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

Effect of Postoperative Hydrocortisone on Cardiovascular and Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass

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.

Study Overview

• Status: Completed
• Conditions: Heart Disease Congenital Complex
• Intervention / Treatment: Drug: Normal Saline; Drug: Hydrocortisone

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 weeks (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Solu Cortef

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Low Cardiac Output Syndrome (LCOS)	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.	first 48 hours after cardiac intensive care unit (CICU) admission post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of Days Subjects Alive and Ventilator Free	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.	up to 28 days post op
Hospital Length of Stay	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.	Admit to CICU till hospital discharge, approximately 3 weeks
Changes in Baseline Inflammatory Mediators	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.	0, 4,12, 24, and 48 hours post bypass
Average Inotrope Score	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.	first 48 hours post-op
Fluid Balance	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.	1st 48 hours post-op
Changes in Baseline Arterial-venous Oxygen Saturation Difference	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.	admit to the CICU
Time Until First Extubation	Respiratory values such as duration of intubation will be used as a secondary outcome.	Until discharge from hospital, approximately 2 weeks
CICU Length of Stay	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.	approximately 1 week
Mortality	Subject mortality will in the CICU will be used as a secondary outcome.	Duration of CICU stay, approximately 1 week
ACTH Stimulation Test	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.	24 hours prebypass and 0 hours post-bypass

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Jeffrey Alten, MD, UAB Pediatric Critical Care

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: March 16, 2012
• First Submitted That Met QC Criteria: May 8, 2012
• First Posted (ESTIMATE): May 10, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 10, 2015
• Last Update Submitted That Met QC Criteria: October 12, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Anti-Inflammatory Agents; Hydrocortisone; Hydrocortisone hemisuccinate
• Other Study ID Numbers: Postop Steroids after CPB