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

Ingran Lingam, Chris Meehan, Adnan Avdic-Belltheus, Kathryn Martinello, Mariya Hristova, Pardis Kaynezhad, Cornelius Bauer, Ilias Tachtsidis, Xavier Golay, Nicola J Robertson

Research output: Contribution to journalArticlepeer-review

Abstract

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 (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 = 0.084) 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 MgSO4 in combination with multiple therapies.

Original languageEnglish
Pages (from-to)699-708
Number of pages10
JournalPediatric Research
Volume86
Issue number6
DOIs
Publication statusPublished - Dec 2019

Keywords

  • Animals
  • Animals, Newborn
  • Blood Gas Analysis
  • Combined Modality Therapy
  • Electroencephalography
  • Hypothermia, Induced
  • Hypoxia-Ischemia, Brain/physiopathology
  • Magnesium/blood
  • Magnesium Sulfate/administration & dosage
  • Male
  • Neuroprotective Agents/administration & dosage
  • Swine

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