Effects of intravenous infusion of hydrogen-rich fluid combined with intra-cisternal infusion of magnesium sulfate in severe aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

Abstract

BackgroundThe failures of recent studies intended to prevent cerebral vasospasm have moved the focus of research into delayed cerebral ischemia away from cerebral artery constriction towards other mechanisms. Recent accumulating evidence has suggested that early brain injury is also involved in the development of delayed cerebral ischemia, and that hydrogen can prevent early brain injury. Therefore, we have established a combination therapy of intravenous hydrogen infusion and intra-cisternal magnesium sulfate infusion for the treatment of both early brain injury and cerebral vasospasm. The present randomized controlled clinical trial is designed to investigate the effects of this novel therapeutic strategy on the occurrence of cerebral vasospasm, delayed cerebral ischemia, and clinical outcomes after high-grade subarachnoid hemorrhage.MethodsThis study is a randomized, double-blind, placebo-controlled design to be conducted in two hospitals. A total of 450 patients with high-grade subarachnoid hemorrhage will be randomized to one of three arms: (i) Mg + H2 group, (ii) Mg group, and (iii) control group. Patients who are assigned to the Mg + H2 group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous hydrogen-rich fluid infusion (200 mL) twice a day for 14 days. Patients who are assigned to the Mg group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Patients who are assigned to the control group will receive intra-cisternal Ringer solution without magnesium sulfate at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Primary outcome measures will be occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures will be modified Rankin scale score at 3, 6, and 12 months and biochemical markers.DiscussionThe present protocol for a randomized, placebo-controlled study of intravenous hydrogen therapy with intra-cisternal magnesium infusion is expected to establish the efficacy and safety of this therapeutic strategy.Trial registrationUMIN-CTR: UMIN000014696

Hydrogen does not exert neuroprotective effects or improve functional outcomes in rats after intracerebral hemorrhage

“…cisternal magnesium infusion in patients with subarachnoid hemorrhage (29). In the present study, hydrogen-rich saline injection as well as hydrogen gas inhalation reduced oxidative DNA damage in the brain, but unexpectedly had no beneficial effects on the brain edema and outcome, indicating that the involvement of ROS in ICH may be more complicated than previously believed.…”

“…4486157, Patent Gazette of Japan 2010) (21,27,29). Bags of physiological saline solution (500 ml; Terumo Co., Tokyo, Japan) were immersed, without opening or altering the bag, in a water tank in which water was electrolyzed periodically to produce water with hydrogen concentrations of up to 1.6 ppm.…”

Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles -

“… In preparation 11/22/2013 Post cardiac arrest syndrome Emergency and Critical care medicine, Keio Univ. Calling for participants 2/22/2014 Eye disease Ophthalmology, Nippon Medical school Finished 7/1/2014 Acute myocardial infarction Cardiology, National Center for Global Health and Medicine Calling for participants 7/29/2014 Subarachnoid hemorrhage Neurosurgery, Self Defense Medical College Calling for participants [ 113 ] 8/1/2014 Lung transplantation General thoracic surgery, Osaka Univ. Calling for participants 10/27/2014 Retinal artery occlusion Ophthalmology, Nippon Medical school Calling for participants 7/3/2015 Type 2 diabetes mellitus Tokyo Metropolitan Institute of Gerontology Calling for participants The department names are shown if they are available in the UMIN clinical trial database …”

Preventive effect of continuous cisternal irrigation with magnesium sulfate solution on angiographic cerebral vasospasms associated with aneurysmal subarachnoid hemorrhages: a randomized controlled trial

“…We also note that continuous irrigation with MgSO 4 solution has been previously shown not to improve functional outcomes compared with several treatments including administration of fasudil hydrochloride (a Rho kinase antagonist), cisternal irrigation therapy with tissue-plasminogen activator, and others. 30,38 Last, the present study was a single-center trial, with too few cases to evaluate the functional outcome in SAH attributed to multifactorial etiologies.…”