A preclinical randomised controlled dose optimization of megadose sodium ascorbate for reversal of gram-negative sepsis-induced cardiovascular, brain and kidney dysfunction - Scorecard - MDSpire
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A preclinical randomised controlled dose optimization of megadose sodium ascorbate for reversal of gram-negative sepsis-induced cardiovascular, brain and kidney dysfunction
Clinical Scorecard: Optimization of High-Dose Sodium Ascorbate in a Preclinical Randomized Controlled Trial for Reversing Cardiovascular, Neurological, and Renal Dysfunction Induced by Gram-Negative Sepsis
At a Glance
Category
Detail
Condition
Gram-negative sepsis-induced multiple organ dysfunction
Key Mechanisms
Sodium ascorbate acts as an antioxidant, anti-inflammatory, anticoagulant, immune stimulant, and cofactor for norepinephrine and vasopressin synthesis; reverses metabolic acidosis and organ dysfunction
Target Population
Critically ill patients with Gram-negative sepsis and septic shock
Care Setting
Intensive care units and preclinical animal models
Key Highlights
Sepsis causes high mortality with no current treatments that reverse multiple organ dysfunction.
Plasma ascorbate levels are reduced in sepsis and correlate with illness severity.
High-dose intravenous sodium ascorbate rapidly reverses cardiovascular, neurological, and renal dysfunction in a large animal model.
Guideline-Based Recommendations
Diagnosis
Diagnosis of sepsis based on clinical criteria and confirmation of Gram-negative infection (e.g., E. coli infusion in preclinical models).
Monitoring plasma ascorbate levels may correlate with severity but is not yet standard.
Management
Consider intravenous sodium ascorbate at high doses (up to 3.75 g/kg) to reverse organ dysfunction in sepsis.
Use sodium ascorbate rather than ascorbic acid to avoid worsening metabolic acidosis.
Administer sodium ascorbate as a bolus followed by infusion to achieve high plasma concentrations.
Monitoring & Follow-up
Continuous monitoring of mean arterial pressure (MAP) to titrate norepinephrine requirements.
Assess renal medullary tissue oxygenation and urine output as markers of renal function.
Evaluate inflammatory markers such as NF-κB and endothelial nitric oxide synthase phosphorylation in research settings.
Risks
Potential metabolic acidosis with ascorbic acid formulations; sodium ascorbate preferred to mitigate this risk.
Safety and tolerability established in preclinical and pilot clinical trials but require further validation.
Patient & Prescribing Data
Critically ill patients with septic shock and organ dysfunction
High-dose sodium ascorbate (e.g., 60 g over 6 hours) increases urine output, reduces vasopressor requirements, and lowers SOFA scores compared to placebo; lower doses may be less effective.
Clinical Best Practices
Use sodium ascorbate instead of ascorbic acid to avoid exacerbating metabolic acidosis in septic patients.
Aim for very high plasma ascorbate concentrations to achieve multi-organ protective effects.
Titrate norepinephrine to maintain target MAP (~70 mmHg) during treatment.
Consider timing of sodium ascorbate administration to match pharmacokinetic profiles demonstrated in preclinical studies.
Monitor organ function parameters closely to assess therapeutic response.
by Connie Pei Chen Ow, Rachel M. Peiris, Anton Trask-Marino, Sally G. Hood, Ashenafi H. Betrie, Darius J. R. Lane, Rinaldo Bellomo, Mark P. Plummer, Clive N. May, Yugeesh R. Lankadeva
