Ingran Lingam1, Chris Meehan2, Adnan Avdic-Belltheus2, Kathryn Martinello2, Mariya Hristova2, Pardis Kaynezhad3, Cornelius Bauer3, Ilias Tachtsidis3, Xavier Golay3,4, Nicola J Robertson2,5. 1. Neonatology, Institute for Women's Health, University College London, London, UK. ingranlingam@nhs.net. 2. Neonatology, Institute for Women's Health, University College London, London, UK. 3. Department of Medical Physics and Biomedical Engineering, University College London, London, UK. 4. Institute of Neurology, University College London, London, UK. 5. Neonatology, Sidra Medicine, Al Luqta Street, Education City, North Campus, Qatar Foundation, PO Box 26999, Doha, Qatar.
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.
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.
Authors: Lauren E Adams; Hunter G Moss; Danielle W Lowe; Truman Brown; Donald B Wiest; Bruce W Hollis; Inderjit Singh; Dorothea D Jenkins Journal: Antioxidants (Basel) Date: 2021-03-20