Tissue Near InfraRed Spectroscopy (NIRS) in Critically Ill Patients
Condition: Sepsis; Inflammation; Shock
MeSH terms: Inflammation
Study type: Observational

Summary: 
      Hypotheses:

        1. In the acute phase of early illness, tissue oxygen saturation and vascular occlusion
           test (VOT) are important adjuncts in differentiating severe critical illness requiring
           ICU admission from patients benefiting from less aggressive therapies (non-ICU
           admission).

        2. An early feature of severe sepsis is abnormal microcirculatory vasoreactivity.

        3. Microvascular reactivity can be measured by means of vascular occlusion test (VOT) using
           non-invasive near infrared spectroscopy (NIRS) to measure tissue Oxygen saturation
           (StO2).

        4. Microvascular reactivity is significantly deranged in patients with early severe sepsis
           and is quantifiably different from non-septic critically ill patients.

        5. Other measures of microcirculatory perfusion ie. sublingual orthogonal polarization
           spectral (OPS) video microscopy, are abnormal and will directionally correlate with VOT
           and StO2 in severe sepsis

        6. In severely septic patients response to therapy can be assessed by VOT and StO2
           monitoring and will correlate with prognosis.

        7. A management protocol incorporating VOT and StO2 monitoring in addition to conventional
           hemodynamic and biochemical parameters as a guide to therapy will result in improved
           outcomes in severely septic patients.

      This project will investigate the use of a non-invasive near infrared light (NIR) device in
      conjunction with brief arm compression to measure the microcirculation in critically ill
      patients. It is know that in patients with overwhelming infections, their blood vessels do
      not respond normally and the NIR device can help measure how abnormal their blood vessels
      are. This type of testing is non-invasive and can be performed repeatedly without harm to the
      patient and may provide an earlier way to determine whether they have overwhelming sepsis and
      also may help to optimize the treatments they receive and better tailor their treatments to
      the degree of blood vessel abnormalities that are found. If our hypotheses are correct, this
      simple non-invasive test could provide a very rapid means of assessing patients that could be
      done more safely and quickly than some of the current methods. This would have an important
      effect to enhance patient safety and improve outcomes in such critically ill patients.
    

Detailed description: 
      Project Overview: This project is focused on the early diagnosis and management of septic
      shock using tissue near infrared spectroscopy (tNIRS) for continuous and non-invasive
      assessment of microcirculatory vasoreactivity as a diagnostic and prognostic indicator in
      critically ill patients. A novel aspect of this study is that point of entry of patients will
      be via the Critical Care Outreach Team (CCOT) which will ensure patients are assessed in the
      early phases of their disease prior to and co-incident with admission to Critical Care Unit
      (CCU). The investigators will employ tNIRS to assess peripheral tissue oxygen saturation
      (StO2) in all patients assessed by CCOT (n = 1031 patients in 2009) and in addition, the
      investigators will employ the NIRS vascular occlusion test (VOT) using a brief episode of
      forearm ischemia to quantify microvascular (dys)function.

      All patients admitted to CCU via CCOT (n = 230 patients in 2009) will have StO2 monitored and
      VOT assessment sequentially throughout the course of their critical illness. Biomarkers to
      assess severity of illness, inflammatory processes and microcirculatory reactivity will be
      obtained, and in a subset of patients (n = 30), correlations between these parameters and
      other indices of microvascular perfusion using sublingual orthogonal polarization spectral
      (OPS) imaging videomicroscopy will be sought. As it is estimated that 20-30% of CCOT
      admissions are for sepsis (n = 40-60), the inclusion of other critically ill non-septic
      patients will enable discrimination of various parameters of VOT to be contrasted between
      groups to determine relative diagnostic and prognostic significance.

      Statement of Objectives:

        1. To assess the diagnostic utility of tNIRS StO2 and VOT in early assessment of critically
           ill patients.

        2. To determine whether significant and pathognomonic differences exist in StO2 and indices
           of VOT between septic patients versus other non-septic critically ill patients and
           healthy age matched volunteers.

        3. To determine whether correlations exist between biomarkers of inflammation and
           vasoreactivity and measures of StO2 and VOT in severely septic patients.

        4. To determine whether incorporation of StO2 and VOT into a treatment protocol can
           positively impact clinical outcomes in critically ill patients.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Critically ill patients early in clinical course of illness.
      
Biospecimen description: 
      Blood: inflammatory markers
    
Keywords: sepsis; tissue oximetry; NIRS; VOT