STeroids to REduce Systemic Inflammation After Infant Heart Surgery (STRESS)

Overview:

Congenital heart diseases (CHD) are the most common birth defects, occurring in nearly 1% of live births. Every year, an estimated 40,000 infants born in the U.S. suffer from CHD. Despite advances in surgical management, CHD requiring neonatal surgery is associated with poor outcomes; national registry data demonstrates post-operative major morbidity in 23% and 10% do not survive to hospital discharge.

Poor outcomes after neonatal heart surgery are often attributable to a severe systemic inflammatory response to cardiopulmonary bypass (CPB). CPB is necessary for most neonatal CHD surgeries. Therefore, to reduce the post-CPB inflammatory reaction, many surgeons administer pre-or intra-operative steroids. Steroids have been shown to reduce inflammatory markers after neonatal heart surgery. However, steroids also have potential harmful effects including an increased risk of post-operative infection. The recent SIRS trial evaluated the safety and efficacy of steroids after CPB in adults and demonstrated no beneficial effect of steroids but increased risk of post-CPB myocardial infarction and other major adverse events.

Adult trial results cannot be reliably extrapolated to neonates because the neonatal response to CPB is markedly different to that seen in adults; neonates demonstrate both a more pronounced inflammatory reaction and a different post-operative complication profile. For these reasons approximately 2/3rds of congenital heart surgeons continue to administer perioperative steroids to neonates undergoing heart surgery. Yet this practice is not evidence based as no safety/efficacy trial has ever evaluated steroids in neonates undergoing heart surgery with CPB. Several smaller steroid trials (all enrolling < 75 patients) have focused on surrogate outcome measures, but none have provided conclusive data.

The major barrier to performing a steroid trial in neonates with CHD has been the high cost associated with trial conduct for these relatively rare defects. To overcome this barrier, the investigators will use a novel approach leveraging existing registry infrastructure at CHD surgical sites that participate in the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD). Sites participating in the STS-CHSD collect data into their institutional databases using standardized case report forms so that the data can be exported to the STS-CHSD. These sites already employ data coordinating specialists to capture patient demographics, procedural variables, and post-operative outcomes (including a list of over 60 complication variables) using strict and consistent data element definitions. By leveraging these site-specific resources the investigators project that the investigators can reduce trial costs by >75%.