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Objective: To investigate whether hydrocortisone supplementation increases blood pressure and decreases inotrope requirements compared with placebo in cooled, asphyxiated neonates with volume-resistant hypotension.Study Design: A double-blind, randomized, placebo-controlled clinical trial was conducted in a Level III neonatal intensive care unit in 2016-2017. Thirty-five asphyxiated neonates with volume-resistant hypotension (defined as a mean arterial pressure [MAP] < gestational age in weeks) were randomly assigned to receive 0.5 mg/kg/6 hours of hydrocortisone or placebo in addition to standard dopamine treatment during hypothermia.Results: More patients reached the target of at least 5-mm Hg increment of MAP in 2 hours after randomization in the hydrocortisone group, compared with the placebo group (94% vs 58%, P = .02, intention-to-treat analysis). The duration of cardiovascular support (P = .001) as well as cumulative (P < .001) and peak inotrope dosage (P < .001) were lower in the hydrocortisone group. In a per-protocol analysis, regression modeling predicted that a 4-mm Hg increase in MAP in response to hydrocortisone treatment was comparable with the effect of 15 μg/kg/min of dopamine in this patient population. Serum cortisol concentrations were low before randomization in both the hydrocortisone and placebo groups (median 3.5 and 3.3 μg/dL, P = .87; respectively), suggesting inappropriate adrenal function. Short-term clinical outcomes were similar in the 2 groups.Conclusions: Hydrocortisone administration was effective in raising the blood pressure and decreasing inotrope requirement in asphyxiated neonates with volume-resistant hypotension during hypothermia treatment.Trial Registration: ClinicalTrials.gov: NCT02700828. [ABSTRACT FROM AUTHOR]