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29 maart 2020: Bron: Chest Journal

Infusen met vitamine C plus hydrocortisone en thiamin verminderde het aantal doden aanzienlijk bij patiënten opgenomen met sepsis en septische shock. het verschil in aantal doden na 7 maanden voor de 2 groepen van 47 patiënten elk was 8.5% (4 of 47) in de behandelingsgroep vergeleken met 40.4% (19 of 47) in de controle groep (P < .001).

In een retrospectieve klinische studie vóór en na vergeleken onderzoekers de uitkomst en het klinische verloop van septische patiënten die gedurende 7 maanden (behandelingsgroep) werden behandeld met intraveneuze vitamine C, hydrocortison en thiamine, met een controlegroep die op hun IC - Intensive Care werd behandeld tijdens de voorafgaande 7 maanden. Het primaire doel was te zien of er verschil in overleving zou zijn bij de twee patiëntengroepen in het ziekenhuis. 

De gecorrigeerde kans op sterfte bij de patiënten behandeld met het vitamine C-protocol was 0,13 (95% BI, 0,04-0,48; P = 0,002). De Sepsis-gerelateerde score voor orgaanfalen nam af bij alle patiënten in de behandelingsgroep, waarbij geen enkele patiënt een progressief orgaanfalen ontwikkelde.

Het volledige studierapport: Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock is tegen betaling in te zien.

Hier het abstract van de studie:

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

A Retrospective Before-After Study

Paul E. Marik, MD, FCCPa,,'Correspondence information about the author MD, FCCP Paul E. Marik
Vikramjit Khangoora, MDa
Racquel Rivera, PharmDb
Michael H. Hooper, MDa
John Catravas, PhD, FCCPc,d


The global burden of sepsis is estimated as 15 to 19 million cases annually, with a mortality rate approaching 60% in low-income countries.


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.


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).


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.



  1. Adhikari, N.K., Fowler, R.A., Bhagwanjee, S. et al, Critical care and the global burden of critical illness in adults. Lancet2010;376:1339–1346
  2. Kaukonen, K.M., Bailey, M., Suzuki, S. et al, Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA2014;311:1308–1316
  3. Gaieski, D.F., Edwards, J.M., Kallan, M.J. et al, Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med2013;41:1167–1174
  4. Kadri, S.S., Rhee, C., Strich, J.R. et al, Estimating ten-year trends in septic shock incidence and morality in United States Academic Medical Centers using clinical data. Chest2017;151:278–285
  5. Marik PE, Linde-Zwirble WT, Bittner EA, et al. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database [published online ahead of print January 27, 2017]. Intensive Care Medhttp://dx.doi.org/10.1007/s00134-016-4675-y.
  6. Silva, E., de Almeida Pedro, M., Beltrami Sogayar, A.C. et al, Brazilian Sepsis Epidemiological Study (BASES study). Crit Care2004;8:R251–R260
  7. Sales, J.A., David, C.M., Hatum, R. et al, Sepsis Brazil Study. Sepse Brasil: Estudo Epidemiologico da Sepse em Unidades de Terapia Intensiva Brasileiras [An epidemiological study of sepsis in intensive care units]. Rev Bras Ter Int2006;18:9–17
  8. World Health Organization. The top 10 causes of death: the 10 leading causes of death by country income group 2012. WHO fact sheet. http://www.who.int/mediacentre/factsheets/fs310/en/index1.html. Published 2016. Accessed December 15, 2016.
  9. Karlsson, S., Ruokonen, E., Varpula, T. et al, Long-term outcome and quality-adjusted life years after severe sepsis. Crit Care Med2009;37:1268–1274
  10. Yende, S., Austin, S., Rhodes, A. et al, Long-term quality of life among survivors of severe sepsis: analyses of two international trials. Crit Care Med2016;44:1461–1467
  11. Ou, S.M., Chu, H., Chao, P.W. et al, Long-term mortality and major adverse cardiovascular events in sepsis survivors: a nationwide population-based study. Am J Respir Crit Care Med2016;194:209–217
  12. Artenstein, A.W., Higgins, T.L., Opal, S.M. Sepsis and scientific revolutions. Crit Care Med2013;41:2770–2772
  13. Fisher, B.J., Kraskauskas, D., Martin, E.J. et al, Attenuation of sepsis-induced organ injury in mice by vitamin C. JPEN2014;38:825–839
  14. Fisher, B.J., Seropian, I.M., Masanori, Y. et al, Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med2011;39:1454–1460
  15. Zhou, G., Kamenos, G., Pendem, S. et al, Ascorbate protects against vascular leakage in cecal ligation and puncture-induced septic peritonitis. Am J Physiol Regulatory Integrative Comp Physiol2012;302:R409–R416
  16. Fowler, A.A., Syed, A.A., Knowlson, S. et al, Phase 1 safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med2014;12:32
  17. Tanaka, H., Matsuda, T., Miyagantani, Y. et al, Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg2000;135:326–331
  18. Long, C.L., Maull, K.L., Krishman, R.S. et al, Ascorbic acid dynamics in the seriously ill and injured. J Surg Res2003;109:144–148
  19. de Grooth, H.J., Choo, W.P., Spoelstra-de Man, A.M. et al, Pharmacokinetics of four high-dose regime[n]s of intravenous vitamin C in critically ill patients. ()Intensive Care Med Exp2016;4:A52
  20. Padayatty, S.J., Sun, H., Wang, Y. et al, Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med2004;140:533–537
  21. Nathens, A.B., Neff, M.J., Jurkovich, G.J. et al, Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg2002;236:814–822
  22. Zabet, M.H., Mohammadi, M., Ramezani, M. et al, Effect of high-dose ascorbic acid on vasopressor requirement in septic shock. J Res Pharm Pract2016;5:94–100
  23. Ascorbic acid injection. Torrance Company. http://medlibrary.org/lib/rx/meds/ascorbic-acid-5/. Updated November 18, 2016. Accessed December 15, 2016.
  24. Ohno, S., Ohno, Y., Suzuki, N. et al, High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Anticancer Res2009;29:809–815
  25. Stephenson, C.M., Levin, R.D., Spector, T. et al, Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemother Pharmacol2013;72:139–146
  26. Marik, P.E., Pastores, S.M., Annane, D. et al, Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med2008;36:1937–1949
  27. Marik, P.E. “Vitamin S” (steroids) and vitamin C for the treatment of severe sepsis and septic shock!. Crit Care Med2016;44:1228–1229
  28. Fiore, L.D., Lavori, P.W. Integrating randomized comparative effectiveness research with patient care. N Engl J Med2016;374:2152–2158
  29. Wacker, C., Prkno, A., Brunkhorst, F.M. et al, Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis2013;13:426–435
  30. Schuetz, P., Maurer, P., Punjabi, V. et al, Procalcitonin decrease over 72 hours in US critical care units predicts fatal outcome in sepsis patients. Crit Care2013;17:R115
  31. Charles, P.E., Tinel, C., Barbar, S. et al, Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and outcome. Crit Care2016;13:R38
  32. Reynolds, S.C., Shorr, A.F., Muscedere, J. et al, Longitudinal changes in procalcitonin in a heterogeneous group of critically ill patients. Crit Care Med2012;40:2781–2787
  33. Arora, S., Singh, P., Singh, P.M. et al, Procalcitonin levels in survivors and non survivors of sepsis: systematic review and meta-analysis. Shock2015;43:212–221
  34. Kutz, A., Briel, M., Christ-Crain, M. et al, Prognostic value of procalcitonin in respiratory tract infections across clinical settings. Crit Care2015;19:74
  35. Society of Critical Care Medicine Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med1992;20:864–874
  36. Mancl, E.E., Muzevich, K.M. Tolerability and safety of enteral nutrition in critically ill patients receiving intravenous vasopressor therapy. JPEN2013;37:641–651
  37. Russell, J.A., Walley, K.R., Singer, J. et al, Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med2008;358:877–887
  38. Kellum, J.A., Lameire, N. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care2013;17:204
  39. Knaus, W.A., Draper, E.A., Wagner, D.P. et al, APACHE II: a severity of disease classification system. Crit Care Med1985;13:818–828
  40. Zimmerman, J.E., Kramer, A.A., McNair, D.S. et al, Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today's critically ill patients. Crit Care Med2006;34:1297–1310
  41. Vincent, J.L., Moreno, R., Takala, J. et al, Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. The SOFA (Sepsis-Related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med1996;22:707–710
  42. Marik, P.E. Early management of severe sepsis: current concepts and controversies. Chest2014;145:1407–1418
  43. Siemieniuk, R.A., Meade, M.P., Alonso-Coello, P. et al, Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med2015;163:519–528
  44. Garnacho-Montero, J., Gutierrez-Pizarraya, A., Escoresca-Ortega, A. et al, De-escalation of emperical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med2014;40:32–40
  45. Marik, P., Bellomo, R. A rational apprach to fluid therapy in sepsis. Br J Anaesth2016;116:339–349
  46. Marik, P.E. Fluid responsiveness and the six guiding principles of fluid resuscitation. Crit Care Med2016;44:1920–1922
  47. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med2000;342:1301–1308
  48. Girardis, M., Busani, S., Damiani, E. et al, Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA2016;316:1583–1589
  49. Barr, J., Fraser, G.L., Puntillo, K. et al, Clinical practice guidelines for the management of pain, agitation and delirium in adult patients in the intensive care unit. Crit Care Med2013;41:263–306
  50. Marik, P.E. Feeding critically ill patients the right “whey”: thinking outside of the box: a personal view. Ann Intensive Care2015;5:51
  51. Marik, P.E. Is early starvation beneficial for the critically ill patient?. Curr Opin Clin Nutr Metab Care2016;19:155–160
  52. Marik, P.E. Tight glycemic control in acutely ill patients: low evidence of benefit, high evidence of harm!. Intensive Care Med2016;42:1475–1477
  53. Marik, P.E. Stress ulcer prophylaxis de-adoption: what is the barrier?. Crit Care Med2016;44:1939–1941
  54. Sprung, C.L., Annane, D., Keh, D. et al, Hydrocortisone therapy for patients with septic shock. N Engl J Med2008;358:111–124
  55. Karlsson, S., Heikkinen, M., Pettila, V. et al, Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study. Crit Care2010;14:R205
  56. Ferreira, F.L., Bota, D.P., Bross, A. et al, Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA2001;286:1754–1758
  57. de Azevedo, J.R., Torres, O.J., Beraldi, R.A. et al, Prognostic evaluation of severe sepsis and septic shock: procalcitonin clearance vs Δ Sequential Organ Failure Assessment. J Crit Care2015;30 (219-212)
  58. Guan, J., Lin, Z., Lue, H. Dynamic change of procalcitonin, rather than concentration itself, is predictive of survival in septic shock patients when beyond 10 ng/mL. Shock2011;36:570–574
  59. Ruiz-Rodriguez, J.C., Caballero, J., Ruiz-Sanmartin, A. et al, Usefulness of procalcitonin clearance as a prognostic biomarker in septic shock: a prospective pilot study. Medicina Intensiva2012;36:475–480
  60. D’Agostino, R.B. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med1998;17:2265–2281
  61. Marik, P.E., Pastores, S.M., Kavanaugh, B.P. Selection bias negates conclusions from the CORTICUS study?. N Engl J Med2008;358:2069–2070
  62. Klenner, F.R. The treatment of poliomyelitis and other virus diseases with vitamin C. South Med Surg1949;111:209–214
  63. Hench, P.S., Kendall, E.C., Slocumb, C.H. et al, The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: compound E) and the pituitary adenocorticotrophic hormone on rheumatoid arthritis: preliminary report. Ann Rheum Dis1949;8:97–104
  64. Donnino, M.W., Andersen, L.W., Chase, M. et al, Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study. Crit Care Med2016;44:360–367
  65. Gibot, S., Cravoisy, A., Kolopp-Sarda, M.N. et al, Time-course of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis. Crit Care Med2005;33:792–796
  66. Gordon, A.C., Mason, A.J., Thirunavukkarasu, N. et al, Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA2016;316:509–518
  67. Hayes, M.A., Yau, E.H., Hinds, C.J. et al, Symmetrical peripheral gangrene: association with noradrenaline administration. Intensive Care Med1992;18:433–436
  68. Dunser, M.W., Wenzel, V., Hasibeder, W.R. Ischemic skin lesions and microcirculatory collapse during vasopressin therapy: a possible role of the microcirculation?. Acta Anaesthesiol Scand2006;50:637–638
  69. Stolk, R.F., van der Poll, T., Angus, D.C. et al, Potentially inadvertant immunomodulation: norepinephrine use in sepsis. Am J Respir Crit Care Med2016;194:550–558
  70. May, J.M. Role of vitamin C in the function of the vascular endothelium. Antioxid Redox Signal2013;19:2068–2083
  71. Wilson, J.X. Evaluation of vitamin C for adjuvant sepsis therapy. Antioxid Redox Signal2013;19:2129–2140
  72. Wilson, J.X. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. Biofactors2009;35:5–13
  73. Han, M., Pendem, S., Teh, S.L. et al, Ascorbate protects endothelial barrier function during septic insult: role of protein phosphatase type 2A. Free Radic Biol Med2010;48:128–135
  74. Dillon, P.F., Root-Bernstein, R.S., Lieder, C.M. Antioxidant-independent ascorbate enhancement of catecholamine-induced contractions of vascular smooth muscle. Am J Physiol Heart Circ Physiol2004;286:H2353–H2360
  75. Marik, P.E. Critical illness related corticosteroid insufficiency. Chest2009;135:181–193
  76. Kalden, J.R. Prolonged skin allograft survival in vitamin C-deficient guinea-pigs: preliminary communication. Eur Surg Res1972;4:114–119
  77. Kim, S.R. Ascorbic acid reduces HMGB1 secretion in lipopolysaccharide-activated RAW 264.7 cells and improves survival rate in septic mice by activation of Nrf2/HO-1 signals. Biochem Pharmacol2015;95:279–289
  78. Manning, J., Mitchell, B., Appadurai, D.A. et al, Vitamin C promotes maturation of T-cells. Antioxid Redox Signal2013;19:2054–2067
  79. Fogarty, A., Scrivener, S.L., Antoniak, M. et al, Corticosteroid sparing effects of vitamin C and magnesium in asthma: a randomised trial. Respir Med2006;100:174–179
  80. Bodwell, J.E., Holbrook, N.J., Munck, A. Sulfhydryl-modifying reagents reversibly inhibit binding of glucocorticoid-receptor complexes to DNA-cellulose. Biochemistry1984;23:1392–1398
  81. Okamoto, K., Tanaka, H., Ogawa, H. et al, Redox-dependent regulation of nuclear import of the glucocorticoid receptor. J Biol Chem1999;274:10363–10371
  82. Okamoto, K., Tanaka, H., Makino, Y. et al, Restoration of the glucocorticoid receptor function by the phosphodiester compound of vitamins C and E, EPC-K1 (l-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt), via a redox-dependent mechanism. Biochem Pharmacol1998;56:79–86
  83. Burzle, M., Hediger, M.A. Functional and physiological role of vitamin C transporters. Curr Top Membr2012;70:357–375
  84. Seno, T., Inoue, N., Matsui, K. et al, Functional expression of sodium-dependent vitamin C transporter 2 in human endothelial cells. J Vasc Res2004;41:345–351
  85. Fujita, I., Hirano, J., Itoh, N. et al, Dexamethasone induces sodium-dependant vitamin C transporter in a mouse osteoblastic cell line MC3T3-E1. Br J Nutr2001;86:145–149
  86. Barabutis N, Khangoora V, Marik PE, et al. Hydrocortisone and ascorbic acid synergistically protect against LPS-induced pulmonary endothelial barrier dysfunction. Chest. In press.
  87. Keh, D., Trips, E., Marx, G. et al, SepNet-Critical Care Trials Group. Effect of hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS Randomized Clinical Trial. JAMA2016;316:1775–1785
  88. Minneci, P.C., Deans, K.J., Eichacker, P.Q. et al, The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis. Clin Microbiol Infect2009;15:308–318
  89. Massey, L.K. Ascorbate increases human oxaluria and kidney stone risk. J Nutr2005;135:1673–1677
  90. Wandzilak, T.R. Effect of high dose vitamin C on urinary oxalate levels. J Urol1994;151:834–837
  91. Hoppe, B., Beck, B.B., Milliner, D. The primary hyperoxalurias. Kidney Int2009;75:1264–1271
  92. Sidhu, H., Gupta, R., Thind, S.K. et al, Oxalate metabolism in thiamine-deficient rats. Ann Nutr Metab1987;31:354–361
  93. Ortiz-Alvarado, O., Muyaoka, R., Kriedberg, C. et al, Pyridoxine and dietary counseling for the management of idiopathic hyperoxaluria in stone-forming patients. Urology2011;77:1054–1058

FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

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