References

Aschauer S, Gouya G, Klickovic U Effect of systemic high dose vitamin C therapy on forearm blood flow reactivity during endotoxemia in healthy human subjects. Vascul Pharmacol.. 2014; 61:(1)25-29 https://doi.org/10.1016/j.vph.2014.01.007

Barabutis N, Khangoora V, Marik PE, Catravas JD. Hydrocortisone and ascorbic acid synergistically prevent and repair lipopolysaccharide-induced pulmonary endothelial barrier dysfunction. Chest.. 2017; 152:(5)954-962 https://doi.org/10.1016/j.chest.2017.07.014

Boisramé-Helms J, Kremer H, Schini-Kerth V, Meziani F. Endothelial dysfunction in sepsis. Curr Vasc Pharmacol.. 2013; 11:(2)150-160 https://doi.org/10.2174/157016113805290317

Brownell SE, Kloser MJ, Fukami T, Shavelson RJ. Context matters: volunteer bias, small sample size, and the value of comparison groups in the assessment of research-based undergraduate introductory biology lab courses. J Microbiol Biol Educ.. 2013; 14:(2)176-182 https://doi.org/10.1128/jmbe.v14i2.609

Carr AC, Shaw GM, Fowler AA, Natarajan R. Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?. Crit Care. 2015; 19 https://doi.org/10.1186/s13054-015-1131-2

Cash TP, Pan Y, Simon MC. Reactive oxygen species and cellular oxygen sensing. Free Radic Biol Med.. 2007; 43:(9)1219-1225 https://doi.org/10.1016/j.freeradbiomed.2007.07.001

Curtis K, Fry M, Shaban RZ, Considine J. Translating research findings to clinical nursing practice. J Clin Nurs.. 2016; 26:(5–6)862-872 https://doi.org/10.1111/jocn.13586

De Grooth H, Spoelstra-de man AM, Oudermans-van S. Early plasma vitamin C concentration, organ dysfunction and ICU mortality. Intensive Care Med.. 2014;

Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health.. 1998; 52:(6)377-384 https://doi.org/10.1136/jech.52.6.377

Fernando SM, Tran A, Taljaard M Prognostic accuracy of the quick sequential organ failure assessment for mortality in patients with suspected infection: a systematic review and meta-analysis. Ann Intern Med.. 2018; 168:(4)266-275 https://doi.org/10.7326/M17-2820

Fowler AA, Syed AA, Knowlson S Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med.. 2014; 12 https://doi.org/10.1186/1479-5876-12-32

Kirby K. Pre-hospital lactate testing in the identification of patients with sepsis; a review of the literature. J Paramed Pract.. 2013; 5:(12) https://doi.org/10.12968/jpar.2013.5.12.698

Lee H. Procalcitonin as a biomarker of infectious diseases. Korean J Intern Med.. 2013; 28:(3)285-291 https://doi.org/10.3904/kjim.2013.28.3.285

Grading of recommendations, assessment, development, and evaluations (GRADE). 2013. https//tinyurl.com/yyolmkfh (accessed 12 December 2020)

Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest.. 2017; 151:(6)1229-1238 https://doi.org/10.1016/j.chest.2016.11.036

Marik PE. Vitamin C for the treatment of sepsis: The scientific rationale. Pharmacol Ther.. 2018; 189:63-70 https://doi.org/10.1016/j.pharmthera.2018.04.007

Moher D, Liberati A, Tetzlaff J, Altman D. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement. 2009; 6:(7) https://doi.org/10.1371/journal.pmed.1000097

Moreno R, Vincent JL, Matos R The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis Related Problems of the ESICM. Intensive Care Med.. 1999; 25:(7)686-696 https://doi.org/10.1007/s001340050931

National Collaborating Centre for Methods and Tools. Quality checklist for health care intervention studies. 2020. http//www.nccmt.ca/knowledge-repositories/search/9 (accessed 12 December 2020)

Pleiner J, Heere-Ress E, Langenberger H Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans. Arterioscler Thromb Vasc Biol.. 2002; 22:(1)95-100 https://doi.org/10.1161/hq0102.101818

Prucha M, Zazula R, Russwurm S. Immunotherapy of sepsis: blind alley or call for personalized assessment?. Arch Immunol Ther Exp (Warsz).. 2017; 65:(1)37-49 https://doi.org/10.1007/s00005-016-0415-9

Ryan R, Hill S. How to GRADE the quality of the evidence. 2016; https://doi.org/10.26181/5b57d95632a2c

Seeley EJ, Bernard GR. Therapeutic targets in sepsis: past, present, and future. Clin Chest Med.. 2016; 37:(2)181-189 https://doi.org/10.1016/j.ccm.2016.01.015

Seymour CW, Band RA, Cooke CR Out-of-hospital characteristics and care of patients with severe sepsis: a cohort study. J Crit Care.. 2010; 25:(4)553-562 https://doi.org/10.1016/j.jcrc.2010.02.010

Smyth MA, Brace-McDonnell SJ, Perkins GD. Identification of adults with sepsis in the prehospital environment: a systematic review. BMJ Open.. 2016; 6:(8) https://doi.org/10.1136/bmjopen-2016-011218

Studnek JR, Artho MR, Garner CL, Jones AE. The impact of emergency medical services on the ED care of severe sepsis. Am J Emerg Med.. 2012; 30:(1)51-56 https://doi.org/10.1016/j.ajem.2010.09.015

Teng J, Pourmand A, Mazer-Amirshahi M. Vitamin C: the next step in sepsis management?. J Crit Care.. 2018; 43:230-234 https://doi.org/10.1016/j.jcrc.2017.09.031

Tupchong K, Koyfman A, Foran M. Sepsis, severe sepsis and septic shock: a review of the literature. Afr J Emerg Med.. 2015; 5:(3)127-135 https://doi.org/10.1016/j.afjem.2014.05.004

Vincent JL, Donadello K, Schmit X. Biomarkers in the critically ill patient: C-reactive protein. Crit Care Clin.. 2011; 27:(2)241-251 https://doi.org/10.1016/j.ccc.2010.12.010

Wilson JX. Evaluation of vitamin C for adjuvant sepsis therapy. Antioxid Redox Signal.. 2013; 19:(17)2129-2140 https://doi.org/10.1089/ars.2013.5401

Should ascorbic acid be a primary therapy for sepsis in prehospital settings?

02 January 2021
Volume 13 · Issue 1

Abstract

Background:

Prehospital emergency medical services (EMS) are believed to be responsible for the initial treatment of 68 000 septic patients annually in the UK, 88% of whom have severely low ascorbic acid levels, which can lead to organ dysfunction, increasing the likelihood of mortality.

Objective:

This review aims to determine if early therapeutic use of ascorbic acid (vitamin C) could reduce the deterioration of septic patients and therefore overall mortality.

Method:

A literature review was conducted using the mySearch, PubMed and Cochrane Library databases. Each was systematically searched for human studies that addressed the use of ascorbic acid as a primary method of treatment during varying stages of sepsis and whether it reduced associated mortality. Studies not published in English or that were more the 5 years old at the time were excluded. The quality of evidence in the remaining articles were appraised using the GRADE method and further assessed for quality with an adjusted Downs and Black scoring tool.

Results:

Nineteen articles were found, three of which met the inclusion criteria. All addressed the use of ascorbic acid as a therapy in the treatment of sepsis; none were conducted in a prehospital setting.

Conclusion:

Intravenous ascorbic acid appears to be a safe and effective therapy in treating septic patients, with the potential to reduce mortality rates if given prophylactically. However, a series of clinical trials would need to be conducted to measure the extent of any improvement and therefore clinical value in the prehospital environment.

Of the 102 000 patients with sepsis who arrive annually at emergency departments in the UK, 68 000 (Smyth et al, 2016) have reportedly been conveyed by emergency medical services (EMS); 80% of them required intensive care treatment (Smyth et al, 2016), all of whom were found to have lowered vitamin C (ascorbic acid) levels (Carr et al, 2015). Recent studies in the intensive care unit (ICU) setting have identified this nutritional deficit as a key factor in the development of organ failure (Wilson, 2016).

Early clinical trials have shown that administering ascorbic acid has reduced mortality from sepsis-related organ dysfunction (Marik, 2017). However, prompt implementation seems to be a key feature for success (Boisramé-Helms et al, 2013) so it can be argued that prehospital clinicians such as paramedics are ideally placed to identify and initiate this form of treatment (Studnek et al, 2012). This is especially pertinent as those arriving by EMS are predominantly in a more advanced and critical stage of the condition (Seymour et al, 2010).

Subscribe to get full access to the Journal of Paramedic Practice

Thank you for visiting the Journal of Paramedic Practice and reading our archive of expert clinical content. If you would like to read more from the only journal dedicated to those working in emergency care, you can start your subscription today for just £48.

What's included

  • CPD Focus

  • Develop your career

  • Stay informed