Prognostic Markers of Inflammation in Infants Undergoing Cardiopulmonary Bypass

Study Overview
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Brief Summary
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This study evaluates the effect of heart-lung bypass on babies undergoing cardiac surgery. The investigators want to learn more about the inflammation that exposure to bypass creates in the body by studying markers of inflammation and cell injury in the bloodstream. Additionally, the investigators want to examine if these markers can predict which babies develop post-surgical complications. The hypothesis is that babies who undergo bypass will have higher levels of these markers than babies not exposed to bypass and that these markers will correlate with how the baby does clinically after surgery. This study will evaluate markers via blood sampling in babies with congenital heart disease who do not undergo cardiac surgery, those that undergo surgery without bypass, and those that undergo surgery with bypass. The overall goal is that this study will lead to useful biomarkers and lay the groundwork for future novel therapies aimed at improving outcomes for babies who require heart-lung bypass.

Detailed Description
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This is a minimal risk observational study looking at markers of inflammation and cell injury in the bloodstream of babies with congenital heart disease, with a particular emphasis on whether these markers can predict low cardiac output syndrome in infants who undergo heart-lung bypass. Low cardiac output syndrome is a common postoperative complication marked by poor blood flow to the body affecting nearly 1/3 of infants post-bypass and is associated with significant morbidity and mortality. Babies not requiring surgery will serve as the control group. Infants in group 1 will have 0.5 ml of blood drawn prior to discharge. This will be scavenged from the laboratory when possible. Infants in groups 2 and 3 will require serial blood draws over peri-operative time points each in the volume of 0.5 ml. Group 2: T0 = Before surgery (in the OR) T1 = After chest closure or end of case (in the OR) T2 = On admission to the pediatric intensive care unit T3 = Timed 4-6 hours after the time of admission T4 = Timed 12 hours (+/- 1 hour) after the time of admission T5 = Timed 24 hours (+/-1 hour) after the time of admission Group 3: T0 =Pre-cardiopulmonary bypass to be obtained in the operating room just prior to surgery T1 = After going on bypass (but prior to modified ultrafiltration) T2 = After modified ultrafiltration T3 = On admission to the pediatric intensive care unit T4 = Timed 4-6 hours after the time of admission T5 = Timed 12 hours (+/- 1 hour) after the time of admission T6 = Timed 24 hours (+/-1 hour) after the time of admission

Official Title
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Prognostic Markers of Inflammation in Infants Undergoing Cardiopulmonary Bypass (ProCard): an Observational Pilot Study

Conditions
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Low Cardiac Output Syndrome, Inflammation, Congenital Heart Defect, Cardiopulmonary Bypass, Inflammatory Response

Intervention / Treatment
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* Procedure: Single blood draw
* Procedure: Multiple blood draws
* Procedure: Multiple blood draws


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants < 6 months of age Born at ≥ 36 weeks gestational age Birth weight ≥ 2.5 kilograms Postnatally confirmed congenital heart disease by echocardiogram Exclusion Criteria: Requiring ≥ 2 vasopressors prior to surgery Preoperative proven sepsis within one week of surgery Prior surgery within one week of cardiac repair (except PA banding which is not excluded) Cardiac catheterization within one week of surgery Significant extra-cardiac anomalies that may impair organ function

Ages Eligible for Study
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Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control/Nonsurgical<br>Infants with postnatally confirmed acyanotic congenital heart disease not expected to require surgery in the first six months of life. | Procedure: Single blood draw<br>* One blood draw of 0.5 ml volume prior to discharge<br>|
| Surgery w/o bypass<br>Infants with postnatally confirmed congenital heart disease requiring cardiac surgery without cardiopulmonary bypass. | Procedure: Multiple blood draws<br>* Blood draw at 6 peri-operative time points.<br>|
| Surgery w/ bypass<br>Infants with postnatally confirmed congenital heart disease requiring cardiac surgery with cardiopulmonary bypass. | Procedure: Multiple blood draws<br>* Blood draw at 7 peri-operative time points<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker levels and their relationship to LCOS | Changes in markers of inflammation and cell injury (histones, IL-6, etc.) and correlation with patients who develop low cardiac output syndrome | Baseline level and described time points over the first twenty-four hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in level of inflammatory response | Changes in markers of inflammation and cell injury (IL-6, IL-8, etc.) in the peri-operative period (prior to surgery up to 24 hours postop) | Baseline, up to 24 hours | 
| Length of mechanical ventilation | Number of days on mechanical ventilation following day of surgery until the point of extubation | Participants will be followed throughout hospital course, maximum length of follow-up one year | 
| Acute kidney injury | Doubling of creatinine in first twenty four hours compared to preoperative levels | Participants will be followed for the first twenty four hours postoperatively | 
| Extracorporeal membrane oxygenation (ECMO) | Whether or not patient requires ECMO cannulation | First 48 hours postoperatively | 
| ICU length of stay | Number of days requiring pediatric/cardiac intensive care unit following day of surgery | Participants will be followed throughout PICU/CVICU stay, maximum length of follow-up one year | 
| Hospital length of stay | Number of hospital days patient requires following the day of surgery | Participants will be followed throughout entire hospital course, maximum length of follow-up one year | 
| Mortality risk | Pediatric risk of mortality-3 scale (PRISM-3) and pediatric index of mortality (PIM-2) | PIM-2 calculated within one hour of admission to PICU and PRISM-3 calculated at 12 and 24 hours after PICU admission | 
| Mortality | Any type of death that occurs during patient's hospitalization | Participants will be followed throughout hospital course, maximum length of follow-up one year | 
| Low cardiac output syndrome | At least two of the following criteria at any post-operative time point within the first twenty four hours: (a) prolonged cap refill >3 sec, SBP <5th %ile for age and gender, low UOP <1 cc/kg/hr for at least 6 hr not responsive to diuretics, persistently elevated arterial lactate >2 and metabolic acidosis defined as an increase in the base deficit of >4, inotropic score >20, cardiac arrest within 48 hr after surgery, or the need for extracorporeal membrane oxygenation (ECMO) for hemodynamic instability within 48 hours postop | Assessed at 48 hours postoperatively |