ArticleCritical care (London, England)2015
Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?
Article in Critical care (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 121 papers, 9 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Early High-dose Vitamin C in Post-cardiac Arrest Syndrome
Effect of Intravenous Vitamin C on Sequential Organ Failure Assessment (SOFA) Score Among Septic Patients: Randomized Controlled Trial
The Synergistic Action of Vitamins and Dietary Supplements in Patients With Coronary Artery Bypass Grafting for Improving the Quality of Healthcare Delivery.
Who cites it
121 citing papers in PubMed, 9 syntheses or guidelines pooled it, 250 citations in OpenAlex.
- Monotherapy or combinations? Intravenous vitamin C in sepsis and septic shock: An umbrella review of 31 systematic reviews.PloS one · 2026Pooled it
- Intravenous vitamin C as micronutrient therapy in patients with sepsis or septic shock: an updated systematic review and meta-analysis of randomized controlled trials.Frontiers in nutrition · 2026Pooled it
- Effects of different vitamins on individuals with septic shock: a Bayesian NMA of RCTs.Frontiers in nutrition · 2025Pooled it
- Therapeutic Impact of Ascorbic Acid on Oral and Periodontal Tissues: A Systematic Literature Review.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.International archives of allergy and immunology · 2024Pooled it
- The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials.Critical care (London, England) · 2023Pooled it
- The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials.Frontiers in nutrition · 2022Pooled it
- Pooled it
- Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials.Diabetes & metabolic syndromePooled it
- Role of vitamin C infusion in postoperative mechanically ventilated neonates with sepsis: a randomized controlled trial.European journal of pediatrics · 2025Trial
- Early administration of vitamin C in patients with sepsis or septic shock in emergency departments: a multicenter, double-blind, randomized controlled trial: the C-EASIE trial.Critical care (London, England) · 2025Trial
- Adjunctive intravenous then oral vitamin C for moderate and severe community-acquired pneumonia in hospitalized adults: feasibility of randomized controlled trial.Scientific reports · 2023Trial
- Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial.Critical care (London, England) · 2022Trial
- Intravenous vitamin C administration to patients with septic shock: a pilot randomised controlled trial.Critical care (London, England) · 2022Trial
- Vitamins impacting mental/physical well-being during viral pandemics: a mechanistic review based on COVID-19: a comprehensive review.Inflammopharmacology · 2026Review
- The role of cellular senescence in sepsis and its mechanism in copper death: An analysis based on machine learning.Medicine · 2026Article
- High-Dose Intravenous Vitamin C in Critical Illness: A Translational Exposure-Response Framework for Biomarker-Guided Precision Therapy.Medical sciences (Basel, Switzerland) · 2026Review
- Performance of New Roche Cobas Pulse Glucose Meter Against Potential Interfering Substances and Hematocrit Variations.Diagnostics (Basel, Switzerland) · 2026Article
- A preclinical randomised controlled dose optimization of megadose sodium ascorbate for reversal of gram-negative sepsis-induced cardiovascular, brain and kidney dysfunction.Critical care (London, England) · 2025Article
- Vitamin C is associated with improved outcomes in patients with sepsis-induced myocardial injury: insights from the MIMIC-IV database.BMC infectious diseases · 2025Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.