(1) A review of the use of high dose vitamin C for the treatment of burns. Dubick, Michael A. US Army Institute of Surgical Research, San Antonio, TX, USA. Recent Research Developments in Nutrition Research (2000), 3 141-156.

Abstract

A review. Thermal injury is assocd. with capillary leakage and tissue edema that increases the challenge of fluid resuscitation for treating the developing hypovolemia. It is postulated that free radical generation assocd. with thermal injury is an important mediator in the development of this capillary leakage. Over the past decade a series of studies in exptl. animals and 2 studies in humans have explored the use of high dose vitamin C in reducing fluid requirements and tissue edema assocd. with burns. The data to date suggest that doses up to 66 mg/kg/h infused for 8-24 h after burn may be required to reduce fluid needs and tissue edema and such doses have produced no overt toxicity. Further study appears warranted.

(2) Rationale and impact of vitamin C in clinical nutrition. McGregor, Gerard P.; Biesalski, Hans K. Institute of Physiology, Faculty of Medicine, Philipps University of Marburg, Marburg, Germany. Current Opinion in Clinical Nutrition and Metabolic Care (2006), 9(6), 697-703.

Abstract

Purpose of review: The impact of vitamin C on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. Parenteral administration (by injection) can increase the benefit of vitamin C supplementation as is evident in critically ill patients. The aim here is to assess recent evidence of the clin. benefit and underlying effects of parenteral vitamin C in conditions of oxidative stress. Recent findings: In critically ill patients and after severe burns, the rapid restoration of depleted ascorbate levels with high-dose parenteral vitamin C may reduce circulatory shock, fluid requirements and edema. Summary: Oxidative stress is assocd. with reduced ascorbate levels. Ascorbate is particularly effective in protecting the vascular endothelium, which is esp. vulnerable to oxidative stress. The restoration of ascorbate levels may have therapeutic effects in diseases involving oxidative stress. The rapid replenishment of ascorbate is of special clin. significance in critically ill patients who experience drastic redns. in ascorbate levels, which may be a causal factor in the development of circulatory shock. Supraphysiol. levels of ascorbate, which can only be achieved by the parenteral and not by the oral administration of vitamin C, may facilitate the restoration of vascular function in the critically ill patient.

(3) Vitamin C regulates keratinocyte viability, epidermal barrier, and basement membrane in vitro, and reduces wound contraction after grafting of cultured skin substitutes. Boyce, Steven T.; Supp, Andrew P.; Swope, Viki B.; Warden, Glenn D. Shriners Hospitals for Children and Department of Surgery, University of Cincinnati, Cincinnati, OH, USA. Journal of Investigative Dermatology (2002), 118(4), 565-572.

Abstract

Cultured skin substitutes have become useful as adjunctive treatments for excised, full-thickness burns, but no skin substitutes have the anatomy and physiol. of native skin. Hypothetically, deficiencies of structure and function may result, in part, from nutritional deficiencies in culture media. To address this hypothesis, vitamin C was titrated at 0.0, 0.01, 0.1, and 1.0 mM in a cultured skin substitute model on filter inserts. Cultured skin substitute inserts were evaluated at 2 and 5 wk for viability by incorporation of 5-bromo-2′-deoxyuridine (BrdU) and by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) conversion. Subsequently, cultured skin substitute grafts consisting of cultured human keratinocytes and fibroblasts attached to collagen-glycosaminoglycan substrates were incubated for 5 wk in media contg. 0.0 mM or 0.1 mM vitamin C, and then grafted to athymic mice. Cultured skin substitutes (n = 3 per group) were evaluated in vitro at 2 wk of incubation for collagen IV, collagen VII, and laminin 5, and through 5 wk for epidermal barrier by surface elec. capacitance. Cultured skin substitutes were grafted to full-thickness wounds in athymic mice (n = 8 per group), evaluated for surface elec. capacitance through 6 wk, and scored for percentage original wound area through 8 wk and for HLA-ABC-pos. wounds at 8 wk after grafting. The data show that incubation of cultured skin substitutes in medium contg. vitamin C results in greater viability (higher BrdU and MTT), more complete basement membrane development at 2 wk, and better epidermal barrier (lower surface elec. capacitance) at 5 wk in vitro. After grafting, cultured skin substitutes with vitamin C developed functional epidermal barrier earlier, had less wound contraction, and had more HLA-pos. wounds at 8 wk than without vitamin C. These results suggest that incubation of cultured skin substitutes in medium contg. vitamin C extends cellular viability, promotes formation of epidermal barrier in vitro, and promotes engraftment. Improved anatomy and physiol. of cultured skin substitutes that result from nutritional factors in culture media may be expected to improve efficacy in treatment of full-thickness skin wounds.

(4) High-dose vitamin C infusion reduces fluid requirements in the resuscitation of burn-injured sheep. Dubick, Michael A.; Williams, Chad; Elgjo, Geir I.; Kramer, George C. U.S. Army Institute of Surgical Research, San Antonio, TX, USA. Shock (2005), 24(2), 139-144. Publisher: Lippincott Williams & Wilkins, CODEN: SAGUAI ISSN: 1073-2322. Journal written in English. CAN 143:319069 AN 2005:975444 CAPLUS (Copyright (C) 2007 ACS on SciFinder (R))

Abstract

Fluid resuscitation to maintain adequate tissue perfusion while reducing edema in the severely burned patient remains a challenge. Recent studies suggest that reactive oxygen species generated by thermal injury are involved in edema formation assocd. with burn. The present study tested the hypothesis that adding a free radical scavenger to the resuscitation fluid would reduce total fluid requirements in the treatment of severe thermal injury. Anesthetized chronically instrumented sheep received a 40% total body surface area full-thickness flame burn. At 1 h after injury, animals were resuscitated with lactated Ringer’s (LR, n = 14) as control, LR contg. high doses of vitamin C (VC, n = 6), 1000 mOsM hypertonic saline (HS, n = 7), or 1000 HS contg. VC (HS/VC, n = 7) in coded bags so that investigators were blinded to the treatment. Fluids were infused at an initial Parkland rate of 10 mL/kg/h, adjusted hourly to restore and maintain urine output at 1 to 2 mL/kg/h. Sheep in the VC or HSA/C group received 250 mg/kg VC in the first 500 mL of LR or HS, and then 15 mg/kg/h thereafter. Hemodynamic variables and indexes of antioxidant status were measured. At 48 h postburn, sheep were euthanized, and heart, liver, lung, skeletal muscle, and ileum were evaluated for antioxidant status. All fluid resuscitation regimens were equally effective in restoring cardiac output to near baseline levels; no treatment effects were apparent on arterial pressure or heart rate. VC infusion significantly reduced fluid requirements and, therefore, net fluid balance (fluid in, urine out) by about 30% at 6 h and about 50% at 48 h in comparison with the LR group (P < 0.05). HS and HS/VC reduced fluid requirements by 30% and 65%, resp., at 6 h, but the vol.-sparing effect of HS was not obsd. after 36 h and that of HSA/C was lost after 12 h.
Plasma total antioxidant potential increased about 25-fold (P < 0.05) at 2 and 3 h in response to VC infusion compared with the LR and HS groups, and remained about 5- to 10-fold higher throughout the rest of the study. VC infusion also prevented the 4-fold increase in plasma thiobarbituric acid reactive substances seen in the LR group early after burn (P< 0.05). Tissue antioxidant status was similar between groups. In this sheep burn model, continuous high-dose VC infusion reduced net fluid balance, reduced indexes of plasma lipid peroxidn., and maintained overall antioxidant status in comparison with std.-of-care LR treatment. (5) Reduced resuscitation fluid volume for second-degree experimental burns with delayed initiation of vitamin C therapy (beginning 6 h after injury). Sakurai, Masaru; Tanaka, Hideharu; Matsuda, Takayoshi; Goya, Tomoyuki; Shimazaki, Shuji; Matsuda, Hiroharu. Hektoen Institute for Medical Research, Burn Center, Cook County Hospital, Chicago, IL, USA. Journal of Surgical Research (1997), 73(1), 24-27. Abstract The authors studied the hemodynamic effects of delayed initiation (6 h postburn) of antioxidant therapy with high-dose vitamin C in second-degree thermal injuries. Seventy percent body surface area burns were produced by subxiphoid immersion of 12 guinea pigs into 100 water for 3 s. The animals were resuscitated with Ringer’s lactate soln. (R/L) according to the Parkland formula (4 mL/kg/% burn during the first 24 h) from 6 h postburn, after which the resuscitation fluid vol. was reduced to 25% of the Parkland formula vol. Animals were divided into 2 groups. The vitamin C group received R/L to which vitamin C (340 mg/kg/24 h) was added after 6 h postburn. The control group received R/L only. Both groups received identical resuscitation vols. Heart rates, mean arterial blood pressure, cardiac output, hematocrit level, and water content of burned and unburned tissue were measured before injury and at intervals thereafter. No animals died. There were no differences in heart rates or blood pressures between the 2 groups throughout the 24-h study period. The vitamin C group showed lower hematocrits 8 and 24 h postburn, and higher cardiac outputs after 7 h postburn. At 24 h postburn, the burned skin in the vitamin C group had a lower water content (73.1) than that of the control group (76.0). Thus, delayed initiation of high-dose vitamin C therapy beginning 6 h postburn with 25% of the Parkland formula vol. reduced edema formation in burned tissue, while maintaining stable hemodynamics. (6) Nutrients as antioxidants – effect of antioxidative trace elements and vitamins on outcome of critically ill burns and trauma patients. Berger, M. M. Surgical Intensive Care Unit and Burns Centre, Lausanne, Switz. Aktuelle Ernaehrungsmedizin (2003), 28(6), 376-379. Abstract Trace elements and vitamins exert numerous functions. The non-nutritional antioxidant effects now appear of utmost importance in trauma and critically ill patients. The balance between the ROS and antioxidants is the key to survival in a world invaded by oxygen. Patients with severe injuries are characterized by ischemia-reperfusion injuries and by increased oxidative stress. The endogenous antioxidant defences may become inadequate through a variety of mechanisms, but mainly through inadequate intakes, or through increased losses of biol. fluids contg. micronutrients. Inadequate intake is widespread in the general population. In addn. critically ill trauma patients are a particular subset of patients exposed to ischemia-reperfusion injury and to severe oxidative stress, while having increased nutritional requirements. Supplementation trials have been conducted in critically ill injured patients using selenium, zinc, vitamin C, vitamin E and N-acetylcysteine in quantities varying between 5 and 20 times the parenteral nutrition doses. Although most of the trials are underpowered, clear clin. benefits have been shown such as improved wound healing, reduced infectious complications, improved neurol. outcome, and less organ failures. The optimal antioxidant micronutrient combination, and the doses required to achieve the clin. effect remain to be detd. and further clin. trials are required to answer these questions. (7) Antioxidant vitamin therapy alters burn trauma-mediated cardiac NF- B activation and cardiomyocyte cytokine secretion. Horton, Jureta W.; White, D. Jean; Maass, David L.; Hybki, Dixie Peters; Haudek, Sandra; Giroir, Brett. Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. Journal of Trauma: Injury, Infection, and Critical Care (2001), 50(3), 397-408. Abstract This study examd. the effects of antioxidant vitamins A, C, and E on nuclear transcription factor-B (NF-B) nuclear translocation, on secretion of inflammatory cytokines by cardiac myocytes, and on cardiac function after major burn trauma. Adult rats were divided into four exptl. groups: group I, shams; group II, shams given oral antioxidant vitamins (vitamin C, 38 mg/kg; vitamin E, 27 U/kg; vitamin A, 41 U/kg 24 h before and immediately after burn); group III, burns (third-degree scald burn over 40% total body surface area) given lactated Ringer’s soln. (4 mL/kg/% burn); and group IV, burns given lactated Ringer’s soln. plus vitamins as described above. Hearts were collected 4, 8, 12, and 24 h after burn to assay for NF-B nuclear translocation, and hearts collected 24 h after burn were examd. for cardiac contractile function or tumor necrosis factor- secretion by cardiomyocytes. Compared with shams, left ventricular pressure was lower in burns given lactated Ringer’s soln. (group III) (883 vs. 645 mm Hg, p < 0.01) as was +dP/dt max (2,19030 vs. 1,321122 mm Hg/s) and -dP/dt max (1,77571 vs. 99996 mm Hg, p < 0.01). Burn injury in the absence of vitamin therapy (group III) produced cardiac NF-B nuclear migration 4 h after burn and cardiomyocyte secretion of tumor necrosis factor-, interleukin-1, and interleukin-6 by 24 h after burn. Antioxidant therapy in burns (group IV) improved cardiac function, producing left ventricular pressure and  dP/dt (822 mm Hg, 1,88044 mm Hg, and 1,57046 mm Hg/s) comparable to those measured in shams. Antioxidant vitamins in burns inhibited NF-B nuclear migration at all times after burn and reduced burn-mediated cytokine secretion by cardiomyocytes. These data suggest that antioxidant vitamin therapy in burn trauma provides cardioprotection, at least in part, by inhibiting translocation of the transcription factor NF-B and interrupting cardiac inflammatory cytokine secretion.
(8) The additive effects of carnitine and ascorbic acid on distally burned dorsal skin flap in rats. Arslan, Emrah; Basterzi, Yavuz; Aksoy, Alper; Majka, Christopher; Unal, Sakir; Sari, Alper; Demirkan, Ferit. Plastic and Reconstructive Surgery, Mersin University Medical School, Mersin, Turk. Medical Science Monitor (2005), 11(6), BR176-BR180.

Abstract

Background: The purpose of this study was to det. the effects of combined use of L-carnitine and vitamin C on partially burned skin flap in an exptl. rat model. Material/Methods: In the rat dorsal skin, a 103 cm flap was marked. The most distal 33 cm part was burned to full thickness. Twenty-four rats were randomized into four groups with 6 animals in each. Group 1 was simply followed up. Group 2 was given 0.5 mg/kg vitamin C per day for 7 days, group 3 100 mg/kg carnitine per day for 7 days, and group 4 both carnitine and vitamin C. On the eighth postoperative day, the animals were sacrificed and examd. The surviving and necrotic areas were detd. by macroscopic examn. and measured with a planimeter. Results: The areas of flap necrosis were measured. The median surviving areas and areas of flap necrosis, resp., of the groups were: group 1, 16.0 cm2 and 14.0 cm2; group 2, 18.25 cm2 and 11.75 cm2; group 3, 20.0 cm2 and 10 cm2; and group 4, 23.75 cm2 and 6.25 cm2. The surviving areas of the groups were found to be significantly different (p=0.000). Conclusions: The risk of ischemia-induced necrosis in flap attempts made in damaged tissues may be reduced by the combination of two promising agents, L-carnitine and vitamin C. L-carnitine appears to be the major contributing factor that reduces necrosis, and vitamin C an additive agent.

(9) Effect of early nutritional support on plasma superoxide dismutase, malondialdehyde and nitric oxide in rats with burns in a hot and humid environment. Wang, Ying; Li, Ya-jie; Zhai, Hui-min; Xu, Cai-xia; Luo, Bing-de. Departments of Nursing Administration, Nanfang Hospital, Southern Medical University, Guangzhou, Peop. Rep. China. Diyi Junyi Daxue Xuebao (2005), 25(1), 93-95.

Abstract

Objective To observe the changes of plasma superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in rats with combined stress of burn injury and hot and humid environment. Methods The rats with superficial second-degree scald were subjected to intragastric administration of double-distd. water for one week (control group) or treated with ascorbic acid and L-arginine mixed with -Tocopherol for one week (treatment group). All the rats were exposed to the same hot and humid environment of Td 370.5 C with relative humidity of 65%5% for 1-2 h. Observation was performed at 1, 2, 4, and 10 h after the heat exposure, resp. Results SOD and MDA changes were significantly different between the two groups (P<0.01, P<0.05). In the control group, NO levels at 1 h were significantly different from those measured at 2 and 6 h after the exposure (P<0.01, P<0.05). Conclusion Early nutritional support can significantly reduce the stress organ injuries, and prevent complications following, injury in a hot and humid environment.