Adjuvant Administration of Vitamin C Improves Mortality of Patients with Sepsis and Septic Shock: A Systems Review and Meta-Analysis — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Adjuvant Administration of Vitamin C Improves Mortality of Patients with Sepsis and Septic Shock: A Systems Review and Meta-Analysis
The First Affiliated Hospital, Xiamen University, Xiamen, China
,
The First Affiliated Hospital, Xiamen University, Xiamen, China
,
The First Affiliated Hospital, Xiamen University, Xiamen, China
,
The First Affiliated Hospital, Xiamen University, Xiamen, China
1 The First Affiliated Hospital, Xiamen University, Xiamen, China
2 The First Affiliated Hospital, Xiamen University, Xiamen, China
3 The First Affiliated Hospital, Xiamen University, Xiamen, China
4 The First Affiliated Hospital, Xiamen University, Xiamen, China
The aim of this study was to examine whether vitamin C reduced mortality when adjutant therapy of patients with septic shock and severe sepsis compared with placebo by meta-analysis. Eligible trials were identified from Pubmed, Embase, Ovid, and the Cochrane database. Four randomized controlled trials (RCT) and two retrospective studies were published between 2000 and 2017 met the inclusion criteria and suitable for meta-analysis. The data were analyzed with randomized-effects or fixed-effects models using Review Manager Version 5.3. Four randomized studies with a total of 109 participants were suitable for meta-analysis. The heterogeneity was assessed by calculating the Q and I 2 methods. A random-effects approach instead of a fixed-effects analysis was undertaken if I 2 > 50%. Adjuvant vitamin C did not associate with a reduction in mortality as compared with placebo, it is occurred similarly in both RCT studies and retrospective studies. However, high doses of vitamin C (>50 mg/kg/day) significant reduced the mortality rate of severe sepsis patients. And administration of high doses of vitamin C to therapy severe sepsis did not significantly reduce the ICU length of stay. The results suggested a trend toward reducing mortality in severe sepsis and septic shock patients’ adjuvant with vitamin C. Further multicenter large randomized controlled trials are necessary to determine the potential benefits of vitamin C in patients with severe sepsis and septic shock.
Teng, J., Pourmand, A. and Mazer-Amirshahi, M. (2017) Vitamin C: The Next Step in Sepsis Management? Journal of Critical Care, 43, 230-234. https://doi.org/10.1016/j.jcrc.2017.09.031
Singer, M., Deutschman, C.S., Seymour, C.W., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G.R., Chiche, J.D., Coopersmith, C.M., Hotchkiss, R.S., Levy, M.M., Marshall, J.C., Martin, G.S., Opal, S.M., Rubenfeld, G.D., van der Poll, T., Vincent, J.L. and Angus, D.C. (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315, 801-810. https://doi.org/10.1001/jama.2016.0287
Shankar-Hari, M., Phillips, G.S., Levy, M.L., Seymour, C.W., Liu, V.X., Deutschman, C.S., Angus, D.C., Rubenfeld, G.D., Singer, M. and Sepsis Definitions Task, F. (2016) Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315, 775-787. https://doi.org/10.1001/jama.2016.0289
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., Deutschman, C.S., Escobar, G.J. and Angus, D.C. (2016) Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315, 762-774. https://doi.org/10.1001/jama.2016.0288
Wilson, J.X. (2013) Evaluation of Vitamin C for Adjuvant Sepsis Therapy. Antioxidants & Redox Signaling, 19, 2129-2140. https://doi.org/10.1089/ars.2013.5401
Seeley, E.J. and Bernard, G.R. (2016) Therapeutic Targets in Sepsis: Past, Present, and Future. Clinics in Chest Medicine, 37, 181-189. https://doi.org/10.1016/j.ccm.2016.01.015
Bernard, G.R., Vincent, J.L., Laterre, P.F., La Rosa, S.P., Dhainaut, J.F., Lopez-Rodriguez, A., Steingrub, J.S., Garber, G.E., Helterbrand, J.D., Ely, E.W., Fisher Jr., C.J. and Recombinant Human Protein CWEiSSsg (2001) Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis. New England Journal of Medicine, 344, 699-709. https://doi.org/10.1056/NEJM200103083441001
Oudemans-van Straaten, H.M., Spoelstra-de Man, A.M. and de Waard, M.C. (2014) Vitamin C Revisited. Critical Care, 18, 460. https://doi.org/10.1186/s13054-014-0460-x
Wilson, J.X. (2009) Mechanism of Action of Vitamin C in Sepsis: Ascorbate Modulates Redox Signaling in Endothelium. Biofactors, 35, 5-13. https://doi.org/10.1002/biof.7
Chen, Y.H., Lin, S.J., Chen, Y.L., Liu, P.L. and Chen, J.W. (2006) Anti-Inflammatory Effects of Different Drugs/Agents with Antioxidant Property on Endothelial Expression of Adhesion Molecules. Cardiovascular & Hematological Disorders Drug Targets, 6, 279-304. https://doi.org/10.2174/187152906779010737
Koekkoek, W.A. and van Zanten, A.R. (2016) Antioxidant Vitamins and Trace Elements in Critical Illness. Nutrition in Clinical Practice, 31, 457-474. https://doi.org/10.1177/0884533616653832
May, J.M. (2000) How Does Ascorbic Acid Prevent Endothelial Dysfunction? Free Radical Biology and Medicine, 28, 1421-1429. https://doi.org/10.1016/S0891-5849(00)00269-0
Shaik-Dasthagirisaheb, Y.B., Varvara, G., Murmura, G., Saggini, A., Caraffa, A., Antinolfi, P., Tete, S., Tripodi, D., Conti, F., Cianchetti, E., Toniato, E., Rosati, M., Speranza, L., Pantalone, A., Saggini, R., Tei, M., Speziali, A., Conti, P., Theoharides, T.C. and Pandolfi, F. (2013) Role of Vitamins D, E and C in Immunity and Inflammation. Journal of Biological Regulators and Homeostatic Agents, 27, 291-295.
Honore, P.M., Jacobs, R., Hendrickx, I., De Waele, E. and Spapen, H.D. (2016) Adjuvant Vitamin C Treatment in Sepsis—How Many Oranges a Day Keep (Vasopressor-Dependent) Septic Shock Away? Journal of Thoracic Disease, 8, E993-E995. https://doi.org/10.21037/jtd.2016.08.60
Rudiger, A. and Singer, M. (2007) Mechanisms of Sepsis-Induced Cardiac Dysfunction. Critical Care Medicine, 35, 1599-1608. https://doi.org/10.1097/01.CCM.0000266683.64081.02
Zabet, M.H., Mohammadi, M., Ramezani, M. and Khalili, H. (2016) Effect of High-Dose Ascorbic Acid on Vasopressor’s Requirement in Septic Shock. Journal of Research in Pharmacy Practice, 5, 94-100. https://doi.org/10.4103/2279-042X.179569
Fowler, A.A., Syed, A.A., Knowlson, S., Sculthorpe, R., Farthing, D., DeWilde, C., Farthing, C.A., Larus, T.L., Martin, E., Brophy, D.F., Gupta, S., Medical Respiratory Intensive Care Unit Nursing, Fisher, B.J. and Natarajan, R. (2014) Phase I Safety Trial of Intravenous Ascorbic Acid in Patients with Severe Sepsis. Journal of Translational Medicine, 12, 32. https://doi.org/10.1186/1479-5876-12-32
Ferron-Celma, I., Mansilla, A., Hassan, L., Garcia-Navarro, A., Comino, A.M., Bueno, P. and Ferron, J.A. (2009) Effect of Vitamin C Administration on Neutrophil Apoptosis in Septic Patients after Abdominal Surgery. Journal of Surgical Research, 153, 224-230. https://doi.org/10.1016/j.jss.2008.04.024
Heyland, D., Muscedere, J., Wischmeyer, P.E., Cook, D., Jones, G., Albert, M., Elke, G., Berger, M.M. and Day, A.G., for the Canadian Critical Care Trials Group. (2013) A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients. New England Journal of Medicine, 368, 1489-1497. https://doi.org/10.1056/NEJMoa1212722
Jadad, A.R., Moore, R.A., Carroll, D., Jenkinson, C., Reynolds, D.J., Gavaghan, D.J. and McQuay, H.J. (1996) Assessing the Quality of Reports of Randomized Clinical Trials: Is Blinding Necessary? Controlled Clinical Trials, 17, 1-12. https://doi.org/10.1016/0197-2456(95)00134-4
Stang, A. (2010) Critical Evaluation of the Newcastle-Ottawa Scale for the Assessment of the Quality of Nonrandomized Studies in Meta-Analyses. European Journal of Epidemiology, 25, 603-605. https://doi.org/10.1007/s10654-010-9491-z
Kaukonen, K.M., Bailey, M., Suzuki, S., Pilcher, D. and Bellomo, R. (2014) Mortality Related to Severe Sepsis and Septic Shock among Critically Ill Patients in Australia and New Zealand, 2000-2012. JAMA, 311, 1308-1316. https://doi.org/10.1001/jama.2014.2637
Rhodes, A., Evans, L.E., Alhazzani, W., Levy, M.M., Antonelli, M., Ferrer, R., Kumar, A., Sevransky, J.E., Sprung, C.L., Nunnally, M.E., Rochwerg, B., Rubenfeld, G.D., Angus, D.C., Annane, D., Beale, R.J., Bellinghan, G.J., Bernard, G.R., Chiche, J.D., Coopersmith, C., De Backer, D.P., French, C.J., Fujishima, S., Gerlach, H., Hidalgo, J.L., Hollenberg, S.M., Jones, A.E., Karnad, D.R., Kleinpell, R.M., Koh, Y., Lisboa, T.C., Machado, F.R., Marini, J.J., Marshall, J.C., Mazuski, J.E., McIntyre, L.A., McLean, A.S., Mehta, S., Moreno, R.P., Myburgh, J., Navalesi, P., Nishida, O., Osborn, T.M., Perner, A., Plunkett, C.M., Ranieri, M., Schorr, C.A., Seckel, M.A., Seymour, C.W., Shieh, L., Shukri, K.A., Simpson, S.Q., Singer, M., Thompson, B.T., Townsend, S.R., Van der Poll, T., Vincent, J.L., Wiersinga, W.J., Zimmerman, J.L. and Dellinger, R.P. (2017) Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Medicine, 43, 304-377. https://doi.org/10.1007/s00134-017-4683-6
Vincent, J.L., Nelson, D.R. and Williams, M.D. (2011) Is Worsening Multiple Organ Failure the Cause of Death in Patients with Severe Sepsis? Critical Care Medicine, 39, 1050-1055. https://doi.org/10.1097/CCM.0b013e31820eda29
Fisher, B.J., Kraskauskas, D., Martin, E.J., Farkas, D., Puri, P., Massey, H.D., Idowu, M.O., Brophy, D.F., Voelkel, N.F., Fowler, A.A. and Natarajan, R. (2014) Attenuation of Sepsis-Induced Organ Injury in Mice by Vitamin C. Journal of Parenteral and Enteral Nutrition, 38, 825-839. https://doi.org/10.1177/0148607113497760
Fisher, B.J., Seropian, I.M., Kraskauskas, D., Thakkar, J.N., Voelkel, N.F., Fowler, A.A. and Natarajan, R. (2011) Ascorbic Acid Attenuates Lipopolysaccharide-Induced Acute Lung Injury. Critical Care Medicine, 39, 1454-1460. https://doi.org/10.1097/CCM.0b013e3182120cb8
Fisher, B.J., Kraskauskas, D., Martin, E.J., Farkas, D., Wegelin, J.A., Brophy, D., Ward, K.R., Voelkel, N.F., Fowler, A.A. and Natarajan, R. (2012) Mechanisms of Attenuation of Abdominal Sepsis Induced Acute Lung Injury by Ascorbic Acid. American Journal of Physiology-Lung Cellular and Molecular Physiology, 303, L20-L32. https://doi.org/10.1152/ajplung.00300.2011
Gaut, J.P., Belaaouaj, A., Byun, J., Roberts, L.J., Maeda, N., Frei, B. and Heinecke, J.W. (2006) Vitamin C Fails to Protect Amino Acids and Lipids from Oxidation during Acute Inflammation. Free Radical Biology and Medicine, 40, 1494-1501. https://doi.org/10.1016/j.freeradbiomed.2005.12.013
Marik, P.E., Khangoora, V., Rivera, R., Hooper, M.H. and Catravas, J. (2017) Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest, 151, 1229-1238. https://doi.org/10.1016/j.chest.2016.11.036
Schorah, C.J., Downing, C., Piripitsi, A., Gallivan, L., Al-Hazaa, A.H., Sanderson, M.J. and Bodenham, A. (1996) Total Vitamin C, Ascorbic Acid, and Dehydroascorbic Acid Concentrations in Plasma of Critically Ill Patients. American Journal of Clinical Nutrition, 63, 760-765. https://doi.org/10.1093/ajcn/63.5.760
Galley, H.F., Davies, M.J. and Webster, N.R. (1996) Ascorbyl Radical Formation in Patients with Sepsis: Effect of Ascorbate Loading. Free Radical Biology and Medicine, 20, 139-143. https://doi.org/10.1016/0891-5849(95)02022-5
Spada, P.L., Rossi, C., Alimonti, A., Bocca, B., Cozza, V., Ricerca, B.M., Bocci, M.G., Vulpio, C. and De Sole, P. (2008) Ferritin Iron Content in Haemodialysis Patients: Comparison with Septic and Hemochromatosis Patients. Clinical Biochemistry, 41, 997-1001. https://doi.org/10.1016/j.clinbiochem.2008.05.003
Levine, M., Padayatty, S.J. and Espey, M.G. (2011) Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries. Advances in Nutrition, 2, 78-88. https://doi.org/10.3945/an.110.000109
Long, C.L., Maull, K.I., Krishnan, R.S., Laws, H.L., Geiger, J.W., Borghesi, L., Franks, W., Lawson, T.C. and Sauberlich, H.E. (2003) Ascorbic Acid Dynamics in the Seriously Ill and Injured. Journal of Surgical Research, 109, 144-148. https://doi.org/10.1016/S0022-4804(02)00083-5
Thomas, L.D., Elinder, C.G., Tiselius, H.G., Wolk, A. and Akesson, A. (2013) Ascorbic Acid Supplements and Kidney Stone Incidence among Men: A Prospective Study. JAMA Internal Medicine, 173, 386-388. https://doi.org/10.1001/jamainternmed.2013.2296
Robitaille, L., Mamer, O.A., Miller, W.H., Levine, M., Assouline, S., Melnychuk, D., Rousseau, C. and Hoffer, L.J. (2009) Oxalic Acid Excretion after Intravenous Ascorbic Acid Administration. Metabolism, 58, 263-269. https://doi.org/10.1016/j.metabol.2008.09.023
Padayatty, S.J., Sun, H., Wang, Y., Riordan, H.D., Hewitt, S.M., Katz, A., Wesley, R.A. and Levine, M. (2004) Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Annals of Internal Medicine, 140, 533-537. https://doi.org/10.7326/0003-4819-140-7-200404060-00010
Du, J., Cullen, J.J. and Buettner, G.R. (2012) Ascorbic Acid: Chemistry, Biology and the Treatment of Cancer. Biochimica et Biophysica Acta, 1826, 443-457.