If a Soldier or patient is burned on a large portion of his/her body, there can be serious side effects beyond those immediately apparent on the skin. The body's immune system starts to become very active causing inflammation, which elevates body temperature and heart rate. This inflammation can disrupt the function of several organs (e.g., heart, liver, lungs, and kidney), even though these organs were not injured directly. If organ dysfunction is severe (such as when it is left untreated), the results can be lethal.
Another reason for this organ failure after burn injury is that blood flow to these organs is compromised. This is especially true in the case of the kidneys, which receive 25% of cardiac output under normal circumstances and are therefore among the first organs that experience reduced blood flow in a 'burn shock' state. Acute kidney injury occurs in many burn patients and sometimes can progress to chronic kidney disease. To improve the delivery of fluids (perfusion) to organs, it has become common practice to resuscitate patients by injecting fluids into the blood stream. The recommended amount of fluids given is based off of the urine output of the patient, and this practice has greatly enhanced the treatment and survival of burned patients.
However, this treatment strategy assumes access to equipment needed for inserting an intravenous line and monitoring urine output, which may not be possible in remote environments. The back-up plan for calculating the amount of i.v. fluids needed is called the modified Brooke formula, which estimates that about 5 liters of fluid would be needed per day for an average, 70 kg-sized individual. This requires lots of fluids, which are very heavy. An alternate strategy that is feasible in these situations could be life-saving. For example, oral resuscitation (in other words, drinking) with a solution that can be prepared on site may be sufficient for restoring kidney perfusion. Also, using different resuscitation fluids may reduce the total volume of liquid needed. These possibilities will be examined in the current proposal.
The studies described in this proposal will use a previously established pig model of burn-induced inflammation and ensuing kidney injury. Pigs are considered the best model for burn research due to similarities in skin healing and structure. After burn injury, we are not going to treat the animal as if it were in the hospital, but rather in the remote environment. Thus, the Military Burn Research Program topic area 4a requesting the use of an animal model to determine the clinical impact of delayed definitive resuscitation will be addressed. The proposed research will impact the topic area by identifying the minimum amount and type of fluids needed to restore kidney function and perfusion following a major burn injury. The timeline for implementation of changes in care is minimal due to the unique juxtaposition of the U.S. Army Institute of Surgical Research laboratory environment and the burn center at Fort Sam Houston, Texas. With minimal clinical risk, the potential benefits for the burned Warfighter are enormous.
Importantly, while the results may shape clinical practice guidelines in the short term, the ultimate value of this research extends further than the current proposal. Life-saving techniques and technologies can be examined moving forward in this model. For example, if fresh frozen plasma proves to be optimal for reversing burn related inflammation and kidney injury, we may then explore the recommendation of freeze-dried plasma to further reduce weight of fluid needed, and maximize benefit. Another example would be to leverage the data concerning the systemic vs. local inflammatory response, which may identify novel biomarkers or targets for eventual pharmacological intervention. The proposed research will not just impact military casualties facing prolonged field care, but also address mass casualty situations in civilian disasters, where definitive clinical care can be delayed. The goal of increased survivability and decreased inflammation and complications can greatly improve the quality of life for Service members and their families.
|Effective start/end date||30/09/16 → 29/09/18|
- Congressionally Directed Medical Research Programs: $749,992.00