Congenital Heart Disease, Hypogammaglobulinemia
Conditions
Keywords
congenital heart disease, Cardiopulmonary Bypass, Hypogammaglobulinemia
Brief summary
The purpose of this study protocol is to determine if administering Intravenous Immunoglobulin (IVIG) for treatment of cardiopulmonary bypass (CPB) induced hypogammaglobulinemia in the early post-operative period can impact post-surgical outcomes (i.e., infection, fluid overload, and associated morbidities).
Detailed description
The intense post-CPB systemic inflammatory response syndrome (SIRS) is well described in neonates and infants. Increased production and release of pro-inflammatory cytokines, including Tumor Necrosis Factor, Interleukin1-B, and Interleukin-6 may suppress myocardial contractility, induce capillary leak, and activate complement and the clotting cascade - together leading to potential organ injury and death. SIRS is also frequently accompanied by impairment of the humoral immune response. One potential reason for this acquired immunodeficiency after cardiac surgery is the removal of immunoglobulins (Ig)s from the vascular space into other compartments where they are either sequestered or lost from the body altogether. We recently demonstrated that such Ig depletion from the intravascular compartment occurs in neonates following cardiac surgery. In a retrospective study of 53 children \<3 months of age, we showed that plasma Immunoglobulin G (IgG) concentration drops precipitously after cardiac surgery and does not return to preoperative levels by 7 days; 51% of patients had hypogammaglobulinemia. An important question is whether post-CPB low IgG has clinical consequence. IgG plays an essential role in the humoral immune system, activating complement and inducing the phagocytic system to neutralize pathogens. IgG deficiency is a known risk factor for infections in other pediatric populations. We were the first to demonstrate that post-CPB hypogammaglobulinemia is associated with worse clinical outcomes, including increased secondary infections (37% vs.12% in those without low IgG, p\<0.05). These novel findings are paramount in that they identify a potential modifiable risk factor to improve outcomes after pediatric cardiac surgery with CPB. Additionally, low IgG is accompanied by fluid overload and prolonged mechanical ventilation. Igs constitute an important component of plasma oncotic pressure, so hypogammaglobulinemia may exacerbate anasarca, prolonging postoperative convalescence and increasing the morbidities associated with increased ICU length of stay.9 Igs have an increasingly recognized role in modulating the innate immune response. Present use of IVIG exceeds mere antibody replacement and extends to the treatment of autoimmune and inflammatory conditions. In fact, more than 75% of IVIG use in the U.S. today is for the treatment of inflammatory conditions, where proposed mechanisms include reduction of pro-inflammatory cytokine and adhesion molecule expression, superantigen neutralization, restoration of glucocorticoid responsiveness, and blockade of complement fragment deposition. It is plausible that IVIG could benefit neonates after cardiac surgery not only via restoration of humoral opsonization capacity, but also as a modulator of innate immunity and SIRS. According to this model, tissue injury, CPB, and shock trigger SIRS, leading to hypogammaglobulinemia and resultant increased susceptibility to inflammatory dysregulation which might be ameliorated via administration of IVIG. In an adult study, IVIG failed to benefit postoperative cardiac patients with severe SIRS. However, the dose of IVIG given was relatively small compared with that typically given for autoimmune and inflammatory conditions. Neonates and infants may be more susceptible to the harmful effects of acquired hypogammaglobulinemia than adults as they may be unable to generate adequate quantities of antibodies in response to pathogens, relying mainly on maternal Igs until around the 4th to 6th month of life. In addition, they display an exaggerated inflammatory response to CPB as compared with older children and adults, so they might stand to benefit more from IVIG as an immunomodulator. Because of the increased vulnerability to acquired infection and other morbidities in the setting of hypogammaglobulinemia as result of enhanced SIRS and immune dysfunction, it is feasible that normalization of IgG concentration in the neonatal and infant population may improve clinical outcomes via restoration of the humoral immune system, modulation of the innate immune system, and restoration of intravascular oncotic pressure. The appropriate IgG level threshold for treatment and optimal plasma IgG level to target after administration of IVIG are presently unknown.
Interventions
DRUGIVIG
Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care.
OTHERPlacebo
If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight.
Sponsors
Grifols Biologicals, LLC
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
No minimum to 6 Months
Healthy volunteers
No
Inclusion criteria
* Infants \<6 months old * Successfully weaned off cardiopulmonary bypass after cardiac surgery
Exclusion criteria
* Requirement of extra corporeal membrane oxygenation in the operating room * Known immune deficiency * Current Do Not Resuscitate or limitation of care order * Current enrollment in another interventional clinical study * Refusal of parental consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-Operative Infections | until Hospital Discharge, an average of 30 days | The primary endpoint of this study is incidence of post-operative infections through hospital discharge |
| Post-operative Infection | within 1 week of surgery | Any positive culture or treatment for culture negative sepsis within 1 week of surgery |
| Blood Stream Infection | until Hospital Discharge, an average of 30 days | Any positive blood culture during the post-operative period until hospital discharge |
| Blood Stream Infection Within 1 Week of Surgery | 7 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Discharge | Approximately 1 month | From admit post-operative to the Pediatric cardiac intensive care unit until discharge from the hospital in days. |
| Plasma Immunoglobulins | 5 days post-op | Plasma Immunoglobulin levels will be checked pre-operatively, 12 hours post-op and 5 days post-op |
| Interferon-gamma Plasma Cytokine Levels | Pre-operative to 48 hours post-operative | Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively. |
| Immunoglobulin Concentration in Chest Tube Drainage | 24 hours post-op | Immunoglobulin concentration will be measured from chest tube every 4 hours for first 12 hours post-operative and then 24 hours post-operative. |
| Mortality | Approximately 1 month | Incidence of mortality from admit to Pediatric cardiac intensive care unit post-operatively until hospital discharge . |
| Intensive Care Unit Length of Stay | 1 month | The length of stay in the pediatric cardiac intensive care unit from admit post-operative until either discharge home, discharge to another unit/hospital/care facility, or death. This value is calculated in hours. Admit post-operative is recorded as hour 0. |
| Interleukin-10 Plasma Cytokine Levels | pre-operative through 48 hours post-operative | Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively. |
| Post-operative Plasma Albumin | up to 48 hours post CPB | Plasma albumin will be assessed at 24 and 48 hours. |
| Interleukin-1b Plasma Cytokine Levels | pre-operative through 48 hours post-operative | Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively. |
| Interleukin-6 Plasma Cytokine Levels | pre-operative through 48 hours post-operative | Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively. |
| Interleukin-8 Plasma Cytokine Levels | pre-operative through 48 hours post-operative | Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively. |
| Tumor Necrosis Factor Plasma Cytokine Levels | pre-operative through 48 hours post-operative | Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively. |
| Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 24 hours post-op | Immunoglobulin concentration will be measured from chest tube and peritoneal drain every 4 hours for first 12 hours post-operative and 24 hours post-operative. |
| Serum Creatinine | 48 hours | Pre-operative and 48 hour post-operative maximum creatinine recorded. |
| Lactic Acid | pre-operative through 24 hours post-operative | — |
| Interleukin-12p70 Plasma Cytokine Levels | pre-operative through 48 hours post-operative | Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively. |
| Fluid Overload Variables | 0-24 hours post-CPB | The following fluid overload variables will be assessed in milliliters per kilogram at 0-24 hours post-cardiopulmonary bypass: blood product and albumin administration, chest tube output, urine output, peritoneal dialysis output, net fluid balance, and percent fluid overload. The total output the subject's produce (urine, chest tube, peritoneal drainage, etc.) will be subtracted from the total input (medications, blood products, albumin administration, etc) to determine the total fluid intake in milliliters. This total number will then be divided by the subject's weight in kilograms to determine the fluid overload in mL/kg. |
| Post-operative Inotrope Score | first 48 hours post-CPB | The average admit, 12 hour, 24 hour, and 48 hour post-operative inotrope score will be calculated excluding Milrinone. To calculate the inotrope score the following formula was used: (Epinephrine/Norepinephrine dose in mcg/kg/min x 100) + (Dopamine dose in mcg/kg/min x 1) + (Phenylephrine dose in mcg/kg/min x 10) + (Vasopressin dose unit/kg/hr x 60/10000). The higher the inotrope score the more cardiac support the subject requires. There is not a normal scale or range used for this calculation. |
| Respiratory Variables | until Hospital Discharge, an average of 30 days | Alive, ventilator free days will be recorded at hospital discharge. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IVIG Those randomized to the study arm will receive a dose of IVIG 1 gram/kg at 12 hours post-cardiopulmonary bypass. This is a one time only dose.
IVIG: Those randomized to the study arm will receive a one time dose of IVIG at 12 our post-Cardiopulmonary bypass. This is significantly early than our current standard of care. | 30 |
| Normal Saline Subject's randomized into the placebo arm of the study will receive a volume of normal saline that is comparative to that if they were to receive IVIG. This will be at 12 hours post-cardiopulmonary bypass. This volume is to ensure blinding of study drug.
Placebo: If the subject is randomized to the placebo group they will receive a volume of normal saline that is equivalent to the volume of IVIG to be administered based on their weight. | 20 |
| Total | 50 |
Baseline characteristics
| Characteristic | Total | IVIG | Normal Saline |
|---|---|---|---|
| Age, Categorical <=18 years | 50 Participants | 30 Participants | 20 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 11.5 days | 9 days | 47 days |
| Aortic cross clamp time | 53.5 minutes | 52 minutes | 56 minutes |
| Cardiopulmonyar bypass time | 97.5 minutes | 105.5 minutes | 91.5 minutes |
| Gestational Age | 38 weeks | 38 weeks | 38.5 weeks |
| Intubated Pre-operatively No | 40 subjects | 25 subjects | 15 subjects |
| Intubated Pre-operatively Yes | 10 subjects | 5 subjects | 5 subjects |
| 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 | 10 Participants | 8 Participants | 2 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 | 40 Participants | 22 Participants | 18 Participants |
| Sex: Female, Male Female | 22 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Male | 28 Participants | 16 Participants | 12 Participants |
| STAT category 1 | 3 participants | 3 participants | 0 participants |
| STAT category 2 | 7 participants | 2 participants | 5 participants |
| STAT category 3 | 15 participants | 7 participants | 8 participants |
| STAT category 4 | 16 participants | 12 participants | 4 participants |
| STAT category 5 | 9 participants | 6 participants | 3 participants |
| Weight | 3.51 kilograms | 3.45 kilograms | 3.85 kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 20 |
| serious Total, serious adverse events | 0 / 30 | 0 / 20 |
Outcome results
Primary
Blood Stream Infection
Any positive blood culture during the post-operative period until hospital discharge
Time frame: until Hospital Discharge, an average of 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IVIG | Blood Stream Infection | No | 25 subjects |
| IVIG | Blood Stream Infection | Yes | 5 subjects |
| Normal Saline | Blood Stream Infection | Yes | 1 subjects |
| Normal Saline | Blood Stream Infection | No | 19 subjects |
p-value: 0.38Chi-squared
Primary
Blood Stream Infection Within 1 Week of Surgery
Time frame: 7 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IVIG | Blood Stream Infection Within 1 Week of Surgery | No | 27 subjects |
| IVIG | Blood Stream Infection Within 1 Week of Surgery | Yes | 3 subjects |
| Normal Saline | Blood Stream Infection Within 1 Week of Surgery | Yes | 0 subjects |
| Normal Saline | Blood Stream Infection Within 1 Week of Surgery | No | 20 subjects |
p-value: 0.26Chi-squared
Primary
Post-operative Infection
Any positive culture or treatment for culture negative sepsis within 1 week of surgery
Time frame: within 1 week of surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IVIG | Post-operative Infection | Yes | 5 Subjects |
| IVIG | Post-operative Infection | No | 25 Subjects |
| Normal Saline | Post-operative Infection | Yes | 3 Subjects |
| Normal Saline | Post-operative Infection | No | 17 Subjects |
p-value: 1Chi-squared
Primary
Post-Operative Infections
The primary endpoint of this study is incidence of post-operative infections through hospital discharge
Time frame: until Hospital Discharge, an average of 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IVIG | Post-Operative Infections | Yes | 9 subjects |
| IVIG | Post-Operative Infections | No | 21 subjects |
| Normal Saline | Post-Operative Infections | Yes | 6 subjects |
| Normal Saline | Post-Operative Infections | No | 14 subjects |
p-value: 1Chi-squared
Secondary
Fluid Overload Variables
The following fluid overload variables will be assessed in milliliters per kilogram at 0-24 hours post-cardiopulmonary bypass: blood product and albumin administration, chest tube output, urine output, peritoneal dialysis output, net fluid balance, and percent fluid overload. The total output the subject's produce (urine, chest tube, peritoneal drainage, etc.) will be subtracted from the total input (medications, blood products, albumin administration, etc) to determine the total fluid intake in milliliters. This total number will then be divided by the subject's weight in kilograms to determine the fluid overload in mL/kg.
Time frame: 0-24 hours post-CPB
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG | Fluid Overload Variables | 30 mililiters/kilogram |
| Normal Saline | Fluid Overload Variables | 58.1 mililiters/kilogram |
p-value: 0.52Wilcoxon (Mann-Whitney)
Secondary
Fluid Overload Variables
The following fluid overload variables will be assessed at 0-24 hours, 25-48 hours, and 0-48 hours post-cardiopulmonary bypass: blood product and albumin administration, chest tube output, urine output, peritoneal dialysis output, net fluid balance, and percent fluid overload.The total output the subject's produce (urine, chest tube, peritoneal drainage, etc.) will be subtracted from the total input (medications, blood products, albumin administration, etc) to determine the total fluid intake in milliliters. This total number will then be divided by the subject's weight in kilograms to determine the fluid overload in mL/kg.
Time frame: 0-48 hours post-CPB
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Fluid Overload Variables | 0-24 hours post-CPB | 30 militers/kilogram |
| IVIG | Fluid Overload Variables | 25-48 hours post-CPB | 7.4 militers/kilogram |
| IVIG | Fluid Overload Variables | 0-48 hours post-CPB | 46.6 militers/kilogram |
| Normal Saline | Fluid Overload Variables | 0-24 hours post-CPB | 58.1 militers/kilogram |
| Normal Saline | Fluid Overload Variables | 25-48 hours post-CPB | 34.9 militers/kilogram |
| Normal Saline | Fluid Overload Variables | 0-48 hours post-CPB | 77 militers/kilogram |
Comparison: 0-48 hours post-CPBp-value: 0.09Wilcoxon (Mann-Whitney)
Comparison: 0-24 hours post CPBp-value: 0.52Wilcoxon (Mann-Whitney)
Secondary
Hospital Discharge
From admit post-operative to the Pediatric cardiac intensive care unit until discharge from the hospital in days.
Time frame: Approximately 1 month
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG | Hospital Discharge | 22 days |
| Normal Saline | Hospital Discharge | 22 days |
p-value: 0.79Wilcoxon (Mann-Whitney)
Secondary
Immunoglobulin Concentration in Chest Tube Drainage
Immunoglobulin concentration will be measured from chest tube every 4 hours for first 12 hours post-operative and then 24 hours post-operative.
Time frame: 24 hours post-op
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Immunoglobulin Concentration in Chest Tube Drainage | 4 hr post-op | 154.3 mg/dL |
| IVIG | Immunoglobulin Concentration in Chest Tube Drainage | 12 hr post-op | 233.5 mg/dL |
| IVIG | Immunoglobulin Concentration in Chest Tube Drainage | 8 hr post-op | 195.2 mg/dL |
| IVIG | Immunoglobulin Concentration in Chest Tube Drainage | 24 hr post-op | 614.2 mg/dL |
| IVIG | Immunoglobulin Concentration in Chest Tube Drainage | 0 hr post-op | 50.9 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Chest Tube Drainage | 24 hr post-op | 268.7 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Chest Tube Drainage | 0 hr post-op | 62.2 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Chest Tube Drainage | 4 hr post-op | 161.3 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Chest Tube Drainage | 8 hr post-op | 227.6 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Chest Tube Drainage | 12 hr post-op | 226.8 mg/dL |
Comparison: 0 hour levelsp-value: 0.27Wilcoxon (Mann-Whitney)
Comparison: 4 hour levelp-value: 0.34Wilcoxon (Mann-Whitney)
Comparison: 8 hour levelp-value: 0.14Wilcoxon (Mann-Whitney)
Comparison: 12 hour levelp-value: 0.13Wilcoxon (Mann-Whitney)
Comparison: 24 hour levelp-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
Immunoglobulin Concentration in Peritoneal Dialysis Drainage
Immunoglobulin concentration will be measured from chest tube and peritoneal drain every 4 hours for first 12 hours post-operative and 24 hours post-operative.
Time frame: 24 hours post-op
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 4 hr post-op | 136.2 mg/dL |
| IVIG | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 12 hr post-op | 387.33 mg/dL |
| IVIG | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 8 hr post-op | 279.8 mg/dL |
| IVIG | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 24 hr post-op | 1613.9 mg/dL |
| IVIG | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 0 hr post-op | 33.1 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 24 hr post-op | 366.9 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 0 hr post-op | 101.6 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 4 hr post-op | 201.6 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 8 hr post-op | 221.2 mg/dL |
| Normal Saline | Immunoglobulin Concentration in Peritoneal Dialysis Drainage | 12 hr post-op | 300.1 mg/dL |
Comparison: 0 hour levelp-value: 0.37Wilcoxon (Mann-Whitney)
Comparison: 4 hour levelp-value: 0.47Wilcoxon (Mann-Whitney)
Comparison: 8 hour levelp-value: 0.47Wilcoxon (Mann-Whitney)
Comparison: 12 hour levelp-value: 0.79Wilcoxon (Mann-Whitney)
Comparison: 24 hour levelp-value: 0.04Wilcoxon (Mann-Whitney)
Secondary
Intensive Care Unit Length of Stay
The length of stay in the pediatric cardiac intensive care unit from admit post-operative until either discharge home, discharge to another unit/hospital/care facility, or death. This value is calculated in hours. Admit post-operative is recorded as hour 0.
Time frame: 1 month
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG | Intensive Care Unit Length of Stay | 357.9 hours |
| Normal Saline | Intensive Care Unit Length of Stay | 189.6 hours |
p-value: 0.4Wilcoxon (Mann-Whitney)
Secondary
Interferon-gamma Plasma Cytokine Levels
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time frame: Pre-operative to 48 hours post-operative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Interferon-gamma Plasma Cytokine Levels | 4 hour post-op | 2.8 pg/mL |
| IVIG | Interferon-gamma Plasma Cytokine Levels | 24 hour post-op | 2 pg/mL |
| IVIG | Interferon-gamma Plasma Cytokine Levels | 12 hour post-op | 2.8 pg/mL |
| IVIG | Interferon-gamma Plasma Cytokine Levels | 0 hour post-op | 2.6 pg/mL |
| IVIG | Interferon-gamma Plasma Cytokine Levels | 48 hour post-op | 2.2 pg/mL |
| IVIG | Interferon-gamma Plasma Cytokine Levels | Pre-operative | 2.2 pg/mL |
| Normal Saline | Interferon-gamma Plasma Cytokine Levels | 48 hour post-op | 3.4 pg/mL |
| Normal Saline | Interferon-gamma Plasma Cytokine Levels | Pre-operative | 3.5 pg/mL |
| Normal Saline | Interferon-gamma Plasma Cytokine Levels | 0 hour post-op | 6 pg/mL |
| Normal Saline | Interferon-gamma Plasma Cytokine Levels | 4 hour post-op | 6.1 pg/mL |
| Normal Saline | Interferon-gamma Plasma Cytokine Levels | 24 hour post-op | 5.6 pg/mL |
| Normal Saline | Interferon-gamma Plasma Cytokine Levels | 12 hour post-op | 6.3 pg/mL |
Comparison: pre-operativep-value: 0.6Wilcoxon (Mann-Whitney)
Comparison: 0 hour post-operativep-value: 0.06Wilcoxon (Mann-Whitney)
Comparison: 4 hour post-operativep-value: 0.06Wilcoxon (Mann-Whitney)
Comparison: 12 hours post-operativep-value: 0.33Wilcoxon (Mann-Whitney)
Comparison: 24 hours post-operativep-value: 0.05Wilcoxon (Mann-Whitney)
Comparison: 48 hours post-operativep-value: 0.83Wilcoxon (Mann-Whitney)
Secondary
Interleukin-10 Plasma Cytokine Levels
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time frame: pre-operative through 48 hours post-operative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Interleukin-10 Plasma Cytokine Levels | Pre-operative | 1.4 pg/mL |
| IVIG | Interleukin-10 Plasma Cytokine Levels | 0 hour post-operative | 54.4 pg/mL |
| IVIG | Interleukin-10 Plasma Cytokine Levels | 4 hour post-operative | 10.1 pg/mL |
| IVIG | Interleukin-10 Plasma Cytokine Levels | 12 hour post-operative | 4.7 pg/mL |
| IVIG | Interleukin-10 Plasma Cytokine Levels | 24 hour post-operative | 1.8 pg/mL |
| IVIG | Interleukin-10 Plasma Cytokine Levels | 48 hour post-operatiave | 1.1 pg/mL |
| Normal Saline | Interleukin-10 Plasma Cytokine Levels | 24 hour post-operative | 4 pg/mL |
| Normal Saline | Interleukin-10 Plasma Cytokine Levels | Pre-operative | 1.8 pg/mL |
| Normal Saline | Interleukin-10 Plasma Cytokine Levels | 12 hour post-operative | 10.2 pg/mL |
| Normal Saline | Interleukin-10 Plasma Cytokine Levels | 0 hour post-operative | 124 pg/mL |
| Normal Saline | Interleukin-10 Plasma Cytokine Levels | 48 hour post-operatiave | 2.3 pg/mL |
| Normal Saline | Interleukin-10 Plasma Cytokine Levels | 4 hour post-operative | 20.1 pg/mL |
Comparison: pre-operativep-value: 0.41Wilcoxon (Mann-Whitney)
Comparison: 0 hour post-operativep-value: 0.34Wilcoxon (Mann-Whitney)
Comparison: 4 hour post-operativep-value: 0.47Wilcoxon (Mann-Whitney)
Comparison: 12 hour post-operativep-value: 0.42Wilcoxon (Mann-Whitney)
Comparison: 24 hour post-operativep-value: 0.82Wilcoxon (Mann-Whitney)
Comparison: 48 hour post-operativep-value: 0.44Wilcoxon (Mann-Whitney)
Secondary
Interleukin-12p70 Plasma Cytokine Levels
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time frame: pre-operative through 48 hours post-operative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Interleukin-12p70 Plasma Cytokine Levels | Pre-operative | 0.2 pg/mL |
| IVIG | Interleukin-12p70 Plasma Cytokine Levels | 0 hour post-operative | 0.2 pg/mL |
| IVIG | Interleukin-12p70 Plasma Cytokine Levels | 4 hour post-operative | 0.4 pg/mL |
| IVIG | Interleukin-12p70 Plasma Cytokine Levels | 12 hour post-operative | 0.5 pg/mL |
| IVIG | Interleukin-12p70 Plasma Cytokine Levels | 24 hour post-operative | 0.3 pg/mL |
| IVIG | Interleukin-12p70 Plasma Cytokine Levels | 48 hour post-operatiave | 0.2 pg/mL |
| Normal Saline | Interleukin-12p70 Plasma Cytokine Levels | 24 hour post-operative | 0.7 pg/mL |
| Normal Saline | Interleukin-12p70 Plasma Cytokine Levels | Pre-operative | 0.2 pg/mL |
| Normal Saline | Interleukin-12p70 Plasma Cytokine Levels | 12 hour post-operative | 1 pg/mL |
| Normal Saline | Interleukin-12p70 Plasma Cytokine Levels | 0 hour post-operative | 0.6 pg/mL |
| Normal Saline | Interleukin-12p70 Plasma Cytokine Levels | 48 hour post-operatiave | 0.4 pg/mL |
| Normal Saline | Interleukin-12p70 Plasma Cytokine Levels | 4 hour post-operative | 0.5 pg/mL |
Comparison: pre-operativep-value: 0.28Wilcoxon (Mann-Whitney)
Comparison: 0 hour post-operativep-value: 0.37Wilcoxon (Mann-Whitney)
Comparison: 4 hour post-operativep-value: 0.42Wilcoxon (Mann-Whitney)
Comparison: 12 hour post-operativep-value: 0.31Wilcoxon (Mann-Whitney)
Comparison: 24 hour post-operativep-value: 0.38Wilcoxon (Mann-Whitney)
Comparison: 48 hour post-operativep-value: 0.4Wilcoxon (Mann-Whitney)
Secondary
Interleukin-1b Plasma Cytokine Levels
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time frame: pre-operative through 48 hours post-operative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Interleukin-1b Plasma Cytokine Levels | Pre-operative | 0.2 pg/mL |
| IVIG | Interleukin-1b Plasma Cytokine Levels | 0 hour post-operative | 0.3 pg/mL |
| IVIG | Interleukin-1b Plasma Cytokine Levels | 4 hour post-operative | 0.3 pg/mL |
| IVIG | Interleukin-1b Plasma Cytokine Levels | 12 hour post-operative | 0.3 pg/mL |
| IVIG | Interleukin-1b Plasma Cytokine Levels | 24 hour post-operative | 0.3 pg/mL |
| IVIG | Interleukin-1b Plasma Cytokine Levels | 48 hour post-operatiave | 0.3 pg/mL |
| Normal Saline | Interleukin-1b Plasma Cytokine Levels | 24 hour post-operative | 0.5 pg/mL |
| Normal Saline | Interleukin-1b Plasma Cytokine Levels | Pre-operative | 0.2 pg/mL |
| Normal Saline | Interleukin-1b Plasma Cytokine Levels | 12 hour post-operative | 0.3 pg/mL |
| Normal Saline | Interleukin-1b Plasma Cytokine Levels | 0 hour post-operative | 0.4 pg/mL |
| Normal Saline | Interleukin-1b Plasma Cytokine Levels | 48 hour post-operatiave | 0.3 pg/mL |
| Normal Saline | Interleukin-1b Plasma Cytokine Levels | 4 hour post-operative | 0.5 pg/mL |
Comparison: pre-operativep-value: 0.1Wilcoxon (Mann-Whitney)
Comparison: 0 hour post-operativep-value: 0.12Wilcoxon (Mann-Whitney)
Comparison: 4 hour post-operativep-value: 0.51Wilcoxon (Mann-Whitney)
Comparison: 12 hour post-operativep-value: 0.27Wilcoxon (Mann-Whitney)
Comparison: 24 hour post-operativep-value: 0.88Wilcoxon (Mann-Whitney)
Comparison: 48 hour post-operativep-value: 0.38Wilcoxon (Mann-Whitney)
Secondary
Interleukin-6 Plasma Cytokine Levels
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time frame: pre-operative through 48 hours post-operative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Interleukin-6 Plasma Cytokine Levels | Pre-operative | 2.1 pg/mL |
| IVIG | Interleukin-6 Plasma Cytokine Levels | 0 hour post-operative | 10.3 pg/mL |
| IVIG | Interleukin-6 Plasma Cytokine Levels | 4 hour post-operative | 32.6 pg/mL |
| IVIG | Interleukin-6 Plasma Cytokine Levels | 12 hour post-operative | 43.6 pg/mL |
| IVIG | Interleukin-6 Plasma Cytokine Levels | 24 hour post-operative | 26.3 pg/mL |
| IVIG | Interleukin-6 Plasma Cytokine Levels | 48 hour post-operatiave | 15.8 pg/mL |
| Normal Saline | Interleukin-6 Plasma Cytokine Levels | 24 hour post-operative | 40.8 pg/mL |
| Normal Saline | Interleukin-6 Plasma Cytokine Levels | Pre-operative | 3.3 pg/mL |
| Normal Saline | Interleukin-6 Plasma Cytokine Levels | 12 hour post-operative | 49.8 pg/mL |
| Normal Saline | Interleukin-6 Plasma Cytokine Levels | 0 hour post-operative | 17.3 pg/mL |
| Normal Saline | Interleukin-6 Plasma Cytokine Levels | 48 hour post-operatiave | 15.5 pg/mL |
| Normal Saline | Interleukin-6 Plasma Cytokine Levels | 4 hour post-operative | 52.4 pg/mL |
Comparison: pre-operativep-value: 0.35Wilcoxon (Mann-Whitney)
Comparison: 0 hour post-operativep-value: 0.39Wilcoxon (Mann-Whitney)
Comparison: 4 hour post-operativep-value: 0.58Wilcoxon (Mann-Whitney)
Comparison: 12 hour post-operativep-value: 0.36Wilcoxon (Mann-Whitney)
Comparison: 24 hour post-operativep-value: 0.61Wilcoxon (Mann-Whitney)
Comparison: 48 hour post-operativep-value: 0.38Wilcoxon (Mann-Whitney)
Secondary
Interleukin-8 Plasma Cytokine Levels
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time frame: pre-operative through 48 hours post-operative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Interleukin-8 Plasma Cytokine Levels | Pre-operative | 18.7 pg/dL |
| IVIG | Interleukin-8 Plasma Cytokine Levels | 0 hour post-operative | 76.5 pg/dL |
| IVIG | Interleukin-8 Plasma Cytokine Levels | 4 hour post-operative | 116.5 pg/dL |
| IVIG | Interleukin-8 Plasma Cytokine Levels | 12 hour post-operative | 67.1 pg/dL |
| IVIG | Interleukin-8 Plasma Cytokine Levels | 24 hour post-operative | 47.7 pg/dL |
| IVIG | Interleukin-8 Plasma Cytokine Levels | 48 hour post-operatiave | 33.6 pg/dL |
| Normal Saline | Interleukin-8 Plasma Cytokine Levels | 24 hour post-operative | 46 pg/dL |
| Normal Saline | Interleukin-8 Plasma Cytokine Levels | Pre-operative | 17.7 pg/dL |
| Normal Saline | Interleukin-8 Plasma Cytokine Levels | 12 hour post-operative | 90 pg/dL |
| Normal Saline | Interleukin-8 Plasma Cytokine Levels | 0 hour post-operative | 163 pg/dL |
| Normal Saline | Interleukin-8 Plasma Cytokine Levels | 48 hour post-operatiave | 38.2 pg/dL |
| Normal Saline | Interleukin-8 Plasma Cytokine Levels | 4 hour post-operative | 147.5 pg/dL |
Comparison: pre-operativep-value: 0.1Wilcoxon (Mann-Whitney)
Comparison: 0 hour post-operativep-value: 0.02Wilcoxon (Mann-Whitney)
Comparison: 4 hour post-operativep-value: 0.34Wilcoxon (Mann-Whitney)
Comparison: 12 hour post-operativep-value: 0.35Wilcoxon (Mann-Whitney)
Comparison: 24 hour post-operativep-value: 0.67Wilcoxon (Mann-Whitney)
Comparison: 48 hour post-operativep-value: 0.47Wilcoxon (Mann-Whitney)
Secondary
Lactic Acid
Time frame: pre-operative through 24 hours post-operative
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IVIG | Lactic Acid | Pre-operative | 1.3 mmol/L | Standard Deviation 0.65 |
| IVIG | Lactic Acid | 24 hour maximum | 5.7 mmol/L | Standard Deviation 4 |
| Normal Saline | Lactic Acid | Pre-operative | 1.4 mmol/L | Standard Deviation 0.75 |
| Normal Saline | Lactic Acid | 24 hour maximum | 5.4 mmol/L | Standard Deviation 4.54 |
Comparison: pre-operativep-value: 0.87t-test, 2 sided
Comparison: 24 hour post-operative maxp-value: 0.79t-test, 2 sided
Secondary
Mortality
Incidence of mortality from admit to Pediatric cardiac intensive care unit post-operatively until hospital discharge .
Time frame: Approximately 1 month
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IVIG | Mortality | Yes | 3 subjects |
| IVIG | Mortality | No | 27 subjects |
| Normal Saline | Mortality | Yes | 2 subjects |
| Normal Saline | Mortality | No | 18 subjects |
p-value: 1Chi-squared
Secondary
Plasma Immunoglobulins
Plasma Immunoglobulin levels will be checked pre-operatively, 12 hours post-op and 5 days post-op
Time frame: 5 days post-op
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IVIG | Plasma Immunoglobulins | Pre-operative serum IgG level | 487 mg/dL | Standard Deviation 226.1 |
| IVIG | Plasma Immunoglobulins | 12 hour post-operative serum IgG level | 496 mg/dL | Standard Deviation 183 |
| IVIG | Plasma Immunoglobulins | Post-operative day 3 serum IgG level | 837 mg/dL | Standard Deviation 243 |
| IVIG | Plasma Immunoglobulins | Post-operative day 5 serum IgG level | 839 mg/dL | Standard Deviation 213 |
| Normal Saline | Plasma Immunoglobulins | Post-operative day 5 serum IgG level | 585 mg/dL | Standard Deviation 212.3 |
| Normal Saline | Plasma Immunoglobulins | Pre-operative serum IgG level | 414 mg/dL | Standard Deviation 230.5 |
| Normal Saline | Plasma Immunoglobulins | Post-operative day 3 serum IgG level | 508 mg/dL | Standard Deviation 215.4 |
| Normal Saline | Plasma Immunoglobulins | 12 hour post-operative serum IgG level | 569 mg/dL | Standard Deviation 272 |
Comparison: 12 hours post-operative IgG levelp-value: 0.36Wilcoxon (Mann-Whitney)
Comparison: pre-operative IgG levelp-value: 0.32t-test, 2 sided
Comparison: post-operative day 3 (72 hours) IgG levelp-value: <0.01Wilcoxon (Mann-Whitney)
Comparison: post-operative day 5 (120 hours) IgG levelp-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Post-operative Inotrope Score
The average admit, 12 hour, 24 hour, and 48 hour post-operative inotrope score will be calculated excluding Milrinone. To calculate the inotrope score the following formula was used: (Epinephrine/Norepinephrine dose in mcg/kg/min x 100) + (Dopamine dose in mcg/kg/min x 1) + (Phenylephrine dose in mcg/kg/min x 10) + (Vasopressin dose unit/kg/hr x 60/10000). The higher the inotrope score the more cardiac support the subject requires. There is not a normal scale or range used for this calculation.
Time frame: first 48 hours post-CPB
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Post-operative Inotrope Score | Admit | 5 inotropic score |
| IVIG | Post-operative Inotrope Score | 12 hr post-op | 5.3 inotropic score |
| IVIG | Post-operative Inotrope Score | 24 hr post-op | 5.3 inotropic score |
| IVIG | Post-operative Inotrope Score | 48 hr post-op | 6.8 inotropic score |
| Normal Saline | Post-operative Inotrope Score | 48 hr post-op | 2 inotropic score |
| Normal Saline | Post-operative Inotrope Score | Admit | 4.5 inotropic score |
| Normal Saline | Post-operative Inotrope Score | 24 hr post-op | 5.8 inotropic score |
| Normal Saline | Post-operative Inotrope Score | 12 hr post-op | 5.3 inotropic score |
Comparison: Admit Inotrope Scorep-value: 0.81Wilcoxon (Mann-Whitney)
Comparison: 12 hours post-operative inotrope scorep-value: 0.82Wilcoxon (Mann-Whitney)
Comparison: 24 hours post-operative inotrope scorep-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: 48 hours post-operative inotrope scorep-value: 0.23Wilcoxon (Mann-Whitney)
Secondary
Post-operative Plasma Albumin
Plasma albumin will be assessed at 24 and 48 hours.
Time frame: up to 48 hours post CPB
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IVIG | Post-operative Plasma Albumin | 24 hour post-op | 3.7 g/dL | Standard Deviation 0.74 |
| IVIG | Post-operative Plasma Albumin | 48 hour post-op | 3.3 g/dL | Standard Deviation 0.57 |
| Normal Saline | Post-operative Plasma Albumin | 24 hour post-op | 4.1 g/dL | Standard Deviation 0.67 |
| Normal Saline | Post-operative Plasma Albumin | 48 hour post-op | 3.6 g/dL | Standard Deviation 0.52 |
Comparison: 24 hour post-CPB albuminp-value: 0.42t-test, 2 sided
Comparison: 48 hour post CPB albuminp-value: 0.06t-test, 2 sided
Secondary
Respiratory Variables
Alive, ventilator free days will be recorded at hospital discharge.
Time frame: until Hospital Discharge, an average of 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG | Respiratory Variables | 24.7 days |
| Normal Saline | Respiratory Variables | 25.5 days |
p-value: 0.49Wilcoxon (Mann-Whitney)
Secondary
Respiratory Variables
Time until first extubation in hours
Time frame: until extubation, an average of 2 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG | Respiratory Variables | 46 hours |
| Normal Saline | Respiratory Variables | 43 hours |
p-value: 0.72Wilcoxon (Mann-Whitney)
Secondary
Respiratory Variables
Total time duration of post-operative length of mechanical ventilation until hospital discharge
Time frame: until extubation, an average of 2 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG | Respiratory Variables | 62.1 hours |
| Normal Saline | Respiratory Variables | 59 hours |
p-value: 0.63Wilcoxon (Mann-Whitney)
Secondary
Serum Creatinine
Pre-operative and 48 hour post-operative maximum creatinine recorded.
Time frame: 48 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IVIG | Serum Creatinine | Pre-operative | 0.4 mg/dL | Standard Deviation 0.15 |
| IVIG | Serum Creatinine | Max | 0.8 mg/dL | Standard Deviation 0.28 |
| Normal Saline | Serum Creatinine | Pre-operative | 0.4 mg/dL | Standard Deviation 0.17 |
| Normal Saline | Serum Creatinine | Max | 0.7 mg/dL | Standard Deviation 0.38 |
Comparison: pre-operativep-value: 0.43t-test, 2 sided
Comparison: maxp-value: 0.68t-test, 2 sided
Secondary
Tumor Necrosis Factor Plasma Cytokine Levels
Plasma cytokine levels measured preoperatively, 0, 4, 12, 24 hours, and 48 hours post-operatively.
Time frame: pre-operative through 48 hours post-operative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IVIG | Tumor Necrosis Factor Plasma Cytokine Levels | Pre-operative | 2.3 pg/dL |
| IVIG | Tumor Necrosis Factor Plasma Cytokine Levels | 0 hour post-operative | 2.9 pg/dL |
| IVIG | Tumor Necrosis Factor Plasma Cytokine Levels | 4 hour post-operative | 3.7 pg/dL |
| IVIG | Tumor Necrosis Factor Plasma Cytokine Levels | 12 hour post-operative | 3.1 pg/dL |
| IVIG | Tumor Necrosis Factor Plasma Cytokine Levels | 24 hour post-operative | 2.9 pg/dL |
| IVIG | Tumor Necrosis Factor Plasma Cytokine Levels | 48 hour post-operatiave | 2.4 pg/dL |
| Normal Saline | Tumor Necrosis Factor Plasma Cytokine Levels | 24 hour post-operative | 3.8 pg/dL |
| Normal Saline | Tumor Necrosis Factor Plasma Cytokine Levels | Pre-operative | 2.9 pg/dL |
| Normal Saline | Tumor Necrosis Factor Plasma Cytokine Levels | 12 hour post-operative | 4.1 pg/dL |
| Normal Saline | Tumor Necrosis Factor Plasma Cytokine Levels | 0 hour post-operative | 4.3 pg/dL |
| Normal Saline | Tumor Necrosis Factor Plasma Cytokine Levels | 48 hour post-operatiave | 3.5 pg/dL |
| Normal Saline | Tumor Necrosis Factor Plasma Cytokine Levels | 4 hour post-operative | 5.3 pg/dL |
Comparison: pre-operativep-value: 0.46Wilcoxon (Mann-Whitney)
Comparison: 0 hour post-operativep-value: 0.04Wilcoxon (Mann-Whitney)
Comparison: 4 hour post-operativep-value: 0.14Wilcoxon (Mann-Whitney)
Comparison: 12 hour post-operativep-value: 0.82Wilcoxon (Mann-Whitney)
Comparison: 24 hour post-operativep-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: 48 hour post-operativep-value: 0.78Wilcoxon (Mann-Whitney)