Magnesium for newborns with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis

Tagin, Mohamed; Shah, PS; Ks, Lee

doi:10.1038/jp.2013.65

Cited by 48 publications

(47 citation statements)

References 33 publications

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“…In addition, posttreatment of newborn piglets did not show any beneficial changes in the severity of the delayed energy failure as measured with cerebral PCr/Pi, NTP/exchangeable phosphate pool (EPP), or Lac/Cr and NAA/Cr [48] . These MRS results complement the discrepant findings regarding magnesium, in terms of histopathological and neurodevelopmental outcome measures, in both preclinical [49] and clinical studies [50] . Xenon, another NMDA receptor antagonist, is used as a gaseous anesthetic.…”

Section: Reduction Of Glutamate Excitotoxicity and Maintenance Of Calsupporting

confidence: 54%

Neuroprotective Treatments after Perinatal Hypoxic-Ischemic Brain Injury Evaluated with Magnetic Resonance Spectroscopy

Berger

Brekke²,

Widerøe³

et al. 2017

Dev Neurosci

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Perinatal hypoxic-ischemic brain injury is a major health problem. Adjuvant treatments that improve the neuroprotective effect of the current treatment, therapeutic hypothermia, are urgently needed. The growing knowledge about the complex pathophysiology of hypoxia-ischemia (HI) has led to the discovery of several important targets for neuroprotection. Early interventions should focus on the preservation of energy metabolism, the reduction of glutamate excitotoxicity and oxidative stress, the maintenance of calcium homeostasis, and the prevention of apoptosis. Delayed interventions should promote injury repair. The multiple metabolic changes following HI as well as the metabolic effects of potential treatments can be observed noninvasively by magnetic resonance spectroscopy (MRS). This mini-review provides an overview of the neuroprotective pharmacological agents that have been evaluated with ¹H/³¹P/¹³C MRS. A better understanding of how these agents influence cerebral metabolism and the use of relevant translational MRS biomarkers can guide future clinical trials.

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Section: Reduction Of Glutamate Excitotoxicity and Maintenance Of Calsupporting

confidence: 54%

Neuroprotective Treatments after Perinatal Hypoxic-Ischemic Brain Injury Evaluated with Magnetic Resonance Spectroscopy

Berger

Brekke²,

Widerøe³

et al. 2017

Dev Neurosci

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“…There were no cases of ‘clinical hypermagnesemia’ related to treatment overdosing (almost exclusively in patients with renal dysfunction). Therefore, MgSO 4 appears to present an optimal safety profile .…”

Section: Therapeutic Index and Cost‐effectivenessmentioning

confidence: 97%

“…There were no cases of 'clinical hypermagnesemia' related to treatment overdosing (almost exclusively in patients with renal dysfunction). Therefore, MgSO 4 appears to present an optimal safety profile (2,5,(17)(18)(19)(20)31,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)48,49,59,(68)(69)(70)(71)(72).…”

Section: Therapeutic Index and Cost-effectivenessmentioning

confidence: 99%

Magnesium sulfate in pediatric anesthesia: the Super Adjuvant

Rebollar

Palacios

Guerrero

et al. 2017

Pediatric Anesthesia

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Magnesium is an essential chemical element in all organisms, intervening in most cellular enzymatic reactions; thus, its importance in homeostasis and as a therapeutic tool in highly challenging patients such as pediatrics. The primary purpose of this paper was to review the role of magnesium sulfate as an adjuvant drug in pediatric anesthesia. This compound already has the scientific backing in certain aspects such as analgesia or muscle relaxation, but only theoretical or empirical backing in others such as organ protection or inflammation, where it seems to be promising. The multitude of potential applications in pediatric anesthesia, its high safety, and low cost make magnesium sulfate could be considered a Super Adjuvant.

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“…While as an individual treatment, magnesium has shown efficacy in experimental brain injury models including perinatal asphyxia, stroke, subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), results of clinical trials for these disorders have been generally disappointing, showing little or no effect. Despite this, in a recent perinatal asphyxia meta-analysis study, it was concluded that magnesium therapy led to improvements in shortterm outcomes and was relatively safe, although there was a trend for increased mortality [4]. More importantly, drawing on our own findings, our laboratory has shown that combined mild hypothermia (35°C) and magnesium treatment has synergistic neuroprotective effects and reduces brain injury when administered several hours after global and focal cerebral ischemia [2].…”

mentioning

confidence: 96%

Magnesium may provide further benefit to hypothermia following perinatal asphyxia encephalopathy

Meloni¹,

Knuckey

2015

Journal of Perinatal Medicine

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A recently published report in the New England Journal of Medicine [1] showing long-term benefits of moderate hypothermia (33°C-34°C for 72 h) in perinatal asphyxial encephalopathy at 6-7 years of age is highly significant, as it confirms the effectiveness of hypothermia therapy to improve outcomes in hypoxic/ischemic conditions, and will no doubt result in a wider clinical adoption of this therapeutic approach. However, despite the usefulness of hypothermia to improve outcomes for this condition, a significant proportion of newborns (≈30%) will inevitably survive with mild to severe physical and neurological disabilities.Our purpose here is to argue in favor of using hypothermia in combination with magnesium following perinatal asphyxia, as it could further improve outcomes. While as an individual treatment, magnesium has shown efficacy in experimental brain injury models including perinatal asphyxia, stroke, subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), results of clinical trials for these disorders have been generally disappointing, showing little or no effect. Despite this, in a recent perinatal asphyxia meta-analysis study, it was concluded that magnesium therapy led to improvements in shortterm outcomes and was relatively safe, although there was a trend for increased mortality [4]. More importantly, drawing on our own findings, our laboratory has shown that combined mild hypothermia (35°C) and magnesium treatment has synergistic neuroprotective effects and reduces brain injury when administered several hours after global and focal cerebral ischemia [2]. A similar finding has also been recently reported in a focal ischemia model of stroke [3].On the basis of these positive findings of the effectiveness of magnesium and hypothermia in stroke models, and given magnesium's multiple potential beneficial effects and relative safety, we suggest that it would make an ideal adjunct therapy for hypothermia. In addition, magnesium has the advantage in that it can be administered relatively quickly (before hypothermia induction) and may aid the cooling process [5]. There is also the possibility that by magnesium acting synergistically with hypothermia, it could reduce the duration and level of hypothermia significantly, while still improving outcomes compared to prolonged hypothermia therapy. References[1] Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, et al. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med. 2014;371:140-9. [2] Meloni BP, Campbell K, Zhu H, Knuckey NW. In search of clinical neuroprotection after brain ischemia: the case for mild hypothermia (35°C) and magnesium. Stroke. 2009;40:2236-40. [3] Song W, Wu YM, Ji Z, Ji YB, Wang SN, Pan SY, et al. Intra-carotid cold magnesium sulfate infusion induces selectivecerebral

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Magnesium for newborns with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis

Cited by 48 publications

References 33 publications

Neuroprotective Treatments after Perinatal Hypoxic-Ischemic Brain Injury Evaluated with Magnetic Resonance Spectroscopy

Neuroprotective Treatments after Perinatal Hypoxic-Ischemic Brain Injury Evaluated with Magnetic Resonance Spectroscopy

Magnesium sulfate in pediatric anesthesia: the Super Adjuvant

Magnesium may provide further benefit to hypothermia following perinatal asphyxia encephalopathy

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