Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial
Open accessAbstract
IMPORTANCE: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. OBJECTIVE: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. INTERVENTIONS: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCE: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A patient-level analysis of two randomized PEEP trials suggested that patients with ARDS who respond to increased PEEP with improved oxygenation have a lower risk of death; this association was stronger in patients with more severe ARDS (PaO2/FiO2 < 150 mm Hg) compared with patients with less severe ARDS.
“A patient-level analysis of two of the randomized PEEP trials (440, 441) suggested that patients with ARDS who respond to increased PEEP with improved oxygenation have a lower risk of death; this association was stronger in patients with more severe ARDS (PaO 2 /FiO 2 < 150 mm Hg) compared with patients with less severe ARDS (444).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [440]
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn the Moskowitz et al. study, no difference in the primary outcome of mean SOFA score change at 72 h post enrolment was observed.
“No difference in the primary outcome of mean SOFA score change at 72 h post enrolment was observed.”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [525]
In the Moskowitz et al. study, at 30 days, 34.7% (35/101) of patients randomised to combination therapy had died versus 29.3% (29/99) randomised to placebo (HR 1.3; 95% CI 0.8-2.2; p = 0.26).
“At 30 days, 34.7% (35/101) of patients randomised to combination therapy had died vs. 29.3% (29/99) randomised to placebo (HR, 1.3; 95% CI 0.8–2.2; p = 0.26).”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [525]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rudd, K. E., Johnson, S. C., Agesa, K. M., Shackelford, K. A., Tsoi, D., Kievlan, D. R., Colombara, D. V., Ikuta, K. S., Kissoon, N., Finfer, S., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(19)32989-7 · Cited by 7,971 · see citing works
Seymour, C. W., Liu, V. X., Iwashyna, T. J., Brunkhorst, F. M., Rea, T. D., Scherag, A., Rubenfeld, G., Kahn, J. M., Shankar-Hari, M., Singer, M., et al. (2016) · JAMA · doi:10.1001/jama.2016.0288 · Cited by 3,939 · see citing works
Ely, E. W., Inouye, S. K., Bernard, G. R., Gordon, S., Francis, J., May, L., Truman, B., Speroff, T., Gautam, S., Margolin, R., et al. (2001) · JAMA · doi:10.1001/jama.286.21.2703 · Cited by 3,210 · see citing works
Serial Evaluation of the SOFA Score to Predict Outcome in Critically Ill Patients
Ferreira, F. L. (2001) · JAMA · doi:10.1001/jama.286.14.1754 · Cited by 2,862 · see citing works
Enhancing Recovery From Sepsis: A Review
Prescott, H. C., & Angus, D. C. (2018) · JAMA · doi:10.1001/jama.2017.17687 · Cited by 1,059 · see citing works
Adjunctive glucocorticoid therapy in patients with septic shock.
Venkatesh, B., Finfer, S., Cohen, J., Rajbhandari, D., Arabi, Y., Bellomo, R., Billot, L., Correa, M., Glass, P., Harward, M., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1705835 · Cited by 1,037 · see citing works
The SOFA score—development, utility and challenges of accurate assessment in clinical trials
Lambden, S., Laterre, P., Levy, M. M., & François, B. (2019) · Critical Care · doi:10.1186/s13054-019-2663-7 · Cited by 1,003 · see citing works
Hydrocortisone plus fludrocortisone for adults with septic shock.
Annane, D., Renault, A., Brun-Buisson, C., Megarbane, B., Quenot, J.-P., Siami, S., Cariou, A., Forceville, X., Schwebel, C., Martin, C., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1705716 · Cited by 939 · see citing works
Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock
Marik, P. E., Khangoora, V., Rivera, R., Hooper, M. H., & Catravas, J. (2017) · Chest · doi:10.1016/j.chest.2016.11.036 · Cited by 887 · see citing works
Fowler, A. A., Truwit, J. D., Hite, R. D., Morris, P. E., DeWilde, C., Priday, A., Fisher, B., Thacker, L. R., Natarajan, R., Brophy, D. F., et al. (2019) · JAMA · doi:10.1001/jama.2019.11825 · Cited by 836 · see citing works
Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis.
Nursing, M. R. I. C. U., Fowler, A. A., Syed, A. A., Knowlson, S., Sculthorpe, R., Farthing, D., DeWilde, C., Farthing, C. A., Larus, T. L., Martin, E., et al. (2014) · Journal of Translational Medicine · doi:10.1186/1479-5876-12-32 · Cited by 573 · see citing works
Fujii, T., Luethi, N., Young, P. J., Frei, D. R., Eastwood, G. M., French, C. J., Deane, A. M., Shehabi, Y., Hajjar, L. A., Oliveira, G., et al. (2020) · JAMA · doi:10.1001/jama.2019.22176 · Cited by 466 · see citing works
Self-citationDonnino, M. W., Andersen, L. W., Chase, M., Berg, K. M., Tidswell, M., Giberson, T. A., Wolfe, R. E., Moskowitz, A. L., Smithline, H. A., Ngo, L. H., et al. (2016) · Critical Care Medicine · doi:10.1097/ccm.0000000000001572 · Cited by 299 · see citing works
Self-citationde Grooth, H., Geenen, I. L., Girbes, A. R. J., Vincent, J., Parienti, J., & Straaten, H. M. O. (2017) · Critical Care · doi:10.1186/s13054-017-1609-1 · Cited by 282 · see citing works
Iwashyna, T. J., Burke, J. F., Sussman, J. B., Prescott, H. C., Hayward, R. A., & Angus, D. C. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201411-2125cp · Cited by 276 · see citing works
Critical care management of adults with community-acquired severe respiratory viral infection
Arabi, Y. M., Fowler, R., & Hayden, F. G. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-05943-5 · Cited by 260 · see citing works
Moskowitz, A. L., Andersen, L. W., Huang, D. T., Berg, K. M., Grossestreuer, A. V., Marik, P. E., Sherwin, R. L., Hou, P. C., Becker, L. B., Cocchi, M. N., et al. (2018) · Critical Care · doi:10.1186/s13054-018-2217-4 · Cited by 158 · see citing works
Self-citationBarabutis, N., Khangoora, V. S., Marik, P. E., & Catravas, J. D. (2017) · CHEST Journal · doi:10.1016/j.chest.2017.07.014 · Cited by 120 · see citing works
Moskowitz, A. L., Andersen, L. W., Cocchi, M. N., Karlsson, M., Patel, P. V., & Donnino, M. W. (2017) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201608-656bc · Cited by 100 · see citing works
Self-citationDo not forget to give thiamine to your septic shock patient!
Mallat, J., Lemyze, M., & Thévenin, D. (2016) · Journal of Thoracic Disease · doi:10.21037/jtd.2016.04.32 · Cited by 52 · see citing works
Doctor—your septic patients have scurvy!
Marik, P. E., & Hooper, M. H. (2018) · Critical Care · doi:10.1186/s13054-018-1950-z · Cited by 40 · see citing works
Hudson, E. P., Collie, J. T. B., Fujii, T., Luethi, N., Udy, A. A., Doherty, S., Eastwood, G. M., Yanase, F., Naorungroj, T., Bitker, L., et al. (2019) · Critical Care and Resuscitation · doi:10.1016/s1441-2772(23)00548-3 · Cited by 35 · see citing works
Hudson, E. P., Collie, J. T. B., Fujii, T., Luethi, N., Udy, A. A., Doherty, S., Eastwood, G. M., Yanase, F., Naorungroj, T., Bitker, L., et al. (2020) · Critical Care and Resuscitation · doi:10.51893/2020.2.err2 · Cited by 28 · see citing works
Moskowitz, A. L., Yankama, T. T., Andersen, L. W., Huang, D. T., Donnino, M. W., & Grossestreuer, A. V. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-034406 · Cited by 17 · see citing works
Self-citation
Flagged first, then by citations
1 of the 25 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.
Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C. M., French, C., Machado, F. R., Mcintyre, L., Ostermann, M., Prescott, H. C., et al. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005337 · Cited by 2,935 · see citing works
Sevransky, J., Rothman, R. E., Hager, D. N., Bernard, G. R., Brown, S. M., Buchman, T. G., Busse, L. W., Coopersmith, C. M., DeWilde, C., Ely, E. W., et al. (2021) · JAMA · doi:10.1001/jama.2020.24505 · Cited by 291 · see citing works
Zhao, S., Chen, F., Yin, Q., Wang, D., Han, W., & Zhang, Y. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.571810 · Cited by 141 · see citing works
Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021
Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C. M., French, C., Machado, F. R., Mcintyre, L., Ostermann, M., Prescott, H. C., et al. (2021) · Intensive Care Medicine · doi:10.1007/s00134-021-06506-y · Cited by 5,082 · see citing works
Fujii, T., Salanti, G., Belletti, A., Bellomo, R., Carr, A. C., Furukawa, T. A., Luethi, N., Luo, Y., Putzu, A., Sartini, C., et al. (2021) · Intensive Care Medicine · doi:10.1007/s00134-021-06558-0 · Cited by 112 · see citing works
Pediatric Sepsis Diagnosis, Management, and Sub-phenotypes
Weiss, S. L., & Fitzgerald, J. C. (2023) · PEDIATRICS · doi:10.1542/peds.2023-062967 · Cited by 86 · see citing works
Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice
Ow, C. P. C., Trask-Marino, A. L., Betrie, A. H., Evans, R. G., May, C. N., & Lankadeva, Y. R. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173798 · Cited by 72 · see citing works
Mortality in septic patients treated with vitamin C: a systematic meta-analysis
Scholz, S. S., Borgstedt, R., Ebeling, N., Menzel, L. C., Jansen, G., & Rehberg, S. W. (2021) · Critical Care · doi:10.1186/s13054-020-03438-9 · Cited by 69 · see citing works
Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy*
Wacker, D. A., Burton, S. L., Berger, J. P., Hegg, A. J., Heisdorffer, J., Wang, Q., Medcraft, E. J., & Reilkoff, R. A. (2022) · Critical Care Medicine · doi:10.1097/ccm.0000000000005427 · Cited by 61 · see citing works
Lyu, Q., Zheng, R., Chen, Q., Yu, J., Shao, J., & Gu, X. (2022) · Critical Care · doi:10.1186/s13054-022-04175-x · Cited by 58 · see citing works
Attention to Immortal Time Bias in Critical Care Research
Vail, E. A., Gershengorn, H. B., Wunsch, H., & Walkey, A. J. (2021) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202008-3238cp · Cited by 58 · see citing works
IV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis
Patel, J. J., Ortiz‐Reyes, L., Dhaliwal, R., Clarke, J. G., Hill, A., Stoppe, C., Lee, Z., & Heyland, D. K. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005320 · Cited by 56 · see citing works
Assouline, B., Faivre, A., Verissimo, T., Sangla, F., Berchtold, L., Giraud, R., Bendjelid, K., Sgardello, S. D., Elia, N., Pugin, J., et al. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005262 · Cited by 55 · see citing works
Pathophysiology, mechanisms, and managements of tissue hypoxia
Mallat, J., Rahman, N., Hamed, F., Glenn Hernández, P., & Fischer, M.-O. (2022) · Anaesthesia Critical Care & Pain Medicine · doi:10.1016/j.accpm.2022.101087 · Cited by 54 · see citing works
High-Dose IV Hydroxocobalamin (Vitamin B12) in Septic Shock
Patel, J. J., Willoughby, R. E., Peterson, J., Carver, T., Zelten, J., Markiewicz, A., Spiegelhoff, K., Hipp, L. A., Canales, B., Szabó, A., et al. (2022) · CHEST Journal · doi:10.1016/j.chest.2022.09.021 · Cited by 51 · see citing works
Management of Sepsis and Septic Shock: What Have We Learned in the Last Two Decades?
Kamath, S., Altaq, H. H., & Abdo, T. (2023) · Microorganisms · doi:10.3390/microorganisms11092231 · Cited by 53 · see citing works
Sato, R., Hasegawa, D., Prasitlumkum, N., Ueoka, M., Nishida, K., Takahashi, K., Nasu, M., & Dugar, S. P. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005263 · Cited by 50 · see citing works
The Japanese Critical Care Nutrition Guideline 2024
Nakamura, K., Yamamoto, R., Higashibeppu, N., Yoshida, M., Tatsumi, H., Shimizu, Y., Izumino, H., Oshima, T., Hatakeyama, J., Ouchi, A., et al. (2025) · Journal of Intensive Care · doi:10.1186/s40560-025-00785-z · Cited by 50 · see citing works
Pitre, T., Drover, K., Chaudhuri, D., Zeraaktkar, D., Menon, K., Gershengorn, H. B., Jayaprakash, N., Spencer-Segal, J. L., Pastores, S. M., Nei, A. M., et al. (2024) · Critical Care Explorations · doi:10.1097/cce.0000000000001000 · Cited by 46 · see citing works
Holse, C., Aasvang, E. K., Vester-Andersen, M., Rasmussen, L. S., Wetterslev, J., Christensen, R., Jorgensen, L. N., Pedersen, S. S., Loft, F. C., Troensegaard, H., et al. (2022) · Anesthesiology · doi:10.1097/aln.0000000000004117 · Cited by 45 · see citing works
Jung, S., Lee, M., Baek, M. S., & Kim, W. (2022) · Critical Care · doi:10.1186/s13054-021-03872-3 · Cited by 46 · see citing works
Parenteral Vitamin C in Patients with Severe Infection: A Systematic Review
Agarwal, A., Basmaji, J., Fernando, S. M., Ge, F. Z., Xiao, Y., Faisal, H., Honarmand, K., Hylands, M., Lau, V. I., Lewis, K. A., et al. (2022) · NEJM Evidence · doi:10.1056/evidoa2200105 · Cited by 43 · see citing works
The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024
Shime, N., Nakada, T.-A., Yatabe, T., Yamakawa, K., Aoki, Y., Inoue, S., Iba, T., Ogura, H., Kawai, Y., Kawaguchi, A., et al. (2025) · Journal of Intensive Care · doi:10.1186/s40560-025-00776-0 · Cited by 43 · see citing works
Use of Hydrocortisone, Ascorbic Acid, and Thiamine in Adults with Septic Shock
Vail, E. A., Wunsch, H., Pinto, R. L., Bosch, N. A., Walkey, A. J., Lindenauer, P. K., & Gershengorn, H. B. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202005-1829oc · Cited by 42 · see citing works
Zhao, B., Liu, M., Liu, P., Peng, Y., HUANG, J. C., Li, M., Wang, Y., Xu, L., Sun, S., Qi, X., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.638556 · Cited by 41 · see citing works
Postbiotics as potential new therapeutic agents for sepsis
Lou, X., Xue, J., Shao, R., Mo, C., Wang, F., & Chen, G. (2023) · Burns & Trauma · doi:10.1093/burnst/tkad022 · Cited by 38 · see citing works
Petsakul, S., Morakul, S., Tangsujaritvijit, V., Kunawut, P., Singhatas, P., & Sanguanwit, P. (2020) · BMC Anesthesiology · doi:10.1186/s12871-020-01195-4 · Cited by 38 · see citing works
Zayed, Y., Alzghoul, B. N., Banifadel, M., Venigandla, H., Hyde, R., Sutchu, S., Khasawneh, M., Borok, Z., Urbine, D., Jantz, M. A., et al. (2021) · Journal of Intensive Care Medicine · doi:10.1177/0885066620987809 · Cited by 38 · see citing works
Roberson, S. W., Nwosu, S., Collar, E. M., Kiehl, A. L., Harrison, F. E., Bastarache, J. A., Wilson, J. E., Mart, M. F., Sevransky, J., Ely, E. W., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.0380 · Cited by 37 · see citing works
Liang, B., Su, J., Shao, H., Chen, H., & Xie, B. (2023) · Critical Care · doi:10.1186/s13054-023-04392-y · Cited by 38 · see citing works
The noncanonical inflammasome-induced pyroptosis and septic shock
Wu, J., Cai, J., Tang, Y., & Lü, B. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101844 · Cited by 37 · see citing works
Wald, E., Badke, C. M., Hintz, L. K., Spewak, M. B., & Sanchez-Pinto, L. N. (2021) · Pediatric Research · doi:10.1038/s41390-021-01673-6 · Cited by 34 · see citing works
Therapeutic potential of megadose vitamin C to reverse organ dysfunction in sepsis and COVID‐19
May, C. N., Bellomo, R., & Lankadeva, Y. R. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15579 · Cited by 32 · see citing works
Guinot, P., Martin, A., Berthoud, V., Voizeux, P., Bartamian, L., Santangelo, E., Bouhemad, B., & Nguyen, M. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10143164 · Cited by 32 · see citing works
Insights Into Thiamine Supplementation in Patients With Septic Shock
Costa, N. A., Pereira, A. G., Sugizaki, C. S. D. A., Vieira, N. M., Garcia, L. R., de Paiva, S. A. R., Zornoff, L. A. M., Azevedo, P. S., Polegato, B. F., & Minicucci, M. F. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2021.805199 · Cited by 31 · see citing works
Leukocyte activation primes fibrinogen for proteolysis by mitochondrial oxidative stress
Han, C. Y., Pichon, T. J., Wang, X., Ringgold, K. M., John, A. E. S., Stern, S. A., & White, N. J. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102263 · Cited by 31 · see citing works
Effect of thiamine supplementation in critically ill patients: A systematic review and meta-analysis
Sedhai, Y. R., Shrestha, D. B., Budhathoki, P., Jha, V., Mandal, S. K., Karki, S., Baniya, R., Cable, C. A., & Kashiouris, M. G. (2021) · Journal of Critical Care · doi:10.1016/j.jcrc.2021.05.016 · Cited by 30 · see citing works
Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection
Li, M., Ching, T. H. S., Hipple, C., López, R., Sahibzada, A., & Rahman, M. H. (2021) · Journal of Pharmacy Practice · doi:10.1177/08971900211015052 · Cited by 30 · see citing works
Vitamin C in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis
Shrestha, D. B., Budhathoki, P., Sedhai, Y. R., Mandal, S. K., Shikhrakar, S., Karki, S., Baniya, R. K., Kashiouris, M. G., Qiao, X., & Fowler, A. A. (2021) · Nutrients · doi:10.3390/nu13103564 · Cited by 29 · see citing works
Moskowitz, A. L., Berg, K. M., Grossestreuer, A. V., Balaji, L., Liu, X., Cocchi, M. N., Chase, M., Gong, M. N., Gong, J. F., Parikh, S. M., et al. (2023) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202301-0034oc · Cited by 30 · see citing works
Self-citationNeuroprotective Properties of Vitamin C: A Scoping Review of Pre-Clinical and Clinical Studies
Kangisser, L., Tan, E., Bellomo, R., Deane, A. M., & Plummer, M. P. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2020.7443 · Cited by 30 · see citing works
Medication and Fluid Management of Pediatric Sepsis and Septic Shock
Burgunder, L., Heyrend, C., Olson, J. A., Stidham, C., Lane, R. D., Workman, J. K., & Larsen, G. Y. (2022) · Pediatric Drugs · doi:10.1007/s40272-022-00497-z · Cited by 33 · see citing works
Na, W., Shen, H., Li, Y., & Qu, D. (2021) · Journal of Intensive Care · doi:10.1186/s40560-021-00589-x · Cited by 28 · see citing works
Unar, A., Bertolino, L., Patauner, F., Gallo, R., & Durante‐Mangoni, E. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12196128 · Cited by 28 · see citing works
Emergency medicine updates: Management of sepsis and septic shock
Long, B., & Gottlieb, M. A. (2025) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2025.01.054 · Cited by 29 · see citing works
Fong, K. M., Au, S. Y., & Ng, G. W. Y. (2021) · Scientific Reports · doi:10.1038/s41598-021-95386-9 · Cited by 29 · see citing works
Vitamin C for sepsis intervention: from redox biochemistry to clinical medicine
Li, Y. R., & Zhu, H. (2021) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04240-z · Cited by 27 · see citing works
Mohamed, A., Abdelaty, M. A., Saad, M. O., Shible, A. A., Mitwally, H., Akkari, A. M., Elbuzidi, A. A. S., Bintaher, A., Hashim, A., Abdelrahim, M., et al. (2023) · Shock · doi:10.1097/shk.0000000000002110 · Cited by 27 · see citing works
Novel aspects of sepsis pathophysiology: NETs, plasma glycoproteins, endotheliopathy and COVID-19
Nishibori, M. (2022) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2022.06.001 · Cited by 25 · see citing works
Dresen, E., Notz, Q., Menger, J., Homayr, A. L., Lindner, M., Radke, D. I., Stoppe, C., & Elke, G. (2023) · Nutrition in Clinical Practice · doi:10.1002/ncp.10984 · Cited by 25 · see citing works
McCune, T. R., Toepp, A. J., Sheehan, B. E., Sherani, M. S. K., Petr, S. T., & Dodani, S. (2021) · BMC Nephrology · doi:10.1186/s12882-021-02599-1 · Cited by 22 · see citing works
Coppock, D., Violet, P.-C., Vásquez, G., Belden, K. A., Foster, M. W., Mullin, B., Magee, D., Mikell, I., Shah, L., Powers, V., et al. (2022) · Life · doi:10.3390/life12030453 · Cited by 21 · see citing works
Corticosteroids for treating sepsis in children and adults
Annane, D., Briegel, J., Granton, D., Bellissant, É., Bollaert, P., Keh, D., Kupfer, Y. Y., Pirracchio, R., & Rochwerg, B. N. (2025) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002243.pub5 · Cited by 23 · see citing works
Han, X., Zhou, J.-H., Li, Y., Zhao, Y., Li, Y.-F., Hua, Y., Dong, T., & Chai, F. (2025) · Food Chemistry · doi:10.1016/j.foodchem.2025.143727 · Cited by 21 · see citing works
Wu, T., Hu, C., Huang, W., Xu, Q., Hu, B., & Li, J. (2021) · Shock · doi:10.1097/shk.0000000000001781 · Cited by 21 · see citing works
Li, T., Zeng, J., Li, D.-H., Yang, G., Wang, K., Deng, H., & Jiang, H. (2021) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2021.08.012 · Cited by 21 · see citing works
Montague, B., Summers, A. M., Bhawal, R. P., Anderson, E. T., Kraus‐Malett, S., Zhang, S., & Goggs, R. A. N. (2022) · PLoS ONE · doi:10.1371/journal.pone.0271137 · Cited by 21 · see citing works
Micronutrients early in critical illness, selective or generous, enteral or intravenous?
Berger, M. M., & Manzanares, W. (2020) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000724 · Cited by 21 · see citing works
Lin, Y., Alhaskawi, A., Chen, L., & Moqbel, S. A. A. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1695992 · Cited by 21 · see citing works
Uckun, F. M., Carlson, J., Orhan, C., Powell, J., Pizzimenti, N. M., van Wyk, H., Özercan, İ. H., Volk, M., & Şahin, K. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.594321 · Cited by 20 · see citing works
Somagutta, M. K. R., Pormento, M. K. L., Khan, M. A., Hamdan, A. H. Y., Hange, N., Manish, K. C., Pagad, S., Jain, M. S., Lingarajah, S., Sharma, V., et al. (2021) · Acute and Critical Care · doi:10.4266/acc.2021.00108 · Cited by 20 · see citing works
Non-conventional immunomodulation in the management of sepsis
Slim, M. A., Turgman, O., van Vught, L. A., van der Poll, T., & Wiersinga, W. J. (2023) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2023.10.032 · Cited by 20 · see citing works
Yanase, F., Raman, S., Naorungroj, T., McCarthy, A., Cree, M., Schlapbach, L. J., & Bellomo, R. (2021) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000002686 · Cited by 20 · see citing works
Rozemeijer, S., van der Horst, F. A. L., & de Man, A. (2021) · Critical Care · doi:10.1186/s13054-021-03670-x · Cited by 20 · see citing works
Thiamine combined with vitamin C in sepsis or septic shock: a systematic review and meta-analysis
Ge, Z., Huang, J., Liu, Y., Xiang, J., Gao, Y., Walline, J. H., Lu, X., Yu, S., Zhao, L., & Li, Y. (2021) · European Journal of Emergency Medicine · doi:10.1097/mej.0000000000000812 · Cited by 19 · see citing works
Almalki, W. H., Ghoneim, M. M., Alshehri, S., Imam, S. S., Kazmi, I. A., & Gupta, G. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04432-1 · Cited by 18 · see citing works
Martimbianco, A. L. C., Pacheco, R. L., Bagattini, Â. M., Moreira, R. D. F. C., Azevedo, L. C. P., & Riera, R. (2022) · Journal of Critical Care · doi:10.1016/j.jcrc.2022.154099 · Cited by 18 · see citing works
Current role of high dose vitamin C in sepsis management: A concise review
Juneja, D., Nasa, P., & Jain, R. (2022) · World Journal of Critical Care Medicine · doi:10.5492/wjccm.v11.i6.349 · Cited by 19 · see citing works
IV Vitamin C in Sepsis: A Latest Systematic Review and Meta-Analysis
Wen, C., Li, Y., Hu, Q., Liu, H., Xu, X., & Lü, M. (2023) · International Journal of Clinical Practice · doi:10.1155/2023/6733465 · Cited by 19 · see citing works
Vitamin C and thiamine for sepsis: time to go back to fundamental principles
Fujii, T., Fowler, R., & Vincent, J. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-06242-9 · Cited by 18 · see citing works
Ascorbic Acid in the Acute Care Setting
Kressin, C., Pandya, K. A., Magnuson, B. L., Donaldson, C., & Flannery, A. H. (2021) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2102 · Cited by 17 · see citing works
Schlapbach, L. J., GIBBONS, K. S., Ridolfi, R., Harley, A., Cree, M., Long, D. A., Buckley, D. H. F., Erickson, S. J., Festa, M., George, S., et al. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2021.663435 · Cited by 17 · see citing works
The Role and Efficacy of Vitamin C in Sepsis: A Systematic Review and Meta-Analysis
Muhammad, M., Jahangir, A., Kassem, A., Sattar, S. B. A., Jahangir, A., Sahra, S., Niazi, M. R. K., Mustafa, A., Zia, Z., Siddiqui, F. S., et al. (2022) · Advances in respiratory medicine · doi:10.3390/arm90040038 · Cited by 17 · see citing works
Wang, J., Song, Q., Yang, S., Wang, H., Meng, S., Huang, L., Li, Q., Xu, J., Xie, J., & Huang, Y. (2023) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-221444 · Cited by 17 · see citing works
Ascorbic acid attenuates activation and cytokine production in sepsis-like monocytes
Schmidt, T., Kahn, R., & Kahn, F. (2022) · Journal of Leukocyte Biology · doi:10.1002/jlb.4ab0521-243r · Cited by 17 · see citing works
Thiamine as a metabolic resuscitator after in-hospital cardiac arrest
Berg, K. M., Grossestreuer, A. V., Balaji, L., Moskowitz, A. L., Berlin, N., Cocchi, M. N., Morton, A., Li, F., Mehta, S. M., Peradze, N., et al. (2024) · Resuscitation · doi:10.1016/j.resuscitation.2024.110160 · Cited by 16 · see citing works
Self-citationThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024
Shime, N., Nakada, T., Yatabe, T., Yamakawa, K., Aoki, Y., Inoue, S., Iba, T., Ogura, H., Kawai, Y., Kawaguchi, A., et al. (2025) · Acute Medicine & Surgery · doi:10.1002/ams2.70037 · Cited by 18 · see citing works
Petitjeans, F., Géloën, A., Pichot, C., Leroy, S., GHIGNONE, M., & Quintin, L. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10194569 · Cited by 17 · see citing works
Han, C. Y., Wang, X., Ringgold, K. M., Bennett, J. C., John, A. E. S., BERENSON, R. J., Stern, S. A., & White, N. J. (2023) · Blood · doi:10.1182/blood.2022019164 · Cited by 15 · see citing works
Vandervelden, S., Cortens, B., Fieuws, S., Eegdeman, W., Malinverni, S., Vanhove, P., Monsieurs, K. G., Breuls, J., Hubloue, I., Stifkens, F., et al. (2025) · Critical Care · doi:10.1186/s13054-025-05383-x · Cited by 15 · see citing works
Self-citationA Systematic Review and Meta-Analysis on Possible Role of Vitamin C in Sepsis
Brown, J. L., Robertson, C., Sevilla, L., Garza, J., Rashid, H., Benitez, A. C., Shipotko, M., & Ali, Z. (2022) · Cureus · doi:10.7759/cureus.32886 · Cited by 14 · see citing works
Recent Data about the Use of Corticosteroids in Sepsis—Review of Recent Literature
Lazăr, A. E. (2024) · Biomedicines · doi:10.3390/biomedicines12050984 · Cited by 14 · see citing works
Marmiere, M., D’Amico, F., Monti, G., & Landoni, G. (2024) · Critical Care Medicine · doi:10.1097/ccm.0000000000006532 · Cited by 14 · see citing works
Aritra, S., Shikha, C. B., & Indu, S. (2025) · Intelligent Pharmacy · doi:10.1016/j.ipha.2024.12.001 · Cited by 17 · see citing works
Agarwal, A., Basmaji, J., Fernando, S. M., Ge, F. Z., Xiao, Y., Faisal, H., Honarmand, K., Hylands, M., Lau, V. I., Lewis, K. A., et al. (2021) · JMIR Research Protocols · doi:10.2196/33989 · Cited by 14 · see citing works
Early ascorbic acid administration prevents vascular endothelial cell damage in septic mice
Madokoro, Y., Kamikokuryo, C., Niiyama, S., Ito, T., Hara, S., Ichinose, H., & Kakihana, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.929448 · Cited by 16 · see citing works
Yao, R.-Q., Zhu, Y., Yu, Y. S., Li, Z., Wang, L., Zheng, L., Li, J., Huang, H., Wu, G., Zhu, F., et al. (2021) · Burns & Trauma · doi:10.1093/burnst/tkab040 · Cited by 13 · see citing works
Kato, T., MIZUNO, T., NAKANISHI, M., Lee, J. K., Yamada, S., Tsuboi, N., & Takahashi, K. (2023) · In Vivo · doi:10.21873/invivo.13200 · Cited by 13 · see citing works
Nakanishi, N., Abe, Y., Matsuo, M., Tampo, A., Yamada, K., Hatakeyama, J., Yoshida, M., Yamamoto, R., Higashibeppu, N., Nakamura, K., et al. (2024) · Clinical Nutrition · doi:10.1016/j.clnu.2024.09.002 · Cited by 13 · see citing works
Rozemeijer, S., de Grooth, H., Elbers, P., Girbes, A. R. J., den Uil, C. A., Dubois, E. A., Wils, E., Rettig, T. C. D., van Zanten, A. R. H., Vink, R., et al. (2021) · Trials · doi:10.1186/s13063-021-05483-3 · Cited by 13 · see citing works
Chen, C.-Y., Chiu, C.-T., Lee, H.-S., & Lai, C. (2022) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2022.11.015 · Cited by 13 · see citing works
Lee, M., Jung, S., Baek, M. S., Shin, J., & Kim, W. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11070610 · Cited by 12 · see citing works
Macrophage activation syndrome in Sepsis: from pathogenesis to clinical management
Chen, S., Zhang, C., Luo, J., Lin, Z., Chang, T., Dong, L., Chen, D., & Tang, Z. (2024) · Inflammation Research · doi:10.1007/s00011-024-01957-7 · Cited by 12 · see citing works
Vitamin C for Sepsis and Septic Shock
Ammar, M. A., Ammar, A. A., Condeni, M. S., & Bell, C. M. (2021) · American Journal of Therapeutics · doi:10.1097/mjt.0000000000001423 · Cited by 12 · see citing works
Remote ischemic conditioning in septic shock: the RECO-Sepsis randomized clinical trial
Cour, M., Klouche, K., Souweine, B., Quenot, J., Schwebel, C., Périnel, S., Amaz, C., Buisson, M., Ovize, M., Mewton, N., et al. (2022) · Intensive Care Medicine · doi:10.1007/s00134-022-06872-1 · Cited by 12 · see citing works
Lauer, A., Burkard, M., Niessner, H., Leischner, C., Renner, O., Vollbracht, C., Michels, H., Busch, C., Sinnberg, T. W., & Venturelli, S. (2021) · Nutrients · doi:10.3390/nu13072366 · Cited by 12 · see citing works
Adverse cognitive effects of glucocorticoids: A systematic review of the literature
Spannenburg, L., & Reed, H. (2023) · Steroids · doi:10.1016/j.steroids.2023.109314 · Cited by 13 · see citing works
Shapiro, L., Scherger, S. J., Franco‐Paredes, C., Gharamti, A. A., & Henao‐Martínez, A. F. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1250483 · Cited by 11 · see citing works
Mashhadi, N. S., Aliyari, A., Hajhashemy, Z., Saadat, S., & Rouhani, M. H. (2022) · Journal of Intensive Care · doi:10.1186/s40560-022-00594-8 · Cited by 11 · see citing works
Miranda, C. T. C. D. S., Soares, S. D., de Oliveira, W. Q., Lima, A. D. S., Numa, I. A. N., & Pastore, G. M. (2024) · Foods · doi:10.3390/foods13182925 · Cited by 10 · see citing works
- Authors
- Moskowitz, A., Huang, D. T., Hou, P. C., Gong, J., Doshi, P. B., Grossestreuer, A. V., Andersen, L. W., Ngo, L., Sherwin, R. L., Berg, K. M., Chase, M., Cocchi, M. N., McCannon, J. B., Hershey, M., Hilewitz, A., Korotun, M., Becker, L. B., Otero, R. M., Uduman, J., Sen, A., Donnino, M. W., & for the ACTS Clinical Trial Investigators
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of Pittsburgh (US)
- Brigham and Women's Hospital (US)
- Hofstra University (US)
- The University of Texas Health Science Center at Houston (US)
- Wayne State University (US)
- Mount Auburn Hospital (US)
- South Shore Hospital (US)
- Oakland University (US)
- Henry Ford Health (US)
- Mayo Clinic (US)
- Corresponding author
- Donnino, Michael W.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2020-08-18
- Volume
- 324
- Issue
- 7
- Pages
- 642
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC7435341
- OpenAlex
- W3069087306
- Semantic Scholar
- a9205794d79affdd861a6a28192f566070b621c8
- Cited by
- 253
- References
- 25
- Citations by year
- 2026: 19 · 2025: 29 · 2024: 25 · 2023: 37 · 2022: 57 · 2021: 75 · 2020: 11
- FWCI
- 32.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- University of Pittsburgh
- Open Philanthropy Project
- National Institutes of Health
- National Institute of General Medical Sciences (K23GM128005)
- 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 › Adrenal Hormones and Disorders
- Keywords
- septic shock, vitamin C, cortisol, thiamine, organ failure, SOFA score, renal failure, 30-day mortality, combination therapy, sepsis
- MeSH terms
- Adrenal Cortex Hormones, Adult, Aged, Ascorbic Acid, Cross Infection, Drug Therapy, Combination, Female, Humans, Hyperglycemia, Hypernatremia, Male, Middle Aged, Multiple Organ Failure, Shock, Septic, Thiamine, Proportional Hazards Models, Treatment Failure, Organ Dysfunction Scores
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
