DEX vs SEVO in Congenital Heart Surgery

Study Overview
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Brief Summary
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Anesthesia-related neurotoxicity in the developing brain is still a concern although evidence in humans is debatable. Moreover, it is unclear whether repeated and/or prolonged exposures are harmless and whether their effects are more pronounced in newborns and infants with brains more vulnerable to injury. One such specific group of patients is children with congenital heart disease (CHD). Nearly, half of the school-age survivors with CHD exhibit neurodevelopmental symptoms. It is thus important to elucidate whether any plausible neurotoxicity of the commonly used anesthetic agents can be observed in this population, and whether specific neuroprotective strategies can be demonstrated within the frame of a randomized controlled trial (RCT). Animal data have shown that dexmedetomidine (DEX) induces neuroprotective effects only at well-adjusted doses. One major issue with trials of anesthetic neurotoxicity is the latency between the conduct of these studies and the assessment of neurodevelopmental outcome. In contrast, the use of biomarkers of neuronal injury could be extremely valuable. Serum Neurofilament Light (NfL) has been shown to be a sensitive and specific marker of neuronal injury and is associated with neurologic outcome of children with various pathologies. The investigators hypothesize that in congenital heart surgery, use of DEX as main anesthetic agent in conjunction with low dose sevoflurane results in less release of serum NfL and is thus potentially less neurotoxic compared to the current standard of care. The hypothesis is tested with a RCT including patients between 0 - 3y undergoing surgery with cardiopulmonary bypass. To avoid any neurotoxicity due to anesthetic overdose, intraoperative burst suppression will be avoided. In addition to postoperative comparison of serum NfL, postoperative electroencephalogram and neurodevelopmental outcome of both groups will be compared taking into consideration the genetic background.

Official Title
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Effect of DEXmedetomidine and LOw Dose Sevoflurane on the Release of Serum Neurofilament Light in Congenital Cardiac Surgery.

Conditions
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Heart Defects, Congenital

Intervention / Treatment
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* Drug: DEX group
* Other: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients up to 3 years Must undergo cardiac surgery with CPB Exclusion Criteria: Preoperative chronic kidney disease (glomerular filtration rate of less than 30 ml/min per 1.73m2 for greater than 3 months) Preoperative cerebral hemorrhage, stroke or Preoperative seizures Abnormal preoperative cerebral ultrasound Preoperative Extracorporeal Life Support Preoperative sedated and intubated patients Preterm newborns (< 32 W gestational age) Newborns weighing < 2 kg Patients with Williams-Beuren syndrome.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 3 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The Intervention Drug is DEXMEDETOMIDINE
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DEX group<br>Participants will receive an intraoperative and postoperative DEX infusion. In addition a low dose of sevoflurane will be administered. | Drug: DEX group<br>* Participants will receive a dexmedetomidine infusion in addition to low dose sevoflurane anesthesia.<br>|
| Active Comparator: Control group<br>Participants will receive general anesthesia with sevoflurane according to institutinal's practice. | Other: Control group<br>* Participants will receive general anesthesia based on institutional's practice with commonly used doses of sevoflurane.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of serum Neurofilament Light | To show a difference of change in serum NfL concentrations between both groups at 24h compared to baseline values. | At 24 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of serum Neurofilament Light |  | Baseline before start of anesthesia | 
| Concentration of serum Neurofilament Light |  | Start of cardiopulmonary bypass | 
| Concentration of serum Neurofilament Light |  | At 72 hours postoperatively | 
| Concentration of serum Neurofilament Light |  | At postoperative day 5 | 
| Neurodevelopmental outcome testing | Bailey Scales of Infant and Toddler Development - Third Edition. Higher scores are better. | 3 months postoperatively | 
| Neurodevelopmental outcome testing | Bailey Scales of Infant and Toddler Development - Third Edition. Higher scores are better. | 6 months postoperatively | 
| Postoperative electroencephalogram registration | Number of seizures | 24 hours | 
| Dose of Analgesics | Use and dose of analgesics | 72 hours postoperatively | 
| Renal function | Defined by pediatric RIFLE criteria | 7 days postoperatively | 
| Concentration of regional cerebral oxygenation | Area Under Curve of time spent below rSO2 levels of 50%; Area Under Curve of time spent below baseline rSO2 levels | Intraoperatively | 
| Postoperative electroencephalogram registration | Number of burst-suppression episodes | 24 hours | 
| Postoperative electroencephalogram registration | Duration of burst-suppression episodes | 24 hours | 
| Postoperative electroencephalogram registration | Duration of seizures | 24 hours | 
| Time of exsudation | time to extubation | 7 days postoperatively | 
| Pediatric Intensive Care Unit stay | Duration of stay in Pediatric Intensive Care Unit | Up to 24 weeks | 
| Hospital stay | Days of hospital stay | Up to 24 weeks |