PRECISION METRICS FOR DRIVING OPEN- AND CLOSED-LOOP RESUSCITATION ALGORITHMS FOR ENTERAL AND IV RESUSCITATION IN BURN CASUALTIES

Background: Currently, resuscitation of burn casualties is guided by either the Brooke or Parkland formulas using intravenous (IV) lactated ringers’ (LR). While neither of these incorporate patient responses in a significant way, current practice then titrates the fluid rate to maintain a desired urine output (UO), with consideration of other endpoints (e.g., base deficit, lactate, creatinine). However, it has been argued that urine output is a poor target for resuscitation, and other drivers should be considered. Traditional hemodynamic parameters have been studied to limited success; however, more functional hemodynamic measurements (currently ignored in resuscitation evaluation) offer hope of predicting patient response to fluid. Specifically, pulse pressure variation (PPV), systolic pressure variation (SPV), and stroke volume variability (SVV) are easily obtained from the aortic waveform and could help establish adequate limits of burn resuscitation.Moreover, as burn resuscitation practices often deliver too much fluid (thus resulting in significant comorbidities), an alternative strategy involving enteral fluid resuscitation could reduce the volumes of IV fluids needed. Indeed, this has previously been shown, but there is a paucity of information regarding fluid type, volumes, and efficacy. A recent randomized controlled trial continues to advocate for oral rehydration post-burn, but this strategy has largely been forgotten by current practice. In short, the need exists for a new personalized approach that incorporates new targets and endpoints for identifying which patients respond to resuscitation (both IV and enteral) versus those that do not. A decision support system based on burn surface area and UO was developed at U.S. Army Institute of Surgical Research and has become commercially available. Parameters identified in this proposal could easily be incorporated into existing decision support system algorithms for identifying which patents respond to both enteral and IV fluids.Hypothesis: We hypothesize that novel indicators of fluid responsiveness will determine how a given burn patient will respond to fluids. Augmenting current clinical practice (UO) with traditional and novel hemodynamic variables will drive resuscitation algorithms for both oral and IV fluid delivery.Specific Aim 1: Examine temporal changes in dynamic waveform measurements (e.g., PPV, SPV, SVV) and their relationships with organ (dys)function after thermal injury using a 40% TBSA pig burn model.Objective 1a: Identify the effect of burn injury and standard of care (IV fluids) on dynamic waveforms.Objective 1b: Define the relationship between dynamic waveforms and MOD/AKI.Specific Aim 2: Use varying levels of enteral and IV fluids to alter organ perfusion in a 40% TBSA pig burn model to examine ensuing differences in PPV, SPV, SVV.Objective 2a: Determine if varying levels of IV fluids increase dynamic waveform variability.Objective 2a: Identify the efficacy of oral fluids in maintaining PPV, SVV, and SPV.Specific Aim 3: Compare traditional resuscitation decision support algorithms (i.e., UO) to new algorithms containing waveform data (e.g., UO+PPV) for the ability to prevent organ damage and maintain organ perfusion in the 40% TBSA porcine burn model.Study Design: The study design involves examining the effect of oral and IV fluids on dynamic waveforms (i.e., SPV, PPV, SVV) after 40% TBSA full thickness contact burn in swine that results in organ dysfunction. This level of burn injury requires diligent management from a resuscitation standpoint and has been postulated to be treatable with oral fluids. Implantation of a high-acuity telemetric device will read blood pressure and ECG in real time throughout the duration of the experiment. The initial selection of 2 days and 7 days represents a time frame that spans the “ebb” and “flow” phases of the response to burn injury. The final phase will be able to directly compare UO alone to UO plus identified variables.Impact: Through this proposal, we will incorporate new knowledge with existing materiel to leverage novel precision metrics for optimizing fluid delivery. The functional hemodynamic variables measured herein represent a dataset that is currently underutilized even though there has been promise in other patient populations. Moreover, the use of oral fluids represents a promising therapeutic strategy that is grossly understudied and may prove vital in austere environments. Therefore, both the burn surgeon and the medic benefit from the information gained in this proposal. As such, this proposal directly addresses Focus Area 4 because both medical and non-medical care providers will be enriched with further knowledge in administering individualized burn injury care. This patient-centered technology is poised to help maintain homeostasis via closed-loop throughout the continuum of care.