This study is designed to validate implementation of the CRI algorithm in the CypherOx CRI
Healthy human subjects will undergo progressive reduction in central blood volume to the
point of hemodynamic instability (defined by a precipitous fall in systolic blood pressure
(SBP) below 70 mmHg and/or voluntary subject termination due to discomfort (such as
sweating, nausea, or dizziness) to validate the following hypotheses:
The CypherOx CRI system will A. Trend intravascular volume changes (hemorrhage) B. Trend
stroke volume changes and C. The CRI trend value is not relative to an initial CRI reading,
instead it is an actual CRI trend value that does not require calibration or being placed
during normal physiological conditions.
Hemorrhagic shock is a leading cause of death in both civilian and battlefield trauma.
Currently available medical monitors provide the capabilities to measure standard vital
signs that are often imprecise, subjective, intermittent and inconsistent. More importantly,
the appearance of hypotension and other signs and symptoms of shock represent a point in
time when it may be too late to apply effective lifesaving interventions. Understanding the
physiological signals that provide the best indicators of blood volume loss and impending
circulatory failure is critical to bridging the capability gap of identifying the need for
early intervention. Under a previous BAMC IRB-approved protocol, we used lower body negative
pressure (LBNP) as an experimental model of central hypovolemia to simulate progressive
blood loss that results in hemodynamic instability (e.g., hypotension, tachycardia,
presyncopal symptoms) in conscious, healthy human subjects. From data collected within this
original protocol, we now understand that arterial waveforms (either blood pressure or pulse
oximetry) are important variables associated with hypovolemia. Feature extraction and
machine learning techniques were applied to these previously collected data and an algorithm
was developed called Compensatory Reserve Index (CRI) which was designed to reflect
progressive blood loss and decreasing stroke volume. This algorithm was installed in a
pulse oximeter in which the photo-plethysmographic waveform (PPG) was used to calculate the
CRI. Using this CRI Pulse oximeter, a pretrial study of 24 subjects indicated a high
correlation in trending of blood volume loss (DOD study at Mayo Clinic) and a mean
correlation of 0.96 when comparing CRI to stroke volume (LBNP at AISR Laboratory). The work
proposed herein will validate those findings. During each experiment each test subject will
wear 4 FDA cleared pulse oximeters which transmit PPG data to an off-the-shelf handheld
tablet (meets military specs) which will calculate and display the CRI value. The subjects
will also wear 2 FDA cleared Nexfin hemodynamic monitors that display stroke volume. LBNP
will be used to produce progressive central hypovolemia in healthy human subjects until the
point of hemodynamic decompensation (presyncope). This approach will validate the
correlation of CRI to stroke volume.
- Healthy nonsmoking normotensive (<140/90) males or females.
- Age 18 to 55 yr.
- Normal clinical results from a Medical History and Physical form DD 2807-1
- Military or civilian.
- Documentation of a negative pregnancy test within 24 hours prior to each study
period, if necessary.
- Not obese, as defined by body mass index (BMI) < 30, unless individual is athletic
(BMI may not be the best method of assessing obesity in athletic individuals). BMI is
calculated as the weight in kilograms divided by the square of the height in meters.
- (a) Age <18 and >55 years.
- Individuals taking prescription drugs, non-prescription drugs or herbal medicines
known to alter autonomic function unless cleared by the Medical Screener.
- Subjects using prescription medications within 30 days before initiation of the
experiments unless cleared by the Medical Screener.
- Subjects with a history of alcohol or drug abuse which inhibits the subject's ability
to complete this study.
- Subjects with signs of cardiovascular abnormalities (e.g., hypertension (> 140/90),
autonomic dysfunction (Shy-Drager Syndrome, Bradbury-Eggleston syndrome, sinus
arrhythmia, idiopathic orthostatic hypotension), fainting disorder, etc.).
- Subjects with respiratory illnesses (e.g., asthma, Chronic Obstructive Pulmonary
Disease, Reactive Airway Disease, etc.).
- Subjects with a history of anaphylaxis.
- Subjects with allergies to medications not cleared by the Medical Screener.
Individuals reporting a history of pre-syncopal/syncopal episodes or orthostatic
- Subjects with a history or family history of abnormal blood clotting, clots in deep
veins in the legs or pelvis, or blood clots to the lungs.
- Individuals taking prescription medications for hypertension (high blood pressure).
(l) Individuals with known or suspected abdominal hernias
- Pregnancy, trying to become pregnant, or breastfeeding