Page 70 - JSOM Fall 2025

2. Determine the total volume of blood products (and fluids TABLE 1 Inclusion and Exclusion Criteria
as covariates) transfused during the first 24 hours after an- Inclusion criteria Exclusion criteria
tibiotic administration. • Trauma patient • Received listed antibiotic(s)
3. Conduct data modeling to explore the correlation between • Hospitalized or anticipated within the past 5 half-lives of
blood transfusions and plasma drug concentrations to in- hospital admission the drug
form data-driven dosing models. • Received any dosage of the • <18 years of age
following antibiotic(s): • Pregnant
– Ampicillin/sulbactam • Incarcerated
Methods – Cefazolin
– Cefepime
We are conducting a prospective observational study at two – Ceftriaxone
major trauma centers. We will conduct regularly scheduled – Clindamycin
blood draws to assess the pharmacokinetics of antibiotic con- – Ertapenem
– Levofloxacin
centration after transfusions and compare those to controls. – Metronidazole
Additionally, we will collect routine clinical care data, includ- – Piperacillin/tazobactam
ing interventions, concomitant medications, and outcomes.
Blood Sampling and Storage
Setting After the antibiotic infusion, blood samples (approximately
We will enroll patients at two level 1 trauma centers: Brooke 1mL) will be collected at six time intervals using standard clin-
Army Medical Center (BAMC) and the University of Colo- ical sample tubes with anticoagulants. The first draw will be
rado Hospital (UCH). BAMC is the Department of Defense’s collected immediately post-infusion, followed by additional
(DoD) only level 1 trauma center and the largest Military draws at 30 minutes, 60 minutes, 2 hours, and 4 hours. The
Treatment Facility in the DoD, with nearly 90,000 emergency final draw will be collected between 12 and 18 hours post-in-
department (ED) visits annually. The UCH cares for more fusion. Given the unpredictable nature of trauma care, the first
42
than 1,800 trauma cases and is the seventh busiest emergency three draws will be allotted a 15-minute draw window, and the
department in the country, treating over 110,000 patients an- final three draws a one-hour draw window. The samples will
nually. Both trauma centers frequently use blood products for be stored on ice or in a 4°C refrigerator until centrifugation.
resuscitation, including the use of whole blood. Together, The samples will be centrifuged as soon as feasible, after which
43
these centers provide a unique opportunity to analyze antibi- the plasma will be removed and frozen at –80°C until further
otic administration and blood product use in diverse patient analysis. Specimens from both sites will be processed at the
populations. United States Army Institute of Surgical Research (USAISR)
using a standardized method for storage.
Ethics and Data Safety Monitoring
Our study has been approved by the Colorado Multiple In- Data Acquisition
stitutional Review Board (COMIRB #23-2559), which serves Sites will manually collect data from their electronic health re-
as the single IRB for this study. BAMC will conduct the study cord system and local trauma registry. Captured data will then
under an institutional agreement for IRB reliance. Our study be de-identified and managed using Research Electronic Data
meets the federal definition and ethical standards for a waiver Capture (REDCap), a secure, encrypted, HIPAA-compliant
of informed consent, as it involves no more than minimal server designed for research data management. Additionally,
risk to subjects, particularly those for whom their condition quality assurance will be assessed by trained project managers
prohibits the ability to obtain consent safely. We will obtain at each site prior to analysis.
consent for all potential subjects only when the primary clin-
ical team determines that obtaining consent will not hinder Statistical Analysis
their care. We anticipate some participants may not be able to This study will primarily use both descriptive and inferential
consent for themselves due to the nature of their injuries. Par- statistical models to analyze the plasma antibiotic concen-
ticipants enrolled under a waiver of informed consent will re- trations in relation to blood transfusion status. Our primary
ceive a patient information sheet regarding their participation analysis will assess the differences in plasma antibiotic con-
in this study after the fact. All participants will have the right centrations between participants who do and do not receive
to refuse to participate in this study. Our study has received blood transfusions using a general linear model (repeated mea-
second-level approval from the Defense Health Agency Office sures analysis of variance (ANOVA)). Blood transfusion status
of Human Research Oversight (memo E05020.1a). will be treated as a between-subjects effect, and time post-
infusion will serve as a within-subjects effect. We will compute
Study Procedures and report pairwise differences between the transfusion and
Participants for enrollment in this study will be identified us- non-transfusion groups at each time point, making necessary
ing site-specific trauma alert and activation protocols, along corrections for multiple comparisons.
with consultations with the trauma care teams. We will en-
roll participants who are hospitalized or anticipate hospital Our secondary analysis will construct a similar model to
admission for acute trauma and receive an antibiotic from compare the plasma antibiotic concentrations among partic-
our predetermined list (Table 1). Site research staff will iden- ipants who received blood transfusions based on the volumes
tify the participants who meet the inclusion criteria (Table 2). of blood administered (e.g., massive transfusion, low volume,
Study team members will collect samples at six designated etc.). We will adjust our model to account for fluctuations in
time intervals after antibiotic administration, striving to com- acute changes in kidney function during treatment and include
plete draws within their designated goal times. Study per- relevant covariates such as the timing of blood transfusion.
sonnel will extract additional relevant data from the medical We will obtain orthogonal polynomial contrasts to examine
records (Table 2). concentration trends over time, calculate and report pairwise

68 | JSOM Volume 25, Edition 3 / Fall 2025