Antibiotic Concentrations After Massive Transfusion (ACME) Study
Abstract
Objectives/Rationale: Combat trauma, as well as civilian trauma, frequently results in open wounds that are at risk for infection. Data from the Department of Defense Trauma Registry demonstrate that 74% of combat trauma have an open wound. As such, the Committee on Tactical Combat Casualty Care, the Prolonged Field Care Working Group, and the Joint Trauma System Clinical practice guidelines recommend wound prophylaxis for open wounds after trauma. The civilian setting has similar risks of open wound infection. In parallel, current practice guidelines recommend the use of aggressive, balanced blood products during resuscitation. It remains unclear how the replacement of blood through hemorrhage and transfusion may affect the antibiotic concentrations for wound prophylaxis. Data modeling is needed to better understand this relationship to enhance wound prophylaxis dosing in severely wound casualties. We will (1) obtain drug concentrations at regular intervals during the first 12 hours after administration; (2) determine how much blood products and fluids are transfused during the first 12 hours after administration, and (3) perform data modeling to understand the relationship between blood transfusions and drug concentrations to inform data-driven dosing models. Focus Area: Our proposed effort will address two focus areas: (1) Managing hemorrhagic shock/super-massive transfusion, traumatic limb ischemia (secondary to vascular disruption or tourniquet use), complex soft tissue injury/blast injury, open fracture, and/or frost bite, including evaluation of antimicrobial dosing and tissue penetration studies and (2) Expanding the understanding of antibiotic use in tissue injury (e.g., systematic versus topical), especially in the setting of hemorrhage/resuscitation, blast, and/or delayed evacuation times. Potential Research Applications/Benefits/Risks: This proposed effort will have primary application primarily in the setting of trauma. We are focusing on wound prophylaxis with antibiotics with hemorrhagic blood and replacement via transfusion. Outside of trauma, this may have other applications. There are other medical indications for wound prophylaxis in the setting of blood loss/transfusion such as massive gastrointestinal bleeding, intra-operative blood loss during procedures such as coronary artery bypass grafting, etc. These other potential areas of medicine highlight the strong need for such data. Our study is minimal risk and only involves small volume blood draws. We will use approved computer systems for data capture and only de-identified data will be shared outside of the originating organization. Projected Timeline: We are anticipating this project will take us 3 years. We will plan a 9-month setup time to include regulatory approvals, required agreements, and hiring of personnel. We will enroll for 14 months which is necessary to get adequate capture of patients undergoing massive and supermassive transfusions. We will then have a 6-month analysis time including time to develop our liquid chromatography/mass spectroscopy methods for drug levels and statistical data modeling. Benefit to Military/Public: Our proposed study will have direct impact to both the military and the civilian setting. Both military and civilian trauma can result in open wounds with devitalized tissue that is at risk for infection. Similarly, both military and civilian trauma systems now aggressively use blood products for resuscitation after hemorrhage. Data to drive dosing of antibiotic wound prophylaxis during resuscitation will directly impact both the military and civilian trauma practices. Our proposal can be quickly translated into a knowledge product for the end-user by way of dissemination into the scientific literature followed by inclusion into clinical practice guidelines.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252311074
Entities
People
- Julie Rizzo
Organizations
- United States Army