{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:31:12Z","timestamp":1785306672211,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ARM"],"abstract":"<jats:p>Clinical rationale for study: Despite advancements in critical care, the mortality rate of sepsis remains high, with an overall poor prognosis. There is a complex pathophysiology of a lethal cascade of cytokines and inflammatory proteins underlying sepsis. The use of vitamin C can theoretically suppress the inflammatory cascade but remains a questionable practice due to a lack of conclusive evidence. Aims of the study: To appraise the therapeutic role of vitamin C in sepsis. Materials and methods: A systematic review was conducted on PubMed, Embase, and the Central Cochrane Registry. The study included randomized clinical trials (RCTs) with vitamin C as an intervention arm in the septic patient population. For continuous variables, the difference in means (MD) and for discrete variables, the odds ratio (OR) was used. For effect sizes, a confidence interval of 95% was used. A p-value of less than 0.05 was used for statistical significance. The analysis was performed using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: 23 studies were included with the total sample size of 2712 patients. In patients treated with vitamin C, there was a statistically significant reduction in the mortality: OR = 0.778 (0.635 to 0.954), p = 0.016; the sequential organ failure assessment score (SOFA): MD = \u22120.749 (\u22121.115 to \u22120.383), p &lt; 0.001; and the duration of vasopressor requirement: MD = \u22121.034 days (\u22121.622 to \u22120.445), p = 0.001. No significant difference was found in the hospital or ICU length of stay. Conclusions and clinical implications: Vitamin C treatment regimens were associated with reduced mortality, SOFA score, and vasopressor requirement compared to the control in sepsis. Given its low cost and minimal adverse effects, we strongly encourage further large, randomized trials to establish vitamin C as a standard of care in sepsis management.<\/jats:p>","DOI":"10.3390\/arm90040038","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T01:41:16Z","timestamp":1659058876000},"page":"281-299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Role and Efficacy of Vitamin C in Sepsis: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1751-2227","authenticated-orcid":false,"given":"Marwah","family":"Muhammad","sequence":"first","affiliation":[{"name":"Sahiwal Medical College, Sahiwal 57000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Jahangir","sequence":"additional","affiliation":[{"name":"Mayo Hospital, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Kassem","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud Bin Abdul","family":"Sattar","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Jahangir","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0119-3329","authenticated-orcid":false,"given":"Syeda","family":"Sahra","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-3147","authenticated-orcid":false,"given":"Muhammad Rafay Khan","family":"Niazi","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeeshan","family":"Zia","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fasih Sami","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Sadiq","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danil","family":"Mishiyev","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleena","family":"Sammar","sequence":"additional","affiliation":[{"name":"Pakistan Institute of Medical Sciences, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loai","family":"Dahabra","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aazib","family":"Irshad","sequence":"additional","affiliation":[{"name":"Jinnah Hospital, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dany","family":"Elsayegh","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Chalhoub","sequence":"additional","affiliation":[{"name":"Staten Island University Hospital, Northwell Health, Staten Island, New York, NY 10305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/330662a0","article-title":"Anti-cachectin\/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia","volume":"330","author":"Tracey","year":"1987","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.molmed.2004.12.007","article-title":"The \u201ccytokine profile\u201d: A code for sepsis","volume":"11","author":"Ulloa","year":"2005","journal-title":"Trends Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0140-6736(10)60446-1","article-title":"Critical care and the global burden of critical illness in adults","volume":"376","author":"Adhikari","year":"2010","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s13054-019-2528-0","article-title":"Trends in sepsis mortality over time in randomised sepsis trials: A systematic literature review and meta-analysis of mortality in the control arm, 2002\u20132016","volume":"23","author":"Luhr","year":"2019","journal-title":"Crit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25467","DOI":"10.1021\/acsomega.0c04318","article-title":"Comparison of Vitamin C and its derivative antioxidant activity: Evaluated by using density functional theory","volume":"5","author":"Liu","year":"2020","journal-title":"ACS Omega"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jclinepi.2010.04.026","article-title":"GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables","volume":"64","author":"Guyatt","year":"2011","journal-title":"J. Clin. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1177\/0962280216669183","article-title":"Optimally estimating the sample mean from the sample size, median, mid-range, and\/or mid-quartile range","volume":"27","author":"Luo","year":"2018","journal-title":"Stat. Methods Med. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wan, X., Wang, W., Liu, J., and Tong, T. (2014). Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range. BMC Med. Res. Methodol., 14.","DOI":"10.1186\/1471-2288-14-135"},{"key":"ref_11","unstructured":"Shi, J., Luo, D., Wan, X., Liu, Y., Liu, J., Bian, Z., and Tong, T. (2020). Detecting the skewness of data from the sample size and the five-number summary. arXiv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13054-022-03900-w","article-title":"Intravenous vitamin C administration to patients with septic shock: A pilot randomised controlled trial","volume":"26","author":"Rosengrave","year":"2022","journal-title":"Crit. Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e458","DOI":"10.1097\/CCM.0000000000005427","article-title":"Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy","volume":"50","author":"Wacker","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s11845-020-02394-1","article-title":"Early use of high-dose vitamin C is beneficial in treatment of sepsis","volume":"190","author":"Lv","year":"2021","journal-title":"Ir. J. Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mahmoodpoor, A., Shadvar, K., Sanaie, S., Hadipoor, M.R., Pourmoghaddam, M.A., and Saghaleini, S.H. (2021). Effect of Vitamin C on mortality of critically ill patients with severe pneumonia in intensive care unit: A preliminary study. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06288-0"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1479-5876-12-32","article-title":"Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis","volume":"12","author":"Syed","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1001\/jama.2019.11825","article-title":"Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients with Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial","volume":"322","author":"Truwit","year":"2019","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4103\/2279-042X.179569","article-title":"Effect of high-dose Ascorbic acid on vasopressor\u2019s requirement in septic shock","volume":"5","author":"Zabet","year":"2016","journal-title":"J. Res. Pharm. Pract."},{"key":"ref_19","first-page":"77","article-title":"Early adjuvant intravenous vitamin C treatment in septic shock may resolve the vasopressor dependence","volume":"5","author":"Ahmed","year":"2017","journal-title":"Int. J. Microbiol. Adv. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jss.2008.04.024","article-title":"Effect of vitamin C administration on neutrophil apoptosis in septic patients after abdominal surgery","volume":"153","author":"Mansilla","year":"2009","journal-title":"J. Surg. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/S0891-5849(97)00059-2","article-title":"The effects of intravenous antioxidants in patients with septic shock","volume":"23","author":"Galley","year":"1997","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e14376","DOI":"10.1111\/ijcp.14376","article-title":"A prospective, randomised clinical study comparing triple therapy regimen to hydrocortisone monotherapy in reducing mortality in septic shock patients","volume":"75","author":"Hussein","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1080\/23744235.2020.1718200","article-title":"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","volume":"52","author":"Wani","year":"2020","journal-title":"Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1001\/jama.2020.24505","article-title":"Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients with Sepsis: The VICTAS Randomized Clinical Trial","volume":"325","author":"Sevransky","year":"2021","journal-title":"JAMA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1001\/jama.2020.11946","article-title":"Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial","volume":"324","author":"Moskowitz","year":"2020","journal-title":"JAMA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"653","DOI":"10.5005\/jp-journals-10071-23517","article-title":"Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock","volume":"24","author":"Menon","year":"2020","journal-title":"Indian J. Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.chest.2020.02.049","article-title":"Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis: The ORANGES Trial","volume":"158","author":"Iglesias","year":"2020","journal-title":"Chest"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1007\/s00134-020-06191-3","article-title":"Combination therapy of vitamin C and thiamine for septic shock: A multi-centre, double-blinded randomized, controlled study","volume":"46","author":"Hwang","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1001\/jama.2019.22176","article-title":"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","volume":"323","author":"Fujii","year":"2020","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.chest.2020.02.065","article-title":"Combined Treatment with Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock: A Randomized Controlled Trial","volume":"158","author":"Chang","year":"2020","journal-title":"Chest"},{"key":"ref_31","first-page":"65","article-title":"Effect of early exogenous vitamin C supplementation on prognosis of sepsis patients","volume":"29","author":"Niu","year":"2019","journal-title":"China J. Mod. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/01.CCM.0000297954.45251.A9","article-title":"Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis: Outcome of a randomized, controlled, double-blind trial","volume":"36","author":"Beale","year":"2008","journal-title":"Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1097\/01.CCM.0000234033.65657.B6","article-title":"Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock","volume":"34","author":"Albuquerque","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.clnu.2011.04.003","article-title":"Tolerability and efficacy of a low-volume enteral supplement containing key nutrients in the critically ill","volume":"30","author":"Schneider","year":"2011","journal-title":"Clin. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1753-4887.2012.00476.x","article-title":"Free radicals and antioxidants: Updating a personal view","volume":"70","author":"Halliwell","year":"2012","journal-title":"Nutr. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev-nutr-071812-161246","article-title":"Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function","volume":"33","author":"Michels","year":"2013","journal-title":"Annu. Rev. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pharmthera.2018.04.007","article-title":"Vitamin C for the treatment of sepsis: The scientific rationale","volume":"189","author":"Marik","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12995","DOI":"10.1021\/bi0263210","article-title":"Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation","volume":"41","author":"Pedraza","year":"2002","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1164\/ajrccm.164.10.2106117","article-title":"HMGB1 as a late mediator of lethal systemic inflammation","volume":"164","author":"Wang","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.3390\/nu5083131","article-title":"Vitamin C: A novel regulator of neutrophil extracellular trap formation","volume":"5","author":"Mohammed","year":"2013","journal-title":"Nutrients"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hemil\u00e4, H. (2017). Vitamin C and Infections. Nutrients, 9.","DOI":"10.3390\/nu9040339"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.intimp.2014.06.026","article-title":"Comparative effect of fucoxanthin and vitamin C on oxidative and functional parameters of human lymphocytes","volume":"22","author":"Molina","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"426740","DOI":"10.1155\/2014\/426740","article-title":"Vitamin C mitigates oxidative stress and tumor necrosis factor-alpha in severe community-acquired pneumonia and LPS-induced macrophages","volume":"2014","author":"Chen","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_44","first-page":"280","article-title":"The effect of ascorbic acid on production of human interferon and the antiviral activity in vitro","volume":"84b","author":"Dahl","year":"1976","journal-title":"Acta. Pathol. Microbiol. Scand. B"},{"key":"ref_45","first-page":"33","article-title":"The influence of ultraviolet irradiation, L-ascorbic acid and calcium chloride on the induction of interferon in human embryo fibroblasts","volume":"30","author":"Kawecki","year":"1982","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/254531a0","article-title":"Enhancement of interferon production by poly(rI)-poly(rC) in mouse cell cultures by ascorbic acid","volume":"254","author":"Siegel","year":"1975","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13054-020-03438-9","article-title":"Mortality in septic patients treated with vitamin C: A systematic meta-analysis","volume":"25","author":"Scholz","year":"2021","journal-title":"Crit. Care"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1097\/CCM.0000000000005263","article-title":"Effect of IV High-Dose Vitamin C on Mortality in Patients with Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"49","author":"Sato","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e304","DOI":"10.1097\/CCM.0000000000005320","article-title":"IV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis","volume":"50","author":"Patel","year":"2022","journal-title":"Crit. Care Med."},{"key":"ref_50","first-page":"942","article-title":"Effect of vitamin C on prognosis of critically ill patients: A Meta-analysis","volume":"31","author":"Du","year":"2019","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/ncp.10832","article-title":"Intravenous vitamin C use and risk of severity and mortality in COVID-19: A systematic review and meta-analysis","volume":"37","author":"Ao","year":"2022","journal-title":"Nutr. Clin. Pract."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2174\/2772432817666211230100723","article-title":"Effect of Vitamin C Supplements on Respiratory Tract Infections: A Systematic Review and Meta-Analysis","volume":"17","author":"Keya","year":"2022","journal-title":"Curr. Rev. Clin. Exp. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00134-021-06558-0","article-title":"Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: A systematic review and a component network meta-analysis","volume":"48","author":"Fujii","year":"2022","journal-title":"Intensive Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1097\/CCM.0000000000005262","article-title":"Thiamine, Ascorbic Acid, and Hydrocortisone as a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis","volume":"49","author":"Assouline","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1097\/SHK.0000000000001781","article-title":"Effect of Combined Hydrocortisone, Ascorbic Acid and Thiamine for Patients with Sepsis and Septic Shock: A Systematic Review and Meta-Analysis","volume":"56","author":"Wu","year":"2021","journal-title":"Shock"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15777","DOI":"10.1038\/s41598-021-95386-9","article-title":"Steroid, ascorbic acid, and thiamine in adults with sepsis and septic shock: A systematic review and component network meta-analysis","volume":"11","author":"Fong","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/MEJ.0000000000000812","article-title":"Thiamine combined with vitamin C in sepsis or septic shock: A systematic review and meta-analysis","volume":"28","author":"Ge","year":"2021","journal-title":"Eur. J. Emerg. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ajem.2021.08.012","article-title":"Efficacy of intravenous vitamin C intervention for septic patients: A systematic review and meta-analysis based on randomized controlled trials","volume":"50","author":"Li","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"172889","DOI":"10.1016\/j.ejphar.2019.172889","article-title":"Efficacy of vitamin C in patients with sepsis: An updated meta-analysis","volume":"868","author":"Wei","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.cgh.2011.04.026","article-title":"Lactated Ringer\u2019s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis","volume":"9","author":"Wu","year":"2011","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_61","unstructured":"Hopkinson, D.A. (2022, January 01). High-Dose Intravenous Vitamin C as an Adjunctive Treatment for Sepsis in Rwanda, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04088591?type=Intr&cond=vitamin+c&draw=3&rank=40."},{"key":"ref_62","unstructured":"Kotanidou, A., and Vitamin, C. (2022, January 01). Hydrocortisone and Thiamine for Septic Shock (CORVICTES). University of Athens, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03592693?type=Intr&cond=vitamin+c&draw=3&rank=41."},{"key":"ref_63","unstructured":"Liu, Z. (2022, January 01). Clinical Efficacy of Megadose Vitamin C in Sepsis (CEMVIS). Zhujiang Hospital, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT05194189?rslt=Without&type=Intr&cond=vitamin+c&draw=2&rank=16."}],"container-title":["Advances in Respiratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2543-6031\/90\/4\/38\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:58:21Z","timestamp":1760140701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2543-6031\/90\/4\/38"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":63,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["arm90040038"],"URL":"https:\/\/doi.org\/10.3390\/arm90040038","relation":{},"ISSN":["2543-6031"],"issn-type":[{"value":"2543-6031","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]}}}