维生素辅助治疗脓毒症及脓毒症休克的研究进展
Research Progress of Vitamin-Assisted Treatment of Sepsis and Septic Shock
DOI: 10.12677/ACM.2023.1351225, PDF,   
作者: 曹志花：青海大学研究生院，青海 西宁；甘桂芬：青海大学附属医院重症医学科，青海 西宁
关键词: 脓毒症；脓毒症休克；维生素D；维生素B1；维生素C；维生素B12；Sepsis； Septic Shock； Vitamin D； Vitamin B1； Vitamin C； Vitamin B12
摘要: 维生素是人体必需的微量营养素，生理作用相当广泛，在许多与脓毒症相关的生物学途径中起着关键作用，包括抗氧化和抗炎作用、蛋白质和激素合成、能量产生和基因转录的调节等。此外，血浆中维生素缺乏在脓毒症及脓毒症休克期间很常见，在一些成人和儿科研究中，维生素辅助治疗与脓毒症及脓毒症休克结局改善有关，本综述就与脓毒症或脓毒症休克研究最多的几种维生素展开谈论。
Abstract: Vitamins are essential micronutrients with a wide range of physiological effects. They play a key role in many biological pathways related to sepsis, including antioxidant and anti-inflammatory ef-fects, protein and hormone synthesis, energy production and gene transcription regulation. In ad-dition, plasma vitamin deficiency is common during sepsis and septic shock. Vitamin adjuvant therapy has been associated with improved outcomes of sepsis and septic shock in several adult and pediatric studies. This review discusses the vitamins most commonly associated with sepsis or septic shock.
文章引用：曹志花, 甘桂芬. 维生素辅助治疗脓毒症及脓毒症休克的研究进展[J]. 临床医学进展, 2023, 13(5): 8761-8768. https://doi.org/10.12677/ACM.2023.1351225

参考文献

[1] Singer, M., Deutschman, C.S., Seymour, C.W., Shankar-Hari, M., Annane, D., Bauer, M., et al. (2016) The Third Inter-national Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315, 801-810. [Google Scholar] [CrossRef] [PubMed]
[2] 黄伟. 《第三版脓毒症与感染性休克定义国际共识》解读[J]. 中国实用内科杂志, 2016, 36(11): 959-962.
[3] 张欢, 殷可婧, 张莉, 杨晓航, 刘力. 大黄煎剂灌肠对脓毒症患者血浆内毒素水平的影响[J]. 现代中医药, 2019, 39(3): 73-75+82. [Google Scholar] [CrossRef] 
[4] Bartley, J. (2010) Vitamin D: Emerging Roles in Infection and Immunity. Expert Review of Anti-Infective Therapy, 8, 1359-1369. [Google Scholar] [CrossRef] [PubMed]
[5] Takeuti, F.A.C., Guimaraes, F.S.F. and Guimaraes, P.S.F. (2018) Applica-tions of Vitamin D in Sepsis Prevention. Discovery Medicine, 25, 291-297.
[6] Cutuli, S.L., Cascarano, L., Tanzarella, E.S., Lombardi, G., Carelli, S., Pintaudi, G., et al. (2022) Vitamin D Status and Potential Therapeutic Options in Critical-ly Ill Patients: A Narrative Review of the Clinical Evidence. Diagnostics (Basel), 12, 2719. [Google Scholar] [CrossRef] [PubMed]
[7] Izadpanah, M. and Khalili, H. (2013) Potential Benefits of Vita-min D Supplementation in Critically Ill Patients. Immunotherapy, 5, 843-853. [Google Scholar] [CrossRef] [PubMed]
[8] Sadeghi, K., Wessner, B., Laggner, U., Ploder, M., Tamandl, D., Friedl, J., et al. (2006) Vitamin D3 Down-Regulates Monocyte TLR Expression and Triggers Hyporesponsiveness to Patho-gen-Associated Molecular Patterns. European Journal of Immunology, 36, 361-370. [Google Scholar] [CrossRef] [PubMed]
[9] Dickie, L.J., Church, L.D., Coulthard, L.R., Mathews, R.J., Emery, P. and McDermott, M.F. (2010) Vitamin D3 Down-Regulates Intracellular Toll-Like Receptor 9 Expression and Toll-Like Receptor 9-Induced IL-6 Production in Human Monocytes. Rheumatology (Oxford), 49, 1466-1471. [Google Scholar] [CrossRef] [PubMed]
[10] Jeng, L., Yamshchikov, A.V., Judd, S.E., Blumberg, H.M., Martin, G.S., Ziegler, T.R. and Tangpricha, V. (2009) Alterations in Vitamin D Status and Anti-Microbial Peptide Levels in Patients in the Intensive Care Unit with Sepsis. Journal of Translational Medicine, 7, Article No. 28. [Google Scholar] [CrossRef] [PubMed]
[11] Ahmad, S., Zaki, A., Manda, K., Mohan, A. and Syed, M.A. (2022) Vitamin-D Ameliorates Sepsis-Induced Acute Lung Injury via Augmenting miR-149-5p and Downregulating ER Stress. The Journal of Nutritional Biochemistry, 110, Article ID: 109130. [Google Scholar] [CrossRef] [PubMed]
[12] Erdoğan, M. and Fındıklı, H.A. (2021) Novel Biomarker for Predicting Sepsis Mortality: Vitamin D Receptor. Journal of International Medical Research, 49, No. 8. [Google Scholar] [CrossRef] [PubMed]
[13] Malinverni, S., Ochogavia, Q., Lecrenier, S., Scorpinniti, M., Preiser, J.C., Cotton, F., et al. (2023) Severe Vitamin D Deficiency in Patients Admitted to the Emergency Department with Severe Sepsis Is Associated with an Increased 90-Day Mortality. Emergency Medicine Journal, 40, 36-41. [Google Scholar] [CrossRef] [PubMed]
[14] Chae, B., Kim, Y.J., Kim, S.M., Hong, S.I., Shin, Y.S., Kim, J.S., et al. (2023) Vitamin D Deficiency on Admission to the Emergency Department Is a Mortality Predictor for Patients with Septic Shock Treated with Early Protocol-Driven Resuscitation Bundle Therapy. The American Journal of the Med-ical Sciences, 365, 361-367. [Google Scholar] [CrossRef] [PubMed]
[15] Ding, F., Zang, B., Fu, J. and Ji, K. (2017) Effect of Vitamin D3 on the Severity and Prognosis of Patients with Sepsis: A Prospective Randomized Double-Blind Placebo Study. Chinese Critical Care Medicine, 29, 106-110.
[16] Leaf, D.E., Raed, A., Donnino, M.W., Ginde, A.A. and Waikar, S.S. (2014) Randomized Controlled Trial of Calcitriol in Severe Sepsis. American Journal of Respiratory and Critical Care Medicine, 190, 533-541. [Google Scholar] [CrossRef] 
[17] Hagag, A.A., El Frargy, M.S. and Houdeeb, H.A. (2020) Therapeutic Value of Vitamin D as an Adjuvant Therapy in Neonates with Sepsis. Infectious Disorders—Drug Targets, 20, 440-447. [Google Scholar] [CrossRef] [PubMed]
[18] Wang, Y., Yang, Z., Gao, L., Cao, Z. and Wang, Q. (2020) Effects of a Single Dose of Vitamin D in Septic Children: A Randomized, Double-Blinded, Controlled Trial. Journal of International Medical Research, 48, No. 6. [Google Scholar] [CrossRef] [PubMed]
[19] Moskowitz, A. and Donnino, M.W. (2020) Thiamine (Vitamin B1) in Septic Shock: A Targeted Therapy. Journal of Thoracic Disease, 12, S78-S83. [Google Scholar] [CrossRef] [PubMed]
[20] Donnino, M.W., Carney, E., Cocchi, M.N., Barbash, I., Chase, M., Joyce, N., Chou, P.P. and Ngo, L. (2010) Thiamine Deficiency in Critically Ill Patients with Sepsis. Journal of Critical Care, 25, 576-581. [Google Scholar] [CrossRef] [PubMed]
[21] de Andrade, J.A.A., Gayer, C.R.M., Nogueira, N.P.A., Paes, M.C., Bastos, V.L.F.C., Neto, J.D.C.B., et al. (2014) The Effect of Thiamine Deficiency on Inflammation, Oxidative Stress and Cellular Migration in an Experimental Model of Sepsis. Journal of Inflammation (London), 11, Article No. 11. [Google Scholar] [CrossRef] [PubMed]
[22] Lindenbaum, G.A., Larrieu, A.J., Carroll, S.F. and Kapusnick, R.A. (1989) Effect of Cocarboxylase in Dogs Subjected to Experimental Septic Shock. Critical Care Medicine, 17, 1036-1040. [Google Scholar] [CrossRef] [PubMed]
[23] Donnino, M.W. andersen, L.W., Chase, M., Berg, K.M., Tidswell, M., Giberson, T., et al. (2016) Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Meta-bolic Resuscitator in Septic Shock: A Pilot Study. Critical Care Medicine, 44, 360-367. [Google Scholar] [CrossRef] 
[24] Woolum, J.A., Abner, E.L., Kelly, A., Thompson Bastin, M., Morris, P.E. and Flannery, A.H. (2018) Effect of Thiamine Administration on Lactate Clearance and Mortality in Pa-tients with Septic Shock. Critical Care Medicine, 46, 1747-1752. [Google Scholar] [CrossRef] 
[25] Petsakul, S., Morakul, S., Tangsujaritvijit, V., Kunawut, P., Singhatas, P. and Sanguanwit, P. (2020) Effects of Thiamine on Vasopressor Requirements in Patients with Septic Shock: A Prospective Randomized Controlled Trial. BMC Anesthesiology, 20, Article No. 280. [Google Scholar] [CrossRef] [PubMed]
[26] Romain, M., Sviri, S., Linton, D.M., Stav, I. and van Heerden, P.V. (2016) The Role of Vitamin B12 in the Critically Ill—A Review. Anaesthesia and Intensive Care, 44, 447-452. [Google Scholar] [CrossRef] 
[27] Gamarra-Morales, Y., Molina-López, J., Herrera-Quintana, L., Vázquez-Lorente, H. and Planells, E. (2022) Folic Acid and Vitamin B12 as Biomarkers of Morbidity and Mortality in Patients with Septic Shock. Nutrición Hospitalaria, 39, 247-255. [Google Scholar] [CrossRef] [PubMed]
[28] Greenberg, S.S., Xie, J., Zatarain, J.M., Kapusta, D.R. and Miller, M.J. (1995) Hydroxocobalamin (Vitamin B12a) Prevents and Reverses Endotoxin-Induced Hypotension and Mortality in Ro-dents: Role of Nitric Oxide. Journal of Pharmacology and Experimental Therapeutics, 273, 257-265.
[29] Sacco, A.J., Cunningham, C.A., Kosiorek, H.E. and Sen, A. (2021) Hydroxocobalamin in Refractory Septic Shock: A Retrospective Case Series. Critical Care Explorations, 3, e0408. [Google Scholar] [CrossRef] 
[30] Ritter, L.A., Maldarelli, M., McCurdy, M.T., Yamane, D.P., Davison, D., Parrino, C., Yim, D.N., et al. (2022) Effects of a Single Bolus of Hydroxocobalamin on Hemodynamics in Vasodilatory Shock. Journal of Critical Care, 67, 66-71. [Google Scholar] [CrossRef] [PubMed]
[31] Patel, J.J., Willoughby, R., Peterson, J., Carver, T., Zelten, J., Mar-kiewicz, A., et al. (2023) Hydroxocobalamin (Vitamin B12) in Septic Shock: A Double-Blind, Allocation-Concealed, Placebo-Controlled Single-Center Pilot Randomized Controlled Trial (The Intravenous Hydroxocobalamin in Septic Shock Trial). Chest, 163, 303-312. [Google Scholar] [CrossRef] [PubMed]
[32] Carr, A.C., Rosengrave, P.C., Bayer, S., Chambers, S., Mehrtens, J. and Shaw, G.M. (2017) Hypovitaminosis C and Vitamin C Deficiency in Critically Ill Patients despite Recommended Enteral and Parenteral Intakes. Critical Care, 21, Article No. 300. [Google Scholar] [CrossRef] [PubMed]
[33] Spoelstra-de Man, A.M.E., Elbers, P.W.G. and Oudemans-Van Straaten, H.M. (2018) Vitamin C: Should We Supplement? Current Opinion in Critical Care, 24, 248-255. [Google Scholar] [CrossRef] 
[34] Park, J.E., Shin, T.G., Jeong, D., Lee, G.T., Ryoo, S.M., Kim, W.Y., et al. (2022) Association between Vitamin C Deficiency and Mortality in Patients with Septic Shock. Bio-medicines, 10, 2090. [Google Scholar] [CrossRef] [PubMed]
[35] Fowler, A.A., Syed, A.A., Knowlson, S., Sculthorpe, R., Far-thing, D., DeWilde, C., et al. (2014) Phase I Safety Trial of Intravenous Ascorbic Acid in Patients with Severe Sepsis. Journal of Translational Medicine, 12, Article No. 32. [Google Scholar] [CrossRef] [PubMed]
[36] Prasad, N., Grossestreuer, A.V., Meyer, N.J., Perman, S.M., Mik-kelsen, M.E., Hollander, J. and Gaieski, D.F. (2021) The Relationship between Vitamin C or Thiamine Levels and Out-comes for Severe Sepsis Patients Admitted to the ICU. Scientific Reports, 11, Article No. 15114. [Google Scholar] [CrossRef] [PubMed]
[37] Padayatty, S.J., Sun, H., Wang, Y., Riordan, H.D., Hewitt, S.M., Katz, A., et al. (2004) Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Annals of Internal Medi-cine, 140, 533-537. [Google Scholar] [CrossRef] [PubMed]
[38] El Driny, W.A., Esmat, I.M., Shaheen, S.M. and Sabri, N.A. (2022) Efficacy of High-Dose Vitamin C Infusion on Outcomes in Sepsis Requiring Mechanical Ventilation: A Double-Blind Randomized Controlled Trial. Anesthesiology Research and Practice, 2022, Article ID: 4057215. [Google Scholar] [CrossRef] [PubMed]
[39] Lamontagne, F., Masse, M.H., Menard, J., Sprague, S., Pinto, R., Heyland, D.K., et al. (2022) Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit. The New England Journal of Medicine, 386, 2387-2398. [Google Scholar] [CrossRef] 
[40] Nathens, A.B., Neff, M.J., Jurkovich, G.J., Klotz, P., Farver, K., Ruzinski, J.T., et al. (2002) Randomized, Prospective Trial of Antioxidant Supplementation in Critically Ill Surgical Pa-tients. Annals of Surgery, 236, 814-822. [Google Scholar] [CrossRef] [PubMed]
[41] Sadaka, F., Grady, J., Organti, N., Donepudi, B., Korobey, M., Tannehill, D. and O’Brien, J. (2020) Ascorbic Acid, Thiamine, and Steroids in Septic Shock: Propensity Matched Analysis. Journal of Intensive Care Medicine, 35, 1302-1306. [Google Scholar] [CrossRef] [PubMed]
[42] Sevransky, J.E., Rothman, R.E., Hager, D.N., Bernard, G.R., Brown, S.M., Buchman, T.G., et al. (2021) Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vas-opressor-Free Days in Patients with Sepsis: The VICTAS Randomized Clinical Trial. JAMA, 325, 742-750.
[43] Fujii, T., Luethi, N., Young, P.J., Frei, D.R., Eastwood, G.M., French, C.J., et al. (2020) Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support among Patients with Septic Shock: The VITAMINS Randomized Clinical Trial. JAMA, 323, 423-431. [Google Scholar] [CrossRef] [PubMed]
[44] Chang, P., Liao, Y., Guan, J., Guo, Y., Zhao, M., Hu, J., et al. (2020) Combined Treatment with Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock: A Randomized Con-trolled Trial. Chest, 158, 174-182. [Google Scholar] [CrossRef] [PubMed]

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