Title : The s100B biomarker as a predictor of neurological damage after open heart surgery and cardiopulmonary bypass machine in cyanotic children.
Abstract:
Congenital heart defect (CHD) is the most common of all congenital defects, affecting nearly 1% of live births. Brain injuries and adverse neurodevelopmental outcomes after pediatric heart surgery remain a dominant focus of improving clinical care Cerebral injury resulting from cardiac surgery depicts a devastating complication that can have severe effects on the neurological outcome. While this can be attributed to the inherent nature of cardiac disease, with possible hypoxemia and cyanosis, the surgical procedure itself poses its own risk, owing in particular to the use of cardio-pulmonary bypass (CPB); potentially leading to compromised circulation, hypoxia and systemic inflammation, as reported after adult cardiac surgery. The exponential reduction of the mortality rate in children with CHD has revealed that neurologic and neurodevelopmental complications are key issues in these patients because they may affect functional outcome, peer-interaction, and overall quality of life. As survival has increased over the past few decades, it has allowed clinicians to document long-term developmental follow-up of these children. A growing body of literature indicates that outcomes of infants with complex CHD, namely children with HLHS, other single-ventricle pathology, or d-transposition of the great arteries (TGA),has shifted from mortality to developmental disability. Surgical approaches have been associated with neurologic complications including seizures, choreoathetosis, ischemic lesions, and encephalopathy. Long term complications include neurocognitive deficits at school starting age in nearly 50% of children who underwent surgery for complex CHD requiring cardiopulmonary bypass (CPB) and aortic cross clamping (ACC), with or without deep hypothermic circulatory arrest (DHCA). Altered brain development and newly acquired brain injuries during CHD surgery influence the overall neurologic outcome in a multifactorial, cumulative, and synergistic manner. The effects of intraoperative interventions that are required to correct the congenital lesion, inadvertent events from the surgical procedure and correctable hypoxia/cyanosis due to the nature of the surgical lesion in the postoperative period, all may have a neurological effect. Critical changes in brain oxygenation during the peri-operative period might put these patients in a more vulnerable situation compare with those patients with normal biventricular physiology and normal saturation. In the days following the operation, neurologic sequelae are hard to assess as the patient is usually sedated and treated with analgesics which affect his level of consciousness. One tool for cerebral monitoring is near infra red spectroscopy (NIRS), which can easily and continuously be used to monitor regional cerebral oxygenation in real time during the vulnerable perioperative phase. Although NIRS is capable of showing changes from a measured baseline quite accurately, it does not provide exact absolute values due to technical limitations. To date ,no absolute lower thresholds stating critical perfusion states have been established. Therefore, new early and accurate biomarkers are needed for the prediction and diagnosis of patients who are at risk for cerebral postoperative damage. Such a biomarker could help in guiding therapy and possibly prevent the damage. Brain-specific proteins detected in serum, so called ‘‘neuromarkers,’’ have been used as indicator of a variety of brain injuries, including traumatic brain injury, hypoxic-ischemic brain injury after cardiac arrest, and others However they have not been shown to correlate with neurological outcomes. In particular, increased serum levels of S100b have been considered evidence for neuronal injury. It had been noted that few biomarkers have been studied in previous research including glial fibrillary acidic protein (GFAP), S100b, miRNA 124a, neuronspecific enolase (NSE) and others. On our study we will focus on the S100b biomarker due to the fact that S100B has been proposed as a consolidated marker of brain damage in infants with congenital heart disease undergoing cardiac surgery and cardiopulmonary bypass. S100 protein family members are acidic proteins characterized by their calcium-dependent biological effect. It is expressed in different tissues, but shows brain tissue specific, and therefore implicated in cerebral damage. S100b is mainly concentrated in astrocytes. Its levels in biological fluids are recognized as a reliable biomarker of active neural distress. Although the wide spectrum of diseases in which the protein is involved reduces its specificity, its levels remain an important aid in monitoring the trend of the disorder. Matheis et al. showed that Uncontrolled hyperoxic reoxygenation on CPB for surgical correction of congenital heart defects is associated with higher S100 levels in cyanotic infants as compared to acyanotic patients undergoing comparable operations. To achieve the goal of neurological protection during this critical time period, sensitive and specific neurological monitoring tools that determine when injuries have occurred must be sought. In particular, these tools must also predict adverse clinical outcomes. We hypothesized that the use of this neurological monitoring tool can predict short-term adverse neurological outcome in children undergoing heart surgery, Also early identification of neurological damage is difficult and a clinically available bedside system to detect such injuries would represent a significant advance.
Audience Take Away Notes:
- The goal of this study is to determine the utility of a serum biomarker, specifically S100b, in identifying children at risk from adverse neurological outcome after heart surgery.
- Does S100b levels differ between Very Canotic congenital heart disease with baseline on saturation between versus mild cyanotic patiants with baseline saturation 85-75% and is there correlation between hyperoxygenation and neurological damage.
