Bedside Resources to Gauge Intravascular Volume Status
Condition: Hypovolemia; Craniosynostoses
MeSH terms: Craniosynostoses; Hypovolemia
Study type: Interventional

Summary: 
      The goal if this study is to employ the CardioQ-Esophageal Aortic Doppler probe to define
      fluid responders from non-responders among infants undergoing cranial vault reconstruction
      for craniosynostosis. After defining these two groups in this single arm prospective trial,
      the investigators will compare the predictive utility of non-invasive devices such as the
      CipherOx-Compensatory Reserve Index (CipherOx-CRI) and Inferior Vena Cava Collapsibility
      Index (IVC CI) to currently employed indices (heart rate, systolic blood pressure, urine
      output and pulse pressure variability) to gauge the need for additional fluid and ongoing
      resuscitation. If the CipherOx-CRI or IVC CI proved to be as predictive or better at
      predicting fluid responders, the investigators hope to replace invasive arterial lines with
      non-invasive tools to guide resuscitation.
    

Detailed description: 
      Predicting fluid responsiveness in the operating room is essential to guide balanced
      resuscitation. Aggressive resuscitation may lead to significant morbidities, such as
      intra-abdominal hypertension, pulmonary edema, difficulty with ventilator liberalization, and
      consequently increased mortality. Alternatively, under resuscitation may lead to
      mal-perfusion and end-organ dysfunction.

      A plethora of indices and tools have been studied and marketed to assess intravascular volume
      status with only a few proven reliable with reproducible results. Based on pre-fluid
      challenge values, several of these tools have been used to predict who may benefit from
      additional fluid (fluid responders). Alternatively, some of these tools have been used to
      distinguish fluid responders from non-responders based on changes in pre- and post-fluid
      challenge values. Among these tools, the pulmonary artery catheter provides measurements of
      both left and right heart pressures which can be applied to calculate the cardiac output (CO)
      and stroke volume (SV). Changes in these values (e.g. an increase in the stroke volume by
      10%) between pre- and post-fluid challenge have been used to define fluid responders. This
      devise, however, is invasive with several significant risks, and therefore is rarely used in
      children. Echocardiography, on the other hand, is a non-invasive bedside study also used to
      assess CO and SV but is expensive and requires trained echosonagraphers for application.
      Further, because a transthoracic probe is required to obtain the images, application in the
      operating room is difficult as the chest is often in the operating field limiting access to
      the echosonagrapher. Lastly, the esophageal aortic blood flow device (CardioQ-Esophageal
      Dopler Monitor (Cardio-EDM), Deltex Medical, Chichester, UK) has been found in multiple adult
      and pediatric studies to reliably distinguish fluid responders from non-responders intensive
      care unit (ICU) and operating room. Much like an orogastric tube, this device is simply
      placed by a provider in the patient's esophagus and uses Doppler waveforms to measure aortic
      blood flow velocities. Variations in the amplitude of peak velocities has been shown to
      corelate with intravascular volume status. Specifically, a change in the peak velocity by
      greater than 10% between pre- and post-fluid challenge values has been shown to accurately
      distinguishes those who are fluid responsive from those who are not with similar accuracy to
      echocardiography and pulmonary artery catheter readings.

      In recent years with continued technological advancements, there has been enthusiasm about
      less invasive, and in some cases, non-invasive, tools to gauge volume status. Among these,
      bedside ultrasonography (performed by providers rather than sonographers) is a common tool
      used to evaluate the inferior vena cava (IVC) collapsibility index (CI) has been shown to be
      a reliable tool in adults. Another non-invasive device uses a photoplethysmoraphic probe
      (CipherOx-CRI) placed on a digit to calculate the compensatory reserve index (CRI), a marker
      of proximity to hemodynamic collapse. Both IVC CI and CRI have been shown in multiple adult
      studies to predictive the need for volume expansion, but their utility in the pediatric
      population is unknown.

      The goal if this proposed study is to employ the CardioQ-EDM probe to define fluid responders
      from non-responders among infants undergoing cranial vault reconstruction for
      craniosynostosis. After defining these two groups in this single arm prospective trial, the
      investigators will compare the predictive utility of non-invasive devices such as the
      CipherOx-CRI and IVC CI to currently employed indices (heart rate, systolic blood pressure,
      urine output and pulse pressure variability) to gauge the need for additional fluid and
      ongoing resuscitation. If the CipherOx-CRI or IVC CI proved to be as predictive or better at
      predicting fluid responders, the investigators hope to replace invasive arterial lines with
      non-invasive tools to guide resuscitation.

      The investigators chose this population for several reasons. First, the investigators
      institution performs approximately 50-70 of these cases a year making them a relatively
      accessible group. Second, these children are generally healthy which will minimize
      physiologic confounders. Additionally, the subjects are paralyzed, have normal respiratory
      compliance, and providers maintain normothermia, all of which will minimizing confounders.
      Another unique benefit to this population is that these infants have been nil per os for
      several hours prior to surgery, putting them at risk for hypovolemia, and after induction,
      independent of the provider's assessment of intravascular volume status, all children receive
      a bolus of crystalloid (10mL/kg). This baseline data should provide sufficient data for
      analysis; but because these procedures are associated with significant blood loss and
      hypovolemia requiring aggressive resuscitation in the form of fluid or blood boluses, the
      investigators plan to continue to collect pre- and post- bolus data with the hope to further
      validate the benefit of non-invasive tools such as the CipherOx-CRI and IVC CI in the setting
      of ongoing blood loss.

      As intravascular volume status is often difficult to assess clinically, the investigators aim
      to determine the predictability of non-invasive devices to guide resuscitation. In this
      prospective observational study, the investigators hope to identify:

        1. The proportion of children within the cohort who are fluid responsive based on
           CardioQ-EDM aortic blood flow velocity changes pre- and post-bolus,

        2. The positive predictive value, negative predictive value, sensitivity, specificity, and
           optimal threshold for CRI, IVC CI, pulse pressure variability, stroke volume
           variability, heart rate, systolic blood pressure, and mean arterial pressures in
           predicting fluid responders as determined by CardioQ-EDM, and

        3. Assess confounding variables that may influence the predictive utility of such devices
    

Intervention name(s): CardioQ-EDM and CipherOx-CRI
Intervention type(s): Device
Intervention description(s): A CardioQ-EDM probe will be placed on the day of surgery after induction of general anesthesia. The anesthesiologist will inform the investigator of plans to provide a fluid or blood bolus per clinical judgement in addition to the protocolized 10 ml/kg bolus provided after induction. While the anesthesiologist is preparing to administer volume expansion, a co-investigator will collect pre-fluid bolus data. Measurements will be recorded for data analysis at the completion of the trial. Additionally, a CipherOx-CRI probe will be placed on the patient's index finger (recorded data will be interpreted post hoc) and a bedside ultrasound will be performed by either the principal investigator (PI) or one of two co-investigators to measure the IVC CI. Ultrasound cine-loops will be recorded, and CI will be calculated post-hoc. Data will be recorded on the Data Collection Form for each fluid bolus administered. The PI and co-investigators will manage all aspects of investigational devices.
Intervention model: Single Group Assignment
Intervention model description: Single arm prospective trial which will define two groups
Masking: None (Open Label)
Primary purpose: Diagnostic