Study Results
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View full resultsBasic Information
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COMPLETED
NA
23 participants
INTERVENTIONAL
2019-04-08
2020-03-12
Brief Summary
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Detailed Description
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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
Conditions
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Study Design
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NA
SINGLE_GROUP
DIAGNOSTIC
NONE
Study Groups
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Fluid Challenge
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.
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.
Interventions
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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.
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* Weight less than 3 kg
* Children who have vasopressors adjusted during a fluid bolus
3 Months
2 Years
ALL
No
Sponsors
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University of Colorado, Denver
OTHER
Responsible Party
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Principal Investigators
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Sarkis Derderian, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital Colorado
Locations
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Children's Hospital Colorado
Aurora, Colorado, United States
Countries
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References
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Malbrain ML, Marik PE, Witters I, Cordemans C, Kirkpatrick AW, Roberts DJ, Van Regenmortel N. Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. Anaesthesiol Intensive Ther. 2014 Nov-Dec;46(5):361-80. doi: 10.5603/AIT.2014.0060.
Feissel M, Michard F, Mangin I, Ruyer O, Faller JP, Teboul JL. Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock. Chest. 2001 Mar;119(3):867-73. doi: 10.1378/chest.119.3.867.
Monnet X, Rienzo M, Osman D, Anguel N, Richard C, Pinsky MR, Teboul JL. Esophageal Doppler monitoring predicts fluid responsiveness in critically ill ventilated patients. Intensive Care Med. 2005 Sep;31(9):1195-201. doi: 10.1007/s00134-005-2731-0. Epub 2005 Jul 30.
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Absi MA, Lutterman J, Wetzel GT. Noninvasive cardiac output monitoring in the pediatric cardiac Intensive Care Unit. Curr Opin Cardiol. 2010 Mar;25(2):77-9. doi: 10.1097/HCO.0b013e3283362452.
Weber T, Wagner T, Neumann K, Deusch E. Low predictability of three different noninvasive methods to determine fluid responsiveness in critically ill children. Pediatr Crit Care Med. 2015 Mar;16(3):e89-94. doi: 10.1097/PCC.0000000000000364.
Pereira de Souza Neto E, Grousson S, Duflo F, Ducreux C, Joly H, Convert J, Mottolese C, Dailler F, Cannesson M. Predicting fluid responsiveness in mechanically ventilated children under general anaesthesia using dynamic parameters and transthoracic echocardiography. Br J Anaesth. 2011 Jun;106(6):856-64. doi: 10.1093/bja/aer090. Epub 2011 Apr 26.
Lanspa MJ, Grissom CK, Hirshberg EL, Jones JP, Brown SM. Applying dynamic parameters to predict hemodynamic response to volume expansion in spontaneously breathing patients with septic shock. Shock. 2013 Feb;39(2):155-60. doi: 10.1097/SHK.0b013e31827f1c6a.
Janak JC, Howard JT, Goei KA, Weber R, Muniz GW, Hinojosa-Laborde C, Convertino VA. Predictors of the Onset of Hemodynamic Decompensation During Progressive Central Hypovolemia: Comparison of the Peripheral Perfusion Index, Pulse Pressure Variability, and Compensatory Reserve Index. Shock. 2015 Dec;44(6):548-53. doi: 10.1097/SHK.0000000000000480.
Czerwinski M, Hopper RA, Gruss J, Fearon JA. Major morbidity and mortality rates in craniofacial surgery: an analysis of 8101 major procedures. Plast Reconstr Surg. 2010 Jul;126(1):181-186. doi: 10.1097/PRS.0b013e3181da87df.
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National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wheeler AP, Bernard GR, Thompson BT, Schoenfeld D, Wiedemann HP, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med. 2006 May 25;354(21):2213-24. doi: 10.1056/NEJMoa061895. Epub 2006 May 21.
Shah MR, Hasselblad V, Stevenson LW, Binanay C, O'Connor CM, Sopko G, Califf RM. Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials. JAMA. 2005 Oct 5;294(13):1664-70. doi: 10.1001/jama.294.13.1664.
Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ, Laporta DP, Viner S, Passerini L, Devitt H, Kirby A, Jacka M; Canadian Critical Care Clinical Trials Group. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med. 2003 Jan 2;348(1):5-14. doi: 10.1056/NEJMoa021108.
Westphal GA, Goncalves AR, Bedin A, Steglich RB, Silva E, Poli-de-Figueiredo LF. Vasodilation increases pulse pressure variation, mimicking hypovolemic status in rabbits. Clinics (Sao Paulo). 2010 Feb;65(2):189-94. doi: 10.1590/S1807-59322010000200011.
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Chytra I, Pradl R, Bosman R, Pelnar P, Kasal E, Zidkova A. Esophageal Doppler-guided fluid management decreases blood lactate levels in multiple-trauma patients: a randomized controlled trial. Crit Care. 2007;11(1):R24. doi: 10.1186/cc5703.
Desgranges FP, Desebbe O, Pereira de Souza Neto E, Raphael D, Chassard D. Respiratory variation in aortic blood flow peak velocity to predict fluid responsiveness in mechanically ventilated children: a systematic review and meta-analysis. Paediatr Anaesth. 2016 Jan;26(1):37-47. doi: 10.1111/pan.12803. Epub 2015 Nov 6.
Zhao J, Wang G. Inferior Vena Cava Collapsibility Index is a Valuable and Non-Invasive Index for Elevated General Heart End-Diastolic Volume Index Estimation in Septic Shock Patients. Med Sci Monit. 2016 Oct 20;22:3843-3848. doi: 10.12659/msm.897406.
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Monnet X, Bleibtreu A, Ferre A, Dres M, Gharbi R, Richard C, Teboul JL. Passive leg-raising and end-expiratory occlusion tests perform better than pulse pressure variation in patients with low respiratory system compliance. Crit Care Med. 2012 Jan;40(1):152-7. doi: 10.1097/CCM.0b013e31822f08d7.
Teboul JL, Monnet X, Chemla D, Michard F. Arterial Pulse Pressure Variation with Mechanical Ventilation. Am J Respir Crit Care Med. 2019 Jan 1;199(1):22-31. doi: 10.1164/rccm.201801-0088CI.
Airapetian N, Maizel J, Alyamani O, Mahjoub Y, Lorne E, Levrard M, Ammenouche N, Seydi A, Tinturier F, Lobjoie E, Dupont H, Slama M. Does inferior vena cava respiratory variability predict fluid responsiveness in spontaneously breathing patients? Crit Care. 2015 Nov 13;19:400. doi: 10.1186/s13054-015-1100-9.
Tibby SM, Hatherill M, Murdoch IA. Use of transesophageal Doppler ultrasonography in ventilated pediatric patients: derivation of cardiac output. Crit Care Med. 2000 Jun;28(6):2045-50. doi: 10.1097/00003246-200006000-00061.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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18-2513
Identifier Type: -
Identifier Source: org_study_id
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