EVALUATION OF HYPOTENSIVE RESUSCITATION IN PROLONGED FIELD CARE: HOW LONG IS PERMISSIVE HYPOTENSION REALLY PERMISSIBLE?

Background: Traumatic injuries with hemorrhage are the leading cause of potentially survivable death in both the military and civilian sector. Implementation of hypotensive resuscitative within the 'golden hour' improved casualty survival in recent conflicts. Future conflicts are likely to occur in resource-constrained environments, not conducive to the 'golden hour,' that will necessitate prolonged field care (PFC) for durations up to 72 hours. However, a key question remaining to be addressed is how long past the 'golden hour' is permissively hypotensive resuscitation really permissible to allow for optimal outcomes? Thus, it is requisite to develop an understanding and appreciation of the clinical implications and limitations of PFC prolonged hypotensive resuscitation. In pursuit of answering this question, it is imperative to identify the physiologic parameter(s) that are most ideal for determination of patient status and guiding resuscitation.Objective/Hypothesis: The overall objectives of the proposed study are: (1) define the limitations of hypotensive resuscitation in the setting of PFC; (2) characterize the pathophysiology of prolonged hypotension or hypotensive resuscitation; and (3) improve understanding of physiologic parameters requiring monitoring and intervention in order to reduce morbidity and mortality during PFC. The central hypothesis of the proposed study is that a comprehensive evaluation of the physiology of hypotensive resuscitation for PFC in a swine model of hemorrhagic shock will improve understanding and help define the limits of current standard of care resuscitation for PFC in combat casualties.Specific Aims: Aim 1: Evaluate the effects of prolonged hypotensive resuscitation during PFC setting following severe hemorrhagic shock. Aim 2: Identify physiologic parameters requiring monitoring to optimize outcomes in PFC.Study Design: The proposed study will determine the survival of PFC permissively hypotensive resuscitation with subsequent full resuscitation. Additionally, this study will comprehensively evaluate both systemic and cerebral hemodynamics and oxygenation using multiple advanced physiologic monitoring modalities. Briefly, a total of 38 male swine will be exposed to hemorrhagic shock (mean arterial pressure between 30-35 mmHg) for 45 minutes. Prior to experimentation, animals will be randomized to one of three groups: (1) Hextend; n=12; (2) non-shocked/hypotensive shams; n=12; or (3) anesthesia/surgical shams; n=5. The non-shocked/hypotensive shams (Group 2) will not be exposed to hemorrhagic shock; however, at a time point consistent with end of shock, the animals will be exposed to hypotensive pressures for the PFC duration. PFC will continue for 24 hours followed by a 2-hour hospital, full resuscitation, phase, and subsequent survival. Primary outcomes include overall survival and time to survival and resuscitation fluid volume requirements. Secondary outcomes include effects on cardiovascular function, metabolism, neurologic function, and end-organ protection.Impact: This study is directly in line with multiple focus areas and specific efforts specified in the Prolonged Field Care Research Award. By determining the duration of hypotensive resuscitation that is truly permissible with optimal outcomes following definitive care and full resuscitation, we are addressing Focus Area 1, with the specific goal of characterizing and mitigating the pathophysiology of prolonged hypotension or hypotensive resuscitation. Additionally, by incorporating multiple advanced physiologic monitoring modalities, we are addressing Focus Area 2, with the specific goal of improve understanding of physiologic parameters requiring monitoring and intervention in order to reduce morbidity and mortality during PFC. If successful, this study will highlight the implications of current standard of care treatment in the PFC setting and led to more improved clinical practice guidelines by defining the limitations of currently implemented hypotensive resuscitative strategies and providing a more detailed understanding of the physiologic derangements that require prompt attention to optimize outcomes following definitive care and full resuscitation.