Main Article Content

Aditya Wardhana
Jessica Halim


Summary: Severe burns are devastating condition identified by loss of hemodynamic stability and intravascular volume. Adequate fluid replacement, nutritional support, and immediate wound grafting can reduce the risk of infection and mortality. Oxidative stress was shown to have significant role in the burn wound conversion, which happens when the zone of stasis can’t be salvaged and progresses to necrosis. Decreasing the level of oxidative stress early may be fundamental in reducing burn injury progression into deeper tissue. Several animal studies have demonstrated the advance of antioxidant supplementation for burns outcomes. Approach to this salvageable burn tissue is a breakthrough for new directions in burn management. Antioxidant supplementations was proven to prevent burn conversion on the ischemic zone. Administering antioxidant post-burn is linked with less progression of burn depth and inflammatory cytokine release, which alleviates burn-related morbidity and mortality and improves patient’s quality of life. To date, no clinical trials have been done to reproduce similar outcomes of this ROS-scavenging therapy as successfully observed in murine models. Antioxidant supplementation is a promising treatment avenue to halt burn wound conversion following severe burns.

Keywords: Burn wound, wound conversion, burn management, antioxidant


Metrics Loading ...

Article Details

How to Cite
Wardhana A, Halim J. Antioxidants Reduce Tissue Necrosis in The Zone of Stasis: Review of Burn Wound Conversion. J Plast Rekons [Internet]. 2020May7 [cited 2020Aug.14];7(1):18-. Available from:
1. Ruiz-Castilla M, Roca O, Masclans JR, Barret JP. Recent Advances In Biomarkers In Severe Burns. Shock. 2016;45(2):117-25.
2. Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, et al. Burn wound healing and treatment: review and advancements. Crit Care. 2015;19:243.
3. Singh V, Devgan L, Bhat S, Milner SM. The pathogenesis of burn wound conversion. Ann Plast Surg. 2007;59(1):109-15.
4. Auger C, Samadi O, Jeschke MG. The biochemical alterations underlying post-burn hypermetabolism. 2017;1863(10):2633-44.
5. Al-Jawad F, Sahib A, Al-Kaisy A. Role of Antioxidants in the Treatment of Burn Lesions. Ann Burns Fire Disasters. 2008;21(4):186-91.
6. Jeschke MG, Chinkes DL, Finnerty CC, Kulp G, Suman OE, Norbury WB, et al. Pathophysiologic response to severe burn injury. Ann Surg. 2008;248(3):387-401.
7. Nielson CB, Duethman NC, Howard JM, Moncure M, Wood JG. Burns: Pathophysiology of Systemic Complications and Current Management. J Burn Care Res. 2017;38(1):e469-81.
8. Hirth D, McClain SA, Singer AJ, Clark RA. Endothelial necrosis at 1h post-burn predicts progression of tissue injury. Wound Repair Regen. 2013;21(4):563-70.
9. Bittner EA, Shank E, Woodson L, Martyn JJ. Acute and Perioperative Care of the Burn-Injured Patient. Anesthesiology. 2015;122(2):448-64.
10. Rodriguez NA, Jeschke MG, Williams FN, Kamolz LP, Herndon DN. Nutrition in Burns: Galveston Contributions. JPEN J Parenter Enteral Nutr. 2011;35(6):704-14.
11. Horton JW. Free radicals and lipid peroxidation mediated injury in burn trauma: the role of antioxidant therapy. Toxicology. 2003;189(1-2):75-88.
12. Agay D, Andriollo-Sanchez M, Claeyssen R, Touvard L, Denis J, Roussel AM, et al. Interleukin-6, TNF-alpha and interleukin-1 beta levels in blood and tissue in severely burned rats. Eur Cytokine Netw. 2008;19(1):1-7.
13. Snell JA, Loh NHW, Mahambrey T, Shokrollahi K. Clinical review: The critical care management of the burn patient. Crit Care. 172013. p. 241.
14. Tricklebank S. Modern trends in fluid therapy for burns. Burns. 2009;35(6):757-67.
15. Chan J, Ghosh S. Fluid Resuscitation in Burns: An Update:. https://doiorg/101177/102490790901600112. 2017.
16. Arlati S, Storti E, Pradella V, Bucci L, Vitolo A, Pulici M. Decreased fluid volume to reduce organ damage: a new approach to burn shock resuscitation? A preliminary study. Resuscitation. 2007;72(3):371-8.
17. Lund T. The 1999 Everett Idris Evans memorial lecture. Edema generation following thermal injury: an update. J Burn Care Rehabil. 1999;20(6):445-52.
18. Sánchez M, García-de-Lorenzo A, Herrero E, Lopez T, Galvan B, Asensio MJ, et al. A protocol for resuscitation of severe burn patients guided by transpulmonary thermodilution and lactate levels: a 3-year prospective cohort study. Crit Care. 172013. p. R176.
19. Kraft R, Herndon DN, Finnerty CC, Cox RA, Song J, Jeschke MG. Predictive Value of IL-8 for Sepsis and Severe Infections after Burn Injury - A Clinical Study. Shock. 2015;43(3):222-7.
20. Greenhalgh DG. Sepsis in the burn patient: a different problem than sepsis in the general population. Burns Trauma. 52017.
21. Venet F, Plassais J, Textoris J, Cazalis MA, Pachot A, Bertin-Maghit M, et al. Low-dose hydrocortisone reduces norepinephrine duration in severe burn patients: a randomized clinical trial. Crit Care. 192015.
22. Adjepong M, Agbenorku P, Brown P, Oduro I. The role of antioxidant micronutrients in the rate of recovery of burn patients: a systematic review. Burns Trauma. 42016.
23. A. Prins RD (SA) M. Nutritional management of the burn patient. http://dxdoiorg/101080/16070658200911734211. 2016.
24. Mandell SP, Gibran NS. Early Enteral Nutrition for Burn Injury. Adv Wound Care (New Rochelle). 32014. p. 64-70.
25. Mochizuki H, Trocki O, Dominioni L, Alexander JW. Reduction of postburn hypermetabolism by early enteral feeding. Curr Surg. 1985;42(2):121-5.
26. He W, Wang Y, Wang P, Wang F. Intestinal barrier dysfunction in severe burn injury. Burns & Trauma. 2019;7(1):1-11.
27. Natarajan M. Recent Concepts in Nutritional Therapy in Critically Ill Burn Patients. International Journal of Nutrition, Pharmacology, Neurological Diseases. 2019;9(1):4-36.
28. Salibian AA, Del Rosario AT, De Almeida Moura Severo L, Nguyen L, Banyard DA, Toranto JD, et al. Current concepts on burn wound conversion – a review of recent advances in understanding the secondary progressions of burns. Burns. 2016;42(5):1025-35.
29. Rawlingson A. Nitric oxide, inflammation and acute burn injury. Burns. 2003;29(7):631-40.
30. Tan JQ, Zhang HH, Lei ZJ, Ren P, Deng C, Li XY, et al. The roles of autophagy and apoptosis in burn wound progression in rats. Burns. 2013;39(8):1551-6.
31. Kim DE, Uniformed Services University of the Health Sciences B, Maryland, Phillips TM, Uniformed Services University of the Health Sciences B, Maryland, Jeng JC, Uniformed Services University of the Health Sciences B, Maryland, et al. Microvascular Assessment of Burn Depth Conversion during Varying Resuscitation Conditions. The Journal of Burn Care & Rehabilitation. 2019;22(6):406-16.
32. Carvajal HF. Fluid resuscitation of pediatric burn victims: a critical appraisal. Pediatr Nephrol. 1994;8(3):357-66.
33. Bacomo FK, Chung KK. A primer on burn resuscitation. J Emerg Trauma Shock. 42011. p. 109-13.
34. Eski M, Ozer F, Firat C, Alhan D, Arslan N, Senturk T, et al. Cerium nitrate treatment prevents progressive tissue necrosis in the zone of stasis following burn. Burns. 2012;38(2):283-9.
35. Abbas OL, Ozatik O, Gonen ZB, Ogut S, Entok E, Ozatik FY, et al. Prevention of Burn Wound Progression by Mesenchymal Stem Cell Transplantation: Deeper Insights Into Underlying Mechanisms. Ann Plast Surg. 2018;81(6):715-24.
36. Oksuz S, Ulkur E, Oncul O, Kose GT, Kucukodaci Z, Urhan M. The effect of subcutaneous mesenchymal stem cell injection on statis zone and apoptosis in an experimental burn model. Plast Reconstr Surg. 2013;131(3):463-71.
37. Singer AJ, Towery H, McClain SA. Effect of tadalafil on reduction of necrosis in the ischemic zone in a rat comb burn model.: Epub; 2019 [
38. Tobalem M, Harder Y, Schuster T, Rezaeian F, Wettstein R. Erythropoietin in the prevention of experimental burn progression. Br J Surg. 2012;99(9):1295-303.
39. Schaser KD, Stover JF, Melcher I, Lauffer A, Haas NP, Bail HJ, et al. Local cooling restores microcirculatory hemodynamics after closed soft-tissue trauma in rats. J Trauma. 2006;61(3):642-9.
40. Guo SX, Jin YY, Fang Q, You CG, Wang XG, Hu XL, et al. Beneficial Effects of Hydrogen-Rich Saline on Early Burn-Wound Progression in Rats. PLoS One. 102015.
41. Turkaslan T, Yogun N, Cimsit M, Solakoglu S, Ozdemir C, Ozsoy Z. Is HBOT treatment effective in recovering zone of stasis? An experimental immunohistochemical study. Burns. 2010;36(4):539-44.
42. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429(6990):417-23.
43. Yadav A. (PDF) Antioxidants and its functions in human body - A Review. 2019.
44. Liu Z, Ren Z, Zhang J, Chuang C-C, Kandaswamy E, Zhou T, et al. Role of ROS and Nutritional Antioxidants in Human Diseases Frontiers Physiology. 2018;17(9):477.
45. Pham-Huy LA, He H, Pham-Huy C. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. 42008. p. 89-96.
46. Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr. 2004;44(4):275-95.
47. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 132018. p. 757-72.
48. Reddy P, Jialal I. Biochemistry, Vitamin, Fat Soluble. 2018.
49. Berger MM, Oudemans-van Straaten HM. Vitamin C supplementation in the critically ill patient. Curr Opin Clin Nutr Metab Care. 2015;18(2):193-201.
50. Parker R, Rice MJ. Benefits of antioxidant supplementation in multi-trauma patients. Romanian Journal of Anaesthesia and Intensive Care. 2015;22:77-8.
51. Bjelakovic G, Nikolova D, Gluud LL, SImonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews. 2012.
52. Sahib A, Al-Jawad F, Alkaisy A. Effect of Antioxidants on the Incidence of Wound Infection in Burn Patients. Ann Burns Fire Disasters. 2010;23(4):199-205.
53. Rizzo JA, Rowan MP, Driscoll IR, Chung KK, Friedman BC. Vitamin C in Burn Resuscitation. Crit Care Clin. 2016;32(4):539-46.
54. Kahn SA, Beers RJ, Lentz CW. Resuscitation after severe burn injury using high-dose ascorbic acid: a retrospective review. J Burn Care Res. 2011;32(1):110-7.
55. Raposio E, Grieco MP, Caleffi E. Evaluation of plasma oxidative stress, with or without antioxidant supplementation, in superficial partial thickness burn patients: a pilot study. J Plast Surg Hand Surg. 2017;51(6):393-8.
56. Ziegler R, Emory University ACR, Pennsylvania State U, Benjamin HC, Bloomberg School of Public H,, et al. Modern nutrition in health and disease: Eleventh edition. 2019.
57. Singer AJ, McClain SA, Romanov A, Rooney J, Zimmerman T. Curcumin reduces burn progression in rats. Acad Emerg Med. 2007;14(12):1125-9.
58. Singer AJ, Taira BR, Lin F, Lim T, Anderson R, McClain SA, et al. Curcumin reduces injury progression in a rat comb burn model. J Burn Care Res. 2011;32(1):135-42.
59. Fang Q, Guo S, Zhou H, Han R, Wu P, Han C. Astaxanthin protects against early burn-wound progression in rats by attenuating oxidative stress-induced inflammation and mitochondria-related apoptosis. Sci Rep. 2017;7:41440.
60. Wang CZ, Ayadi AE, Goswamy J, Finnerty CC, Mifflin R, Sousse L, et al. Topically applied metal chelator reduces thermal injury progression in a rat model of brass comb burn. Burns. 2015;41(8):1775-87.
61. Shalom A, Kramer E, Westreich M. Protective effect of human recombinant copper-zinc superoxide dismutase on zone of stasis survival in burns in rats. Ann Plast Surg. 2011;66(6):607-9.

Author Biography

Aditya Wardhana, Burn Section, Division of Plastic Surgery, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia

dr. Aditya Wardhana, Sp.BP-RE(K)

Consultant of Plastic and Reconstructive Surgery

Burns Unit of Cipto Mangunkusumo Hospital

Faculty of Medicine, Universitas Indonesia, Jakarta