Comparison of Hydrocortisone with Combined Hydrocortisone, Ascorbic Acid, and Thiamine as an Adjuvant Therapy on Septic Shock Patients on Mortality: A Systematic Review and Meta-analysis

Authors

  • Sudaryadi Sudaryadi Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
  • Eddy Harijanto Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
  • Indro Mulyono Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2023.9952

Keywords:

Sepsis, Septic shock, Mortality, Hydrocortisone, Ascorbic acid, Thiamine

Abstract

BACKGROUND: Septic shock is still considered a global health problem because it is the main cause of morbidity and mortality in critical patients. Various clinical studies have proven that intravenous administration of high dose ascorbic acid and corticosteroid helps slow the inflammation cascade. These studies help lower the global sepsis and septic shock burden with cost-effective methods and minimum side effects. We systematically reviewed the comparison between hydrocortisone and hydrocortisone-ascorbic acid-thiamine (HAT) combined therapy as an adjuvant in the mortality rate of septic shock patients.

METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane) are comprehensively searched using specific keywords up to October 18, 2021. All published studies on the use of HAT on septic shock patients were collected and reviewed.

RESULTS: Three randomized controlled trials and two controlled trials enrolling 635 patients were included in the study. HAT therapy was found to be not significant in reducing the intensive care unit (ICU) mortality rate (respiratory rate [RR] 0.89 95% confidence interval [CI] [0.60–1.32], p = 0.56), hospital mortality rate (RR 1.2 95% CI [0.90–1.59], p = 0.21), and 28 days mortality (RR 0.95, 95% CI [0.56–1.58], p = 0.83).

CONCLUSION: HAT is ineffective in reducing ICU, hospital, and 28-days mortality in septic shock patients when compared with hydrocortisone therapy, although HAT adjuvant therapy significantly reduces ICU length of stay, ventilator usage duration, and vasopressor usage duration.

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References

Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: For the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):762-74. https://doi.org/10.1001/jama.2016.0288 PMid:26903335 DOI: https://doi.org/10.1001/jama.2016.0288

Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global burden of disease study. Lancet. 2020;395(10219):200-11. https://doi.org/10.1016/S0140-6736(19)32989-7 PMid:31954465 DOI: https://doi.org/10.1016/S0140-6736(19)32989-7

World Health Organization. Global Report on the Epidemiology and Burden of Sepsis: Current Evidence, Identifying Gaps and Future Directions. Geneva: World Health Organization; 2020.

Martin GS. Sepsis, severe sepsis and septic shock: Changes in incidence, pathogens and outcomes. Expert Rev Anti Infect Ther. 2012;10(6):701-6. https://doi.org/10.1586/eri.12.50 PMid:22734959 DOI: https://doi.org/10.1586/eri.12.50

Mehta Y, Kochhar G. Sepsis and septic shock. J Cardiac Crit Care. 2017;1:3-5. https://doi.org/10.1055/s-0037-1604204 DOI: https://doi.org/10.1055/s-0037-1604204

Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet. 2010;376(9749):1339-46. https://doi.org/10.1016/s0140-6736(10)60446-1 PMid:20934212 DOI: https://doi.org/10.1016/S0140-6736(10)60446-1

Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304-77. https://doi.org/10.1007/s00134-017-4683-6 PMid:28101605 DOI: https://doi.org/10.1007/s00134-017-4683-6

Marik PE. Hydrocortisone, ascorbic acid and thiamine (HAT Therapy) for the treatment of sepsis. focus on ascorbic acid. Nutrients. 2018;10(11):1762. https://doi.org/10.3390/nu10111762 PMid:30441816 DOI: https://doi.org/10.3390/nu10111762

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):1229-38. https://doi.org/10.1016/j.chest.2016.11.036 PMid:27940189 DOI: https://doi.org/10.1016/j.chest.2016.11.036

Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12:32. https://doi.org/10.1186/1479-5876-12-32 PMid:24484547 DOI: https://doi.org/10.1186/1479-5876-12-32

Fujii T, Luethi N, Young PJ, Frei DR, Eastwood GM, French CJ, et al. Effect of Vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: The VITAMINS randomized clinical trial. JAMA. 2020;323(5):423-31. https://doi.org/10.1001/jama.2019.22176 PMid:31950979 DOI: https://doi.org/10.1001/jama.2019.22176

Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097 PMid:19621072 DOI: https://doi.org/10.1371/journal.pmed.1000097

Stang A. Critical evaluation of the newcastle-ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-5. DOI: https://doi.org/10.1007/s10654-010-9491-z

Risk of Bias 2 (RoB 2) Tool. Available from: https://www.methods.cochrane.org/risk-bias-2 [Last accessed on 2022 Apr 13].

Hussein AA, Sabry NA, Abdalla MS, Farid SF. A prospective, randomised clinical study comparing triple therapy regimen to hydrocortisone monotherapy in reducing mortality in septic shock patients. Int J Clin Pract. 2021;75(9):e14376. https://doi.org/10.1111/ijcp.14376 PMid:34003568 DOI: https://doi.org/10.1111/ijcp.14376

Long MT, Kory P, Marik P. Vitamin C, hydrocortisone, and thiamine for septic shock. JAMA. 2020;323(21):2203-4. https://doi.org/10.1001/jama.2020.5844 PMid:32484528 DOI: https://doi.org/10.1001/jama.2020.5844

Coloretti I, Biagioni E, Venturelli S, Munari E, Tosi M, Roat E, et al. Adjunctive therapy with Vitamin c and thiamine in patients treated with steroids for refractory septic shock: A propensity matched before-after, case-control study. J Crit Care. 2020;59:37-41. https://doi.org/10.1016/j.jcrc.2020.04.014 PMid:32512351 DOI: https://doi.org/10.1016/j.jcrc.2020.04.014

Reddy PR, Samavedam S, Aluru N, Yelle S, Rajyalakshmi B. Metabolic resuscitation using hydrocortisone, ascorbic acid, and thiamine: Do individual components influence reversal of shock independently? Indian J Crit Care Med. 2020;24(8):649-52. https://doi.org/10.5005/jp-journals-10071-23515 PMid:33024369 DOI: https://doi.org/10.5005/jp-journals-10071-23515

Zheng R, Zhang Y, Rong Z, Huang W, Fu X. Surviving sepsis Campaign: International guidelines for management of sepsis and septic shock 2021, interpretation and expectation. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021;33(10):1159-64. https://doi.org/10.3760/cma.j.cn121430-20211009-01442 PMid:34955122

Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2013;369(18):1726-34. https://doi.org/10.1056/nejmra1208943 PMid:24171518 DOI: https://doi.org/10.1056/NEJMra1208943

Gupta RG, Hartigan SM, Kashiouris MG, Sessler CN, Bearman GM. Early goal-directed resuscitation of patients with septic shock: Current evidence and future directions. Crit Care. 2015;19(1):286. https://doi.org/10.1186/s13054-015-1011-9 PMid:26316210 DOI: https://doi.org/10.1186/s13054-015-1011-9

Cunningham C. Microglia and neurodegeneration: The role of systemic inflammation. Glia. 2013;61(1):71-90. https://doi.org/10.1002/glia.22350 PMid:22674585 DOI: https://doi.org/10.1002/glia.22350

Annane D, Pastores SM, Rochwerg B, Arlt W, Balk RA, Beishuizen A, et al. Correction to: Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of critical care medicine (SCCM) and European society of intensive care medicine (ESICM) 2017. Intensive Care Med. 2018;43(3):401-2. DOI: https://doi.org/10.1007/s00134-018-5071-6

Vandewalle J, Libert C. Glucocorticoids in sepsis: To be or not to be. Front Immunol. 2020;11:1318. https://doi.org/10.3389/fimmu.2020.01318 PMid:32849493 DOI: https://doi.org/10.3389/fimmu.2020.01318

Zayed Y, Alzghoul BN, Banifadel M, Venigandla H, Hyde R, Sutchu S, et al. Vitamin C, Thiamine, and hydrocortisone in the treatment of sepsis: A meta-analysis and trial sequential analysis of randomized controlled trials. J Intensive Care Med. 2022;37(3):327-36. https://doi.org/10.1177/0885066620987809 PMid:33511898 DOI: https://doi.org/10.1177/0885066620987809

Chang K, Harbin M, Shuster C, Griesdale DE, Foster D, Sweet D, et al. Adding Vitamin C to hydrocortisone lacks benefit in septic shock: A historical cohort study. Can J Anaesth. 2020;67(12):1798-805. https://doi.org/10.1007/s12630-020-01814-1 PMid:32939746 DOI: https://doi.org/10.1007/s12630-020-01814-1

Greenley R, Fryckberg A, Kirkham J, Willsie P, Wiley J, Schiers K, et al. 557: Ascorbic acid, thiamine, and hydrocortisone for improving ICU mortality outcomes in septic shock. Crit Care Med. 2019;47:754. https://doi.org/10.1097/01.ccm.0000552300.40275.a8 DOI: https://doi.org/10.1097/01.ccm.0000552300.40275.a8

Wald EL, Sanchez-Pinto LN, Smith CM, Moran T, Badke CM, Barhight MF, et al. 25: Hydrocortisone/ascorbic acid/thiamine use associated with lower mortality in pediatric septic shock. Crit Care Med. 2020;48(1):13. https://doi.org/10.1097/01.ccm.0000618600.13062.e9 DOI: https://doi.org/10.1097/01.ccm.0000618600.13062.e9

Wani SJ, Mufti SA, Jan RA, Shah SU, Qadri SM, Khan UH, et al. Combination of Vitamin C, thiamine and hydrocortisone added to standard treatment in the management of sepsis: Results from an open label randomised controlled clinical trial and a review of the literature. Infect Dis (Lond). 2020;52(4):271-8. https://doi.org/10.1080/23744235.2020.1718200 PMid:31990246 DOI: https://doi.org/10.1080/23744235.2020.1718200

Masood H, Burki AM, Sultan A, Sharif H, Ghauri A, Khan S, et al. Effect of intravenous Vitamin C, thiamine, and hydrocortisone (The metabolic resuscitation protocol) on early weaning from vasopressors in patients with septic shock. A descriptive case series study. Cureus. 2019;11(6):e5016. https://doi.org/10.7759/cureus.5016 PMid:31497446 DOI: https://doi.org/10.7759/cureus.5016

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Published

2023-01-02

How to Cite

1.
Sudaryadi S, Harijanto E, Mulyono I. Comparison of Hydrocortisone with Combined Hydrocortisone, Ascorbic Acid, and Thiamine as an Adjuvant Therapy on Septic Shock Patients on Mortality: A Systematic Review and Meta-analysis. Open Access Maced J Med Sci [Internet]. 2023 Jan. 2 [cited 2024 Nov. 23];11(F):171-9. Available from: https://oamjms.eu/index.php/mjms/article/view/9952

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