Proactive Targeted Coagulation Management During Trauma and Acute Respiratory Distress Syndrome
Abstract
This proposal addresses the FY21 PRMRP topic area of Acute Lung Injury (ALI) and the following Areas of Encouragement: (1) Development/testing of innovative treatments to prevent/delay progression of acute respiratory distress syndrome (ARDS); (2) research on etiology and prevention of ARDS caused by host responses to trauma, mechanical ventilation, hemorrhagic shock, and transfusion; (3) strategies to stabilize/support transport of patients with ARDS to optimize therapeutic interventions, particularly in operational scenarios requiring prolonged/extended care prior to definitive care. Project Overview: ALI and ARDS affect hundreds of thousands of civilians annually and occur in nearly one-third of military casualties injured in combat. Currently, the leading intervention to support patients with lung failure is mechanical ventilation. Mechanical ventilators are breathing machines that use positive pressure to push air or oxygen into the lungs and to control the rate and size of breaths delivered. In patients with severe lung injury, however, high mechanical ventilator settings are needed to adequately provide oxygen to support the patient. Introducing high pressure into the lungs can damage the already injured lung tissue, causing the patient’s condition to worsen. Additionally, during combat field care, there may be a limited number of ventilators available and few clinical providers that know how to safely use them. An alternative therapy for lung support is called extracorporeal life support (ECLS). During ECLS, de-oxygenated blood is removed from a major vein and pumped through plastic tubing to an artificial lung called a membrane oxygenator. In the membrane oxygenator, oxygen is added to the blood and carbon dioxide is removed, just as occurs in the healthy lung. The oxygenated blood is then pumped back to the patient. This therapy provides oxygenation and carbon dioxide removal outside of the native lung, allowing the lungs to recover and avoid damage caused by high pressure mechanical ventilation. A complication during ECLS, however, is the formation of blood clots inside the devices when the patient’s blood contacts the foreign plastic materials the devices are made of. To prevent clotting, clinicians administer anti-clotting drugs to the patient during ECLS therapy; however, it is extremely challenging to administer adequate doses of these drugs to prevent clotting without causing the patient to have bleeding side effects – including internal bleeding and bleeding at surgical sites. This challenge is escalated in trauma patients and combat casualties, as they often have injury-related bleeding complications that would prevent clinicians from giving them anticoagulant drugs – and therefore prevent them from using ECLS. Trauma patients also receive lots of fluids, have a low blood pH, and in the field may have low body temperature – all environmental conditions that make them prone to bleeding. Currently, the guidelines for monitoring bleeding and clotting in patients receiving ECLS are very general, with no special modifications for trauma patients whose bleeding/clotting function is compromised due to their injuries. In this proposed study, we will perform the first evaluation of specific regulators of bleeding and clotting in the blood that are known to be altered or disturbed after trauma injury to see how these regulators are affected specifically during ECLS after combat-relevant trauma injury. This will be done by analyzing stored blood plasma samples collected from ongoing large animal studies exploring the use of ECLS devices in healthy subjects versus trauma subjects, as well as investigating disease progression in trauma subjects treated with and without ECLS. Central Research Objective: Identify key blood markers that explain underlying causes of bleeding and clotting after combat-relevant trauma treated with ECLS, to develop targeted clotting/bleeding monitoring strategies during ECLS specifica
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210028
Entities
People
- Teryn R. Roberts
Organizations
- Geneva Foundation
- United States Army