Congenital Heart Disease
Conditions
Brief summary
The overall goal of this project is to determine the role of anesthetic management in children undergoing cardiac surgery utilizing CPB in the setting of fast tracking and early extubation. An ideal anesthetic technique would ensure abolishing or diminishing stress response as would be evident by the stress markers levels and the level of two cerebral injury biomarkers (S 100 B and NSE). This should translate to better immediate postoperative outcome and hopefully improve both the short and the long term neurodevelopmental outcome in these children. The project is prospective, randomized and blinded study. The first and second aim of the study should be conducted over 2 year period. Our long term aim will be concluded when these children reach the school age.
Interventions
DRUGDexmedetomidine
DRUGPlacebo
Sponsors
Aymen N Naguib
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Months to 12 Months
Healthy volunteers
No
Inclusion criteria
* Patients with the following diagnosis: 1. ASD 2. VSD 3. AVSD 4. TOF 5. Biventricular repair with left to right shunt.
Exclusion criteria
* Patients with the diagnosis of AVSD and pulmonary hypertension * Patients less than 1 year and require any of the following repairs: 1. HLHS 2. Aortic arch reconstruction 3. Arterial switch 4. TOF with pulmonary atresia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cytokine Levels | From baseline to 24 hrs post-op | Cytokine levels in plasma samples will be measured at induction of anesthesia (baseline), after sternotomy, after initiation of CPB, at the conclusion of surgery (separation from CPB and administration of protamine and prior to skin closure) and at 24 hours post-operatively. |
| Change in Hormone Levels | From baseline to 24 hrs post-op | ACTH, cortisol, epinephrine, & norepinephrine will be measured at induction of anesthesia (baseline), after sternotomy, after initiation of CPB, at the conclusion of surgery (separation from CPB and administration of protamine and prior to skin closure) and at 24 hours post-operatively. |
| Change in Bayley Cognitive Composite Scores | From baseline to 1 year post-op | Children will have a baseline neurodevelopmental Bayley score during the preoperative period. These children will be retested prior to discharge from the hospital, at their post-op cardiology visit (usually 1-3 months post-op), six month and one year postoperatively to evaluate neurodevelopment progress. Mean score of 100 (SD=15) at the 50th percentile signifies mid-average functioning, scores below 85 (1 SD below the mean), at the 16th percentile, indicate mild impairment of being 'at risk' of developmental delay. Score below 70 (2 SD below the mean), at the second percentile, indicate moderate to severe impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bayley Language Composite Scores | From baseline to 1 year post-op | Children will have a baseline neurodevelopmental Bayley score during the preoperative period. These children will be retested prior to discharge from the hospital, at their post-op cardiology visit (usually 1-3 months post-op), six month and one year postoperatively to evaluate neurodevelopment progress. Mean score of 100 (SD=15) at the 50th percentile signifies mid-average functioning, scores below 85 (1 SD below the mean), at the 16th percentile, indicate mild impairment of being 'at risk' of developmental delay. Score below 70 (2 SD below the mean), at the second percentile, indicate moderate to severe impairment. |
| Change in Bayley Motor Composite Scores | From baseline to 1 year post-op | Children will have a baseline neurodevelopmental Bayley score during the preoperative period. These children will be retested at their post-op cardiology visit (usually 1-3 months post-op), six month and one year postoperatively to evaluate neurodevelopment progress. Mean score of 100 (SD=15) at the 50th percentile signifies mid-average functioning, scores below 85 (1 SD below the mean), at the 16th percentile, indicate mild impairment of being 'at risk' of developmental delay. Score below 70 (2 SD below the mean), at the second percentile, indicate moderate to severe impairment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexmedetomidine Dexmedetomidine in addition to 15 µg/kg of fentanyl
Dexmedetomidine | 14 |
| Placebo Normal saline as a placebo in addition to 15 µg/kg of fentanyl
Placebo | 16 |
| Total | 30 |
Baseline characteristics
| Characteristic | Placebo | Dexmedetomidine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 16 Participants | 14 Participants | 30 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 | 6 months STANDARD_DEVIATION 2 | 6 months STANDARD_DEVIATION 2 | 6 months STANDARD_DEVIATION 2 |
| Diagnosis Atrioventricular septal defect | 2 Participants | 6 Participants | 8 Participants |
| Diagnosis Tetralogy of Fallot | 9 Participants | 6 Participants | 15 Participants |
| Diagnosis Ventricular Septal Defect | 5 Participants | 7 Participants | 12 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 16 participants | 14 participants | 30 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
| Weight | 7 kilograms STANDARD_DEVIATION 1 | 6 kilograms STANDARD_DEVIATION 1 | 6.6 kilograms STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 0 / 14 | 0 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 |
Outcome results
Primary
Change in Bayley Cognitive Composite Scores
Children will have a baseline neurodevelopmental Bayley score during the preoperative period. These children will be retested prior to discharge from the hospital, at their post-op cardiology visit (usually 1-3 months post-op), six month and one year postoperatively to evaluate neurodevelopment progress. Mean score of 100 (SD=15) at the 50th percentile signifies mid-average functioning, scores below 85 (1 SD below the mean), at the 16th percentile, indicate mild impairment of being 'at risk' of developmental delay. Score below 70 (2 SD below the mean), at the second percentile, indicate moderate to severe impairment.
Time frame: From baseline to 1 year post-op
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexmedetomidine | Change in Bayley Cognitive Composite Scores | Prior to discharge | 102.14 score on a scale | Standard Deviation 13.26 |
| Dexmedetomidine | Change in Bayley Cognitive Composite Scores | 6 months post-op | 98.57 score on a scale | Standard Deviation 7.95 |
| Dexmedetomidine | Change in Bayley Cognitive Composite Scores | 1-3 month post-op | 102.86 score on a scale | Standard Deviation 14.9 |
| Dexmedetomidine | Change in Bayley Cognitive Composite Scores | 1 yr. post-op | 94.64 score on a scale | Standard Deviation 12 |
| Dexmedetomidine | Change in Bayley Cognitive Composite Scores | Baseline | 102.14 score on a scale | Standard Deviation 11.04 |
| Placebo | Change in Bayley Cognitive Composite Scores | 1 yr. post-op | 94.09 score on a scale | Standard Deviation 12 |
| Placebo | Change in Bayley Cognitive Composite Scores | Baseline | 95 score on a scale | Standard Deviation 16.12 |
| Placebo | Change in Bayley Cognitive Composite Scores | Prior to discharge | 88.33 score on a scale | Standard Deviation 17.49 |
| Placebo | Change in Bayley Cognitive Composite Scores | 1-3 month post-op | 96.82 score on a scale | Standard Deviation 17.07 |
| Placebo | Change in Bayley Cognitive Composite Scores | 6 months post-op | 97.27 score on a scale | Standard Deviation 16.49 |
Primary
Change in Cytokine Levels
Cytokine levels in plasma samples will be measured at induction of anesthesia (baseline), after sternotomy, after initiation of CPB, at the conclusion of surgery (separation from CPB and administration of protamine and prior to skin closure) and at 24 hours post-operatively.
Time frame: From baseline to 24 hrs post-op
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexmedetomidine | Change in Cytokine Levels | Baseline IL-6 | 0.57 picograms per milliliter | Standard Deviation 0.71 |
| Dexmedetomidine | Change in Cytokine Levels | Baseline IL-8 | 6.55 picograms per milliliter | Standard Deviation 5.02 |
| Dexmedetomidine | Change in Cytokine Levels | End of surgery TNF-alpha | 3.12 picograms per milliliter | Standard Deviation 1.94 |
| Dexmedetomidine | Change in Cytokine Levels | Post-sternotomy IL-8 | 6.8 picograms per milliliter | Standard Deviation 4.68 |
| Dexmedetomidine | Change in Cytokine Levels | Post-bypass IL-8 | 7.04 picograms per milliliter | Standard Deviation 5.26 |
| Dexmedetomidine | Change in Cytokine Levels | Post-sternotomy IL-6 | 0.61 picograms per milliliter | Standard Deviation 0.53 |
| Dexmedetomidine | Change in Cytokine Levels | End of surgery IL-8 | 28.83 picograms per milliliter | Standard Deviation 28.97 |
| Dexmedetomidine | Change in Cytokine Levels | Post-bypass TNF-alpha | 2.88 picograms per milliliter | Standard Deviation 1.14 |
| Dexmedetomidine | Change in Cytokine Levels | 24 hr. post-op IL-8 | 20.86 picograms per milliliter | Standard Deviation 16.76 |
| Dexmedetomidine | Change in Cytokine Levels | Post-bypass IL-6 | 0.87 picograms per milliliter | Standard Deviation 0.59 |
| Dexmedetomidine | Change in Cytokine Levels | Baseline IL-10 | 0.27 picograms per milliliter | Standard Deviation 0.62 |
| Dexmedetomidine | Change in Cytokine Levels | 24 hr. post-op TNF-alph | 2.68 picograms per milliliter | Standard Deviation 1.25 |
| Dexmedetomidine | Change in Cytokine Levels | Post-sternotomy IL-10 | 0.87 picograms per milliliter | Standard Deviation 0.46 |
| Dexmedetomidine | Change in Cytokine Levels | End of surgery IL-6 | 11.95 picograms per milliliter | Standard Deviation 21.71 |
| Dexmedetomidine | Change in Cytokine Levels | Post-bypass IL-10 | 1.05 picograms per milliliter | Standard Deviation 1.02 |
| Dexmedetomidine | Change in Cytokine Levels | Baseline TNF-alpha | 4.38 picograms per milliliter | Standard Deviation 1.63 |
| Dexmedetomidine | Change in Cytokine Levels | End of surgery IL-10 | 44.41 picograms per milliliter | Standard Deviation 48.95 |
| Dexmedetomidine | Change in Cytokine Levels | 24 hr. post-op IL-6 | 30.2 picograms per milliliter | Standard Deviation 17.04 |
| Dexmedetomidine | Change in Cytokine Levels | 24 hr. post-op IL-10 | 1.37 picograms per milliliter | Standard Deviation 0.51 |
| Dexmedetomidine | Change in Cytokine Levels | Post-sternotomy TNF-alpha | 3.98 picograms per milliliter | Standard Deviation 1.58 |
| Placebo | Change in Cytokine Levels | 24 hr. post-op IL-10 | 1.62 picograms per milliliter | Standard Deviation 1.03 |
| Placebo | Change in Cytokine Levels | Post-sternotomy IL-8 | 8.46 picograms per milliliter | Standard Deviation 6.03 |
| Placebo | Change in Cytokine Levels | Baseline TNF-alpha | 4.2 picograms per milliliter | Standard Deviation 2.55 |
| Placebo | Change in Cytokine Levels | Post-sternotomy TNF-alpha | 3.85 picograms per milliliter | Standard Deviation 2.37 |
| Placebo | Change in Cytokine Levels | Post-bypass TNF-alpha | 2.72 picograms per milliliter | Standard Deviation 1.76 |
| Placebo | Change in Cytokine Levels | End of surgery TNF-alpha | 2.96 picograms per milliliter | Standard Deviation 1.7 |
| Placebo | Change in Cytokine Levels | 24 hr. post-op TNF-alph | 3.30 picograms per milliliter | Standard Deviation 2.43 |
| Placebo | Change in Cytokine Levels | Baseline IL-6 | 0.96 picograms per milliliter | Standard Deviation 1.59 |
| Placebo | Change in Cytokine Levels | Post-sternotomy IL-6 | 0.99 picograms per milliliter | Standard Deviation 1.29 |
| Placebo | Change in Cytokine Levels | Post-bypass IL-6 | 1.19 picograms per milliliter | Standard Deviation 1.3 |
| Placebo | Change in Cytokine Levels | End of surgery IL-6 | 11.32 picograms per milliliter | Standard Deviation 14.73 |
| Placebo | Change in Cytokine Levels | 24 hr. post-op IL-6 | 41.93 picograms per milliliter | Standard Deviation 74.34 |
| Placebo | Change in Cytokine Levels | Baseline IL-8 | 7.28 picograms per milliliter | Standard Deviation 5.61 |
| Placebo | Change in Cytokine Levels | Post-bypass IL-8 | 8.35 picograms per milliliter | Standard Deviation 5.94 |
| Placebo | Change in Cytokine Levels | End of surgery IL-8 | 34.37 picograms per milliliter | Standard Deviation 32.76 |
| Placebo | Change in Cytokine Levels | 24 hr. post-op IL-8 | 32.52 picograms per milliliter | Standard Deviation 29.81 |
| Placebo | Change in Cytokine Levels | Baseline IL-10 | 0.9 picograms per milliliter | Standard Deviation 0.65 |
| Placebo | Change in Cytokine Levels | Post-sternotomy IL-10 | 1.26 picograms per milliliter | Standard Deviation 0.89 |
| Placebo | Change in Cytokine Levels | Post-bypass IL-10 | 1.24 picograms per milliliter | Standard Deviation 0.88 |
| Placebo | Change in Cytokine Levels | End of surgery IL-10 | 78.27 picograms per milliliter | Standard Deviation 54.11 |
Primary
Change in Hormone Levels
ACTH, cortisol, epinephrine, & norepinephrine will be measured at induction of anesthesia (baseline), after sternotomy, after initiation of CPB, at the conclusion of surgery (separation from CPB and administration of protamine and prior to skin closure) and at 24 hours post-operatively.
Time frame: From baseline to 24 hrs post-op
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexmedetomidine | Change in Hormone Levels | Baseline Epinephrine | 108.26 picograms per milliliter | Standard Deviation 98.2 |
| Dexmedetomidine | Change in Hormone Levels | Post-sternotomy ACTH | 105.63 picograms per milliliter | Standard Deviation 141.15 |
| Dexmedetomidine | Change in Hormone Levels | Post-sternotomy Epinephrine | 250.1 picograms per milliliter | Standard Deviation 261.97 |
| Dexmedetomidine | Change in Hormone Levels | 24 hr. post-op ACTH | 18.21 picograms per milliliter | Standard Deviation 9.8 |
| Dexmedetomidine | Change in Hormone Levels | Post-bypass Epinephrine | 830.45 picograms per milliliter | Standard Deviation 757.89 |
| Dexmedetomidine | Change in Hormone Levels | Baseline ACTH | 150.10 picograms per milliliter | Standard Deviation 119.78 |
| Dexmedetomidine | Change in Hormone Levels | End of surgery Epinephrine | 203.73 picograms per milliliter | Standard Deviation 103.58 |
| Dexmedetomidine | Change in Hormone Levels | Baseline Cortisol | 448.27 picograms per milliliter | Standard Deviation 187.73 |
| Dexmedetomidine | Change in Hormone Levels | 24 hr. post-op Epinephrine | 172.05 picograms per milliliter | Standard Deviation 235.48 |
| Dexmedetomidine | Change in Hormone Levels | Post-bypass Cortisol | 314.42 picograms per milliliter | Standard Deviation 81.66 |
| Dexmedetomidine | Change in Hormone Levels | Baseline Norepinephrine | 492.58 picograms per milliliter | Standard Deviation 475.2 |
| Dexmedetomidine | Change in Hormone Levels | Post-bypass ACTH | 108.09 picograms per milliliter | Standard Deviation 114.86 |
| Dexmedetomidine | Change in Hormone Levels | Post-sternotomy Norepinephrine | 545.88 picograms per milliliter | Standard Deviation 656.81 |
| Dexmedetomidine | Change in Hormone Levels | End of surgery Cortisol | 553.88 picograms per milliliter | Standard Deviation 220.52 |
| Dexmedetomidine | Change in Hormone Levels | Post-bypass Norepinephrine | 499.37 picograms per milliliter | Standard Deviation 428.34 |
| Dexmedetomidine | Change in Hormone Levels | Post-sternotomy Cortisol | 449.71 picograms per milliliter | Standard Deviation 144.4 |
| Dexmedetomidine | Change in Hormone Levels | End of surgery Norepinephrine | 229.32 picograms per milliliter | Standard Deviation 207.5 |
| Dexmedetomidine | Change in Hormone Levels | 24 hr. post-op Cortisol | 344.83 picograms per milliliter | Standard Deviation 344.79 |
| Dexmedetomidine | Change in Hormone Levels | 24 hr. post-op Norepinephrine | 913.12 picograms per milliliter | Standard Deviation 950.97 |
| Dexmedetomidine | Change in Hormone Levels | End of surgery ACTH | 186.69 picograms per milliliter | Standard Deviation 170.06 |
| Placebo | Change in Hormone Levels | 24 hr. post-op Norepinephrine | 1320.9 picograms per milliliter | Standard Deviation 2263.32 |
| Placebo | Change in Hormone Levels | Post-sternotomy Cortisol | 316.58 picograms per milliliter | Standard Deviation 264.12 |
| Placebo | Change in Hormone Levels | Baseline ACTH | 139.48 picograms per milliliter | Standard Deviation 96.11 |
| Placebo | Change in Hormone Levels | Post-sternotomy ACTH | 94.2 picograms per milliliter | Standard Deviation 93.8 |
| Placebo | Change in Hormone Levels | Post-bypass ACTH | 199.34 picograms per milliliter | Standard Deviation 160.34 |
| Placebo | Change in Hormone Levels | End of surgery ACTH | 201.49 picograms per milliliter | Standard Deviation 171.01 |
| Placebo | Change in Hormone Levels | 24 hr. post-op ACTH | 26.78 picograms per milliliter | Standard Deviation 19.19 |
| Placebo | Change in Hormone Levels | Post-bypass Cortisol | 298.64 picograms per milliliter | Standard Deviation 217.82 |
| Placebo | Change in Hormone Levels | End of surgery Cortisol | 474.66 picograms per milliliter | Standard Deviation 256.16 |
| Placebo | Change in Hormone Levels | 24 hr. post-op Cortisol | 357.3 picograms per milliliter | Standard Deviation 475.88 |
| Placebo | Change in Hormone Levels | Baseline Epinephrine | 112.13 picograms per milliliter | Standard Deviation 145.52 |
| Placebo | Change in Hormone Levels | Post-sternotomy Epinephrine | 379.68 picograms per milliliter | Standard Deviation 344.15 |
| Placebo | Change in Hormone Levels | Post-bypass Epinephrine | 830.73 picograms per milliliter | Standard Deviation 488.22 |
| Placebo | Change in Hormone Levels | End of surgery Epinephrine | 423.06 picograms per milliliter | Standard Deviation 406.03 |
| Placebo | Change in Hormone Levels | 24 hr. post-op Epinephrine | 154.05 picograms per milliliter | Standard Deviation 176.39 |
| Placebo | Change in Hormone Levels | Baseline Norepinephrine | 696.5 picograms per milliliter | Standard Deviation 568.89 |
| Placebo | Change in Hormone Levels | Post-sternotomy Norepinephrine | 891.86 picograms per milliliter | Standard Deviation 966.44 |
| Placebo | Change in Hormone Levels | Post-bypass Norepinephrine | 1145.05 picograms per milliliter | Standard Deviation 1281.1 |
| Placebo | Change in Hormone Levels | End of surgery Norepinephrine | 477.66 picograms per milliliter | Standard Deviation 745.6 |
| Placebo | Change in Hormone Levels | Baseline Cortisol | 293.92 picograms per milliliter | Standard Deviation 138.53 |
Secondary
Change in Bayley Language Composite Scores
Children will have a baseline neurodevelopmental Bayley score during the preoperative period. These children will be retested prior to discharge from the hospital, at their post-op cardiology visit (usually 1-3 months post-op), six month and one year postoperatively to evaluate neurodevelopment progress. Mean score of 100 (SD=15) at the 50th percentile signifies mid-average functioning, scores below 85 (1 SD below the mean), at the 16th percentile, indicate mild impairment of being 'at risk' of developmental delay. Score below 70 (2 SD below the mean), at the second percentile, indicate moderate to severe impairment.
Time frame: From baseline to 1 year post-op
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexmedetomidine | Change in Bayley Language Composite Scores | Prior to discharge | 91.14 score on a scale | Standard Deviation 20 |
| Dexmedetomidine | Change in Bayley Language Composite Scores | Baseline | 98.14 score on a scale | Standard Deviation 13.95 |
| Dexmedetomidine | Change in Bayley Language Composite Scores | 1-3 month post-op | 92.5 score on a scale | Standard Deviation 13.35 |
| Dexmedetomidine | Change in Bayley Language Composite Scores | 6 months post-op | 86 score on a scale | Standard Deviation 11.81 |
| Dexmedetomidine | Change in Bayley Language Composite Scores | 1 yr. post-op | 93.08 score on a scale | Standard Deviation 13.1 |
| Placebo | Change in Bayley Language Composite Scores | 6 months post-op | 91.36 score on a scale | Standard Deviation 8.98 |
| Placebo | Change in Bayley Language Composite Scores | 1 yr. post-op | 91.2 score on a scale | Standard Deviation 18.64 |
| Placebo | Change in Bayley Language Composite Scores | Baseline | 86.81 score on a scale | Standard Deviation 14.45 |
| Placebo | Change in Bayley Language Composite Scores | 1-3 month post-op | 92.36 score on a scale | Standard Deviation 14.43 |
| Placebo | Change in Bayley Language Composite Scores | Prior to discharge | 77.6 score on a scale | Standard Deviation 12.26 |
Secondary
Change in Bayley Motor Composite Scores
Children will have a baseline neurodevelopmental Bayley score during the preoperative period. These children will be retested at their post-op cardiology visit (usually 1-3 months post-op), six month and one year postoperatively to evaluate neurodevelopment progress. Mean score of 100 (SD=15) at the 50th percentile signifies mid-average functioning, scores below 85 (1 SD below the mean), at the 16th percentile, indicate mild impairment of being 'at risk' of developmental delay. Score below 70 (2 SD below the mean), at the second percentile, indicate moderate to severe impairment.
Time frame: From baseline to 1 year post-op
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexmedetomidine | Change in Bayley Motor Composite Scores | Baseline | 95.14 score on a scale | Standard Deviation 15.02 |
| Dexmedetomidine | Change in Bayley Motor Composite Scores | 1-3 month post-op | 92.07 score on a scale | Standard Deviation 13.9 |
| Dexmedetomidine | Change in Bayley Motor Composite Scores | 1 yr. post-op | 91.69 score on a scale | Standard Deviation 10.62 |
| Dexmedetomidine | Change in Bayley Motor Composite Scores | 6 months post-op | 92 score on a scale | Standard Deviation 13.98 |
| Placebo | Change in Bayley Motor Composite Scores | 1 yr. post-op | 87.5 score on a scale | Standard Deviation 17.37 |
| Placebo | Change in Bayley Motor Composite Scores | Baseline | 84.2 score on a scale | Standard Deviation 15.89 |
| Placebo | Change in Bayley Motor Composite Scores | 1-3 month post-op | 84.27 score on a scale | Standard Deviation 16.84 |
| Placebo | Change in Bayley Motor Composite Scores | 6 months post-op | 87.18 score on a scale | Standard Deviation 10.66 |