Vitamin C-Fortified Oral Rehydration Solution for Burn Shock Resuscitation: A Dose- Finding Study Demonstrating Optimal Survival and Intestinal Protection in Rats

Background Burn shock is a life-threatening, capillary-leak-driven hypovolemic state in which standard oral rehydration solution (ORS) fails to address the underlying endothelial dysfunction and oxidative stress. Vitamin C is an essential cofactor for catecholamine synthesis and endothelial barrier stabilization, yet the optimal oral concentration for burn shock resuscitation remains undefined, hindering clinical translation in mass casualty and resource-limited settings where intravenous access is unavailable. Methods Male Wistar rats (n = 350) with 50% total body surface area full-thickness scald burns were randomized to seven groups: sham, burn control, standard WHO-ORS, or one of four vitamin C-fortified ORS groups (1.16, 3.5, 5.98, and 11.6 g/L). Resuscitation was administered via oral gavage following a modified Parkland formula (half-volume regimen to avoid aspiration). Primary outcome was 72-hour survival (n = 20/group). Secondary assessments included intestinal microcirculation (laser speckle contrast imaging), hemodynamic parameters (hematocrit, lactate), oxidative stress markers (malondialdehyde, total antioxidant capacity), systemic inflammation (interleukin-17), and intestinal barrier integrity (serum diamine oxidase activity and histopathology). Results Gastrointestinal absorption of vitamin C was confirmed in the setting of burn shock, with a dose-dependent but nonlinear pharmacokinetic profile suggestive of saturable transport. The 3.5 g/L concentration achieved the highest 72-hour survival (85% versus 65% with standard ORS; P < 0.05). This concentration optimally restored intestinal microcirculatory perfusion, attenuated hemoconcentration (lower hematocrit and hemoglobin; P < 0.05), and accelerated lactate clearance. Mechanistically, the 3.5 g/L group demonstrated superior suppression of malondialdehyde and interleukin-17, with correspondingly enhanced total antioxidant capacity. Intestinal barrier preservation was most pronounced in this group, as evidenced by the lowest serum diamine oxidase activity and histopathological injury scores ( P < 0.001 versus ORS). Conclusion The 3.5 g/L vitamin C concentration represents the optimal oral formulation for burn shock resuscitation in this preclinical model. Its efficacy is mechanistically linked to preserved microvascular perfusion, endothelial barrier stabilization, and attenuation of oxidative-inflammatory injury. This low-cost, field-deployable intervention warrants further clinical investigation as a bridge therapy when intravenous resuscitation is unavailable.