Feasibility and Safety of Combining Therapeutic Hypothermia with Magnesium Sulfate Administration, in the Management of Neonates with Hypoxic Ischemic Encephalopathy - Randomized Control Trial

Objective: The aim of the study was to confirm the therapeutic effectiveness and no significant side effects of therapeutic hypothermia plus magnesium sulfate in the group of newborns with HIE. Materials and methods: Neonates born at ≥36 GA, with perinatal asphyxia and confirmed moderate or severe HIE were randomized to study (TH+Mg) or control (TH) groups. Neonates in study group received three doses of MgSO4 (250 mg/kg) as intravenous infusion on three consecutive days in addition to therapeutic hypothermia. Newborns in control group were treated only with therapeutic hypothermia. Primary outcome was risk of death during initial hospitalization, secondary outcome: short-term neurological status. Additionally the circulatory, respiratory and hematological parameters were assessed. Results: 75 patients were included in this study. There were no statistically significant differences in the rate of death (OD 1.053; 95% CI 0.26-4.25; p=0.943). Neonates in study group had better neurological outcome after cooling procedure, their neurological assessment at 5 days of age (by Thompson scale) improved (4.75 vs. 7.03; p=0.032). They had shorter time to full oral feeding 14.5 vs. 16.5 days; p=0.006 and shorter hospitalization time 23.55 (±8.0) vs. 27.77 (±14.1); p=0.003. Coagulation parameters, number of blood products transfusions and incidence of intracranial bleedings were not affected by the magnesium administration. Risk of PPHN incidences was lower (OD 4.5; 95% CI 0.90-22.38; p=0.049, NNT=7). Conclusion: Applied therapy was not associated with increased risk of death or other significant adverse effects. Faster normalization of short-term neurological functions in study (TH+Mg) group was observed.