title: High-dose vitamin C infusion reduces fluid requirements in the resuscitation of burn-injured sheep.
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 associated 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 containing high doses of vitamin C (VC, n = 6), 1000 mOsM hypertonic saline (HS, n = 7), or 1000 HS containing 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 HS/VC 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 indices 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%, respectively, at 6 h, but the volume-sparing effect of HS was not observed after 36 h and that of HS/VC 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 indices of plasma lipid peroxidation, and maintained overall antioxidant status in comparison with standard-of-care LR treatment.
authors.affiliation: U.S. Army Institute of Surgical Research, San Antonio, Texas 78234-6315, USA. Michael.Dubick@amedd.army.mil
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
authors.forename: Chad
authors.initials: C
authors.lastname: Williams
authors.forename: Geir I
authors.initials: GI
authors.lastname: Elgjo
authors.forename: George C
authors.initials: GC
authors.lastname: Kramer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001158:Arteries / Q000473:pathology; D001205:Ascorbic Acid / Q000378:metabolism / Q000627:therapeutic use*; D002056:Burns / Q000628:therapy*; D004487:Edema / Q000473:pathology; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D016166:Free Radical Scavengers / Q000378:metabolism / Q000627:therapeutic use*; D006400:Hematocrit; D006439:Hemodynamics; D015227:Lipid Peroxidation; D012151:Resuscitation / Q000379:methods*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D012756:Sheep; D012774:Shock, Traumatic / Q000628:therapy; D012965:Sodium Chloride / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D012462:Saline Solution, Hypertonic; D017392:Thiobarbituric Acid Reactive Substances; D012965:Sodium Chloride; D001205:Ascorbic Acid