作者: Peiris, Rachel M ; Jufar, Alemayehu H ; Lankadeva, Yugeesh R ; Pustovit, Ruslan V ; Trask-Marino, Anton ; Gunn, Adam ; Lane, Darius J ; Booth, Lindsea C ; Plummer, Mark P ; May, Clive N ; Bellomo, Rinaldo ; Ow, Connie P

BACKGROUNDThe mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We determined its effects on cerebral perfusion, oxygenation, and temperature, and plasma levels of inflammatory biomarkers, nitrates, nitrites, and ascorbate in ovine Gram-negative sepsis.METHODSSepsis was induced by i.v. infusion of live Escherichia coli for 31 h in unanaesthetised Merino ewes instrumented with a combination sensor in the frontal cerebral cortex to measure tissue perfusion, oxygenation, and temperature. Fluid resuscitation at 23 h was followed by i.v. megadose sodium ascorbate (0.5 g kg^-1 over 30 min+0.5 g kg^-1 h^-1 for 6.5 h) or vehicle (n=6 per group). Norepinephrine was titrated to restore mean arterial pressure (MAP) to 70-80 mm Hg.RESULTSAt 23 h of sepsis, MAP (mean [sem]: 85 [2] to 64 [2] mm Hg) and plasma ascorbate (27 [2] to 15 [1] μM) decreased (both P<0.001). Cerebral ischaemia (901 [58] to 396 [40] units), hypoxia (34 [1] to 19 [3] mm Hg), and hyperthermia (39.5 [0.1]°C to 40.8 [0.1]°C) (all P<0.001) developed, accompanied by malaise and lethargy. Sodium ascorbate restored cerebral perfusion (703 [121] units], oxygenation (30 [2] mm Hg), temperature (39.2 [0.1]°C) (all P_Treatment<0.05), and the behavioural state to normal. Sodium ascorbate slightly reduced the sepsis-induced increase in interleukin-6, returned VEGF-A to normal (both P_GroupxTime<0.01), and increased plasma ascorbate (20 000 [300] μM; P_Group<0.001). The effects of sodium ascorbate were not reproduced by equimolar sodium bicarbonate.CONCLUSIONSMegadose sodium ascorbate rapidly reversed sepsis-induced cerebral ischaemia, hypoxia, hyperthermia, and sickness behaviour. These effects were not reproduced by an equimolar sodium load.

2023-04-01·Future Microbiology

Safety of Megadose Meropenem in the Empirical Treatment Of Nosocomial Sepsis: A Pilot Randomized Clinical Trial

Article

作者: Khalili, Hossein ; Ramezani, Masoud ; Salehi, Mohammadreza ; Dashtkoohi, Mohammad ; Dashtkoohi, Mohadese ; Fattah-Ghazi, Samrand ; Aghdami, Nasser ; Rezazade-Moayed, Farah ; Beig-Mohammadi, Mohammad-Taghi ; Hajiabdolbaghi, Mahboobeh ; Hemati, Homa

Objective: To evaluate the safety of megadose meropenem as empirical treatment of nosocomial sepsis. Materials & methods: Critically ill patients diagnosed with sepsis received either high-dose (2 g every 8 h) or megadose (4 g every 8 h) meropenem as an intravenous infusion over 3 h. Results: A total of 23 patients with nosocomial sepsis were eligible and included in the megadose (n = 11) or high-dose (n = 12) group. No treatment-related adverse events were observed during a 14-day follow-up. Clinical response was also comparable between the groups. Conclusion: Megadose meropenem may be considered for empirical treatment of nosocomial sepsis without serious concern regarding its safety.

2021-10-01·British Journal of Pharmacology2区 · 医学

Therapeutic potential of megadose vitamin C to reverse organ dysfunction in sepsis and COVID‐19

2区 · 医学

Review

作者: May, Clive N. ; Lankadeva, Yugeesh R. ; Bellomo, Rinaldo

Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti‐inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID‐19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram‐negative bacteria‐induced sepsis. In a critically ill COVID‐19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID‐19.

100 项与 Megadose drug combination(Cell Source, Inc.) 相关的药物交易

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