Lingam, I;
Meehan, C;
Avdic-Belltheus, A;
Martinello, K;
Hristova, M;
Kaynezhad, P;
Bauer, C;
... Robertson, NJ; + view all
(2019)
Short-term effects of early initiation of magnesium infusion combined with cooling after hypoxia-ischemia in term piglets.
Pediatric Research
, 86
pp. 699-708.
10.1038/s41390-019-0511-8.
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Abstract
Introduction: Neuroprotection from therapeutic hypothermia (HT) is incomplete, therefore additional strategies are necessary to improve long-term outcomes. We assessed the neuroprotective efficacy of magnesium sulfate (MgSO4) bolus and infusion over 48 h plus HT in a piglet model of term neonatal encephalopathy (NE). / Methods: Fifteen newborn piglets were randomized following hypoxia–ischemia (HI) to: (i) MgSO4 180 mg/kg bolus and 8 mg/kg/h infusion with HT (Mg+HT) or (ii) HT and saline 0.5 ml/h (HT). Treatments were initiated 1 h post-HI; HT administered for 12 h (33.5 °C). HI was performed by transient carotid occlusion and inhalation of 6% O2 for 20–25 min. Primary outcomes included aEEG, magnetic resonance spectroscopy (MRS) at 24, and 48 h, and immunohistochemistry. / Results: MgSO4 bolus and infusion was well tolerated (no hypotension) and doubled serum magnesium (0.72 vs 1.52 mmol/L) with modest (16%) rise in CSF. In Mg+HT compared to HT, there was overall reduced cell death (p = 0.01) and increased oligodendrocytes (p = 0.002). No improvement was seen on aEEG recovery (p = 0.08) or MRS (Lac/NAA; PCr/Pi; NTP/epp) (p > 0.05). / Conclusion: Doubling serum magnesium with HT was safe; however, the small incremental benefit of Mg+HT compared to HT is unlikely to translate into substantive long-term improvement. Such an incremental effect might justify further study of Mg in combination with multiple therapies.
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