Safety of intravenous administration of hydrogen-enriched fluid in patients with acute cerebral ischemia: initial clinical studies

Abstract

BackgroundMost of the results regarding hydrogen (H2) therapy for acute cerebral ischemia are derived from in vitro studies and animal experiments, with only a few obtained from human trials with a limited number of subjects. Thus, there is a paucity of information regarding both the beneficial therapeutic effects as well as the side effects of H2 on acute cerebral ischemia in humans. We designed a pilot study to investigate single dose intravenous H2-administration in combination with edaravone, aiming to provide an initial estimate of the possible risks and benefits in select patients presenting with acute ischemic stroke.MethodsAn open-label, prospective, non-randomized study of intravenous H2-administration was performed in 38 patients hospitalized for acute ischemic stroke. All patients received an H2-enriched intravenous solution in addition to edaravone immediately after the diagnosis of acute ischemic stroke. Acute stroke patients within 3 h of onset received intravenous tissue plasminogen activator (t-PA) (0.6 mg/kg) treatment, and patients receiving t-PA had to commence the administration of the H2-enriched intravenous solution and edaravone before or at the same time as the t-PA was infused.ResultsComplications were observed in 2 patients (5.3%), which consisted of diarrhea in 1 patient (2.6%) and cardiac failure in 1 patient (2.6%). No deterioration in laboratory tests, urinary tests, ECG, or chest X-ray radiograms occurred in any patient in this study. In all patients, the mean National Institutes of Health Stroke Scale (NIHSS) scores at baseline, and 7, 30, and 90 d after admission were 8.2 ± 7.5, 5.6 ± 7.1, 4.9 ± 6.5, and 4.5 ± 6.3, respectively. The early recanalization was identified in 4 of 11 patients (36.4%) who received intravenous t-PA administration. Hemorrhagic transformation was observed in 2 patients (18.2%). None of the patients in this study that were treated with t-PA developed symptomatic intracranial hemorrhage.ConclusionsData from the current study indicate that an H2-enriched intravenous solution is safe for patients with acute cerebral infarction, including patients treated with t-PA.

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

“…Hydrogen-rich fluid is produced using a non-destructive hydrogen diffusion apparatus (Miz Co., Fujisawa, Japan; Patent No. 4486157, Patent Gazette of Japan 2010) as reported before [23,33]. Bags of glucose-electrolyte solution (Soldem 1, 200 mL/bag, Terumo, Tokyo, Japan) are immersed, without opening or altering the bag, in a water tank in which water is electrolyzed periodically to produce water with hydrogen concentrations of up to 1.6 ppm.…”

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

“…H 2 can be used as an inert gas at body temperature or dissolved in water or saline at a concentration up to 0.8 mM (1.6 ppm) under atmospheric pressure to produce hydrogenated water or hydrogen-rich saline, or for producing hydrogen-generating nanomaterials [20]. In the past 10 years, H 2 has been used to treat cancer and metabolic disease or to correct ischemia and reperfusion injury of various organs, taking advantage of its high bio-safety [20][21][22]. With respect to cancer, hydrogen can inhibit cellular activity, proliferation, invasion, and migration in a dose-and time-dependent manner; promote apoptosis in cervical cancer, breast cancer, cutaneous melanoma [23], ovarian cancer [24], lung cancer [25], colon cancer [26], thymic lymphoma [27], Ehrlich ascites tumor cells [28], oral squamous cell carcinoma, and fibrosarcoma cells [29]; reduce tumor volume and weight; and inhibit tumor growth in xenografted mice, thus prolonging the survival of tumor-bearing mice [23].…”

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

“… Reduction of the bladder pain score in 11 % of patients. Nagatani et al [ 106 ]/2013 Cerebral ischemia 38 OL Intravenous infusion Confirmation of safety of intravenous H 2 infusion. Decrease of MDA-LDL, a serum marker for oxidative stress, in a subset of patients.…”