Plasma Angiopoietin Levels in Children Following Cardiopulmonary Bypass

Study Overview
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Brief Summary
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During cardiopulmonary bypass (CPB) after heart surgery, a child's blood is exposed to many foreign entities. These conditions trigger the body's inflammatory response which results in leaky capillaries, increased swelling and possibly organ dysfunction. Since the early 1990's, modified ultrafiltration (MUF) has been shown to decrease excess swelling, reduce bleeding, improve heart function, and decrease hospital length of stay. Angiopoietins are a family of proteins necessary for both normal and abnormal blood vessel formation. They also appear to play a role in capillary leak. Though MUF has been shown to improve clinical outcome following CPB, there continues to be conflicting reports whether this is a result of the filtration of inflammatory proteins or simply from excess fluid removal. Since angiopoietins appear to play a role in both inflammation and capillary leak, the investigators hypothesize that the benefit seen after MUF is also secondary to its ability to filter out these proteins, especially angiopoietin-2.

Detailed Description
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During cardiopulmonary bypass (CPB) for corrective or palliative congenital heart surgery, a child's blood is subjected to hemodilution, hypothermia, nonpulsatile blood flow and exposure to foreign and non-endothelialized surfaces. These non-physiologic conditions trigger the host's innate systemic inflammatory response which results in capillary leak, increased total body water and can lead to end organ dysfunction. Since the early 1990's, modified ultrafiltration (MUF) has been shown to decrease excess tissue edema, reduce postoperative bleeding, improve cardiac contractility, maintain hemodynamic stability, and decrease hospital length of stay. Angiopoietins are a family of vascular growth factors necessary for both normal and abnormal blood vessel formation and appear to play a role in capillary leak. Though MUF has been shown to improve clinical outcome following CPB, there continues to be conflicting reports whether this is a result of the filtration of inflammatory cytokines or simply excess fluid removal. Since angiopoietins appear to play a role in both inflammation and capillary leak, the investigators aim to determine whether MUF's clinical benefit is also secondary to its ability to filter out these molecules, more specifically angiopoietin-2.

Official Title
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Plasma Angiopoietin Levels in Children Undergoing Modified Ultrafiltration Following Cardiopulmonary Bypass

Conditions
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Congenital Heart Defects

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients with congenital heart disease undergoing surgical intervention requiring cardiopulmonary bypass and modified ultrafiltration. Exclusion Criteria: Any patients with congenital heart disease who will not require modified ultrafiltration.

Ages Eligible for Study
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Maximum Age: 18 Years

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pro- and anti-inflammatory protein levels after modified ultrafiltration | Modified ultrafiltration (MUF) is the process after cardiopulmonary bypass during which a filtration unit is added and blood is filtered and returned back to the patient. The goal of this project is to evaluate the effect of MUF on concentrations of Angiopoietin-2 (Ang-2) and IL 8, two known pro-inflammatory markers involved in capillary leakage, as well as Ang-1 and IL 10, two anti-inflammatory mediators. Levels will be drawn prior to bypass, after MUF and at ICU admission. | baseline to completion of MUF, on average 2 hours | 
| Change from baseline in pro- and anti-inflammatory protein levels at ICU admission | Modified ultrafiltration (MUF) is the process after cardiopulmonary bypass during which a filtration unit is added and blood is filtered and returned back to the patient. The goal of this project is to evaluate the effect of MUF on concentrations of Angiopoietin-2 (Ang-2) and IL 8, two known pro-inflammatory markers involved in capillary leakage, as well as Ang-1 and IL 10, two anti-inflammatory mediators. Levels will be drawn prior to bypass, after MUF and at ICU admission. | baseline to ICU admission, on average 7 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker correlation with patient outcome | The biomarkers will be compared to the age of patient, type of surgery performed as well as to post procedure outcome measurements to see if specific protein levels correlate with patient outcomes. | Duration of pediatric ICU admission, on average 7 days | 
| Pro- and anti-inflammatory protein presence in ultrafiltration fluid | MUF fluid samples will be drawn following bypass. Ang-2, Ang-1, IL-8 and IL-10 levels will be measured to determine if present. | Upon MUF completion, on average 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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children, congenital heart defects, cardiopulmonary bypass, modified ultrafiltration, angiopoietins, cytokines