Clinical trial NCT01595386: Effect of Postop Steroids on Cardiovascular/Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass
Official title: Effect of Postoperative Hydrocortisone on Cardiovascular and Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Disease Congenital Complex
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2012-05-10
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This protocol is designed to offer insight into critical illness related corticosteroid insufficiency and steroid supplementation in neonates undergoing cardiac surgery with cardiopulmonary bypass by administering exogenous steroids in the immediate post-operative period.

Detailed description: Open-heart surgery with cardiopulmonary bypass (CPB) induces an acute systemic inflammatory response (SIRS) via synthesis and release of inflammatory mediators. These inflammatory cascades may result in the development of capillary leak and generalized tissue edema, which are associated with multiorgan dysfunction involving the myocardium, lungs, kidneys, pancreas, and central nervous system. Neonates are especially susceptible to the injurious effects of SIRS. In attempt to blunt post-bypass SIRS, most neonatal heart programs have protocols in which patients receive preoperative and/or intraoperative steroids. Despite this widespread use, studies have not demonstrated consistent benefit in this therapy, and neonates often continue to suffer the deleterious effects of SIRS postoperatively. Only one study was designed to evaluate the impact of prophylactic postoperative steroid administration on outcomes after neonatal CPB. The early postoperative periods is a crucial time during which attenuation of CPB-induced SIRS by exogenous steroids may lead to improved clinical outcomes.

Adrenal insufficiency in neonates post-CPB may accentuate the harmful effects of SIRS by diminishing the anti-inflammatory and hemodynamic stabilization benefits of endogenous cortisol. Evidence suggests that neonates may suffer from inadequate cortisol activity relative to the severity of illness post-CPB, in part related to immaturity of their hypothalamic-pituitary-adrenal (HPA) axis. This so-called critical illness-related corticosteroids insufficiency (CIRCI) may contribute to low cardiac output syndrome (LCOS), respiratory dysfunction, and capillary leak in the postoperative period.

Much of the support for CIRCI as a contributor to LCOS after CPB originates from small clinical studies that demonstrate benefit of exogenous steroid supplementation on various short term clinical outcomes in patients with shock. Yet it is not clear if benefit from exogenous steroids suggests by dysregulation of the HPA axis or whether these are merely alternative effects of steroids. Investigators have recently begun to describe the cortisol response in neonates post-CPB, but there is no consensus regarding the incidence of clinically important adrenal insufficiency, its identification, or who should receive exogenous steroids.

Eligibility criteria: Inclusion Criteria:

1. Neonate (\< 28 days old) undergoing correct cardiac surgery, or infants undergoing the following surgery procedures: Norwood, Arterial Switch, Total Anomalous Pulmonary Venous Return Repair, Interrupted Aortic Arch Repair, Truncus Arteriosus Repair
2. Successfully weaned off cardiopulmonary bypass after cardiac surgery

Exclusion Criteria:

1. requirement for extracorporeal membrane oxygenation (ECMO) in the operating room
2. Known immune deficiency
3. Having previously received systemic steroids (except for two routine preoperative doses)
4. A current signed Do not resuscitate (DNR) or limitation of care order
5. Current enrollment in another interventional clinical study
6. Refusal of parental consent
7. Previous diagnosis of adrenal insufficiency
8. \> 28 days old at time of surgery whose repair dose not require CPB

Primary outcomes:
measure: Incidence of Low Cardiac Output Syndrome (LCOS)
timeFrame: first 48 hours after cardiac intensive care unit (CICU) admission post-op
Secondary outcomes:
measure: Mean Number of Days Subjects Alive and Ventilator Free
timeFrame: up to 28 days post op
measure: Hospital Length of Stay
timeFrame: Admit to CICU till hospital discharge, approximately 3 weeks
measure: Changes in Baseline Inflammatory Mediators
timeFrame: 0, 4,12, 24, and 48 hours post bypass
measure: Average Inotrope Score
timeFrame: first 48 hours post-op
measure: Fluid Balance
timeFrame: 1st 48 hours post-op
measure: Changes in Baseline Arterial-venous Oxygen Saturation Difference
timeFrame: admit to the CICU
measure: Time Until First Extubation
timeFrame: Until discharge from hospital, approximately 2 weeks
measure: CICU Length of Stay
timeFrame: approximately 1 week
measure: Mortality
timeFrame: Duration of CICU stay, approximately 1 week
measure: ACTH Stimulation Test
timeFrame: 24 hours prebypass and 0 hours post-bypass
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: UAB Pediatric Critical Care
name: Jeffrey Alten, MD
role: PRINCIPAL_INVESTIGATOR
References: