Prognostic Markers of Inflammation in Infants Undergoing Cardiopulmonary Bypass

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

• Single blood draw (Procedure): One blood draw of 0.5 ml volume prior to discharge
• Multiple blood draws (Procedure): Blood draw at 6 peri-operative time points.
• Multiple blood draws (Procedure): Blood draw at 7 peri-operative time points

Primary outcomes

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

Secondary outcomes

• Change in level of inflammatory response [Baseline, up to 24 hours]: 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)
• Length of mechanical ventilation [Participants will be followed throughout hospital course, maximum length of follow-up one year]: Number of days on mechanical ventilation following day of surgery until the point of extubation
• Acute kidney injury [Participants will be followed for the first twenty four hours postoperatively]: Doubling of creatinine in first twenty four hours compared to preoperative levels
• Extracorporeal membrane oxygenation (ECMO) [First 48 hours postoperatively]: Whether or not patient requires ECMO cannulation
• ICU length of stay [Participants will be followed throughout PICU/CVICU stay, maximum length of follow-up one year]: Number of days requiring pediatric/cardiac intensive care unit following day of surgery
• Hospital length of stay [Participants will be followed throughout entire hospital course, maximum length of follow-up one year]: Number of hospital days patient requires following the day of surgery
• Mortality risk [PIM-2 calculated within one hour of admission to PICU and PRISM-3 calculated at 12 and 24 hours after PICU admission]: Pediatric risk of mortality-3 scale (PRISM-3) and pediatric index of mortality (PIM-2)
• Mortality [Participants will be followed throughout hospital course, maximum length of follow-up one year]: Any type of death that occurs during patient's hospitalization
• Low cardiac output syndrome [Assessed at 48 hours postoperatively]: 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

Sex: All, ages: any to 6 Months

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

• Hala Chaaban, MD, Principal investigator, University of Oklahoma