Clinical trial NCT03915587: Bedside Resources to Gauge Intravascular Volume Status
Official title: Bedside Resources to Gauge Intravascular Volume Status in Hypovolemic Infants in the Operating Room
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypovolemia
Craniosynostoses
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2019-04-16
Enrollment: 23
Sex: ALL
Minimum age (years): 3
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm prospective trial which will define two groups
Primary purpose: DIAGNOSTIC

Brief 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

Eligibility criteria: Inclusion Criteria:

* Children with craniosynostosis undergoing cranial vault reconstruction

Exclusion Criteria:

* Children with known underlying cardiac anomalies or cardiac arrhythmias
* Weight less than 3 kg
* Children who have vasopressors adjusted during a fluid bolus

Primary outcomes:
measure: Utility of Compensatory Reserve Index (CRI) Which Ranges From 0-1 in Order to Predict Fluid Responders From Non-responders
timeFrame: Through study completion (3-4 hours)
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: Children's Hospital Colorado
name: Sarkis Derderian, MD
role: PRINCIPAL_INVESTIGATOR
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