TECHNOLOGY AREA(S): Biomedical OBJECTIVE: Develop and refine filtration technologies that bind serum potassium in the context of hyperkalemia induced by traumatic injury and acute kidney injury. DESCRIPTION: Hyperkalemia has been a recognized complication of combat injury since World War II, when severe renal dysfunction was associated with a mortality rate of 90%.1 In the Korean War, hyperkalemia was a leading cause of death in patients with post-traumatic acute kidney injury (AKI), until the use of renal replacement therapy (RRT) improved mortality to 53%.2,3 Renal replacement therapy remains the standard of care for the treatment of hyperkalemia that does not respond to medical management. Rapid evacuation out of Iraq and Afghanistan ensured that most hyperkalemia occurred further up the evacuation chain (Role IV to Role V). However, the occasional need for RRT in theater led to the deployment of the NxStage System One (NxStage Medical, Lawrence, MA) to Craig Joint Theater Hospital, Bagram Airfield, Afghanistan.4 In future theaters of operation, the military research community should prepare for prolonged field care and extended evacuation times.5 One implication of this delay is that complications of combat injury, including hyperkalemia, will be more common in the forward deployed setting. During the Korean War, approximately one-third of combat casualties with oliguric renal dysfunction had a potassium greater than 7mEq/L within four days of injury.3 Rapid evacuation times less than four days from Iraq and Afghanistan as well as fixed facilities with RRT capability negated the need for field care of hyperkalemia, however the future battlefield may not have these robust capabilities. Hyperkalemia will continue to be a concern in the treatment of combat casualties. Future armed conflict and humanitarian crisis interventions may involve large numbers of patients with AKI or with prolonged extraction times. Similar to other stabilizing interventions such as damage control resuscitation, the development of Bridge Dialysis for damage control of hyperkalemia may impact the survival of patients with post-traumatic AKI. This technology would require a minimal resource footprint, portability, and simplicity of use. While this is intended for use in the forward deployed setting, it could also be used in large scale humanitarian disasters. For example earthquakes, which result in building collapses with resultant crush injury that can be complicated by AKI and hyperkalemia. Another example would be for the treatment of hyperkalemia in hemodialysis patient after large scale floods or storms, such as Hurricane Katrina. Under normal circumstances traditional renal replacement therapies are more than adequate for the treatment of hyperkalemia. However, in these rare settings, the need can outstrip capacity. Because this occurs in less than 200,000 patients per year, the FDA Orphan Products Program can be utilized. Using this mechanism will greatly simplify the approvals process for the end product of this SBIR. Preliminary requirements for filtration media and delivery system: Long duration: Be able to decrease potassium to a safe range (i.e. <6meq/L) and maintain it at that level for up to 6 hours Pump systems: If a pump system is used, it should be light-weight (<5 pounds), have a minimal footprint (<1 square foot) and be able to operate with battery power (for at least 6 hours) Filtration media should be minimally bioactive (i.e. not cause inflammation or be likely to clot) Filtration media should have multiple methods of delivery (e.g. extracorporeal blood purification and intra-peritoneal dialysis methods) PHASE I: Identify ideal filtration or binding compound for efficacious K+ removal over 6 hours without adverse reactions with whole blood (in vitro or ex vivo, ex. Platelet aggregation, filtration of calcium etc.). Product should be compatible with intra-peritoneal dialysis technology including but not limited to the following form factors: 1) intra-abdominal mesh packing, 2) extracorporeal filtration canister, 3) wound vacuum systems for temporary closure of the abdomen. Phase I should result in prototype products appropriate for testing in large animal translational models of hyperkalemia. PHASE II: Demonstrate efficacy of filtration or binding media in animal models of trauma or ischemia-reperfusion induced hyperkalemia. Identify, design and test delivery mechanism for application of filtration or binding media ideal for use in austere environments (logistically limited/remote).Product should meet requirements of Phase I funding. Product(s) will be small in cube and weight while remaining efficacious for primary indication and shelf stable at extremes of temperature (ex. desert or arctic tundra). End-users for product would include but not be limited to the following: 1) United States Department of Defense Acute Care Providers, 2) Special Operations Forces Acute Care Providers, 3) Multi-disciplinary providers of Austere Medicine or Prolonged Field care that are not necessarily trained or certified in the provision of acute care. The end state of Phase II is a prototype that can enter the FDA approval process. PHASE III DUAL USE APPLICATIONS: The filtration technology can be applied in an austere environment with minimal clinical footprint and support (ex. Role II/II+ facilities in a combat theater, Role III facilities) or in a civilian treatment facility for the treatment of hyperkalemia in end stage renal disease patients. The technology can be applied by two methods of delivery in a manner approved for use by the Food and Drug Administration. Phase III should include the generation of an IDE filing for each technological application as well as appropriate clinical trials to garner FDA approval for the technology. As noted above, the Orphan Products Program can be utilized for approvals. Phase III endpoints will serve customers described in Phase II. The end state of Phase III is an approved, deployable product for the treatment of hyperkalemia in the austere combat environment. REFERENCES: Beecher HK BC, Shapiro SL, Simeone FA, Smith LD, Sullivan ER, Mallory TB. The physiologic effects of wounds. Office of the Surgeon General, Department of the Army 1952.http://history.amedd.army.mil/booksdocs/wwii/PhysiologicEffetsofWounds/default.htm Smith LH, Jr., Post RS, Teschan PE, et al. Post-traumatic renal insufficiency in military casualties. II. Management, use of an artificial kidney, prognosis. Am J Med 1955;18:187-198. Teschan PE. Acute renal failure during the Korean War. Ren Fail 1992;14:237-239. Neff LP, Cannon JW, Stewart IJ, et al. Extracorporeal organ support following trauma: the dawn of a new era in combat casualty critical care. J Trauma Acute Care Surg 2013;75:S120-128; discussion S128-129 Rasmussen TE BD, Doll BA, Caravalho J In the Golden Hour. Army AL&T Magazine 2015;January-March:80-85. http://asc.army.mil/web/access-st-in-the-golden-hour/ KEYWORDS: hyperkalemia, trauma, acute kidney injury, dialysis TPOC-1: James Suttles Phone: 618-229-6791 Email: james.suttles.1@us.af.mil
