Characterisation of physiological and blood biomarker changes in paediatric congenital cardiac interventions

Background: Physiological and blood biomarker changes could give new insights into brain injury mechanisms associated with paediatric congenital heart disease (CHD) surgery. Objectives: This thesis aimed to characterise physiological and blood biomarker changes associated with paediatric CHD interventions. Methods: A systematic review was performed to investigate the incidence of perioperative brain MRI findings from studies that had conducted both pre- and post-surgery brain MRI. As preparation for our clinical study, a neonatal TCD probe holder was developed, and the accuracy of our TCD equipment was verified through development of a Doppler phantom mimicking the middle cerebral artery. Finally, a prospective observational study was conducted involving measurement of pre-, intra- and post-operative cerebral blood flow velocity (CBFV), physiological monitoring, analysis of blood-based brain injury and inflammatory biomarkers, and brain MRI in infants undergoing CHD interventions (on-pump, off-pump, and catheterisation). Results: Our systematic review demonstrated that new brain MRI findings are typically present in 51% of infants following CHD surgery. Our in vitro study provided a better understand of TCD CBFV measurements and revealed differences between manufacturers at high velocities. CBFV monitoring using TCD at various perioperative time-points in 38 CHD infants revealed differences in cerebral haemodynamics between CHD repair groups. Analysis of 12 blood-based brain injury and inflammatory biomarkers in 20 infants revealed high levels of biomarkers, especially in infants undergoing on-pump surgery. Finally, a case-study is reported, which includes brain MRI findings in a 3-month-old infant who underwent trans-catheter CHD repair. Conclusion: TCD monitoring, blood biomarkers, and MRI, could be valuable in addressing knowledge gaps around perioperative brain injury and have the potential to support the evaluation of methods for improving outcome. Further work should also assess neurodevelopmental outcome for comparison with TCD, blood biomarkers, and brain MRI outcomes around the time of surgery in a larger group of patients.