A Randomized Controlled Study of Low-Dose Hydrocortisone Versus Placebo in Dopamine-Treated Hypotensive Neonates Undergoing Hypothermia Treatment for Hypoxic−Ischemic Encephalopathy

Kata Kovacs, Eniko Szakmar, Unoke Meder, Laszlo Szakacs, Anna Cseko, Barbara Vatai, Attila J. Szabo, Patrick J. McNamara, M. Szabó, Agnes Jermendy

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalJournal of Pediatrics
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Brain Diseases
Hypothermia
Hydrocortisone
Dopamine
Placebos
Newborn Infant
Hypotension
Arterial Pressure
Therapeutics
Random Allocation
Blood Pressure
Intention to Treat Analysis
Neonatal Intensive Care Units
Gestational Age
Randomized Controlled Trials
Serum
Population

Keywords

  • adrenal insufficiency
  • hydrocortisone supplementation
  • hypoxic−ischemic encephalopathy
  • low blood pressure

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

A Randomized Controlled Study of Low-Dose Hydrocortisone Versus Placebo in Dopamine-Treated Hypotensive Neonates Undergoing Hypothermia Treatment for Hypoxic−Ischemic Encephalopathy. / Kovacs, Kata; Szakmar, Eniko; Meder, Unoke; Szakacs, Laszlo; Cseko, Anna; Vatai, Barbara; Szabo, Attila J.; McNamara, Patrick J.; Szabó, M.; Jermendy, Agnes.

In: Journal of Pediatrics, 01.01.2019.

Research output: Contribution to journalArticle

Kovacs, Kata ; Szakmar, Eniko ; Meder, Unoke ; Szakacs, Laszlo ; Cseko, Anna ; Vatai, Barbara ; Szabo, Attila J. ; McNamara, Patrick J. ; Szabó, M. ; Jermendy, Agnes. / A Randomized Controlled Study of Low-Dose Hydrocortisone Versus Placebo in Dopamine-Treated Hypotensive Neonates Undergoing Hypothermia Treatment for Hypoxic−Ischemic Encephalopathy. In: Journal of Pediatrics. 2019.
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abstract = "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.",
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AU - Vatai, Barbara

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