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Cardiac pathology is a major risk for brain injury and neurodevelopmental deficit. The most common cause of cardiac pathology is congenital heart defects (CHD) about 4-8/1000 live births a year. The most common etiology of the brain insult is hypoxic ischemic injury (HII) as result of hemodynamic instability in the perioperative period. Similar insults in adults with cardiac arrest or infants with neonatal asphyxia, was successfully treated with hypothermia, initiated within 6 hours after the event. Although, hypothermia is most likely an effective treatment for HII in children with cardiac anomaly, it also carries a risk for bleeding or infection of the surgical wound. In this randomized control trial, hypothermia treatment will be compared to normothermia treatment of patients in the pediatric cardiac intensive care unit (PCICU) following severe HII in the PCICU or operating room. The effect will be quantified by MRI, serum biomarkers of brain injury, amplitude integrated EEG, neurological evaluation coagulation and infection evaluation in the acute phase and by developmental assessment at 1, 6 months and 2, 5 years. Favorable effect of hypothermia with minimal risks may open the door for the implementation of hypothermia as a standard care in PCICUs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Whole body hypothermia | Active Comparator | Children that had an event suspected for hypoxic ischemic brain injury, according to the inclusion criteria, will be randomly allocated for whole body hypothermia therapy. Treatment will be initiated within 6 hours of the event, the child will be dressed with a cooling suit and their temperature will be monitored. Whole body hypothermia will be to 33 +/- 1 °C . Treatment period will be 48 hours with 24 hours warming up period. |
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| Whole body normothermia | Placebo Comparator | Children that had an event suspected for hypoxic ischemic brain injury, according to the inclusion criteria, will be randomly allocated for normothermia therapy. Treatment will be initiated within 6 hours of the event, the child will be dressed with a cooling suit and their temperature will be monitored. Cooling will be to 36-37 °C . Treatment period will be 72 hrs. |
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| Control | No Intervention | A group of children that underwent a cardiac surgery and was not suspected to have an hypoxic ischemic brain injury. This group will be undergo the similar biomarkers collection as arm 1 and 2. The information will be used to measure the change in biomarkers between surgeries with no HII to those in arm 1+2. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Whole body hypothermia | Device | Treatment will be initiated within 6 hours of the event, the child will be dressed with a cooling suit and their temperature will be monitored. Cooling will be to 33 +/- 1 °C . Treatment period will be 48 hours with 24 hours warming up period. |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarkers | Each child will have 4 blood samples for biomarkers including S100B, Glial Fibrillary Acidic Protein and Specific Neuronal Enolase at the following schedule: before the cardiac surgery, within 6 hr after the surgery, 24 and 48 hrs after the surgery | 48 hours after the surgery |
| Magnetic Resonance Imaging | In arms 1 and 2 an MRI with the sequences of T1, T2, Diffusion Weighted Imaging, Diffuse Tensor Imaging and Magnetic Resonance Spectroscopy | 10 days after |
| Neurological Evaluation | Neurological assessment will be done prior to the cardiac surgery and and one week (or earlier if the child will be fully recovered and discharged before) using standard neurological evaluation, pediatric stroke outcome measure | 1 week |
| Measure | Description | Time Frame |
|---|---|---|
| Short term neuro-developmental outcome | Neurological assessment using standard neurological evaluation, pediatric stroke outcome measure and pediatric cerebral performance category | 2 months |
| Short term neuro-developmental outcome |
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Inclusion Criteria:
Every child entering the PCICU, age < 7 years
The child will enter arm 1 or 2 if he underwent the event described in section 3.
Hypoxic ischemic event that would render hypothermia treatment is defined as
Resuscitation comprised of chest compressions for more than 2 minutes, and the first blood tests immediately after the resuscitation show a serum lactate level of more than 90 mg/dl OR Resuscitation comprised of chest compressions for more than 2 minutes, and the first blood tests immediately after the resuscitation shows a serum lactate level of more than 40 mg/dl and a blood pH level of less than 7.1
Initiation of hypothermia treatment within 6 hours following the hypoxic ischemic event defined in section 3.
Exclusion criteria
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Omer Bar Yosef, MD-PhD | Contact | 972-52-6667344 | omer.baryosef@sheba.health.gov.il | |
| Amir Vardi, MD | Contact | 927-3-5308010 | amir.vardi@sheba.health.gov.il |
| Name | Affiliation | Role |
|---|---|---|
| Omer B Bar Yosef, MD-PhD | Chain Sheba Medical Ceneter | Principal Investigator |
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| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| D002545 | Brain Ischemia |
| D002534 | Hypoxia, Brain |
| D007035 | Hypothermia |
| D020925 | Hypoxia-Ischemia, Brain |
| ID | Term |
|---|---|
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
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At 2 and 5 yrs after the hypothermia treatment a c. Vineland adaptive behavior scale (Vineland™-II) will be done
| 5 yrs |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D000860 | Hypoxia |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001832 | Body Temperature Changes |