New treatment strategies to reduce burn wound progression

[english] Background: After a burn injury certain superficial partial-thickness burn wounds spontaneously progress into deep partial-thickness or full-thickness burn wounds. This poorly understood phenomenon is called burn wound progression. The aim of this study was to investigate whether treatment strategies using warm water (preservation of microcirculation) on the one side and erythropoietin (EPO) (molecule with anti-inflammatory, anti-apoptotic, vasodilatory and neoangiogenic properties) can prevent, delay and/or reduce secondary burn wound progression in a rat model.Methods: We used a burn comb model in 63 rats, creating eight rectangular contact burns (2x1 cm each) intercalated by unburned zones (2x0.5 cm) prone to burn wound progression. In a first experimental set we treated burn wounds with locally applied warm (37°C) or cold (17°C) water for 20 minutes.In a second experimental set, animals were treated systemically with EPO at two different dosages of 500 and 2,500 IU/kg bodyweight (bw) and initiated at 2 different time-points (45 minutes vs. 6 hours after burn injury). Evaluation of microcirculatory perfusion, interspace necrosis and burn depth was performed using respectively laser Doppler flowmetry, planimetry and histology. For statistical analysis the two-way ANOVA-test followed by an adequate post-hoc test (Bonferroni) were used. Results: In untreated control animals a conversion from superficial to full-thickness burns was observed within 24 hours. Warm and cold water treatment significantly delayed burn depth progression, nevertheless after 4 days, burn depth was similar in all three groups. Warm water significantly reduced interspace necrosis compared to untreated controls and cold water with a significantly improved perfusion in the warm water group. Surface extension and particularly burn depth progression were significantly decreased by EPO only if administered at a dosage of bw and initiated 45 minutes after burn injury. EPO administration was associated with an early hyperperfusion resulting from an increase in inducible nitric oxide synthase (iNOS) and a late angiogenic response indicated by increased microvascular density.Conclusion: First aid treatment with warm water prevents extension of the burn on the surface and delays burn depth progression, thereby creating a “therapeutic window” of approximately 4–6 hours after burn injury. This window might be used for systemic use of EPO which prevents burn progression both at the surf