An interventional study of CardioQ-EDM and CipherOx-CRI in Hypovolemia and Craniosynostoses, sponsored by University of Colorado, Denver. Completed at 1 site in United States. Open to participants aged 3 Months to 2 Years. Per ClinicalTrials.gov, last updated 2023-06-29.
Sponsored by University of Colorado, Denver · Not applicable, Interventional, and Diagnostic
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.
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:
122 studies on the registry are indexed under Hypovolemia; 14 are open to participants now.
This study's enrollment of 23 is below the median of 40 across 61 interventional studies indexed under Hypovolemia.
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Of its 147 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
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After defining fluid responders from non-responders in this single arm prospective trial, we 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.
Device: CardioQ-EDM and CipherOx-CRI
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.
Utility of Compensatory Reserve Index (CRI) Which Ranges From 0-1 in Order to Predict Fluid Responders From Non-responders
Using a delta peak aortic velocity threshold of 10% (measured from CardioQ-EDM) before and after a bolus to define fluid responders (=/\>10%) from non-responders (\<10%), we will determine the performance of pre-bolus CRI reading which is an index between 0 and 1 (0=poor reserve and 1=excellent reserve) in order to predict fluid responders from non-responders. Measurements will be recorded three times with one minute between measurements and then averaged. Vital signs analyzed included heart rate, systolic blood pressure, mean arterial pressure, shock index (heart rate/systolic blood pressure), pulse pressure variability, and end-tidal carbon dioxide level. Infants were also monitored with a Compensatory Reserve Index (CRI) monitor, which provides a continuous, individual-specific, beat-to-beat estimate of central volume status, from normovolemia (CRI=1) to decompensation (CRI=0). Each variable's performance was compared using area under the receiver operator curves (AUC).
Time frame: Through study completion (3-4 hours)
| Milestone | Fluid Challenge Responders | Fluid Challenge Non-responders |
|---|---|---|
| Started | 7 | 16 |
| Completed | 7 | 16 |
| Not completed | 0 | 0 |
Using a delta peak aortic velocity threshold of 10% (measured from CardioQ-EDM) before and after a bolus to define fluid responders (=/\>10%) from non-responders (\<10%), we will determine the performance of pre-bolus CRI reading which is an index between 0 and 1 (0=poor reserve and 1=excellent reserve) in order to predict fluid responders from non-responders. Measurements will be recorded three times with one minute between measurements and then averaged. Vital signs analyzed included heart rate, systolic blood pressure, mean arterial pressure, shock index (heart rate/systolic blood pressure), pulse pressure variability, and end-tidal carbon dioxide level. Infants were also monitored with a Compensatory Reserve Index (CRI) monitor, which provides a continuous, individual-specific, beat-to-beat estimate of central volume status, from normovolemia (CRI=1) to decompensation (CRI=0). Each variable's performance was compared using area under the receiver operator curves (AUC).
| units on a scale | Fluid Challenge Responders | Fluid Challenge Non-responders |
|---|---|---|
| Utility of Compensatory Reserve Index (CRI) Which Ranges From 0-1 in Order to Predict Fluid Responders From Non-responders | 0.06 ± 0.03 | 0.05 ± 0.02 |
Collected over Data was collected from the time of probe placement in the operating room until discharge (0-3 days). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fluid Challenge Responders | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) |
| Fluid Challenge Non-responders | 0/16 (0%) | 0/16 (0%) | 0/16 (0%) |
| Age, Categorical(Participants) | Fluid Challenge Responders | Fluid Challenge Non-responders | Total |
|---|---|---|---|
| <=18 years | 7 | 16 | 23 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Fluid Challenge Responders | Fluid Challenge Non-responders | Total |
|---|---|---|---|
| Female | 3 | 4 | 7 |
| Male | 4 | 12 | 16 |
| Ethnicity (NIH/OMB)(Participants) | Fluid Challenge Responders | Fluid Challenge Non-responders | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 2 |
| Not Hispanic or Latino | 5 | 14 | 19 |
| Unknown or Not Reported | 1 | 1 | 2 |
| Race (NIH/OMB)(Participants) | Fluid Challenge Responders | Fluid Challenge Non-responders | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 7 | 13 | 20 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 2 | 2 |
| Region of Enrollment(participants) | Fluid Challenge Responders | Fluid Challenge Non-responders | Total |
|---|---|---|---|
| United States | 7 | 16 | 23 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — No plan to share individual participant data with other researchers is planned
Ran from Apr 2019 to primary completion in Mar 2020, 11 months.
Results were first posted in Jun 2023, 3 years 3 months after primary completion.
Of 19 interventional studies with no phase under Hypovolemia, half reached primary completion within 12 months of starting (the median); a quarter within 8 and three quarters within 20. This study's 11 months is close to that.
How these figures are worked out, and which studies are left out of them.
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