Analysis of serum vitamin C and nitric oxide in children with septic shock

  • Yuliana Yunarto Department of Pediatrics, Faculty of Medicine, Diponegoro University-Dr. Kariadi Hospital
  • Dewi Ratih
  • Wistiani Wistiani
Keywords: septic shock; vitamin c; nitric oxide

Abstract

Background  Imbalance of oxidants and antioxidants contributes to the sepsis process. Nitric oxide (NO) is an oxidant produced abundantly during sepsis and plays key role in the pathogenesis of hypotension in septic shock. Vitamin C functions as a potent antioxidant to scavenge free radicals, reduce endothelial permeability, cellular apoptosis, and endogenous vasopressor synthesis cofactor. Vitamin C prevents excessive production of NO by suppressing inducible nitric oxide synthase (iNOS) expression.

Objective To analyze for a possible correlation between serum vitamin C and NO levels in children with septic shock.

Methods This cross-sectional study was conducted in Dr. Kariadi Hospital, Semarang, Central Java, Indonesia. A total of 40 children with septic shock aged 1 month - 18 years were consecutively recruited. Serum vitamin C and serum NO levels were measured using colorimetric assay kits.

Results Of 40 children with septic shock, 21 (52.5%) were male, 21 (52.5%) were undernourished, 25 (62.5%) were on mechanical ventilators, and 10 (25%) required more than one vasoactive agent. Blood gas analysis revealed acidosis in 31 (77.5%) children. Subjects’ median age was 20 months (2-214 months). Mean serum vitamin C level was 7.35 (SD 2.723) µg/mL and mean serum NO was 47.25 (SD 19.278) µmol/L. There was no significant correlation between serum vitamin C levels and serum NO in children with septic shock (r=0.056; P=0.732).

Conclusion Serum vitamin C levels and serum NO has no correlation in children with septic shock.

References

1. 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;6:223–30. DOI: https://doi.org/10.1016/S2213-2600(18)30063-8.
2. Mantzarlis K, Tsolaki V, Zakynthinos E. Role of oxidative stress and mitochondrial dysfunction in sepsis and potential therapies. Oxid Med Cell Longev. 2017;2017:5985209. DOI: https://doi.org/10.1155/2017/5985209.
3. Lambden S. Bench to bedside review: therapeutic modulation of nitric oxide in sepsis—an update. Intensive Care Med Exp. 2019;7:64. DOI: https://doi.org/10.1186/s40635-019-0274-x.
4. Luiking YC, Engelen MPKJ, Deutz NEP. Regulation of nitric oxide production in health and disease. Curr Opin Clin Nutr Metab Care. 2010;13:97–104. DOI: https://doi.org/10.1097/MCO.0b013e328332f99d.
5. Kuhn S-O, Meissner K, Mayes LM, Bartels K. Vitamin C in sepsis. Curr Opin Anaesthesiol. 2018;31:55–60. DOI: https://doi.org/10.1097/ACO.0000000000000549.
6. Berger MM, Oudemans-Van Straaten HM. Vitamin C supplementation in the critically ill patient. Curr Opin Clin Nutr Metab Care. 2015;18:193–201. DOI: https://doi.org/10.1097/MCO.0000000000000148.
7. Gunawijaya E, BNP A. Peran nitrogen oksida pada infeksi. Sari Pediatr. 2000;2:113–9.
8. Decker ML, Grobusch MP, Ritz N. Influence of age and other factors on cytokine expression profiles in healthy children-a systematic review. Front Pediatr. 2017;5:255. DOI: 10.3389/fped.2017.00255
9. Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017;9:1211. DOI: https://doi.org/10.3390/nu9111211.
10. Litwak J, Cho N, Nguyen H, Moussavi K, Bushell T. Vitamin C, hydrocortisone, and thiamine for the treatment of severe sepsis and septic shock: a retrospective analysis of real-world application. J Clin Med. 2019;8:478. DOI: https://doi.org/10.3390/jcm8040478.
11. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228. DOI: https://doi.org/10.1097/CCM.0b013e31827e83af.
12. Shah S, Deshmukh C, Tullu M. The predictors of outcome and progression of pediatric sepsis and septic shock: a prospective observational study from western India. J Postgrad Med. 2020;66:67-72. DOI: https://doi.org/10.4103/jpgm.JPGM_171_19.
13. Gobinathan S, Suresh Kannan K. Study of prevalence, etiology, response to treatment and outcome of paediatric shock in a tertiary care hospital. Int J Contemp Pediatr. 2018;5:1104–8. DOI: https://doi.org/10.18203/2349-3291.ijcp20181551
14. Vekaria-Hirani V, Kumar R, Musoke RN, Wafula EM, Chipkophe IN. prevalence and management of septic shock among children admitted at the Kenyatta National Hospital, Longitudinal Survey. Int J Pediatr. 2019;2019:1502963. DOI: https://doi.org/10.1155/2019/1502963
15. Chandra R, Mandei JM, Manoppo JIC, Wilar R, Runtunuwu AL, Liana P. Serum nitric oxide and pediatric sepsis outcomes. Paediatr Indones. 2014;54:213–8. DOI: https://doi.org/10.14238/pi54.4.2014.213-8
16. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003;167:695–701. DOI: https://doi.org/10.1164/rccm.200207-682OC
17. Saraswati DD, Pudjiadi AH, Djer MM, Supriyatno B, Syarif DR, Kurniati N. Faktor risiko yang berperan pada mortalitas sepsis. Sari Pediatr. 2014;15:281.
18. Rusmawatiningtyas D, Nurnaningsih N. Mortality rates in pediatric septic shock. Paediatr Indones. 2017;56:304-10. DOI: https://doi.org/10.14238/pi56.5.2016.304-10
19. Da Costa São Pedro T, Morcillo AM, Baracat ECE. Etiology and prognostic factors of sepsis among children and adolescents admitted to the intensive care unit. Rev Bras Ter Intensiva. 2015;27:240–6. DOI: https://doi.org/10.5935/0103-507X.20150044
20. Folgori L, Bielicki J. Future challenges in pediatric and neonatal sepsis: emerging pathogens and antimicrobial resistance. J Pediatr Intensive Care. 2019;08:17–24. DOI: https://doi.org/10.1055/s-0038-1677535.
21. German Nutrition Society (DGE). New reference values for vitamin C intake. Ann Nutr Metab. 2015;67:13–20. DOI: https://doi.org/10.1159/000434757.
22. Cherian S, Jameson S, Rajarajeswari C, Helena V, Latha L, Rekha A, et al. Oxidative stress in sepsis in children. Indian J Med Res. 2007;125:143–8.
23. Choi DH, Basu S, Steinhorn D. Ascorbic acid levels in critically-ill children and the impact of nutrition. Sect Child Death Rev Prev Progr. 2021;147(3_MeetingAbstract):421.2-3. DOI: https://doi.org/10.1542/peds.147.3MA5.421b.
24. Runtunuwu AL, Manoppo JIC, Daud D, Yusuf I, Ganda IJ. Prognostic value of nitric oxide in pediatric septic shock. Paediatr Indones. 2016;56:211-4. DOI: https://doi.org/10.14238/pi56.4.2016.211-4
25. Abd El-Gawad TAA, El-Sahrigy SAF, Abdel-Rahman AMO, Ghaffar EA, El-Rasheed EA. Plasma levels of nitric oxide and carbon monoxide in critically ill children with septic syndrome. J Med Sci. 2007;7:769–75. DOI: https://doi.org/10.3923/jms.2007.769.775
26. Rowe S, Carr AC. Factors affecting vitamin C status and prevalence of deficiency?: a global health perspective. Nutrients. 2020;1:1963. DOI: https://doi.org/10.3390/nu12071963
27. Elli M, Söylemezoglu O, Erbas D, Bakkaloglu SA, Buyan N, Ozkaya O, et al. Plasma and urine nitric oxide levels in healthy Turkish children. Pediatr Nephrol. 2005;20:1605–9. DOI: https://doi.org/10.1007/s00467-005-1988-4.
28. Titheradge MA. Nitric oxide in septic shock. Biochim Biophys Acta. 1999;1411:437–55. DOI: https://doi.org/10.1016/S0005-2728(99)00031-6
29. Morin L, Kneyber M, Jansen NJG, Peters MJ, Javouhey E, Nadel S, et al. Translational gap in pediatric septic shock management: an ESPNIC perspective. Ann Intensive Care. 2019;9:73. DOI: https://doi.org/10.1186/s13613-019-0545-4.
30. Garcia PCR, Tonial CT, Piva JP. Septic shock in pediatrics: the state-of-the-art. J Pediatr (Rio J). 2020;96:87–98. DOI: https://doi.org/10.1016/j.jped.2019.10.007.
31. Doughty L, Carcillo JA, Kaplan S, Janosky J. Plasma nitrite and nitrate concentrations and multiple organ failure in pediatric sepsis. Crit Care Med. 1998;26:157–62. DOI: https://doi.org/10.1097/00003246-199801000-00032
32. Fowler AA, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12:32. DOI: https://doi.org/10.1186/1479-5876-12-32
33. Kellum JA. Metabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology? Crit Care Resusc. 2004;6:197–203.
34. Aisa-Alvarez A, Soto ME, Guarner-Lans V, Camarena-Alejo G, Franco-Granillo J, Martínez-Rodríguez EA, et al. Usefulness of antioxidants as adjuvant therapy for septic shock: A randomized clinical trial. Med. 2020;56:619. DOI: https://doi.org/10.3390/medicina56110619
35. Spoelstra–de Man AME, Oudemans–van Straaten HM, Berger MM. Adjuvant vitamin C for sepsis: mono or triple? Crit Care. 2019;23:425. DOI: https://doi.org/10.1186/s13054-019-2717-x.
36. Zweier JL, Samouilov A, Kuppusamy P. Non-enzymatic nitric oxide synthesis in biological systems. Biochim Biophys Acta. 1999;1411:250–62. DOI: https://doi.org/10.1016/s0005-2728(99)00018-3.
Published
2023-11-20
How to Cite
1.
Yunarto Y, Ratih D, Wistiani W. Analysis of serum vitamin C and nitric oxide in children with septic shock. PI [Internet]. 20Nov.2023 [cited 3Dec.2024];63(6):425-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2948
Section
Emergency & Pediatric Intensive Care
Received 2022-01-12
Accepted 2023-11-20
Published 2023-11-20