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Magnesium and hydrogen may be neuroprotective in subarachnoid hemorrhage

Reuters Health - 08/01/2021 - A small clinical trial from Japan suggests a role for magnesium alone or with hydrogen in improving outcomes of patients with poor-grade subarachnoid hemorrhage (SAH).

The study found that intracisternal magnesium sulfate infusion started right after surgery reduced the incidence of cerebral vasospasm and delayed cerebral ischemia and improved clinical outcomes without complications. Combining intracisternal magnesium infusion with intravenous hydrogen had additive benefits.

Dr. Satoru Takeuchi and colleagues with the National Defense Medical College in Saitama report their findings in the journal Stroke.

While many questions remain, these results are "encouraging . . . and demonstrate a real possibility of neuroprotection for intracisternal infusion of magnesium and with a promising additional effect of intravenous hydrogen," write editorialists Dr. Colum Amory and Dr. Panayiotis Varelas of Albany Medical Center in New York.

The study included 37 adults with poor-grade SAH (Hunt and Kosnik grade 4 or 5) and aneurysm treated by surgical clipping (36 patients) or coiling (one patient) within 72 hours of the onset.

The patients were randomly allocated to one of three groups: intracisternal magnesium sulfate infusion (2.5 mmol/L at 20 mL/h) started immediately after surgery and continuing for 14 days (Mg group, 12 patients); intracisternal magnesium sulfate infusion combined with intravenous infusion of a hydrogen-rich glucose-electrolyte solution for 14 days (Mg+H2 group, 12 patients); and a control group given Ringers lactate intracisternally and non-hydrogenated glucose-electrolyte solution intravenously (13 patients).

Patients who received the magnesium infusion had significantly higher magnesium levels in the cerebrospinal fluid (CSF) but not serum. They also had lower neuron-specific enolase, a marker of neuronal injury, compared with controls, in both serum and CSF.

Patients in the Mg+H2 group had lower levels of serum malondialdehyde, a marker of oxidative stress, compared with controls.

Cerebral vasospasm or delayed cerebral ischemia, the primary outcomes, were significantly less common in both the Mg group (one case of each) and Mg+H2 group (three and two cases, respectively) compared with controls (eight and seven cases).

Modified Rankin Scale (mRS) and Karnofsky performance status (two secondary outcomes) did not significantly differ between the three groups at three months, but low (better) mRS scores of 0 to 2 were more common in the Mg and Mg+H2 groups at one year.

Scores on the Barthel index, which measures functional independence, were higher (better) in the Mg+H2 group than in the control group.

There were no complications associated with magnesium and hydrogen therapy, "indicating that our therapeutic protocol is safe," the authors say.

In their editorial, Drs. Amory and Varelas say "These data argue a need for a larger, multicenter and international trial," which will be able to adjust for treatment differences, such as use of fasudil (the standard of care in Japan) versus nimodipine (used in Europe and North America), or approaches, such as intracisternal versus intraventricular infusion.

"It will be important to see if there is an interaction with nimodipine, and whether this invasive protocol is justified in patients who are otherwise receiving less invasive endovascular care for their aneurysms or present with lower Hunt and Kosnik score and develop vasospasm at a later time," they conclude.

Dr. Takeuchi did not respond to a request for comments by press time.

The study had no funding and the authors made no disclosures.

SOURCE: https://bit.ly/2KTbVBh and https://bit.ly/2KJpP98 Stroke, online December 22, 2020.

By Reuters Staff

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