Heart Disease Congenital Complex
Conditions
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.
Interventions
DRUGHydrocortisone
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.
DRUGNormal Saline
This will be bolused and infused in the same manner as the hydrocortisone arm to ensure blinding of study arm.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Days to 28 Days
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Low Cardiac Output Syndrome (LCOS) | 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
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay | 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. |
| Changes in Baseline Inflammatory Mediators | 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. |
| Average Inotrope Score | 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. |
| Fluid Balance | 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. |
| Mean Number of Days Subjects Alive and Ventilator Free | 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. |
| Time Until First Extubation | Until discharge from hospital, approximately 2 weeks | Respiratory values such as duration of intubation will be used as a secondary outcome. |
| CICU Length of Stay | 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. |
| Mortality | Duration of CICU stay, approximately 1 week | Subject mortality will in the CICU will be used as a secondary outcome. |
| ACTH Stimulation Test | 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. |
| Changes in Baseline Arterial-venous Oxygen Saturation Difference | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normal Saline-Placebo 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. | 21 |
| 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.
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. | 19 |
| Total | 40 |
Baseline characteristics
| Characteristic | Hydrocortisone | Total | Normal Saline-Placebo |
|---|---|---|---|
| Age, Continuous | 5 Days | 6 Days | 6 Days |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 32 Participants | 16 Participants |
| Region of Enrollment United States | 19 participants | 40 participants | 21 participants |
| Sex: Female, Male Female | 5 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Male | 14 Participants | 27 Participants | 13 Participants |
| Surgical Procedure Aortic arch augmentation | 1 number of patients | 2 number of patients | 1 number of patients |
| Surgical Procedure Arterial switch operation | 6 number of patients | 12 number of patients | 6 number of patients |
| Surgical Procedure Interrupted aortic arch repair | 4 number of patients | 7 number of patients | 3 number of patients |
| Surgical Procedure Norwood | 6 number of patients | 13 number of patients | 7 number of patients |
| Surgical Procedure other | 2 number of patients | 3 number of patients | 1 number of patients |
| Surgical Procedure Truncus arteriosus repair | 0 number of patients | 3 number of patients | 3 number of patients |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 21 | 17 / 19 |
| serious Total, serious adverse events | 3 / 21 | 1 / 19 |
Outcome results
Primary
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.
Time frame: first 48 hours after cardiac intensive care unit (CICU) admission post-op
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline-Placebo | Incidence of Low Cardiac Output Syndrome (LCOS) | 57 percentage of patients |
| Hydrocortisone | Incidence of Low Cardiac Output Syndrome (LCOS) | 26 percentage of patients |
p-value: 0.049t-test, 2 sided
Secondary
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.
Time frame: 24 hours prebypass and 0 hours post-bypass
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Normal Saline-Placebo | ACTH Stimulation Test | Pre-op Post-stimulation cortisol | 43.6 microg/dL |
| Normal Saline-Placebo | ACTH Stimulation Test | Pre-op ACTH | 24.5 microg/dL |
| Normal Saline-Placebo | ACTH Stimulation Test | Pre-op Pre-stimulation cortisol | 18.2 microg/dL |
| Normal Saline-Placebo | ACTH Stimulation Test | Post-op ACTH | 10.5 microg/dL |
| Normal Saline-Placebo | ACTH Stimulation Test | Post-op Pre-Stimulation cortisol | 89.4 microg/dL |
| Normal Saline-Placebo | ACTH Stimulation Test | Post-op Post-stimulation cortisol | 112.3 microg/dL |
| Hydrocortisone | ACTH Stimulation Test | Post-op Pre-Stimulation cortisol | 87.2 microg/dL |
| Hydrocortisone | ACTH Stimulation Test | Post-op ACTH | 7.5 microg/dL |
| Hydrocortisone | ACTH Stimulation Test | Pre-op ACTH | 31 microg/dL |
| Hydrocortisone | ACTH Stimulation Test | Post-op Post-stimulation cortisol | 118.8 microg/dL |
| Hydrocortisone | ACTH Stimulation Test | Pre-op Pre-stimulation cortisol | 23.3 microg/dL |
| Hydrocortisone | ACTH Stimulation Test | Pre-op Post-stimulation cortisol | 47.1 microg/dL |
p-value: <0.05Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.004Fisher Exact
p-value: 0.02Fisher Exact
Secondary
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.
Time frame: first 48 hours post-op
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Normal Saline-Placebo | Average Inotrope Score | Inotrope Score at 12 hours post bypass | 5.3 Inotrope Score |
| Normal Saline-Placebo | Average Inotrope Score | Inotrope Score 24 hours post bypass | 0 Inotrope Score |
| Normal Saline-Placebo | Average Inotrope Score | Inotrope Score 48 hours post bypass | 0 Inotrope Score |
| Hydrocortisone | Average Inotrope Score | Inotrope Score at 12 hours post bypass | 4.7 Inotrope Score |
| Hydrocortisone | Average Inotrope Score | Inotrope Score 24 hours post bypass | 4 Inotrope Score |
| Hydrocortisone | Average Inotrope Score | Inotrope Score 48 hours post bypass | 0 Inotrope Score |
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: admit to the CICU
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Saline-Placebo | Changes in Baseline Arterial-venous Oxygen Saturation Difference | 14 percentage of arterial-venous saturation |
| Hydrocortisone | Changes in Baseline Arterial-venous Oxygen Saturation Difference | 9.5 percentage of arterial-venous saturation |
p-value: 0.03Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: 0, 4,12, 24, and 48 hours post bypass
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 0 hr post bypass Il-1 beta | 0.44 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 12 hr post bypass Il-6 | 93.7 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 12 hr post bypass Il-10 | 17.5 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 24 hr post bypass Il-6 | 110 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 4 hr post bypass Il-1 beta | 0.83 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 48 hr post bypass Il-6 | 40.1 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | Pre-op Il-10 | 4 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | Pre-op Il-8 | 27.1 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 12 hr post bypss Il-1 beta | 0.49 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 0 hr post bypass Il-8 | 118 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 24 hr post bypass Il-10 | 11.4 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 4 hr post bypss IL-8 | 212 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 24 hr post bypass Il-1 beta | 1.71 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 12 hr post bypass IL-8 | 153 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 4 hr post bypss Il-10 | 53.5 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 24 hr post bypass Il-8 | 129 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 48 hr post bypass Il-1 beta | 0.76 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 48 hr post bypass Il-8 | 67.3 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 48 hr post bypass Il-10 | 7.9 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | Pre-op tumor necrosis factor (TNF)-alpha | 4.7 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | Pre-op Il-6 | 3.6 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 0 hr post bypass TNF-alpha | 3.6 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 0 hr post bypass Il-10 | 225 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 4 hr post bypass TNF-alpha | 6.4 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 0 hr post bypass IL-6 | 13.6 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 12 hr post bypss TNF-alpha | 6.6 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | Pre-op Il-1 beta | 0.49 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 24 hr post bypass TNF-alpha | 5.8 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 48 hr post bypass TNF-alpha | 5.1 pg/mL |
| Normal Saline-Placebo | Changes in Baseline Inflammatory Mediators | 4 hr post bypsas Il-6 | 58 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 48 hr post bypass TNF-alpha | 3 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | Pre-op Il-10 | 4.3 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | Pre-op Il-1 beta | 0.53 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 0 hr post bypass Il-10 | 164 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 4 hr post bypss Il-10 | 92.2 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 12 hr post bypass Il-10 | 20.1 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 24 hr post bypass Il-10 | 10.7 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 48 hr post bypass Il-10 | 9.4 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 0 hr post bypass Il-1 beta | 0.5 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 4 hr post bypass Il-1 beta | 1.2 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 12 hr post bypss Il-1 beta | 0.33 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 24 hr post bypass Il-1 beta | 0.77 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 48 hr post bypass Il-1 beta | 0.29 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | Pre-op Il-6 | 5.8 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 0 hr post bypass IL-6 | 12.4 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 4 hr post bypsas Il-6 | 65.2 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 12 hr post bypass Il-6 | 50.4 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 24 hr post bypass Il-6 | 45.5 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 48 hr post bypass Il-6 | 15.3 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | Pre-op Il-8 | 23.5 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 0 hr post bypass Il-8 | 99.8 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 4 hr post bypss IL-8 | 261.5 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 12 hr post bypass IL-8 | 97 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 24 hr post bypass Il-8 | 103 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 48 hr post bypass Il-8 | 50.3 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | Pre-op tumor necrosis factor (TNF)-alpha | 4.3 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 0 hr post bypass TNF-alpha | 2.9 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 4 hr post bypass TNF-alpha | 5.5 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 12 hr post bypss TNF-alpha | 4.2 pg/mL |
| Hydrocortisone | Changes in Baseline Inflammatory Mediators | 24 hr post bypass TNF-alpha | 4.1 pg/mL |
p-value: 0.03Wilcoxon (Mann-Whitney)
p-value: <0.05Wilcoxon (Mann-Whitney)
p-value: <0.01Wilcoxon (Mann-Whitney)
p-value: <0.01Wilcoxon (Mann-Whitney)
p-value: <0.05Wilcoxon (Mann-Whitney)
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: approximately 1 week
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Saline-Placebo | CICU Length of Stay | 162 hours |
| Hydrocortisone | CICU Length of Stay | 213 hours |
p-value: 0.76Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: 1st 48 hours post-op
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Saline-Placebo | Fluid Balance | -64 mL/kg |
| Hydrocortisone | Fluid Balance | -114 mL/kg |
p-value: 0.04Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Admit to CICU till hospital discharge, approximately 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Saline-Placebo | Hospital Length of Stay | 13.5 days |
| Hydrocortisone | Hospital Length of Stay | 19 days |
p-value: 0.62Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: up to 28 days post op
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Saline-Placebo | Mean Number of Days Subjects Alive and Ventilator Free | 24 days |
| Hydrocortisone | Mean Number of Days Subjects Alive and Ventilator Free | 25 days |
p-value: 0.44Chi-squared
Secondary
Mortality
Subject mortality will in the CICU will be used as a secondary outcome.
Time frame: Duration of CICU stay, approximately 1 week
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline-Placebo | Mortality | 14 percentage of patients |
| Hydrocortisone | Mortality | 0 percentage of patients |
p-value: 0.23Fisher Exact
Secondary
Time Until First Extubation
Respiratory values such as duration of intubation will be used as a secondary outcome.
Time frame: Until discharge from hospital, approximately 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Saline-Placebo | Time Until First Extubation | 55 hours |
| Hydrocortisone | Time Until First Extubation | 51 hours |
p-value: 0.7Wilcoxon (Mann-Whitney)