Short-term effects of early initiation of magnesium infusion combined with cooling after hypoxia-ischemia in term piglets.

Background: 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 (MgSO) 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) MgSO 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% O for 20-25 min. Primary outcomes included aEEG, magnetic resonance spectroscopy (MRS) at 24, and 48 h, and immunohistochemistry.

Results: MgSO 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 = 0.084) or MRS (Lac/NAA; PCr/Pi; NTP/epp) (p > 0.05) at 48 h.

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 MgSO in combination with multiple therapies.