Vitamin C Deficiency in Septic Shock
Condition: Septic Shock
MeSH terms: Shock, Septic; Scurvy; Ascorbic Acid Deficiency; Shock
Study type: Interventional
Phase: Phase 4

Summary: 
      Objectives: investigators aim to study the effect of addition of vitamin C as a part of
      treatment in septic shock patients on: Hemodynamics, Inflammation status and ICU outcome.

      Subjects and methods: A prospective interventional randomized cohort study, was conducted on
      150 consecutive patients who were admitted to the ICU with septic shock based on SIRS, SOFA
      and APACHE II. Treatment group (n=75) had given ascorbic acid (Vitamin C) parenterally 6gm
      daily and control group (n=75). Measuring the level of Vitamin C in all study population
      (normal range 50-70 μM/L) before and after period of 4 days.
    

Detailed description: 
      AIM OF THE WORK investigators aim to study the effect of addition of vitamin C in septic
      shock patients on:

        -  Mean arterial pressure

        -  C-reactive protein as an inflammatory marker

        -  Vasopressors ( norepinephrine) dose and duration.

        -  ICU outcome ( ICU stay, 7 and 28 days mortality)

      SUBJECTS AND METHODS

      Study type A prospective interventional randomized cohort study carried out at Critical Care
      Department, Cairo University Hospitals with 25 ICU beds for medical and surgical patients, in
      the period between December 2021 to January 2023.

      An informed consent from 1st degree relatives was taken and confidentiality of information
      was assured.

      Permission from the faculty of medicine ethical committee was obtained. Ethical committee
      approval number: MS-362-2019

      Study design of the study population The patients' demographic data (including age, sex,
      baseline diseases, and causes of ICU admission) were extracted from their medical charts, and
      the patients' clinical characteristics (such as vital signs and hemodynamic parameters) were
      monitored as daily interval.

      Laboratory data such as serum electrolyte concentrations, serum creatinine levels were
      extracted from the patients' medical charts.

      Vit C level was measured for all patients (normal range 50-70 μM/L).

      The patients' Acute Physiology and Chronic Health Evaluation II (APACHE II) and sequential
      organ failure assessment (SOFA) scores were calculated at the time of admission.

      Patients were randomly divided into 2 groups into:

      A) Treatment group (n=75) B) Control group (n=75) Ascorbic acid (Vitamin C) was given
      parenterally for the treatment group (2 gm every 8hrs) for 4 days.

      Remeasuring the level of Vitamin C in all study population after 4 days.

      • Measurement and administration of Vitamin C Vitamin C (Ascorbic Acid) parenteral formula
      Manufacturer: Arco Life sciences ( Http://www.arcolifesciences.co.in/ ) Ampules: each ampule
      contains 500 mg of ascorbic acid (5 ml each 1 ml contains 100mg) The dose and duration of
      intervention were selected based on the literature review.

      Each dose of ascorbic acid was diluted in 50 ml of dextrose 5% solution and was administered
      as intravenous infusion over 30 minutes.

      During the study period, patients were followed for any ascorbic acid-related adverse effects
      including nausea, vomiting, abdominal pain, hematuria, flushing, and significant arterial
      blood pressure change.

      Measurement Kits This kit is an Enzyme-Linked Immunosorbent Assay (ELISA). The plate has been
      pre-coated with human Vitamin C antibody (VC). VC present in the sample is added and binds to
      antibodies coated on the wells. Substrate solution is then added and color develops in
      proportion to the amount of human VC and absorbance is measured at 450 nm.

        -  Manufacturer Bioassay Technology Labs

        -  Serial number: E1538Hu

        -  Standard Curve Range: 200 Mg/ml - 300 Mg/ml

        -  Sensitivity: 0.52 Mg/ml

        -  Size: 96 wells

        -  Storage: Store the reagents at 2-8°C. For over 6-month storage refer to the expiration
           date keep it at -20°C. Avoid repeated thaw cycles. If individual reagents are opened it
           is recommended that the kit be used within 1 month.

        -  Specimen Collection Serum Allow serum to clot for 10-20 minutes at room temperature.
           Centrifuge at 2000-3000 RPM for 20 minutes Plasma Collect plasma using EDTA or heparin
           as an anticoagulant. Centrifuge samples for 15 minutes at 2000-3000 RPM at 2 - 8°C
           within 30 minutes of collection.

        -  Calculation of results :

      Plasma vitamin C level were measured by Vitamin C ELISA Kits by microgram /milliliter (μg/ml)
      and calculated to micromole/ L (μM/L) in factor of 5.6679 and results were given accordingly

      • Normal range of Vitamin C in plasma : Multiple ranges are given in the level of vitamin C
      but recent studies consider range of (50-70μ M/L) is the reference in patients with sepsis
      and septic shock .

      Statistical analysis Analysis of data was done using Statistical Program for Social Science
      version 20 (SPSS Inc., Chicago, IL, USA). Quantitative variables were described in the form
      of mean and standard deviation. Qualitative variables were described as number and percent.
      In order to compare parametric quantitative variables between two groups, Student t test was
      performed. Qualitative variables were compared using chi-square (X2) test or Fisher's exact
      test when frequencies were below five. Pearson correlation coefficients were used to assess
      the association between two normally distributed variables. When a variable was not normally
      distributed, A P value < 0.05 is considered significant The used tests were Chi-square test
      For categorical variables, to compare between different groups, Fisher's Exact or Monte Carlo
      correction for chi-square when more than 20% of the cells have expected count less than
      5,Student t-test For normally distributed quantitative variables, to compare between two
      studied groups, ANOVA with repeated measures for normally distributed quantitative variables,
      to compare between more than two periods or stages, and Post Hoc test (Bonferroni adjusted)
      for pairwise comparisons, Pearson coefficient To correlate between two normally distributed
      quantitative variables, Mann Whitney test For abnormally distributed quantitative variables,
      to compare between two studied groups, Friedman test For abnormally distributed quantitative
      variables, to compare between more than two periods or stages and Post Hoc Test (Dunn's) for
      pairwise comparisons and Q: Cochran's test For non-parametric test for binary response
      variable and Post Hoc Test (Dunn's) for pairwise comparisons.
    

Intervention name(s): Ascorbic acid
Intervention type(s): Drug
Intervention description(s): 2 gm every 8hrs for 4 days
Intervention MeSH terms: Ascorbic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care