Trial Outcomes & Findings for Effect of Postop Steroids on Cardiovascular/Respiratory Function in Neonates Undergoing Cardiopulmonary Bypass (NCT NCT01595386)

Last Updated: 2015-11-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

40 participants

Primary outcome timeframe

first 48 hours after cardiac intensive care unit (CICU) admission post-op

Results posted on

2015-11-10

Participant Flow

Participant milestones

Participant milestones
Measure	Normal Saline The subjects will receive a bolus after successful completion of bypass and the post-pump adrenocorticotrophic 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. Normal Saline: 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 cardiopulmonary bypass (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. 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.
Overall Study STARTED	21	19
Overall Study COMPLETED	21	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.	Total n=40 Participants Total of all reporting groups
Age, Continuous	6 Days n=5 Participants	5 Days n=7 Participants	6 Days n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	19 participants n=7 Participants	40 participants n=5 Participants
Surgical Procedure Norwood	7 number of patients n=5 Participants	6 number of patients n=7 Participants	13 number of patients n=5 Participants
Surgical Procedure Arterial switch operation	6 number of patients n=5 Participants	6 number of patients n=7 Participants	12 number of patients n=5 Participants
Surgical Procedure Interrupted aortic arch repair	3 number of patients n=5 Participants	4 number of patients n=7 Participants	7 number of patients n=5 Participants
Surgical Procedure Aortic arch augmentation	1 number of patients n=5 Participants	1 number of patients n=7 Participants	2 number of patients n=5 Participants
Surgical Procedure Truncus arteriosus repair	3 number of patients n=5 Participants	0 number of patients n=7 Participants	3 number of patients n=5 Participants
Surgical Procedure other	1 number of patients n=5 Participants	2 number of patients n=7 Participants	3 number of patients n=5 Participants

PRIMARY outcome

Timeframe: first 48 hours after cardiac intensive care unit (CICU) admission post-op

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Incidence of Low Cardiac Output Syndrome (LCOS)	57 percentage of patients	26 percentage of patients

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Mean Number of Days Subjects Alive and Ventilator Free	24 days Interval 17.0 to 26.5	25 days Interval 23.0 to 26.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Hospital Length of Stay	13.5 days Interval 9.0 to 24.0	19 days Interval 9.0 to 24.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Changes in Baseline Inflammatory Mediators 48 hr post bypass Il-10	7.9 pg/mL Interval 4.8 to 10.2	9.4 pg/mL Interval 7.0 to 15.4
Changes in Baseline Inflammatory Mediators 24 hr post bypass Il-1 beta	1.71 pg/mL Interval 0.89 to 4.01	0.77 pg/mL Interval 0.38 to 1.13
Changes in Baseline Inflammatory Mediators 48 hr post bypass Il-1 beta	0.76 pg/mL Interval 0.45 to 1.08	0.29 pg/mL Interval 0.13 to 0.54
Changes in Baseline Inflammatory Mediators 4 hr post bypsas Il-6	58 pg/mL Interval 44.8 to 83.4	65.2 pg/mL Interval 40.3 to 89.0
Changes in Baseline Inflammatory Mediators 24 hr post bypass Il-6	110 pg/mL Interval 59.2 to 199.0	45.5 pg/mL Interval 33.4 to 91.6
Changes in Baseline Inflammatory Mediators 48 hr post bypass TNF-alpha	5.1 pg/mL Interval 4.5 to 8.7	3 pg/mL Interval 2.3 to 4.4
Changes in Baseline Inflammatory Mediators Pre-op Il-10	4 pg/mL Interval 2.9 to 5.4	4.3 pg/mL Interval 3.0 to 6.7
Changes in Baseline Inflammatory Mediators 0 hr post bypass Il-10	225 pg/mL Interval 119.0 to 298.0	164 pg/mL Interval 105.3 to 312.0
Changes in Baseline Inflammatory Mediators 4 hr post bypss Il-10	53.5 pg/mL Interval 31.4 to 84.9	92.2 pg/mL Interval 54.5 to 141.0
Changes in Baseline Inflammatory Mediators 12 hr post bypass Il-10	17.5 pg/mL Interval 8.9 to 28.0	20.1 pg/mL Interval 17.3 to 34.8
Changes in Baseline Inflammatory Mediators 24 hr post bypass Il-10	11.4 pg/mL Interval 7.9 to 21.7	10.7 pg/mL Interval 7.0 to 16.4
Changes in Baseline Inflammatory Mediators Pre-op Il-1 beta	0.49 pg/mL Interval 0.28 to 0.87	0.53 pg/mL Interval 0.29 to 0.78
Changes in Baseline Inflammatory Mediators 0 hr post bypass Il-1 beta	0.44 pg/mL Interval 0.28 to 1.15	0.5 pg/mL Interval 0.28 to 0.63
Changes in Baseline Inflammatory Mediators 4 hr post bypass Il-1 beta	0.83 pg/mL Interval 0.55 to 1.24	1.2 pg/mL Interval 0.58 to 1.57
Changes in Baseline Inflammatory Mediators 12 hr post bypss Il-1 beta	0.49 pg/mL Interval 0.37 to 1.37	0.33 pg/mL Interval 0.21 to 0.8
Changes in Baseline Inflammatory Mediators Pre-op Il-6	3.6 pg/mL Interval 1.2 to 18.8	5.8 pg/mL Interval 2.8 to 15.1
Changes in Baseline Inflammatory Mediators 0 hr post bypass IL-6	13.6 pg/mL Interval 9.2 to 20.6	12.4 pg/mL Interval 9.7 to 19.8
Changes in Baseline Inflammatory Mediators 12 hr post bypass Il-6	93.7 pg/mL Interval 61.5 to 164.0	50.4 pg/mL Interval 39.8 to 84.7
Changes in Baseline Inflammatory Mediators 48 hr post bypass Il-6	40.1 pg/mL Interval 23.2 to 78.9	15.3 pg/mL Interval 10.9 to 24.6
Changes in Baseline Inflammatory Mediators Pre-op Il-8	27.1 pg/mL Interval 21.7 to 37.7	23.5 pg/mL Interval 19.2 to 32.3
Changes in Baseline Inflammatory Mediators 0 hr post bypass Il-8	118 pg/mL Interval 88.7 to 255.0	99.8 pg/mL Interval 71.4 to 188.5
Changes in Baseline Inflammatory Mediators 4 hr post bypss IL-8	212 pg/mL Interval 160.0 to 456.0	261.5 pg/mL Interval 183.3 to 331.5
Changes in Baseline Inflammatory Mediators 12 hr post bypass IL-8	153 pg/mL Interval 105.0 to 223.0	97 pg/mL Interval 62.9 to 139.0
Changes in Baseline Inflammatory Mediators 24 hr post bypass Il-8	129 pg/mL Interval 97.8 to 277.0	103 pg/mL Interval 63.3 to 134.5
Changes in Baseline Inflammatory Mediators 48 hr post bypass Il-8	67.3 pg/mL Interval 43.3 to 127.0	50.3 pg/mL Interval 37.4 to 59.1
Changes in Baseline Inflammatory Mediators Pre-op tumor necrosis factor (TNF)-alpha	4.7 pg/mL Interval 3.4 to 5.4	4.3 pg/mL Interval 2.9 to 5.0
Changes in Baseline Inflammatory Mediators 0 hr post bypass TNF-alpha	3.6 pg/mL Interval 2.5 to 5.4	2.9 pg/mL Interval 2.2 to 4.1
Changes in Baseline Inflammatory Mediators 4 hr post bypass TNF-alpha	6.4 pg/mL Interval 4.5 to 8.7	5.5 pg/mL Interval 4.9 to 6.9
Changes in Baseline Inflammatory Mediators 12 hr post bypss TNF-alpha	6.6 pg/mL Interval 4.5 to 8.7	4.2 pg/mL Interval 3.2 to 4.8
Changes in Baseline Inflammatory Mediators 24 hr post bypass TNF-alpha	5.8 pg/mL Interval 4.5 to 8.7	4.1 pg/mL Interval 3.2 to 5.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Average Inotrope Score Inotrope Score at 12 hours post bypass	5.3 Inotrope Score Interval 1.5 to 12.7	4.7 Inotrope Score Interval 1.7 to 10.7
Average Inotrope Score Inotrope Score 24 hours post bypass	0 Inotrope Score Interval 0.0 to 7.7	4 Inotrope Score Interval 0.0 to 7.3
Average Inotrope Score Inotrope Score 48 hours post bypass	0 Inotrope Score Interval 0.0 to 7.1	0 Inotrope Score Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Fluid Balance	-64 mL/kg Interval -107.0 to 12.0	-114 mL/kg Interval -148.0 to -60.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Changes in Baseline Arterial-venous Oxygen Saturation Difference	14 percentage of arterial-venous saturation Interval 10.0 to 24.2	9.5 percentage of arterial-venous saturation Interval 7.7 to 13.5

SECONDARY outcome

Timeframe: Until discharge from hospital, approximately 2 weeks

Respiratory values such as duration of intubation will be used as a secondary outcome.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Time Until First Extubation	55 hours Interval 21.0 to 195.0	51 hours Interval 34.0 to 83.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
CICU Length of Stay	162 hours Interval 137.0 to 389.0	213 hours Interval 118.0 to 501.0

SECONDARY outcome

Timeframe: Duration of CICU stay, approximately 1 week

Subject mortality will in the CICU will be used as a secondary outcome.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
Mortality	14 percentage of patients	0 percentage of patients

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Normal Saline-Placebo n=21 Participants The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 Participants 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. 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.
ACTH Stimulation Test Pre-op Post-stimulation cortisol	43.6 microg/dL Interval 34.6 to 51.0	47.1 microg/dL Interval 35.0 to 53.3
ACTH Stimulation Test Post-op ACTH	10.5 microg/dL Interval 6.5 to 14.0	7.5 microg/dL Interval 6.4 to 9.6
ACTH Stimulation Test Pre-op ACTH	24.5 microg/dL Interval 10.0 to 33.0	31 microg/dL Interval 16.5 to 54.0
ACTH Stimulation Test Pre-op Pre-stimulation cortisol	18.2 microg/dL Interval 7.5 to 26.0	23.3 microg/dL Interval 11.4 to 30.4
ACTH Stimulation Test Post-op Pre-Stimulation cortisol	89.4 microg/dL Interval 40.5 to 130.8	87.2 microg/dL Interval 58.1 to 131.0
ACTH Stimulation Test Post-op Post-stimulation cortisol	112.3 microg/dL Interval 66.6 to 145.9	118.8 microg/dL Interval 72.9 to 143.4

Adverse Events

Normal Saline-Placebo

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

Hydrocortisone

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Normal Saline-Placebo n=21 participants at risk The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 participants at risk 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. 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.
Cardiac disorders Extracorporeal Membrane Oxygenation	9.5% 2/21 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.	5.3% 1/19 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.
Surgical and medical procedures Death	14.3% 3/21 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.	0.00% 0/19 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.

Other adverse events

Other adverse events
Measure	Normal Saline-Placebo n=21 participants at risk The subjects will receive a bolus after successful completion of bypass and the post-pump 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. Normal Saline: This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.	Hydrocortisone n=19 participants at risk 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. 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.
Renal and urinary disorders Acute Kidney injury	33.3% 7/21 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.	36.8% 7/19 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.
Endocrine disorders Hyperglycemia	71.4% 15/21 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.	52.6% 10/19 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.
Infections and infestations Antibiotics for suspected infection	38.1% 8/21 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.	36.8% 7/19 • Adverse events were collected from admit to the cardiac intensive care unit post-op until discharge from the cardiac intensive care unit.

Additional Information

Jeffrey Alten, M.D., Director of Clinical and Translational Research Department

University of Alabama at Birmingham, Pediatric Cardiac Critical Care

Phone: 205-975-3123

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place