Effect of Postop Steroids on Cardiovascular/Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass

NCT ID: NCT01595386

Last Updated: 2015-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2013-11-30

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.

Conditions

Heart Disease Congenital Complex

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Normal Saline

The subjects will receive a bolus after successful completion of bypass and the post-pump adrenal corticotrophin hormone (ACTH) stim test equal to a 50mg/m2 dose of Hydrocortisone. This will be followed by a continuous infusion comparable to the rates a Hydrocortisone drip would run at. This infusion will be tapered down over the next 120 hours.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

Hydrocortisone

Subjects enrolled in this arm of the study will receive a 50mg/m2 bolus of Hydrocortisone after successful completion of CPB and the post-pump ACTH stim test has been performed. This will be followed by a continuous infusion of Hydrocortisone that will be tapered over the next 120 hours.

Group Type: EXPERIMENTAL

Hydrocortisone

Intervention Type: DRUG

The drug will be bolused at 50mg/m2 followed by a continuous infusion that will start at 50mg/m2 for the first 48 hours and then be tapered as follows: 40mg/m2/day over 24 hours, 30mg/m2/day over 12 hours, 20 mg/m2/day over 12 hours, 10mg/m2/day over 24 hours, then off.

Interventions

Hydrocortisone

The drug will be bolused at 50mg/m2 followed by a continuous infusion that will start at 50mg/m2 for the first 48 hours and then be tapered as follows: 40mg/m2/day over 24 hours, 30mg/m2/day over 12 hours, 20 mg/m2/day over 12 hours, 10mg/m2/day over 24 hours, then off.

Intervention Type: DRUG

Normal Saline

This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.

Intervention Type: DRUG

Other Intervention Names

Solu Cortef; 0.9% Sodium Chloride

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 28 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Alten, MD

Principal Investigator, Associate Professor of Pediatrics, Medical Director of the UAB Pediatric Cardiac Intensive Care Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Alten, MD

Role: PRINCIPAL_INVESTIGATOR

UAB Pediatric Critical Care

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

Postop Steroids after CPB

Identifier Type: -

Identifier Source: org_study_id