Resuscitation Strategies for Burn Injuries Sustained in Austere Environments to Improve Renal Perfusion and Function

Background: While large total body surface area (TBSA) burns are becoming increasingly survivable, they are often associated with adverse effects such as systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction (MOD), which may be a consequence of reduced plasma volume associated with burns. MOD is a significant cause of morbidity and mortality in both civilian and military populations, attributing to 65% of burn mortality. For example, acute kidney injury (AKI) affects over 30% of all combat casualties (>50% in burned patients) and occurs early post-injury. Moreover, the recent military shift to prolonged field care scenarios precludes definitive clinical care with unknown consequences. Ultimately, the period of ischemia/hypoxia will be extended, exacerbating burn-related complications. Clearly, there is a need to develop a comprehensive burn resuscitation strategy in prolonged pre-hospital environments for maintaining tissue viability. Resuscitation has been described as the single most important early intervention in burn management and is vital for restoring end-organ (e.g., kidney) perfusion. The proposed research directly addresses Fiscal Year 2015 Military Burn Injury Research Program Burn Injuries Topic Area 4a by utilizing an animal burn model with minimal intervention to identify an effective and minimal resuscitation strategy.Hypothesis: Our overall hypothesis is that oral or intravenous resuscitation results in distinct improvements in burn-induced SIRS, MOD, and AKI. Specifically, while oral resuscitation (i.e., drinking) helps in reducing SIRS, MOD, and AKI post-burn injury, we predict it will not be as effective as i.v. fluid resuscitation, the volumes of which may be reduced when using fresh frozen plasma (FFP) compared to lactated Ringer's.Specific Aims:Aim 1: Compare a standard dose of oral resuscitation solution (ORS) with a lower dose, and fluid deprivation to determine 2-day survival, inflammatory responses, and renal function.Objective 1a: Identify the effect of oral resuscitation on renal perfusion and AKI.Objective 1b: Identify the effect of oral resuscitation on systemic and local inflammation.Aim 2: Compare limited-volume i.v. resuscitation using different fluids with the clinical standard of care for ensuing effects on SIRS, MOD, and AKI.Objective 2a: Identify changes in renal perfusion and function after i.v. resuscitation with the modified Brooke Formula versus a limited resuscitation volume paradigm.Objective 2b: Identify the effects of a limited volume of two different colloids: 5% albumin and FFP on SIRS and MOD.Study Design: The study design involves different resuscitation paradigms in the acute time frame (2 days) after an extensive 35% TBSA full thickness contact burn in swine. A negative control (no i.v. or fluid access) and a positive control (i.v. resuscitation via the modified Brooke formula) will be compared with resuscitation strategies that are feasible in prolonged field care scenarios. These groups include varying volumes of oral fluid intake with the World Health Organization's oral rehydration solution, and limited volume i.v. resuscitation with lactated Ringer's LR, fresh frozen plasma and LR + 5% albumin. Outcomes will be multidisciplinary with specific emphasis on systemic inflammation and kidney perfusion, function, and structure. Military Benefit: Without the benefits of clinical standard of care therapy (e.g., intubation, urine output monitoring), Service members burned in prolonged field care scenarios face unknown outcomes. The hypothesis tested herein will explore resuscitation methods for maintaining end organ perfusion in austere environments. Whether oral solutions or limited i.v. fluids provide the best treatment strategy in role 1 or 2 settings, data from this proposal will ultimately influence clinical practice guidelines in prolonged field care and mass casualty situations to improve survival from extensive burns and reduce the possibility of AKI. This research program has the potential to be a platform for testing other strategies (e.g., FDP) in the future.