT 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 MAPOPT was associated with temperature >34 °C. Additional studies are needed in a more heterogeneous population.
Impact
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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).
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Temperature fluctuations >33–34 °C were associated with blood pressures that exceeded the range of optimal autoregulatory vasoreactivity.
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Cooling time within 6 h of birth and temperatures >33–34 °C were not associated with qualitative brain injury on MRI.
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Regional apparent diffusion coefficient scalars on diffusion tensor imaging MRI were not appreciably affected by cooling time or temperature >33–34 °C.
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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.
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Acknowledgements
We are grateful to Claire Levine, MS, ESL for her editorial assistance. This study was supported by funding from the National Institutes of Health (grant numbers R01NS107417, R01NS109029, and K08NS080984 [to J.K.L.]; K08NS096115 [to R.C.-V.]; R01HD070996 and R01HD086058 [to F.J.N.]; and R01NS107417 [to A.T.]); the American Heart Association Transformational Project Award (co-funded by the Lawrence J. and Florence A. DeGeorge Charitable Trust; 18TPA34170077 [to J.K.L.]); the Johns Hopkins University-School of Medicine Clinician Scientist Award (to R.C.-V.); and the Sutland-Pakula Endowment for Neonatal Research (to R.C.-V.).
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Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: all authors. Drafting the article or revising it critically for important intellectual content: M.M.G., A.T., J.P., R.C.-V., F.J.N., and J.K.L. Final approval of the version to be published: all authors.
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J.K.L., F.J.N., M.M.G., and R.C.-V. received research support from Medtronic for a separate study. J.K.L. was also a paid consultant for Medtronic, and she received research support from Casmed. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Medtronic and Casmed had no role in the design of the current study, collection or analysis of the data, interpretation of the results, manuscript writing, or in our decision to submit this manuscript for publication. A.T., J.P., H.S., and C.P. have nothing to declare.
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Gilmore, M.M., Tekes, A., Perin, J. et al. Later cooling within 6 h and temperatures outside 33–34 °C are not associated with dysfunctional autoregulation during hypothermia for neonatal encephalopathy. Pediatr Res 89, 223–230 (2021). https://doi.org/10.1038/s41390-020-0876-8
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DOI: https://doi.org/10.1038/s41390-020-0876-8
