The body's immune system and a subsequent inflammatory response are triggered during
infection. The detection of an activated immune system, and an indication of the degree
of the host response, is helpful to the clinician both in assessing the severity of
infection and in patient treatment and management. Currently, the white blood cell count
and the differential are the most common laboratory parameters for measuring host
response. The sedimentation rate and CRP are also used to detect inflammation. However,
these tests are all imperfect predictors, and a test providing a better assessment of
immune response would be helpful to the clinician in patient care. Additionally,
understanding host response to infection may be helpful in understanding the biology and
pathophysiology of sepsis. There are other biomarkers and inflammatory markers that may
be found early in the initial presentation of infection such as cytokines (VEGF
IL-1,IL-4,IL-6, IL-10, PAF, TNF, lectins iNoS,etc.) and clotting factors (protein C,
d-dimer, complements involved in the clotting cascade, CRP, etc) that may provide a means
of early detection of systemic inflammation, cell dysfunction, and related conditions.
Early identification of patients at risk for systemic inflammatory syndromes, sepsis and
septic shock may help direct patients to earlier antibiotic administration and early
intervention with goal directed therapy. It may also serve as a tool for risk
stratification when components such as age, comorbid illness and infection type are
included.
The endothelium and endothelial cell markers are important in sepsis, yet a somewhat
under-studied field of research. Additionally, the endothelium is a key regulator of the
microcirculation, a place where oxygen diffusion occurs. One focus of this study is to
measure endothelial markers (ie VEGF) and other cytokines with the goal of correlating
these markers with severity of sepsis. Another focus is to study the response of various
components in the blood, including the leukocytes, red cells, the endothelium, as well as
cellular components such as the mitochondria. We will specifically look at alterations in
thiamine, Vitamin D, CoQ10,l-carnitine and other nutrients as part of (and as related to)
the body's response. Recently, a non-invasive method of assessing microvascular
circulation by orthogonal polarization spectral (OPS) imagery has become available using
a non-invasive technology known as orthogonal polarization spectroscopy. This technique
enables direct visualization and quantification of microcirculatory blood flow, and
represents an important surrogate outcome to which endothelial cell marker may be
correlated. This will involve placing the microscopy probe gently against the sublingual
mucosa and collecting a videotape of the circulation lasting about twenty seconds. This
process involves minimal (or no) risk - it is akin to taking a temperature and uses no
radiation. This videotape will be examined later by a novel software program that
quantifies the circulation and used as an important surrogate outcome measure.
Additionally, we are going to perform echocardiography to better understand the heart's
response to sepsis, and correlated the molecular responses that we find with the changes
in the responses by the heart. In addition, we will assess microvascular flow in the
skeletal muscle in the forearm using diffuse correlation spectroscopy (DCS). DCS is a
novel technique that can be used to measure peripheral tissue perfusion noninvasively and
has the potential to provide insight into microcirculatory health and end-organ
perfusion. DCS measurement is performed using a small sensor, similar to a pulse oximeter
sensor, that attaches to the skin using adhesive. It uses near-infrared light to
illuminate the tissue. The change in the transmitted light through the tissue due to the
moving red blood cells is characterized to quantify the microvascular flow. DCS is
noninvasive, uses no radiation, and involves minimal (or no) risk. DCS measurement will
be performed in conjunction with vascular occlusion test (VOT), which involves having a
blood pressure cuff placed on the upper arm to cause occlusion and reperfusion of blood
flow distally to measure dynamic changes in microvascular flow. We will measure
endothelial glycocalyx degradation products (e.g. heparin sulfate, syndecan, etc) in the
urine.
This is a multicenter, observational pilot study which aims to evaluate how early
biomarkers of infection an inflammation perform in identifying patients at risk for poor
outcomes in sepsis and septic shock. The study will utilize a cohort of patients
presenting to the ED with suspected infection as well as non-infected control population.
These patients will be compared with a non-infected population.
Enrolled subjects in the infected group will have blood samples and chart review obtained
at enrollment, 24, 48 and 72 hours. For the control group, only a single blood draw will
be collected at enrollment. Urine may be collected in a convenience sample of patients
Enrolled subjects will also undergo physiologic assessments using echocardiography,
Microscan, Non-invasive cardiac output monitor (NICOM), DCS, extremity temperature as
well as End-Tidal C02 measurements if a trained researcher is present.