Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage

Abstract

Background and Purpose: Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage. Methods: Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H 2 , Mg, and control groups. Mg and Mg+H 2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H 2 group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase. Results: Serum neuron-specific enolase levels were significantly lower in the Mg+H 2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H 2 group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H 2 groups at 1 year. Barthel index was higher in the Mg+H 2 group than in the control group. Conclusions: Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000014696.

Basic considerations on magnesium in the management of neurocritical patients

“…In spite of this divergence, the neuroprotective effect of MgSO 4 was remarkable. Similar results are evident in studies that used groups of patients with subarachnoid hemorrhage in both the prehospital and hospital phases [70,71].…”

“…To date, few randomized clinical trials and prospective studies have evaluated the role of MgSO 4 in both ischemic and hemorrhagic stroke, mostly using mixed groups (ischemic and hemorrhagic stroke) (Table 1) [63,[65][66][67][68][69][70][71][72]. In 2004, one of the first representative studies, a clinical trial with the objective of determining whether the administration of MgSO 4 in the prehospital phase of stroke was safe and favorable, was published; in this study, it was observed that neuroprotective activity was indeed observed [65].…”

Neuroprotective Strategies in Aneurysmal Subarachnoid Hemorrhage (aSAH)

“…Recent results of two clinical trials with the intracisternal application of magnesium sulfate demonstrated significantly less CVS or delayed cerebral ischemia while establishing a better functional outcome in contrast to the control groups. The additional administration of intravenous hydrogen could further show supplementary effects by finding reduced liquor levels of neuron-specific enolase, as a marker of neuronal injury, as well as reduced malondialdehyde, which is an indicator of oxidative stress [ 203 , 204 ].…”

Cross-Talks between the Cardiovascular Disease-Sarcopenia-Osteoporosis Triad and Magnesium in Humans

“…Mg supplementation for cerebral ischemia has been administered with more invasive techniques (in the lateral ventricle, combined with hypothermia therapy, or with intracarotid Mg supplementation and selective hypothermia). A recent paper showed that subintracisternal MgSO 4 infusion improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage, with additional effects when combined with intravenous hydrogen therapy [107].…”