Prognostic Uncertainty During Therapeutic Hypothermia and Hemodynamic Instability- the Link between Vasoactive Therapies and Adverse Outcomes in the Neonatal Intensive Care Unit

BACKGROUND: Evaluate whether hemodynamic instability, defined as the need for vasoactive support, predicts vital signs, cerebral near-infrared spectroscopy (cNIRS), mechanical ventilator support, biochemical parameters, and neurodiagnostics in neonates with moderate-severe Hypoxic Ischemic Encephalopathy (HIE). METHODS: A retrospective cohort study of thirty-four newborns diagnosed with moderate-severe HIE from 2010 to 2013 at a quaternary NICU with neurodevelopmental assessments until 2016. Data points were extracted from electronic medical records and chart review. The dataset was analyzed to compare primary and secondary outcomes between two groups, patients with vasoactive agents (n=18) and without vasoactive agents (n=16). The primary outcome compared primary hemodynamic parameters (heart rate, blood pressures) and cerebral NIRS. Secondary outcomes were differences in mechanical ventilation, laboratory indices, and neurodiagnostics. RESULTS: There were no statistically significant differences between heart rate, blood pressure, or oxygen delivery as measured by cerebral NIRS (6,12, 24, 48, and 72 hours time points after birth) in babies with and without vasoactive support. Neonates with vasoactive requirements during therapeutic hypothermia had higher hypoxemia severity, higher blood lactate, lower albumin, and hemoglobin, and required prolonged ventilation (P=0.027). Additionally, they were 30% more likely to have abnormal background EEG with a low voltage pattern (p <0.05). Moderate or severe brain injury on MRI at 10-12 days was seen in almost 50% of the patients exposed to vasoactive support. Despite these important differences at NICU discharge, neurodevelopmental delays (Bay- ley III scaled and composite scores) at six months were not significantly worse in the newborns exposed to vasoactive medications during cooling. CONCLUSION: It is critical to study the benefits and risks of medical interventions for hemodynamic instability and assess for feedback on whether therapy is meeting the intended goal of appropriate oxygen delivery. Vasoactive medication requirement in neonates with moderate-severe HIE predicts or perhaps contributes to adverse outcomes at NICU discharge. Prognosticating risks for neurocognitive deficits beyond infancy thus remains an important research question in pediatrics.