BEFAST (Bubble-Enhanced FAST) for the Evaluation of Solid Organ Injury in Hemodynamically Stable Blunt Abdominal Trauma
Phase: PHASE4
Conditions: Abdominal Trauma
Sponsor: Emory University

Study Protocol 
 
TITLE: BEFAST (Bubble-Enhanced FAST) for the Evaluation of Solid 
Organ Injury in Hemodynamically Stable Blunt Abdominal Trauma 
 
NCT NUMBER: NCT05025449 
 
Protocol Date: December 21, 2021 

Title Page
Full Study Title: BEFAST (Bubble-Enhanced FAST) for the Evaluation of Solid Organ 
Injury in Hemodynamically Stable Blunt Abdominal Trauma
Short Study Title: BEFAST
Laura Oh, MD, Department of Emergency Medicine
Sponsor: Department of Defense; Sponsor # 00003566, EPEX # 0000063966
Protocol Version 7.0; 12/21/21

2. External Collaborators: n/a
3. Precis/Abstract
Title: BEFAST: Bubble-Enhanced FAST for the Evaluation of Solid Organ Injury in 
Patients with Hemodynamically Stable Blunt Abdominal Trauma 
Rationale: The Focused Assessment with Sonography for Trauma (FAST) exam is 
widely used and accepted as part of ATLS protocol, but its low sensitivity for identifying 
solid organ injury in the absence of hemoperitoneum is a significant limitation. Contrast-
enhanced ultrasound (CEUS) has the potential to significantly enhance the evaluation of 
the trauma patient with acute intra-abdominal injury through the use of intravascular 
microbubbles that allow direct visualization of lacerations to solid organs. European 
studies have demonstrated that ultrasound contrast markedly improves the sensitivity of 
ultrasound in detecting solid organ injury, when the exam is performed in the radiology 
suite. CEUS, however, has never been validated in the US in the hands of emergency 
medicine providers. 
Research Hypothesis: We hypothesize that the bubble-enhanced or BEFAST exam will 
be more sensitive than traditional FAST for identification of solid organ injury in 
hemodynamically stable blunt abdominal trauma patients when performed by emergency 
providers. 
Specific Aims: 
Objective 1: To determine if contrast-enhanced, i.e. bubble-enhanced FAST (BEFAST) 
outperforms non-enhanced FAST in the evaluation of solid organ injury in 
hemodynamically stable blunt abdominal trauma patients when performed by frontline 
providers using CT as gold-standard. 
Objective 2: To determine whether emergency physicians can incorporate BEFAST 
evaluation at the point-of-care in a trauma evaluation of a hemodynamically stable adult 
blunt abdominal trauma patient. 
Objective 3: To determine the inter-rater reliability between bedside emergency 
physicians and radiologists for identifying solid organ injury with BEFAST. 
Significance: A specific concern that the BEFAST exam addresses is the low sensitivity 
of FAST for identification of solid organ injury in the absence of hemoperitoneum. If the 
proposed work is successful we will demonstrate that the BEFAST exam adds critical 
information at the point-of-care by identifying intra-abdominal injury that would be 
missed by the traditional FAST exam. The BEFAST exam may be able to replace the 
FAST exam as a more sensitive screening tool of intra-abdominal injury. In addition, 
while CT remains the gold standard for blunt abdominal trauma, BEFAST has the 
potential to impact the field by providing an alternative imaging strategy to CT in cases 
of medical necessity (renal failure, allergy to contrast dye), patient preference (pediatric 
or pregnant patient), or limited resource (surge/MCI, austere environment, international 
EM).

4. Introduction and Background
Our primary hypothesis is that the bubble-enhanced or BEFAST exam will be more 
sensitive than traditional FAST for identification of solid organ injury in 
hemodynamically stable blunt abdominal trauma patients when performed by emergency 
providers. The purpose of this study is to ascertain whether the BEFAST exam is a more 
sensitive screening tool than traditional FAST exam. BEFAST addresses a major 
limitation of conventional FAST in that it can identify lacerations to solid organs even in 
the absence of hemoperitoneum. Acceptance of the BEFAST exam as an appropriate 
alternative to CT in select situations may positively impact patient care by leading to 
decreased CT utilization and a change to current trauma algorithms.
Blunt abdominal trauma - whether from motor vehicle crash, assault, fall, or recreational 
injury - is a leading cause of morbidity and mortality [1]. According to the 2016 National 
Trauma Database, 12 % of all patients with trauma admissions had abdominal trauma, the 
majority of which is blunt [2]. The diagnosis of intra-abdominal injury due to blunt 
abdominal trauma can be challenging. The physical exam is unreliable in patients with 
altered mental status or with impairment due to drugs or alcohol. Utilization of the FAST 
exam has dramatically improved clinical care by enabling frontline providers to screen 
for injury non-invasively.
While the FAST exam is considered a first line tool in the triage of hemodynamically 
unstable patients with abdominal trauma to CT scanner versus the OR, its inability to 
identify lacerations to the solid organs in the absence of hemoperitoneum limits its utility 
in the hemodynamically stable patient. A 2018 Cochran review noted substantial 
heterogeneity of reported sensitivity of the FAST exam; pooling results from 34 studies it 
estimated FAST sensitivity for abdominal trauma to be 68% and specificity to be 95% 
[3]. Most studies use free fluid as the only criteria for a positive FAST exam. When 
FAST is used to detect solid organ injury it is less sensitive; both McGahan et al and 
Rothlin et al. showed a sensitivity of 41% for the ability of FAST to detect solid organ 
injury [4-6].  In comparison, gold standard CT has a sensitivity of 97-98% and specificity 
of 97-99% for intra-abdominal injury [7]. The use of the BEFAST exam may bridge this 
diagnostic gap between FAST and CT if it can demonstrate improved sensitivity in 
detecting lacerations to liver, kidney, spleen, and pancreas. 
While CT can rapidly and accurately diagnose injury, emergency physicians have raised 
concerns that the use of CT has become overly liberal [8]. Over the last few decades there 
has been a paradigm shift in the management of solid organ trauma with increasingly 
nonoperative management of both low and high-grade injuries in hemodynamically stable 
patients [9-10]. 25% of all CTs are ordered through the ED, but less than 20% of 
abdominal CTs obtained in patients with blunt trauma have intra-abdominal injury, and 
less than 3% require a surgical intervention [7].
The risks of overutilization of CT in hemodynamically stable blunt abdominal trauma 
include increased health care costs, lengthy stays in the emergency department, risks of 
contrast-induced nephropathy and radiation-induced malignancy, and patient anxiety 
when “incidentalomas” are discovered that need extensive and often unnecessary workup 

[11]. And yet, CT usage in trauma patients has increased dramatically by 3.5-fold 
between 1995-2007 [12]. With the yearly rise in ED census and CT utilization, it is 
becoming an increasingly impractical and expensive strategy to “pan-scan” trauma 
patients without further risk stratification. This is especially true when the patient is 
hemodynamically stable and unlikely to need an operative intervention. Strategies for 
minimizing radiation burden of CT include use of clinical decision tools, guidelines for 
appropriate use such as the Image Wisely and Image Gently campaigns, reduced CT 
dosage, and technological innovations such as contrast-enhanced ultrasound [12-14]. 
Contrast-enhanced ultrasound uses microbubble contrast agents consisting of an inert gas 
surrounded by a stabilizing shell. The microbubbles reflect sound waves and enhance the 
ultrasound image. These gas-filled microspheres are about the size of a red blood cell and 
remain in the intravascular space; unlike CT contrast, microbubble contrast agents do not 
leak or diffuse into the tissue [15-6]. Microbubbles metabolize when they break via 
exhalation of the gas, and the shell is metabolized by the liver. The contrast is completely 
eliminated from the body within 10-15 min [17-8].
In 2016, the Food and Drug Administration (FDA) approved Lumason (sulfur 
hexafluoride lipidtype A microsphere) for characterization of focal liver lesions with 
CEUS in both adult and pediatric patients, opening new areas of research in the United 
States [19]. Lumason is a second generation contrast agent that is more stable than 
previous ultrasound contrast agents and does not require refrigeration. Other currently 
approved indications include use in echocardiography and in evaluation of urinary reflux 
in children. Although approved for intravascular and intravesical use, Lumason’s use in 
trauma is off-label and an emerging application in the United States [12].
Previous European literature supports the superiority of CEUS to conventional ultrasound 
for the identification of solid organ injury. In a 2009 multi-center study by Catalano et al. 
of 156 patients, the use of contrast by radiologists improved the sensitivity and specificity 
of renal trauma seen on conventional US from 36% to 69% and from 98% to 99% [12]. 
For liver trauma, ultrasound contrast agents improved the sensitivity and specificity from 
68% to 84% and from 97% to 99% [12]. For splenic trauma, contrast improved the 
sensitivity and specificity from 77% to 93% and from 96% to 99% [12]. CEUS performs 
even better when used only for lowenergy isolated trauma where it has a sensitivity of up 
to 95% [20]. An example of a liver laceration seen on contrast-enhanced ultrasound vs 
conventional FAST is depicted in Figure 1.

Figure 1. Comparison of liver laceration seen with CEUS on left and no contrast on right
CEUS may also be used to grade injury to solid organs using AAST criteria. In a 2014 
study by Lv et al., two radiologists were able to classify contrast-enhanced images into 
mild, moderate, and severe injury with high inter-rater reliability (κ = 0.973) [21]. CEUS 
can also identify active extravasation as a pool of contrast or a jet outside of blood vessels 
[22]. In a 2011 study by Lv, et al., 392 patients with hepatic injury were examined by 
both CEUS and CT; CEUS detected extravasation in 16% of cases and had a similar 
performance to CT with sensitivity of 72% vs 81%. [23]. The presence of active bleeding 
is critical information in the management algorithm of blunt abdominal trauma and 
suggests the need for emergent surgical or interventional radiology consultation and/or 
treatment.
Contrast-enhanced ultrasound (CEUS) has the potential to enhance the diagnostic 
capabilities of point-of-care ultrasound while still offering the traditional advantages of 
ultrasound over other imaging modalities. These advantages include its portability, 
repeatability, lack of ionizing radiation, lack of necessity for labs prior to study, and lack 
of necessity for transport of the patient to the radiology suite. If the BEFAST outperforms 
the FAST exam in identification of intra-abdominal injury, our study would lay the 
groundwork for the argument that just as the FAST exam largely replaced DPL, the use 
of microbubble contrast agents in contrast-enhanced ultrasound is the next evolution in 
trauma triage. We wish to show that the BEFAST is a more advanced trauma screening 
tool. As providers become more comfortable with the BEFAST exam and the use of 
contrast in the trauma bay, CEUS may find an increasing role in decreasing the utilization 
of CT in select scenarios. CEUS may also play a role as a risk-stratification tool for 
disposition decisions to ICU vs floor via grading of injury by AAST criteria. Although 
CT with IV contrast provides the most information in the evaluation of intra-abdominal 
injury, CEUS may play a substantial role in the future in a multi-modal approach to 

trauma. Further investigation is needed to discover the capabilities and limitations of 
CEUS in the hands of emergency providers.
Our study is distinct from previous European literature because the CEUS exam would be 
performed and interpreted by emergency physicians rather than by radiologists. We wish 
to demonstrate the feasibility of this exam outside of the radiology suite because of the 
potential for BEFAST to impact patient care by enabling frontline providers to make real-
time clinical decisions at the bedside.
5. Objectives:
Objective 1: To determine if contrast-enhanced, i.e. bubble-enhanced FAST (BEFAST) 
outperforms non-enhanced FAST in the evaluation of solid organ injury in 
hemodynamically stable blunt abdominal trauma patients when performed by frontline 
providers using CT as gold-standard. 
Objective 2: To determine whether emergency physicians can incorporate BEFAST 
evaluation at the point-of-care in a trauma evaluation of a hemodynamically stable adult 
blunt abdominal trauma patient. 
Objective 3: To determine the inter-rater reliability between bedside emergency 
physicians and radiologists for identifying solid organ injury with BEFAST. 
6. Study Design and Methods:
This single center prospective study will enroll 267 adult patients with hemodynamically 
stable blunt abdominal trauma who present to a Level 1 ACS verified Trauma Center.
Inclusion Criteria: 
Age 18 and older
Clinical suspicion of intra-abdominal injury
Presentation within 24 hours of injury
Planned CT of the abdomen/pelvis within 24 hours
Ability of patient to provide informed consent 
Exclusion Criteria:
Co-existing penetrating abdominal injury
Known hypersensitivity reaction to contrast agent
Pregnant patients
Prisoners
No appropriate IV Line able to be inserted 
Hemodynamic instability at time of enrollment (sustained systolic blood pressure < 90 
mm Hg or sustained HR >120 despite initial resuscitation) 
   

Study Interventions/Procedures:
1) Baseline Grayscale US Exam
2) Contrast Enhanced US exam with IV administration of LUMASON
3) Chart Review for abstraction of clinical and demographic data
Risks/discomforts:
Risks from ultrasound use are minimal – this modality does not use ionizing radiation. 
Most commonly the patient may complain of coldness of gel or minor discomfort from 
pressure of the ultrasound probe. 
The less common risks and discomforts expected in this study are (in 0.02% of patients):
Headache, nausea, dizziness, flushing, back pain, kidney pain, chest pain, shortness of 
breath, hypertension, mild allergic reactions
Rare but possible risks include: hypersensitivity to contrast resulting in low blood 
pressure (0.007% of patients). 
Potential benefits include: identification of injuries with BEFAST not seen with 
conventional FAST
Ultrasound studies will be performed by a team of ultrasound faculty who have 
attended a didactic session on the BEFAST exam and grading of solid organ injury by 
AAST criteria. They will be evaluated with a post-test to check for comprehension.
After consent, a baseline FAST exam will be performed and documented. This 
FAST will be distinct from the initial ATLS resuscitation FAST in order to avoid any 
interference in the trauma evaluation. A 20g or larger intravenous line if not already 
placed, will be established according to standard practice for trauma patients. The 
investigator will use a phased array or curvilinear transducer to record video of their 
baseline FAST exam. The investigator will also note start/stop time of the FAST exam. 
Using the same machine, a BEFAST exam will be performed using a low mechanical 
index setting in contrast-specific imaging mode. Lumason will be injected into the 
patient’s IV for the CEUS exam by either a nurse research coordinator or one of the 
clinical staff.  The contrast will be injected using the straight port of a 3-way stopcock 
and flushed through the side port. To eliminate shear of microbubbles, contrast will not 
be injected through a clave connector. The contrast will be injected once for the right side 
of the body, and once for the left side of the body looking for disruptions in the normal 
enhancement pattern and evidence of active bleeding. If an antecubital line is placed, 2.4 
mL contrast will be given over slow IV push (2-3 seconds) and flushed with 5 ml saline; 
if only a peripheral hand IV is established, the investigator may use a 10 ml saline flush.
To examine the right side of the body: the right kidney and liver will be imaged. The 
investigator will examine the RUQ for evidence of solid organ injury, free fluid, or active 
extravasation by examining the kidney in short and long views and the liver in coronal, 
anterior, and subcostal views. 

The examiner will screen the liver during approximately the first 10-20 seconds after 
IV contrast administration to see hypoperfusion in the arterial phase or extravasation 
before scanning through all organs in the venous phase (kidney, then back to liver).  
The exam will be timed from start of saline flush after contrast and video clips will be 
saved (stored using patient study number).
To examine the left side of the body: the pancreas will be imaged first, followed by 
the kidney and the spleen. The investigator will note evidence of solid organ injury, free 
fluid, or active extravasation in the LUQ. The pancreas, kidney, and spleen will be 
visualized in short and long. The exam will be timed from start of saline flush after 
contrast and video clips will be saved. If adrenal glands are visualized on either side these 
may be recorded as well. 
In general, the investigator will scan one side of body at time but may cross to the 
other side if imaging on one side is complete. Investigators will be allowed to re-dose 
contrast on either or both sides if the first examination is not clear or if there is 
inadequate time to complete the exam. Either right side or left side may be examined 
first. 
The investigator will note the presence or absence of injury to the liver, kidney, 
spleen, or pancreas, as well as the presence or absence of free fluid or active 
extravasation. If an injury to a solid organ is detected, the investigator will grade injury 
per American Association for the Surgery of Trauma (AAST) criteria.  There will be an 
attestation noting whether there was unintended disclosure of either the primary team’s 
FAST exam or CT imaging read prior to bedside interpretation of the BEFAST study. 
The investigator will note whether there were physical exam signs suggestive of injury 
that may have biased their interpretation. The investigator will note start/stop time of 
BEFAST exam.  Exams will be saved to QPATH and to the US machine; the data will 
also be archived on an encrypted USB.  QPATH will be password protected, and the 
USB will be kept in a locked file in a locked office.  The US machine will be kept in a 
locked area.     
     A study is complete if the patient tolerates the study (no severe adverse event to 
contrast, patient allows the provider to complete the scan) and if it results in images of 
adequate quality to answer the focused clinical question. 
     A serious adverse event (SAE) is defined by the FDA as any adverse drug event 
(experience) occurring at any dose that in the opinion of either the investigator or sponsor 
results in any of the following outcomes: 1) death 2) life-threatening adverse drug 
experience 3) inpatient hospitalization or prolongation of existing hospitalization (for > 
24 hours) 4) persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 5) congenital anomaly/birth defect 6) important medical 
event (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered a serious adverse drug experience when, based upon medical 
judgment, it may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition.
For the FAST exam, the focused clinical question is whether there is free fluid in 
the abdomen or fluid in the pericardium.  The following views should be obtained to meet 
minimum requirements: RUQ, LUQ, suprapubic, and subxiphoid views with adequate 
visualization of Morison’s pouch, inferior pole of right kidney/liver tip, area under the 
diaphragm on the LUQ side, pelvic views in transverse and sagittal. If an adequate 

subxiphoid view is not possible, a parasternal long view may be substituted. For the 
BEFAST exam the focused clinical question is if there is solid organ injury to the liver, 
kidney, spleen, or pancreas. For the BEFAST exam the liver, kidney, spleen, and 
pancreas should be examined using a low mechanical index setting in contrast-specific 
imaging mode. 
     In order to determine interrater reliability of the ultrasound exams, the interpretation 
of the point-of-care EM physician (who will attest they are blind to the CT read and the 
ATLS FAST read) will be compared to the interpretations of two board-certified 
radiologists (blinded to the FAST reads and the CT read) for the presence or absence of 
solid organ injury, free fluid, or active extravasation. Injured organs will be graded per 
AAST criteria.  
7. Video clips collected for this study will be saved for future education and training 
purposes, and also used in research presentations at national conferences.
8. N/a: The study does not target a particular community.
9. Participant Selection:
Requested sample size: 267; expected refusal or withdrawal rate – conservatively we 
set at 90%. 
Inclusion Criteria: 
Age 18 and older
Clinical suspicion of intra-abdominal injury (IAI)
Presentation within 24 hours of injury
Planned CT of the abdomen/pelvis within 24 hours
Ability of patient to provide informed consent 
Exclusion Criteria:
Co-existing penetrating abdominal injury
Known hypersensitivity reaction to contrast agent
Pregnant patients
Prisoners
No appropriate IV Line able to be inserted 
Hemodynamic instability at time of enrollment (sustained systolic blood pressure < 90 
mm Hg or sustained HR >120 despite initial resuscitation) 
Justification: 
We did not include pediatric population because FAST sensitivities are different in adult 
and pediatric populations.    
HD stable because unstable patients might go immediately to OR
Clinical suspicion of IAI and presentation within 24 hours because this would be the most 
clinically relevant presentation for an emergency physician using the BEFAST exam which 
is a point-of-care study in the acute presentation of possible IAI.
Planned CT because of the need for confirmatory gold standard study.

Exclusion Criteria:
We excluded penetrating abdominal injury to focus on blunt abdominal injury in isolation.
We excluded patients with known hypersensitivity reaction so that we could avoid SAE.
We excluded pregnant patients and prisoners as vulnerable populations.
We excluded patients without sufficient access because we would not be able to insert 
contrast.
Subject recruitment plan:
Initial contact will be made by the study staff (clinical research coordinator, ASSET team, 
PI, co-investigator) upon presentation of potential subjects (i.e. subjects meeting the 
inclusion criteria) in the emergency room/hospital. Study staff will obtain written informed 
consent.
Screening for eligibility:
In order to effectively screen potential patients for the study, the study personnel will ID 
subjects in the ED as appropriate through conferring with medical records, trauma logs, 
triage notes, radio reports of trauma alerts, and on-duty doctor and nurses to identify 
potential subjects. Many of the inclusion/exclusion criteria can be evaluated by a review of 
the potential subject’s medical records such as: mechanism of injury, time of injury, 
presence or absence of concurrent penetrating trauma. All female patients of childbearing 
age will be offered a serum or urine pregnancy test (standard of care for evaluation of 
female trauma patient with suspected intra-abdominal injury). A patient may exercise their 
autonomy and waive pregnancy testing (due to reasons such as prior hysterectomy, tubal 
ligation) but are still eligible for the study as long as they are informed that Lumason is a 
Category B medication which means that animal studies have failed to demonstrate a risk 
to the fetus and there are no adequate and well-controlled studies in pregnant women.  The 
patient’s refusal of pregnancy test will be documented in the medical record. No 
identifiable data will be collected from subjects during screening.  
Procedures when a subject withdraws from a study:
In the case of withdrawal from study, videos saved up to the point of withdrawal may be 
kept as outlined in the study consent form. Once linkages are destroyed it will not be 
possible to identify an individual’s video clips for destruction.
10. Informed Consent Process
A research team member will consent the patient at Grady Memorial Hospital. 
We are requesting a partial HIPAA waiver to look at identifiable patient information prior 
to consent as part of the screening process in order to see if a patient meets 
inclusion/exclusion criteria. Elements of interest include: name, medical record number, 
age, mechanism of injury, timing of injury, pregnancy status, institutionalization, vital 
signs, allergies.
We are not studying children, prisoners, pregnant women/fetuses, or patients with 
cognitive impairment.  Students and employees are not targeted groups for enrollment.

We will ensure comprehension of the informed consent information by allowing the patient 
ample time to ask questions and have the patient express understanding of the study. The 
study team will explain the purpose, risks, and potential benefits of the study and patient 
will be given the option of continuing participation or stopping.
Study consent discussion will take place in Grady Memorial Hospital.  Study staff (research 
coordinator, ASSET team, PI, or co-I) will conduct the discussion and obtain consent. We 
are not requesting a waiver of signed documentation of informed consent.
In the event that the patient is cognitively capable of consent for the study but has a physical 
impairment (such as a broken arm) that prevents them from signing the consent document, 
the research team will obtain a signature from a witness to the consent process who is not 
a member of the research team. The witness will sign the consent paperwork (their 
signature, time, and date), leaving the patient fields blank. An informed consent process 
note will also be filed to document the circumstances, who served as a witness, and the 
relationship of the witness to the patient (e.g. related or unrelated to subject). 
11. Incidental Findings
The research team will relay any findings related to injury to solid organs and 
hemoperitoneum to the primary treatment team for further management.  The FAST and 
BEFAST exams are screening exams only and not comprehensive abdominal exams; 
additional findings are not anticipated. If additional incidental findings are noted they will 
be relayed to primary treatment team for appropriate triage, referral to clinical specialists, 
and patient education as needed if the finding is clinically significant. All study patients 
will also obtain confirmatory imaging with CT study.
12. Compensation for time and effort: $25 single payment as reimbursement for parking 
expenses, time, effort.
13. Statistical Analysis:
Objective 1: To determine if contrast-enhanced, i.e. bubble-enhanced FAST (BEFAST) 
outperforms non-enhanced FAST in the evaluation of solid organ injury in 
hemodynamically stable blunt abdominal trauma patients when performed by frontline 
providers using CT as gold-standard.
Descriptive Statistics. The primary results will be described using sensitivities and 
specificities with 95% confidence intervals. Categorical variables will be described using 
frequencies and percentages. Continuous variables will be described using means and/or 
medians as appropriate.
Primary Analyses. Agreement with the CT results will be examined using a mixed-
effects/multi-level logistic regression in order to account for clustered measurements. 
Results from this regression will also be adjusted for the following covariates: 

demographics (e.g. age, sex, race), BMI, sonographer experience, contrast redosing, the 
presence of outward signs of injury.  In the event that the logistic regression fails to estimate 
properly or provides poor fit to the data and/or to show consistent results across methods, 
alternative methods will be explored: (1) P-values and confidence intervals will be 
computed using a bias-corrected and accelerated bootstrapping procedure (≥5,000 
resamples); (2) Sensitivities and specificities for BEFAST and FAST will be compared 
using McNemar’s test. 
Sample Size Calculations. Two primary issues were taken into consideration when 
calculating the required sample size: 1) statistical power, and 2) the expected rate of 
positive outcomes.
1) Power calculations were based on previous studies examining the sensitivity and 
specificity on standard and contrast-enhanced ultrasound. The results from these studies 
were meta-analyzed (fixed-effects, inverse-variance method) and indicated that (1) the 
sensitivity for CEUS (lower limit = 0.87) is greater than the sensitivity for standard 
ultrasound (upper limit = 0.68); and (2) the specificity for CEUS (0.98) is similar to the 
specificity for standard ultrasound (0.95). This analysis aimed to ensure that the present 
study has sufficient power to show improved sensitivity when using CEUS. Note that, 
because this sample size calculation uses the lower limit of the CEUS estimate and the 
upper limit of the standard ultrasound estimate, actual power will likely be greater. Given 
the small meta-analytic difference in specificities between methods, it is unlikely that 
differences in specificity will be detected. These values were used to estimate the sample 
size required to achieve 80% power using Monte Carlo simulations (10,000 samples) 
implemented in R v3.4.1. This analysis determined that the sample size would need to be 
at least 187. 
2) Using the rule of thumb 10 positive results for each predictor, we aimed to ensure that 
there will be a sufficient number of positive results for a model with two predictors (i.e. at 
least 20 positives. Thus, the current study will aim for a sample size of at least 187; 
however, data collection will not end until at least 20 CT+ patients are enrolled. 
Importantly, this stopping rule is entirely a priori and ceasing data collection will not be 
dependent on any statistical analyses, significance tests, or interim analyses. No analyses 
will be conducted until after this stopping rule is reached.
Missing Data. In the event of substantial missing data, data will be imputed using a multiple 
imputation procedure. The type of procedure and the number of imputed data sets will be 
determined by the amount of missing data and the pattern of missingness. As a sensitivity 
analysis, we will 1) assume the worst and assign a “does not agree” outcome for that patient 
and 2) assume the best and assign an “agrees” outcome for that patient. These analyses will 
describe the boundary conditions for the models described above.
Objective 2: To determine whether emergency physicians can incorporate BEFAST 
evaluation at the point-of-care in a trauma evaluation of a hemodynamically stable adult 
blunt abdominal trauma patient. 

An exam is complete if the patient tolerates the exam (no severe adverse reaction to 
contrast, patient allows the provider to complete the scan) and if it results in images of 
adequate quality to answer the focused clinical question.
Completion rates will be described as percentages with 95% confidence intervals. 
Assuming maximal variance for a binomial variable (π = 0.5), a sample size of 187-267 
(approximate) will result in 95% CIs that are no wider than ± 7.2% to 6.0%. FAST and 
BEFAST completion rates will be compared using either the multilevel/mixed effects 
logistic regression described above or McNemar’s test.
Objective 3: To determine the interrater reliability between bedside emergency physicians 
and radiologists for identifying solid organ injury with BEFAST.  
Inter-rater Reliability for the presence/absence of an injury will be evaluated using Cohen’s 
or Fleiss’ kappa as appropriate. The reliability of AAST scores will be evaluated using a 
weighted kappa statistic.
Assuming a minimal sample size of 187, the current study will have sufficient power (≥ 
80%) to detect reliability coefficients exceeding 0.23. For clinically relevant ratings, such 
as this, reliability is generally required to be high. Guidelines vary and are generally 
arbitrary; however, 0.8 and 0.9 are often used as cutoffs for “high” agreement, whereas a 
value such as 0.23 would be considered unacceptable. Thus, the current study is sufficiently 
powered to detect clinically acceptable levels of agreement. 
14. Data and Safety Monitoring and Reporting:
Monitoring the Progress and Safety of the Trial
During the screening process, patients will be excluded if they belong to vulnerable 
populations such as pediatric, pregnant, or imprisoned patients or if they have a known 
hypersensitivity to ultrasound contrast agent.     
Measures to protect participants against risk include use of a physician or certified health 
care professional (nurse practitioner, physician assistant or registered nurse) to administer 
contrast.  Confidentiality of participants will be protected by keeping data and US images 
password protected. The study will utilize a code number as the only identifier for each 
subject and the master list will be kept under lock and key with access limited to the PI 
and study coordinator. 
Site Monitoring Plan
This study will not be followed by a separate Data and Safety Monitoring Board. A 
medical monitor will be responsible for monitoring the data and for conducting safety 
reviews on a quarterly basis.  Scope of monitoring includes informed consent process, 
eligibility, adverse event reporting. 
During the review process, the monitor will evaluate whether the study should continue 
unchanged, require modification or amendment, continue or close to enrollment. A 
monitoring report will be provided to the PI within 5 days of review. PI will document 

receipt & review of the monitoring report, resolutions, and/or corrective actions to 
findings on the Site Monitoring Log; PI will notify IRB according to policies and 
procedures. 
Oversight of the progress and safety of the trial will be provided by the PI.  Adverse 
events are not anticipated, but any occurring will be documented and reported according 
to Emory IRB policies and procedures. Cumulative adverse events and study progress 
summary will be communicated to the IRB at the time of continuing review. 
A serious adverse event (SAE) is defined by the FDA as any adverse drug event 
(experience) occurring at any dose that in the opinion of either the investigator or sponsor 
results in any of the following outcomes: 1) death 2) life-threatening adverse drug 
experience 3) inpatient hospitalization or prolongation of existing hospitalization (for > 
24 hours) 4) persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 5) congenital anomaly/birth defect 6) important medical 
event (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered a serious adverse drug experience when, based upon medical 
judgment, it may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition.
The PI will be responsible for reviewing protocol compliance, data collection and 
verification.  The PI will immediately notify IRB in the event of a serious adverse event 
according to the Emory IRB reporting requirements. Once an unanticipated event is 
recognized and reported, the event will be investigated to determine if the event 
represents an unreasonable risk to the subject so as to terminate all or part of the study. 
15. Confidentiality:
We plan to protect subjects’ privacy during the course of their participation in the study 
by de-identifying data and assigning each patient a code. The linkage between code and 
patient will be kept in secure location – locked file cabinet, locked office, accessible only 
to PI and study team members and only during the duration of active study.  Whenever 
possible, a study number, rather than the patient’s name will be used on study records. 
The patient’s name and other identifying information will not appear when the study is 
published or results presented. 
Electronic data will be secured via a secure network that is password protected. Studies 
will be backed up to encrypted USB. Hard copy will be secured in a locked office in a 
locked filing cabinet. 
All links to identifiable data will be destroyed after publication and presentation of 
research data.  De-identified video clips will be archived indefinitely (as outlined in 
consent) for education and future research.

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