Abstract
BACKGROUND: Severe burns continue to be associated with significant morbidity and mortality despite advances in resuscitation techniques. Concomitant injury, such as traumatic brain injury, adds complexity to resuscitation paradigms as high-volume fluid resuscitation together with high losses of plasma proteins may lead to poor outcomes with respect to traumatic brain injury and associated cerebral edema. Currently, "goal-directed" methods of resuscitation are utilized in which clinical end points guide fluid volume needs. Unfortunately, clinical changes often indicate that significant organ dysfunction has already occurred. In this targeted metabolomics study, we compare "aggressive" versus "restrictive" fluid resuscitation strategies to identify compounds indicative of injury progression. METHODS: A porcine model of combined brain injury and severe burns was utilized. Injured animals were randomized to receive either "aggressive" fluid resuscitation using the Parkland formula or "restrictive" resuscitation with the modified Brooke formula. Resuscitation was continued for 8 hours. Plasma and urine samples were collected for targeted analysis of oxylipins and steroids by ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: Sixty-nine serum and urinary oxylipins were identified. Significant elevations of 15 urinary oxylipins were noted in animals that received the restrictive resuscitation strategy. No significant differences in plasma oxylipins were found. Twenty-eight serum steroids and 29 urinary steroids were isolated. The concentrations of three serum steroids were significantly higher in the "restricted" resuscitation group. No differences in urinary steroids were identified. CONCLUSIONS: In this study, targeted metabolomics was used to identify plasma and urinary oxylipins and steroids in both the restrictive and aggressive resuscitation groups. Notably, significant elevations in 15 urinary oxylipins and three serum steroids were identified only in animals that were randomized to "restricted" resuscitation. These findings demonstrate detectable differences in lipid metabolites within 8 hours of severe injury, which may correlate with differences in inflammation and facilitate goal-directed resuscitation.