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

Stroke. 2021 Jan;52(1):20-27. doi: 10.1161/STROKEAHA.120.031260. Epub 2020 Dec 22.

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+H2, Mg, and control groups. Mg and Mg+H2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H2 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+H2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H2 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+H2 groups at 1 year. Barthel index was higher in the Mg+H2 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.

Keywords: control groups; hydrogen; incidence; magnesium; subarachnoid hemorrhage.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Double-Blind Method
  • Female
  • Humans
  • Hydrogen / administration & dosage*
  • Infusions, Intravenous
  • Infusions, Intraventricular
  • Magnesium Sulfate / administration & dosage*
  • Male
  • Middle Aged
  • Neuroprotective Agents / administration & dosage
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / drug therapy*
  • Vasospasm, Intracranial / etiology
  • Vasospasm, Intracranial / prevention & control

Substances

  • Neuroprotective Agents
  • Magnesium Sulfate
  • Hydrogen

Associated data

  • CTRI/UMIN000014696