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The Effect of the Vitamin Protocol for Treating Sepsis or Septic Shock in Pediatric Intensive Care Unit

패혈증 및 패혈성 쇼크로 진단 받은 소아 중환자에서 vitamin protocol의 효과 비교

  • Ko, Hyun Jung (Department of Pharmacy, Severance Hospital, College of Medicine, Yonsei University) ;
  • Jung, Min Jae (Department of Pharmacy, Severance Hospital, College of Medicine, Yonsei University) ;
  • Kim, Jae Song (Department of Pharmacy, Severance Hospital, College of Medicine, Yonsei University) ;
  • Son, Eun Sun (Department of Pharmacy, Severance Hospital, College of Medicine, Yonsei University) ;
  • Yu, Yun Mi (Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University)
  • 고현정 (연세대학교 의과대학 세브란스병원 약무국) ;
  • 정민재 (연세대학교 의과대학 세브란스병원 약무국) ;
  • 김재송 (연세대학교 의과대학 세브란스병원 약무국) ;
  • 손은선 (연세대학교 의과대학 세브란스병원 약무국) ;
  • 유윤미 (연세대학교 약학대학)
  • Received : 2020.02.28
  • Accepted : 2020.08.24
  • Published : 2020.09.30

Abstract

Background: Recently, a study comprising adult patients with sepsis admitted in the intensive care unit (ICU) was conducted. The patients were treated with high doses of intravenous ascorbic acid, thiamine, and hydrocortisone; the clinical outcomes demonstrated significant therapeutic benefits. The mortality rate in children with sepsis is approximately 25%. However, the effects of additional treatment with ascorbic acid and thiamine ("vitamin protocol") in children are rarely investigated. Methods: A retrospective analysis was performed using medical records of patients diagnosed with sepsis and admitted to the pediatric ICU (PICU) between September 2016 and June 2019. The control group received treatment only as per sepsis protocol, whereas the treated group received both sepsis protocol and the vitamin protocol. The primary endpoint was change in Vasoactive-Inotropic Score (VIS) for 5 days. The secondary endpoints included the length of stay in the PICU, duration of using mechanical ventilators and vasopressors, and mortality rate. Results: The number of patients in the treated and control groups was 33 and 24, respectively. The treated group showed greater decrease in their VIS for 5 days than the control group (44.4 vs 18.6); however, the difference was not statistically significant. The length of stay in the PICU was significantly longer for the treated group than for the control group [10.0 days (Interquartile range (IQR), 6-18) vs 4.5 days (IQR, 4-10.3); p=0.004]. Conclusions: No significant treatment benefits were observed following vitamin protocol administration to the pediatric patients with sepsis. Further studies are necessary for improving the efficacy and safety of the vitamin protocol.

Keywords

References

  1. Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Intensive Care Med 2018;44(6):925-8. https://doi.org/10.1007/s00134-018-5085-0
  2. Weiss SL, Peters MJ, Alhazzani W, et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med 2020;46(Suppl 1):10-67. https://doi.org/10.1007/s00134-019-05878-6
  3. Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 2016;193(3):259-72. https://doi.org/10.1164/rccm.201504-0781OC
  4. Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med 2018;6(3):223-30. https://doi.org/10.1016/S2213-2600(18)30063-8
  5. Tan B, Wong JJ, Sultana R, et al. Global case-fatality rates in pediatric severe sepsis and septic shock: a systematic review and meta-analysis. JAMA Pediatr 2019;173(4):352-62. https://doi.org/10.1001/jamapediatrics.2018.4839
  6. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: A retrospective before-after study. Chest 2017;151(6):1229-38. https://doi.org/10.1016/j.chest.2016.11.036
  7. Moskowitz A, Andersen LW, Huang DT, et al. Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation. Crit Care 2018;22(1):283. https://doi.org/10.1186/s13054-018-2217-4
  8. Amrein K, Oudemans-van Straaten HM, Berger MM. Vitamin therapy in critically ill patients:focus on thiamine, vitamin C, and vitamin D. Intensive Care Med 2018;44:1940-44. https://doi.org/10.1007/s00134-018-5107-y
  9. Fowler AA 3rd, Syed AA, Knowlson S, et al. Phase 1 safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med 2014;12:32. https://doi.org/10.1186/1479-5876-12-32
  10. Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of highdose ascorbic acid on vasopressor's requirement in septic shock. J Res Pharm Pract 2016;5(2):94-100. https://doi.org/10.4103/2279-042X.179569
  11. Shin TG, Kim YJ, Ryoo SM, et al. Early vitamin C and thiamine administration to patients with septic shock in emergency departments: Propensitiy score-based analysis of a before-and-after cohort study. J Clin Med 2019;8(1):102. https://doi.org/10.3390/jcm8010102
  12. Fowler AA 3rd, Truwit JD, Hite RD, et al. 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. JAMA 2019;322(13):1261-70. https://doi.org/10.1001/jama.2019.11825
  13. von Dessauer B, Bongain J, Molina V, Quilodran J, Castillo R, Rodrigo R. Oxidative stress as a novel target in pediatric sepsis management. J Crit Care 2011;26(1):103.
  14. Nathens AB, Neff MJ, Jurkovich GJ, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg 2002;236(6):814-22. https://doi.org/10.1097/00000658-200212000-00014
  15. Lima LF, Leite HP, Taddei JA. Low blood thiamine concentrations in children upon admission to intensive care unit:risk factors and prognostic significance. Am J Clin Nutr 2011;93(1):57-61. https://doi.org/10.3945/ajcn.2009.29078
  16. Kim WY, Jo EJ, Eom JS, et al. Combined vitamin C, hydrocortisone, and thiamine therapy for patients with severe pneumonia who were admitted to the intensive care unit: Propensity score-based analysis of a before-after cohort study. J Crit Care 2018;47:211-8. https://doi.org/10.1016/j.jcrc.2018.07.004
  17. Almeda A, Martinez B, Ozuna R. High-dose intravenous vitamin C and thiamine as adjuct therapy for septic shock in the pediatric ICU: A case report. Int J Pharmacovigil 2018;3(2):1-5.
  18. Wald EL, Sanchez-Pinto LN, Smith CM, et al. Hydrocortisoneascorbic acid-thiamine use associated with lower mortality in pediatric septic shock. Am J Respir Crit Care Med 2020;201(7):863-7. https://doi.org/10.1164/rccm.201908-1543le
  19. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. 2017;43(3):304-77. https://doi.org/10.1007/s00134-017-4683-6
  20. Haque A, Siddiqui NR, Munir O, Saleem S, Mian A. Association between vasoactive-inotropic score and mortality in pediatric septic shock. Indian Pediatr 2015;52(4):311-3. https://doi.org/10.1007/s13312-015-0630-1
  21. McIntosh AM, Tong S, Deakyne SJ, Davidson JA, Scott HF. Validation of the vasoactive-inotropic score in pediatric sepsis. Pediatr Crit Care Med 2017;18(8):750-7. https://doi.org/10.1097/PCC.0000000000001191
  22. Lee SH, Park KH, Park DH, et al. Usefulness of the pediatric risk of mortality score III as a predictor of severity or mortality for injured children. J Korean Soc Emerg Med 2013;24(2):174-80.
  23. Colliou E, Mari A, Delas A, Delarche A, Faguer S. Oxalate nephropathy following vitamin C intake within intensive care unit. Clin Nephrol 2017;88(12):354-8. https://doi.org/10.5414/CN109118
  24. Michelle Buehner, Jeremy Pamplin, Lynette Studer et al. Oxalate nephropathy after continuous infusion of high-dose vitamin C as an adjunct to burn resuscitation. J Burn Care Res 2016;37:e374-e379. https://doi.org/10.1097/BCR.0000000000000233