足月仔猪缺氧缺血后早期给予镁输注联合冷却的短期影响。
Short-term effects of early initiation of magnesium infusion combined with cooling after hypoxia-ischemia in term piglets.
机构信息
Neonatology, Institute for Women's Health, University College London, London, UK.
Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
出版信息
Pediatr Res. 2019 Dec;86(6):699-708. doi: 10.1038/s41390-019-0511-8. Epub 2019 Jul 29.
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.
背景
治疗性低温（HT）的神经保护作用并不完全，因此需要额外的策略来改善长期预后。我们评估了硫酸镁（MgSO）推注和 48 小时输注联合 HT 在足月新生儿脑病（NE）猪模型中的神经保护作用。
方法
15 只新生仔猪在缺氧缺血（HI）后随机分为以下两组：（i）MgSO 180mg/kg 推注和 8mg/kg/h 输注加 HT（Mg+HT）或（ii）HT 和生理盐水 0.5ml/h（HT）。治疗在 HI 后 1 小时开始；HT 持续 12 小时（33.5°C）。HI 通过短暂的颈动脉闭塞和 6%O2 吸入 20-25 分钟来完成。主要结局包括 aEEG、24 小时和 48 小时的磁共振波谱（MRS）和免疫组织化学。
结果
MgSO 推注和输注耐受良好（无低血压），血清镁增加一倍（0.72 对 1.52mmol/L），脑脊液增加 16%。与 HT 相比，Mg+HT 中总的细胞死亡减少（p=0.01），少突胶质细胞增加（p=0.002）。48 小时时，aEEG 恢复（p=0.084）或 MRS（Lac/NAA；PCr/Pi；NTP/epp）（p>0.05）未见改善。
结论
HT 时血清镁加倍是安全的；然而，与 HT 相比，Mg+HT 的小增量获益不太可能转化为实质性的长期改善。这种增量效应可能 justifies 进一步研究硫酸镁与多种治疗方法的联合应用。
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