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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01595386
Recruitment Status : Completed
First Posted : May 10, 2012
Results First Posted : November 10, 2015
Last Update Posted : November 10, 2015
Information provided by (Responsible Party):
Jeffrey Alten, MD, University of Alabama at Birmingham

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.

Condition or disease Intervention/treatment Phase
Heart Disease Congenital Complex Drug: Hydrocortisone Drug: Normal Saline Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Postoperative Hydrocortisone on Cardiovascular and Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass
Study Start Date : April 2012
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Arm Intervention/treatment
Placebo Comparator: 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.
Drug: Normal Saline
This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.
Other Name: 0.9% Sodium Chloride

Experimental: 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.
Drug: 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.
Other Name: Solu Cortef

Primary Outcome Measures :
  1. Incidence of Low Cardiac Output Syndrome (LCOS) [ Time Frame: first 48 hours after cardiac intensive care unit (CICU) admission post-op ]
    Low Cardiac Output Syndrome (LCOS) within the first 48 hours after post-operative admission to the Pediatric Cardiac Intensive Care Unit was used as the primary outcome. This was defined as a double in inotropic support from post-operative admit, requiring Extracorporeal Membrane Oxygenation (ECMO) support, receiving Cardiopulmonary Resuscitation, or death.

Secondary Outcome Measures :
  1. Mean Number of Days Subjects Alive and Ventilator Free [ Time Frame: up to 28 days post op ]
    Respiratory variables include such as alive, ventilator free days at 28 days post-op will be used as secondary outcome. The mean number of days subjects were live and ventilator free up to the 28 days after surgery.

  2. Hospital Length of Stay [ Time Frame: Admit to CICU till hospital discharge, approximately 3 weeks ]
    The average length of hospital stay from the time the subject is admitted to the CICU post-op until they are discharged will be used as a secondary outcome.

  3. Changes in Baseline Inflammatory Mediators [ Time Frame: 0, 4,12, 24, and 48 hours post bypass ]
    Changes in pre-op inflammatory mediators will be assessed at 0, 4, 12, 24 and 48 hours post bypass and used as a secondary outcome.

  4. Average Inotrope Score [ Time Frame: first 48 hours post-op ]
    Average inotrope score over first 48 hours after Cardiac Intensive Care Unit admission was used as a secondary outcome. Inotrope Score is calculated based on the dose of inotropes currently infusing at a given time points. The formula for calculation is as follows: Epinephrine/Norepinephrine (mcg/kg/min) dose x100, plus Dopamine/Dobutamine (mcg/kg/min) dose x 1, plus Neosynephrine (mcg/kg/min) dose x10, plus Vasopressin (units/kg/hr) [(dose x60)/10,000] = Inotrope Score. Our institution does not include Milrinone in our inotrope score calculation because every patient receives a continuous infusion in the immediate post-operative period. The higher the inotrope score the more cardiac support the patient is requiring or the worse their cardiac function is becoming.

  5. Fluid Balance [ Time Frame: 1st 48 hours post-op ]
    Hemodynamic variable such as total fluid balance within the first 48 hours post-op will be used as a secondary outcome. Fluid balance is a calculation of the overall fluid status for a given time period. The total input (fluid, medications, etc) that are given to a patient during a given time frame (24 hours) minus the total output (urine, stool, drainage, etc. ) that comes out of a patient during a given time frame.

  6. Changes in Baseline Arterial-venous Oxygen Saturation Difference [ Time Frame: admit to the CICU ]
    Respiratory values such as changes in baseline arterial-venous oxygen saturation difference at admission to the pediatric cardiac intensive care unit will be used as a secondary outcome.

  7. Time Until First Extubation [ Time Frame: Until discharge from hospital, approximately 2 weeks ]
    Respiratory values such as duration of intubation will be used as a secondary outcome.

  8. CICU Length of Stay [ Time Frame: approximately 1 week ]
    CICU length of stay will be calculated from the time the subject is admitted to the CICU post-op until they are discharged from the unit. This will be used as a secondary outcome.

  9. Mortality [ Time Frame: Duration of CICU stay, approximately 1 week ]
    Subject mortality will in the CICU will be used as a secondary outcome.

  10. ACTH Stimulation Test [ Time Frame: 24 hours prebypass and 0 hours post-bypass ]
    AdrenoCorticoTropic Hormone stimulation test will be performed at least 24 hours pre-bypass and immediately after successful discontinuation of bypass and compared. These outcomes will be used as a secondary outcome.

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Ages Eligible for Study:   up to 28 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01595386

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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Sponsors and Collaborators
University of Alabama at Birmingham
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Principal Investigator: Jeffrey Alten, MD UAB Pediatric Critical Care
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Responsible Party: Jeffrey Alten, MD, Principal Investigator, Associate Professor of Pediatrics, Medical Director of the UAB Pediatric Cardiac Intensive Care Unit, University of Alabama at Birmingham Identifier: NCT01595386    
Other Study ID Numbers: Postop Steroids after CPB
First Posted: May 10, 2012    Key Record Dates
Results First Posted: November 10, 2015
Last Update Posted: November 10, 2015
Last Verified: October 2015
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents