Delayed Rewarming for Neuroprotection in Infants Following Cardiopulmonary Bypass Surgery

Study Overview
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Brief Summary
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This is an unblinded, single center, randomized study of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, randomized to either the delayed rewarming intervention or to the standard of care (strict normothermia).

Detailed Description
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Control Group: The congenital heart surgery will be performed according to usual practice with the degree of intra-operative hypothermia determined by the cardiothoracic surgeon based on the anticipated complexity of the case. Following completion of the surgical procedure, the infant will be rapidly rewarmed on CPB at a rate of 0.2 to 0.3°C per minute to a normothermic temperature of 36.5°C. Infants in this group will be given a single weight-based 15 mg/kg dose of intravenous Tylenol in the operating room (OR) by the anesthesiologist as the chest is being closed. The infant will be transported to the Pediatric Intensive Care Unit (PICU) for routine post-operative monitoring. If the infant develops a fever, ice packs will be applied to the axilla and groin per usual routine and removed once the fever has abated. Experimental group: Partial rewarming will occur on CPB to 35°C. During the last hour of surgery, the infant's temperature will be maintained at 35°C while the chest is closed by using a BairHugger and lowering the room temperature. Transfusions of packed red blood cells, fresh frozen plasma and cryoprecipitate will not be automatically warmed. Infants will be given a single 15 mg/kg dose of IV Tylenol in the OR. The infant will be transported to the PICU at 35°C and placed on the temperature-regulating blanket. The infant will be incrementally rewarmed with increases in temperature of 0.3°C every 2 hours for 6 hours, then 0.2°C every 2 hours for 6 hours to the goal temperature of 36.5°C. Once the infant is stable, EEG will be performed for 48 hours to screen for seizures. The PI will interpret the EEG every 6-8 hours. The infant will remain on the blanket at 36.5°C for another 12 hours. The blanket and esophageal temperature probe will then be removed a total of 24 hours after surgery was completed.

Official Title
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Delayed Rewarming for Neuroprotection in Infants Following Cardiopulmonary Bypass Surgery

Conditions
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Post-Op Complication

Intervention / Treatment
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* Other: Strict normothermia
* Device: Delayed Rewarming


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of congenital heart disease requiring congenital heart surgery on bypass Age less than 6 months at the time of surgery Intra-operative hypothermia less than or equal to 35°C Exclusion Criteria: Concern for underlying coagulation disorder such as hemophilia Death in the operating room Inability to wean of cardiopulmonary bypass at conclusion of surgery

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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Strict Normothermia<br>Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU. | Other: Strict normothermia<br> <br> |
| Experimental: Delayed Rewarming<br>Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours. | Device: Delayed Rewarming<br>* Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infants With Elevated s100b and NSE | In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, does delayed rewarming administered during the 12 hours after surgery, compared to standard care, decrease brain injury as measured by levels of serum biomarkers of brain injury, s100b and neuron specific enolase during the four days after surgery? | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, is there evidence for increased frequency of severe, moderate or other adverse events in the delayed rewarming group compared to the standard of care group? | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapeutic Hypothermia