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Cited by 887Sepsis Diagnosis and TreatmentVitamin C and Antioxidants ResearchHyperglycemia and glycemic control in critically ill and hospitalized patients

Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock

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Marik, Paul E., Khangoora, Vikramjit, Rivera, Racquel, Hooper, Michael H., Catravas, John·2017·Chest
DOI 10.1016/j.chest.2016.11.036
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Abstract

Background The global burden of sepsis is estimated as 15 to 19 million cases annually, with a mortality rate approaching 60% in low-income countries.Methods In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone, and thiamine during a 7-month period (treatment group) with a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome.Results There were 47 patients in both treatment and control groups, with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared with 40.4% (19 of 47) in the control group (P < .001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI, 0.04-0.48; P = .002). The Sepsis-Related Organ Failure Assessment score decreased in all patients in the treatment group, with none developing progressive organ failure. All patients in the treatment group were weaned off vasopressors, a mean of 18.3 ± 9.8 h after starting treatment with the vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 h in the control group (P < .001).Conclusions Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine, are effective in preventing progressive organ dysfunction, including acute kidney injury, and in reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings.

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Crossref · 10.1016/j.chest.2016.11.036

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  • Oxidative stress is observed in severe critical care conditions requiring mechanical ventilation, such as septic shock, severe pancreatitis, ARDS, major burns and trauma.

    “Oxidative stress, defined as an imbalance between increased reactive oxygen and nitrogen species and endogenous antioxidant mechanisms, is observed in severe critical care conditions requiring mechanical ventilation (280), such as septic shock, severe pancreatitis, ARDS, major burns and trauma”

    From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [280]

    The discussion (p. 16) describes oxygen free radicals and antioxidant defenses in sepsis, supporting the oxidative-stress aspect for that condition. The methods (p. 7) record mechanical-ventilation requirements, but the paper does not establish oxidative stress specifically in ventilated patients or across severe pancreatitis, ARDS, major burns, and trauma. (LLM, conf=0.78)

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  • Marik et al. retrospectively studied 47 septic patients before and 47 patients after treatment with vitamin C, thiamine, and hydrocortisone; hospital mortality was 8.5% in the treatment group compared with 40.4% in the control group (p < 0.001).

    “Hospital mortality was 8.5% in the treatment group compared with 40.4% in the control group (p < 0.001) [85].”

    From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [85]

  • A secondary analysis of five observational studies identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death.

    “A secondary analysis of five observational studies identified a plateau pressure cut-off value of 29 cm H 2 O, above which an ordinal increment was accompanied by an increment of risk of death (436).”

    From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [436]

    The Data analysis section (manuscript p. 10) describes a before–after comparison of sepsis treatment groups, and the Results report mortality by treatment group. Searches for the 29 cm H2O plateau-pressure cut-off and for a secondary analysis of five observational studies found no passage addressing either claim in our copy. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • In 2017, a single centre before and after study reported shorter duration of vasopressor therapy and lower mortality following administration of high dose vitamin C, hydrocortisone, and thiamine to patients with sepsis and septic shock.

    “In 2017, a single centre before and after study reported shorter duration of vasopressor therapy and lower mortality following the administration of combination of high dose vitamin C, hydrocortisone, and thiamine to patients with sepsis and septic shock [521].”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [521]

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Research works printed but not linked: 4

  1. [22]22. Zabet MH, Mohammadi M, Ramezani M et al. Effect of high-dose ascorbic acid on vasopressor requirement in septic shock. J Res Pharm Pract 2016; 5:94-100.
  2. [53]53. Marik PE. Stress ulcer prophylaxis de-adoption: What the barrier? Crit Care Med 2016; 44:1939-1941.
  3. [61]61. Marik PE, Pastores SM, Kavanaugh BP. Selection bias negates conclusions from the CORTICUS study? N Engl J Med 2008; 358:2069-2070.
  4. [63]63. Hench PS, Kendall EC, Slocumb CH et al. The effect of a hormone of the adreanl cortex (17-hydroxy-11-dehydrocorticosterone:compund E) and the pituitary adenocorticotrophic hormone on rheumatoid arthritis. Preliminary report. Ann Rheum DIs 1949; 8:97-104.

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Authors
Marik, P. E., Khangoora, V., Rivera, R., Hooper, M. H., & Catravas, J.
Affiliations
  • Eastern Virginia Medical School (US)
  • Sentara Norfolk General Hospital (US)
Corresponding author
Marik, Paul E.
ORCID
Venue
Chest
Publisher
Elsevier BV
Published
2017-06
Volume
151
Issue
6
Pages
1229-1238
ISSN
0012-3692 (ISSN-L)
DOI
10.1016/j.chest.2016.11.036
OpenAlex
W2560240742
Semantic Scholar
1d6972ac35fc0d34a615e58cb9faf40d7e6f28cd
Cited by
887
References
95
Citations by year
2026: 28 · 2025: 55 · 2024: 48 · 2023: 87 · 2022: 121 · 2021: 158 · 2020: 151 · 2019: 103 · 2018: 90 · 2017: 45
FWCI
74.27
Type
journal article
Language
en
Update notices
addendum (2023-07-01)
Open access
Licence
Locations
  • CHEST Journal (publishedVersion)
  • PubMed (publishedVersion)
  • ODU Digital Commons (Old Dominion University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
Keywords
severe sepsis, septic shock, cortisol, intravenous vitamin C, thiamine, corticosteroids, in-hospital mortality, organ dysfunction, acute kidney injury, vasopressor weaning, sepsis-related organ failure assessment
MeSH terms
Adult, Aged, Anti-Inflammatory Agents, Antioxidants, Ascorbic Acid, Drug Therapy, Combination, Female, Humans, Hydrocortisone, Intensive Care Units, Male, Middle Aged, Retrospective Studies, Shock, Septic, Thiamine, Vasoconstrictor Agents, Vitamin B Complex, Treatment Outcome, Hospital Mortality, Sepsis, Acute Kidney Injury, Administration, Intravenous, Controlled Before-After Studies

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