Comparison of Non-Invasive Methods of Assessing Fluid Responsiveness in ED and ICU Patients
Condition: Sepsis; Fluid Overload; Hypovolemia
MeSH terms: Hypovolemia
Study type: Observational

Summary: 
      Accurate assessment of fluid responsiveness (FRes) is central to guiding fluid management in
      septic and critically ill patients. As evidence accumulates that both inadequate and
      excessive fluid resuscitation are associated with increased morbidity and mortality, it is
      simultaneously becoming increasingly clear that current widely used methods to predict FRes
      are of questionable accuracy. The optimal technique to predict FRes would be a non-invasive
      point-of-care test with not only a high degree of accuracy, but also one which requires
      minimal training to perform correctly and may be easily performed repeatedly for serial
      evaluation of FRes during the ongoing management of the critically ill patient.

      To date, three major ultrasonographic modalities have emerged as viable candidates for the
      bedside assessment of FRes: 1) measurement of dynamic changes in inferior vena caval diameter
      (IVC-CI), 2) measurement of dynamic changes in peripheral arterial waveform derived variables
      (PA Doppler), and 3) echocardiographic measurement of dynamic changes in left ventricular
      outflow tract waveform derived variables (LVOT Doppler). In this study, the investigators
      will perform the first direct comparison of techniques representing all three of the above
      modalities in the prediction of FRes against a non-invasive bioreactance cardiac output
      monitor (the Cheetah NICOM™), which has been extensively validated against gold-standard
      invasive methods of cardiac output measurement. The investigators will compare the accuracy
      of these modalities in both spontaneously breathing and mechanically ventilated patients
      using passive leg raise testing (PLR) as a surrogate for volume challenge. In addition, the
      investigators will also elicit information from the treating physician(s) on their clinical
      assessment of FRes.

      The investigators will recruit adult patients in the ED and ICU with sepsis, who have
      received an initial bolus of 20-30 cc/kg of IV fluid, and can tolerate the PLR and US
      procedures. Prior to US and NICOM measurement, investigators will ask the attending physician
      managing the patient regarding their assessment of the their fluid status. Then, separate
      investigators will perform US and NICOM measurements independently to ensure blinding. NICOM
      data, which has been well validated in septic patients, will be shared with the attending
      physician. They will then be asked if this new data will change management.
    

Detailed description: 
      This is a diagnostic accuracy study comparing selected ultrasound techniques to a well
      validated standard for predicting fluid responsiveness in septic patients (NICOM). The
      primary outcomes will be reported in sensitivity, specificity, positive predictive value,
      negative predictive value, likelihood ratios, and receiver operating characteristic curves.

      The timeframe for measurement is within 72 hours of the subjects' admission. Determination of
      the outcome (i.e., whether a subject is fluid responsive) is based upon the data generated by
      the NICOM device. The NICOM generates data within 5 minutes of assessment. The ultrasound
      modalities to be studied will generate data within 5 minutes of assessment as well. The US
      data will be compared to the NICOM data to generate the statistics listed in this protocol.
      There is no further planned follow-up for the subjects.

        1. The investigators will compare the ability of dynamic changes in inferior vena caval
           diameter (IVC-CI), dynamic changes in peripheral arterial waveform derived variables (PA
           Doppler), and dynamic changes in left ventricular outflow tract waveform derived
           variables (LVOT Doppler) to detect fluid responsiveness (FRes) relative to FRes as
           assessed by bioreactance cardiac output monitoring before and after passive leg raise
           (PLR).

           Hypothesis: PA Doppler and LVOT Doppler will have superior sensitivity and specificity
           to predict FRes in comparison to IVC-CI.

        2. The investigators will evaluate data acquisition duration and data acquisition failure
           rate of IVC-CI, PA Doppler, and LVOT Doppler. Hypothesis: PA Doppler will have shorter
           data acquisition durations in comparison to LVOT velocity variation and IVC-CI.

           Hypothesis: PA Doppler will have lower data acquisition failure rates in comparison to
           LVOT velocity variation and IVC-CI.

        3. The investigators will compare the ability of IVC-CI, PA Doppler, and LVOT Doppler to
           predict FRes in comparison to FRes as predicted by clinical judgment.

           Hypothesis: PA Doppler and LVOT Doppler will have superior sensitivity and specificity
           to predict FRes in comparison to clinical judgment.

        4. The investigators will evaluate the ability of dynamic changes in PA corrected flow
           times (cFT) to detect FRes relative to FRes as assessed by bioreactance cardiac output
           monitoring before and after PLR. Hypothesis: cFT will have greatest sensitivity and
           specificity to predict FRes at a Δflow time threshold of ≥15% after PLR.

      Hypothesis: At a Δflow time threshold of ≥15%, cFT will have superior sensitivity and
      specificity to detect FRes in comparison to IVC-CI.
    

Intervention name(s): Ultrasound and NICOM
Intervention type(s): Device
Intervention description(s): All patients enrolled will have all three ultrasound-based modalities for fluid responsiveness performed, as well as have NICOM data to serve as the comparison standard.
Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The investigators will recruit adult patients in the ED and ICU who are septic, have
        received an initial bolus of 20-30 cc/kg of IV fluid, and there is still a question by the
        clinical team of whether they are still fluid responsive.
      
Keywords: Fluid responsiveness, ultrasound