HYPER-HIE Phenotype: Postrewarming Systemic Hypertension Following Hypoxic-Ischemic Encephalopathy-A Case Report and Mechanistic Review.

Background: Perinatal asphyxia is frequently complicated by cardiovascular instability. Although hypotension and myocardial dysfunction are widely recognized, systemic hypertension after asphyxia has been described in human neonates and may represent a distinct hemodynamic phenotype. Case Report: We present two infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia who developed systemic hypertension following rewarming and received milrinone as part of hemodynamic management. Blood pressure normalized during the recovery phase while the infants were receiving milrinone; however, the observational nature of these cases precludes conclusions regarding treatment efficacy. Review of Literature: We provide a narrative review summarizing the available human evidence for postrewarming systemic hypertension and discuss potential mechanisms, implications for phenotype-directed management, and priorities for future research. Conclusion: These cases suggest the existence of systemic hypertension emerging after therapeutic hypothermia as a distinct postrewarming hemodynamic phenotype (HYPER-HIE phenotype), characterized by elevated systemic vascular resistance despite recovering myocardial function. Recognition of this phenotype has important implications for postrewarming cardiovascular surveillance and phenotype-directed hemodynamic management in neonatal encephalopathy.