Tetralogy of Fallot (TOF), Ventricular Septal Defects (VSD), Atrioventricular Septal Defects (AVSD)
Conditions
Keywords
pediatric cardiac surgery, stress response, early extubation, Dexmedetomidine, TOF, VSD, AVSD
Brief summary
Cardiac surgery induces a measurable stress response in patients which leads to increased morbidity and mortality post-operatively. Through clinical observation, anesthesiologists have determined that varying the combinations of anesthesia drugs used during surgery and just after reduces the stress response, and by extension, morbidity and mortality. However, only a few studies have explored this phenomenon scientifically.
Detailed description
In this study, we aim to demonstrate comparatively that use of dexmedetomidine in addition to low dose narcotics reduces the stress response in cardiac surgical patients and results in less morbidity and mortality. Additionally, dexmedetomidine (Dex) should facilitate safe early extubation in pediatric cardiac patients, which results in decreased ventilator associated co-morbidities. Patients will be randomly assigned to three groups; one group will receive low dose fentanyl (LDF), one will receive low dose fentanyl with dexmedetomidine (LDF + Dex), and one will receive high dose fentanyl (HDF). Blood samples will be collected post-induction, post-sternotomy, after going on cardiopulmonary bypass, at the completion of surgery, and post-operatively to determine the patients' stress hormone levels. The patients will receive standard post-operative care, and clinical data collected as part of this care will be used to determine the incidence of morbidity and mortality. The results of the blood tests will be correlated with the incidence of morbidity and mortality to demonstrate the relative effectiveness of the different anesthesia methods. Blood samples will be analyzed for the presence of the stress hormones cortisol, epinephrine, norepinephrine, adrenocorticotropic hormone (ACTH), Interleukin 8 (IL-8), TNF-alpha (Tumor Necrosis Factor), and nitrated albumin. Arterial blood gas, glucose and lactate levels, heart rate, blood pressure, use of vasoactive support, length of ventilator use, post-operative mortality, post-operative morbidity, length of Intensive Care Unit (ICU) stay, and length of hospital stay will be recorded. Children previously enrolled in the surgery study will complete assessments of their cognitive ability, developmental status, and emotional and behavioral adjustment. For the neuro-developmental outcome follow up, Children's cognitive ability will be assessed using the Stanford-Binet Intelligence Scales, 5th Edition (SB5). The SB5 is a widely-used measure of intellectual functioning that is normed for ages 2 and up. The test takes 30-50 minutes to administer to young children, and provides an overall Intelligence Quotient (IQ) score, as well as scores for five primary factors of cognitive ability: Fluid Reasoning, Knowledge, Quantitative Reasoning, Visual-Spatial Processing; and Working Memory. The SB5 has demonstrated excellent reliability and validity.
Interventions
Fentanyl (High Dose) 25 mcg/kg in two divided doses. Half-dose will be given at induction and the second half-dose given prior to incision.
Fentanyl (Low Dose) 10 mcg/kg in two divided doses. Half-dose will be given at induction and the second half-dose given prior to incision.
DRUGFentanyl (Low Dose) + Dexmedetomidine
Fentanyl (Low Dose) + Dexmedetomidine. Dexmedetomidine at 1mcg/kg loading dose over 10 minutes, followed by an infusion at a rate of 0.5mcg/kg/hr. In addition, this group will receive a total of 10 mcg/kg Fentanyl (Low Dose). Half the dose will be given at induction and the second half before incision.
Sponsors
Nationwide Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Months to 3 Years
Healthy volunteers
No
Inclusion criteria
* Childrens with the diagnosis of tetralogy of fallot, ventricular septal defect and atrioventricular septal defect who are under one year of age.
Exclusion criteria
* Patients who are having reoperation. * Patients with comorbidities, such as heart failure. * Patients receiving digoxin preoperatively.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Length of CTICU Stay. | Hospital admission to discharge from CTICU (average of 2-4 days) | — |
| Stanford-Binet Intelligence Scales | 1-4 yrs. post-surgery | The Stanford-Binet test evaluates the overall IQ score from the assessment of cognitive ability. The test consists of 15 subtests, grouped into the four area scores. Six subtests are administered to all age levels. The subtests are: Vocabulary, Comprehension, Pattern Analysis, Quantitative, Bead Memory, and Memory for Sentences. Number of tests administered and test difficulty are based on the test taker's age and performance on subtest measuring word knowledge. The word knowledge subtest is given to all test takers and is the first subtest administered. A score of 100 is in the normal or average range. Higher scores suggest a higher level of functioning related to each category. (University of Cincinnati, 2003) Raw scores for each subtest within the overall test are converted to scaled scores using a table within each test manual to look up equivalents. Scaled scores are then converted to standard scores (range=50-150). |
| Stress Hormone Levels | Blood draws to measure stress hormone levels within one hour of draw: after induction; after sternotomy; after starting cardiopulmonary bypass; at the end of the procedure; and 24 hours after the procedure. | Cortisol, epinephrine, and norepinephrine assayed by enzyme-linked immunosorbent assay (ELISA). |
| ACTH and Cytokine Levels | Blood draws to measure cytokines levels within one hour of draw: after induction; after sternotomy; after starting cardiopulmonary bypass; at the end of the procedure; and 24 hours after the procedure. | N = 48 n = 16 (LDF); n = 17 (HDF); n = 15 (LDF + Dex) ACTH assayed by enzyme-linked immunosorbent assay (ELISA); Cytokine levels in plasma were measured using the Immulite automated chemiluminometer. Measured cytokines include interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-α. |
| Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator. | Time of intubation to extubation (variable) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ABAS-II | 1-4 yrs post-surgery | The ABAS-II is designed to evaluate whether an individual displays various functional skills necessary for daily living without the assistance of others. Thus, this instrument focuses on independent behaviors and measures what an individual actually does, in addition to measuring what he or she may be able to do. In addition, the ABAS-II focuses on behaviors an individual displays on his or her own, without assistance from others. The Parent/Primary Caregiver Form is a comprehensive, diagnostic measure of the adaptive skills that have primary relevance for the functioning of infants, toddlers, and preschoolers in the home and other settings, and can be completed by parents or other primary care providers. Each composite or domain score is determined by summing the appropriate scaled scores and then determining its equivalent composite or domain score by looking it up in a table located in the manual.The range for all scores is 50-150, with a higher score equaling a better outcome. |
| Stanford-Binet Cognitive Ability | 1-4 yrs post-surgery | The Stanford-Binet Intelligence Scale is now in its fifth edition (SB5) and was released in 2003. It is a cognitive ability and intelligence test that is used to diagnose developmental or intellectual deficiencies in young children. The test measures five weighted factors and consists of both verbal and nonverbal subtests. The five factors being tested are knowledge, quantitative reasoning, visual-spatial processing, working memory, and fluid reasoning. Raw scores for each subtest within the overall test are converted to scaled scores using a table within each test manual to look up equivalents. Scaled scores are then converted to standard scores (range=50-150). Higher scores suggest a higher level of functioning related to each category. |
Countries
United States
Participant flow
Recruitment details
A total of 51 study subjects completed the study.
Pre-assignment details
Total number of subjects recruited was 52 patients (one enrollee withdrew prior to any study-related procedures) resulting in a total number of subjects participating of 51. The enrollee was withdrawn from the study after signing the consent and prior to enrolling to one of the arms of the study.
Participants by arm
| Arm | Count |
|---|---|
| Fentanyl (High Dose) patients in this arm will receive a total of 25 mcg/kg of Fentanyl (High Dose) in two divided doses. first half will be given at induction and the second half will be given before incision.
Fentanyl (High Dose): 25 mcg/kg in two divided doses. half the dose will be given at induction and the second half will be given prior to incision. | 17 |
| Fentanyl (Low Dose) patients in this group will receive a total of 10mcg/kg of fentanyl. half the dose will be given at induction and the second half will be given before incision
Fentanyl (Low Dose): patients will receive a total of 10mcg/kg of fentanyl. half the dose will be given at induction and the second half before incision. | 16 |
| Fentanyl (Low Dose) + Dexmedetomidine patients in this group will receive a total of 10mcg/kg of Fentanyl (Low Dose) in two divided doses and Dexmedetomidine at a loading dose of 1mcg/kg over 10 minutes and then an infusion of Dexmedetomidine at 0.5mcg/kg/hr.
Fentanyl (Low Dose) + Dexmedetomidine: Dexmedetomidine at 1mcg/kg loading dose over 10 minutes, followed by an infusion at a rate of 0.5mcg/kg/hr. In addition, this group will receive a total of 10 mcg/kg Fentanyl (Low Dose). Half the dose will be given at induction and the second half before incision. | 15 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | surgical complications unrelated to stud | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Fentanyl (Low Dose) | Fentanyl (Low Dose) + Dexmedetomidine | Fentanyl (High Dose) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 16 Participants | 15 Participants | 17 Participants | 48 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 4 months | 5 months | 4 months | 4 months |
| Region of Enrollment United States | 16 participants | 15 participants | 17 participants | 48 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 9 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 16 | 1 / 18 |
| serious Total, serious adverse events | 0 / 17 | 0 / 16 | 2 / 18 |
Outcome results
Primary
ACTH and Cytokine Levels
N = 48 n = 16 (LDF); n = 17 (HDF); n = 15 (LDF + Dex) ACTH assayed by enzyme-linked immunosorbent assay (ELISA); Cytokine levels in plasma were measured using the Immulite automated chemiluminometer. Measured cytokines include interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-α.
Time frame: Blood draws to measure cytokines levels within one hour of draw: after induction; after sternotomy; after starting cardiopulmonary bypass; at the end of the procedure; and 24 hours after the procedure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (High Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery TNF-alpha (pg/mL) | 15.79 pg/mL | Standard Deviation 30.8563 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Sternotomy IL-8 (pg/mL) | 20.77647 pg/mL | Standard Deviation 42.23163 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Bypass TNF-alpha (pg/mL) | 24.30615 pg/mL | Standard Deviation 23.03753 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Sternotomy ACTH (pg/mL) | 44.5 pg/mL | Standard Deviation 39.7 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Baseline IL-8 (pg/mL) | 17.12353 pg/mL | Standard Deviation 24.88048 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | End-Of-Surgery TNF-alpha (pg/mL) | 23.87077 pg/mL | Standard Deviation 17.18903 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Baseline ACTH (pg/mL) | 116.9 pg/mL | Standard Deviation 117 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-6 (pg/mL) | 126.0813 pg/mL | Standard Deviation 141.7456 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | End-Of-Surgery IL-10 (pg/mL) | 345.4412 pg/mL | Standard Deviation 445.7443 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | End-Of-Surgery IL-6 (pg/mL) | 20.48571 pg/mL | Standard Deviation 11.00962 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Baseline IL-6 (pg/mL) | 6.637058824 pg/mL | Standard Deviation 4.356124661 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Bypass IL-10 (pg/mL) | 9.488235 pg/mL | Standard Deviation 1.872793 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Sternotomy IL-10 (pg/mL) | 9.911765 pg/mL | Standard Deviation 2.749291 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Bypass IL-6 (pg/mL) | 5.098824 pg/mL | Standard Deviation 3.10355 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Bypass ACTH (pg/mL) | 57.2 pg/mL | Standard Deviation 61.2 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | End-Of-Surgery ACTH (pg/mL) | 66.4 pg/mL | Standard Deviation 77.9 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Sternotomy IL-6 (pg/mL) | 5.402353 pg/mL | Standard Deviation 3.623996 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-8 (pg/mL) | 49.07143 pg/mL | Standard Deviation 69.39429 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery ACTH (pg/mL) | 12.7 pg/mL | Standard Deviation 7.4 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Baseline IL-10 (pg/mL) | 10.82353 pg/mL | Standard Deviation 1.952412 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | End-Of-Surgery IL-8 (pg/mL) | 28.1 pg/mL | Standard Deviation 17.28596 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Baseline TNF-alpha (pg/mL) | 15.70077 pg/mL | Standard Deviation 16.401 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-10 (pg/mL) | 10.80667 pg/mL | Standard Deviation 1.907304 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Bypass IL-8 (pg/mL) | 9.770588 pg/mL | Standard Deviation 2.389499 |
| Fentanyl (High Dose) | ACTH and Cytokine Levels | Post-Sternotomy TNF-alpha (pg/mL) | 26.51846 pg/mL | Standard Deviation 33.64902 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Bypass TNF-alpha (pg/mL) | 25.787 pg/mL | Standard Deviation 29.267 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Sternotomy ACTH (pg/mL) | 86.2 pg/mL | Standard Deviation 76.5 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Bypass ACTH (pg/mL) | 172.7 pg/mL | Standard Deviation 121.8 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Baseline IL-10 (pg/mL) | 9.9 pg/mL | Standard Deviation 0 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-6 (pg/mL) | 117.975 pg/mL | Standard Deviation 95.86805 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Baseline ACTH (pg/mL) | 182.7 pg/mL | Standard Deviation 111.3 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | End-Of-Surgery ACTH (pg/mL) | 155.0 pg/mL | Standard Deviation 107.5 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery ACTH (pg/mL) | 53.2 pg/mL | Standard Deviation 24.3 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Baseline TNF-alpha (pg/mL) | 25.294 pg/mL | Standard Deviation 31.22396 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Sternotomy TNF-alpha (pg/mL) | 24.497 pg/mL | Standard Deviation 33.8474 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | End-Of-Surgery TNF-alpha (pg/mL) | 24.857 pg/mL | Standard Deviation 18.82328 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery TNF-alpha (pg/mL) | 11.954 pg/mL | Standard Deviation 17.23623 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Baseline IL-6 (pg/mL) | 4.757142857 pg/mL | Standard Deviation 2.178819118 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Sternotomy IL-6 (pg/mL) | 12.17333 pg/mL | Standard Deviation 28.79942 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Bypass IL-6 (pg/mL) | 5.509375 pg/mL | Standard Deviation 3.93354 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | End-Of-Surgery IL-6 (pg/mL) | 22.47333 pg/mL | Standard Deviation 12.59657 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Baseline IL-8 (pg/mL) | 10.44286 pg/mL | Standard Deviation 1.839195 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Sternotomy IL-8 (pg/mL) | 10.66667 pg/mL | Standard Deviation 2.941736 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Bypass IL-8 (pg/mL) | 10.13125 pg/mL | Standard Deviation 2.15769 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | End-Of-Surgery IL-8 (pg/mL) | 33.12667 pg/mL | Standard Deviation 25.1446 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-8 (pg/mL) | 47.25 pg/mL | Standard Deviation 99.4908 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Sternotomy IL-10 (pg/mL) | 9.9 pg/mL | Standard Deviation 0 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | Post-Bypass IL-10 (pg/mL) | 9.9 pg/mL | Standard Deviation 2.581989 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | End-Of-Surgery IL-10 (pg/mL) | 325.55 pg/mL | Standard Deviation 262.3603 |
| Fentanyl (Low Dose) | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-10 (pg/mL) | 14.80833 pg/mL | Standard Deviation 10.65888 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Sternotomy TNF-alpha (pg/mL) | 17.88636 pg/mL | Standard Deviation 16.96651 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Bypass ACTH (pg/mL) | 191.6 pg/mL | Standard Deviation 220.2 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Sternotomy IL-8 (pg/mL) | 10.86667 pg/mL | Standard Deviation 1.980861 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Baseline TNF-alpha (pg/mL) | 8.018182 pg/mL | Standard Deviation 10.68364 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Bypass IL-10 (pg/mL) | 12.30667 pg/mL | Standard Deviation 10.78136 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Bypass IL-8 (pg/mL) | 9.673333 pg/mL | Standard Deviation 1.182894 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | 24 hour Post-Surgery ACTH (pg/mL) | 22.4 pg/mL | Standard Deviation 130.3 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Baseline IL-6 (pg/mL) | 5.542857143 pg/mL | Standard Deviation 3.455366904 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | End-Of-Surgery IL-8 (pg/mL) | 37.22143 pg/mL | Standard Deviation 43.66227 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | End-Of-Surgery ACTH (pg/mL) | 154.1 pg/mL | Standard Deviation 166.6 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-10 (pg/mL) | 9.692857 pg/mL | Standard Deviation 0.775058 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-8 (pg/mL) | 24.27143 pg/mL | Standard Deviation 14.72541 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Baseline IL-10 (pg/mL) | 12.76429 pg/mL | Standard Deviation 9.373252 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Sternotomy ACTH (pg/mL) | 106.9 pg/mL | Standard Deviation 153.5 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Sternotomy IL-6 (pg/mL) | 6.241333 pg/mL | Standard Deviation 4.0798 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | End-Of-Surgery IL-10 (pg/mL) | 569.2714 pg/mL | Standard Deviation 858.2538 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Bypass IL-6 (pg/mL) | 5.040667 pg/mL | Standard Deviation 2.583747 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | 24 hour Post-Surgery TNF-alpha (pg/mL) | 21.13909 pg/mL | Standard Deviation 19.00043 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Sternotomy IL-10 (pg/mL) | 14.10667 pg/mL | Standard Deviation 13.63863 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | End-Of-Surgery IL-6 (pg/mL) | 20.79231 pg/mL | Standard Deviation 12.55537 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | End-Of-Surgery TNF-alpha (pg/mL) | 23.06091 pg/mL | Standard Deviation 18.8737 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | 24 hour Post-Surgery IL-6 (pg/mL) | 142.1571 pg/mL | Standard Deviation 129.4279 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Post-Bypass TNF-alpha (pg/mL) | 20.34364 pg/mL | Standard Deviation 14.03041 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Baseline ACTH (pg/mL) | 135.3 pg/mL | Standard Deviation 129.8 |
| Fentanyl (Low Dose) + Dexmedetomidine | ACTH and Cytokine Levels | Baseline IL-8 (pg/mL) | 10.25714 pg/mL | Standard Deviation 1.336306 |
Primary
Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Length of CTICU Stay.
Time frame: Hospital admission to discharge from CTICU (average of 2-4 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fentanyl (High Dose) | Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Length of CTICU Stay. | 1 Days |
| Fentanyl (Low Dose) | Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Length of CTICU Stay. | 1 Days |
| Fentanyl (Low Dose) + Dexmedetomidine | Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Length of CTICU Stay. | 2 Days |
Primary
Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator.
Time frame: Time of intubation to extubation (variable)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fentanyl (High Dose) | Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator. | 10.75 Hours |
| Fentanyl (Low Dose) | Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator. | 3.79 Hours |
| Fentanyl (Low Dose) + Dexmedetomidine | Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator. | 2.4 Hours |
Primary
Stanford-Binet Intelligence Scales
The Stanford-Binet test evaluates the overall IQ score from the assessment of cognitive ability. The test consists of 15 subtests, grouped into the four area scores. Six subtests are administered to all age levels. The subtests are: Vocabulary, Comprehension, Pattern Analysis, Quantitative, Bead Memory, and Memory for Sentences. Number of tests administered and test difficulty are based on the test taker's age and performance on subtest measuring word knowledge. The word knowledge subtest is given to all test takers and is the first subtest administered. A score of 100 is in the normal or average range. Higher scores suggest a higher level of functioning related to each category. (University of Cincinnati, 2003) Raw scores for each subtest within the overall test are converted to scaled scores using a table within each test manual to look up equivalents. Scaled scores are then converted to standard scores (range=50-150).
Time frame: 1-4 yrs. post-surgery
Population: Six patients underwent their surgical repair after 1 y of age and were excluded from the follow-up neurodevelopmental testing post-surgery. 2 patients were deceased, 11 families refused to participate, 8 patients could not be reached due to relocation to other states or outside the country leaving a total of 21 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (High Dose) | Stanford-Binet Intelligence Scales | Verbal IQ composite score | 93 IQ | Standard Deviation 26 |
| Fentanyl (High Dose) | Stanford-Binet Intelligence Scales | Nonverbal IQ composite score | 92 IQ | Standard Deviation 19 |
| Fentanyl (High Dose) | Stanford-Binet Intelligence Scales | Full-scale IQ composite score | 93 IQ | Standard Deviation 24 |
| Fentanyl (Low Dose) | Stanford-Binet Intelligence Scales | Verbal IQ composite score | 91 IQ | Standard Deviation 17 |
| Fentanyl (Low Dose) | Stanford-Binet Intelligence Scales | Nonverbal IQ composite score | 98 IQ | Standard Deviation 15 |
| Fentanyl (Low Dose) | Stanford-Binet Intelligence Scales | Full-scale IQ composite score | 94 IQ | Standard Deviation 15 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stanford-Binet Intelligence Scales | Nonverbal IQ composite score | 89 IQ | Standard Deviation 6 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stanford-Binet Intelligence Scales | Full-scale IQ composite score | 83 IQ | Standard Deviation 5 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stanford-Binet Intelligence Scales | Verbal IQ composite score | 80 IQ | Standard Deviation 8 |
Primary
Stress Hormone Levels
Cortisol, epinephrine, and norepinephrine assayed by enzyme-linked immunosorbent assay (ELISA).
Time frame: Blood draws to measure stress hormone levels within one hour of draw: after induction; after sternotomy; after starting cardiopulmonary bypass; at the end of the procedure; and 24 hours after the procedure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (High Dose) | Stress Hormone Levels | Baseline Cortisol | 334.7762 ng/mL | Standard Deviation 314.6592 |
| Fentanyl (High Dose) | Stress Hormone Levels | 24 hour Post-Surgery Norepinephrine | 19.03031 ng/mL | Standard Deviation 17.41692 |
| Fentanyl (High Dose) | Stress Hormone Levels | End-of-Surgery Epinephrine | 14.65742 ng/mL | Standard Deviation 18.34983 |
| Fentanyl (High Dose) | Stress Hormone Levels | Baseline ephinephrine | 2.7848 ng/mL | Standard Deviation 3.127335 |
| Fentanyl (High Dose) | Stress Hormone Levels | 24 hour Post-Surgery Cortisol | 237.5506 ng/mL | Standard Deviation 243.8181 |
| Fentanyl (High Dose) | Stress Hormone Levels | Post-Bypass Epinephrine | 18.176 ng/mL | Standard Deviation 22.04968 |
| Fentanyl (High Dose) | Stress Hormone Levels | Post-Sternotomy Epinephrine | 2.376012 ng/mL | Standard Deviation 2.273879 |
| Fentanyl (High Dose) | Stress Hormone Levels | Post-Sternotomy Norepinephrine | 16.2606 ng/mL | Standard Deviation 9.929948 |
| Fentanyl (High Dose) | Stress Hormone Levels | 24 hour Post-Surgery Epinephrine | 5.004787 ng/mL | Standard Deviation 6.666509 |
| Fentanyl (High Dose) | Stress Hormone Levels | Post-Bypass Cortisol | 279.0063 ng/mL | Standard Deviation 188.1155 |
| Fentanyl (High Dose) | Stress Hormone Levels | Post-Bypass Norepinephrine | 23.35796 ng/mL | Standard Deviation 13.54953 |
| Fentanyl (High Dose) | Stress Hormone Levels | Baseline Norepinephrine | 13.32618 ng/mL | Standard Deviation 10.1541 |
| Fentanyl (High Dose) | Stress Hormone Levels | Post-Sternotomy Cortisol | 353.5396 ng/mL | Standard Deviation 281.4853 |
| Fentanyl (High Dose) | Stress Hormone Levels | End-of-Surgery Norepinephrine | 11.22376 ng/mL | Standard Deviation 8.599634 |
| Fentanyl (High Dose) | Stress Hormone Levels | End-of-Surgery Cortisol | 333.0644 ng/mL | Standard Deviation 294.8148 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Baseline Norepinephrine | 19.34153 ng/mL | Standard Deviation 9.880667 |
| Fentanyl (Low Dose) | Stress Hormone Levels | End-of-Surgery Cortisol | 463.3857 ng/mL | Standard Deviation 251.6977 |
| Fentanyl (Low Dose) | Stress Hormone Levels | 24 hour Post-Surgery Norepinephrine | 20.85433 ng/mL | Standard Deviation 18.38192 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Post-Sternotomy Norepinephrine | 17.08766 ng/mL | Standard Deviation 8.419782 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Post-Bypass Norepinephrine | 22.31064 ng/mL | Standard Deviation 17.06955 |
| Fentanyl (Low Dose) | Stress Hormone Levels | End-of-Surgery Norepinephrine | 10.74731 ng/mL | Standard Deviation 8.144776 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Baseline ephinephrine | 6.439221 ng/mL | Standard Deviation 7.528216 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Post-Sternotomy Epinephrine | 9.843591 ng/mL | Standard Deviation 8.670264 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Post-Bypass Epinephrine | 21.9075 ng/mL | Standard Deviation 15.02187 |
| Fentanyl (Low Dose) | Stress Hormone Levels | End-of-Surgery Epinephrine | 8.620669 ng/mL | Standard Deviation 6.799042 |
| Fentanyl (Low Dose) | Stress Hormone Levels | 24 hour Post-Surgery Epinephrine | 3.537063 ng/mL | Standard Deviation 2.466451 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Baseline Cortisol | 449.1974 ng/mL | Standard Deviation 279.4671 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Post-Sternotomy Cortisol | 363.5948 ng/mL | Standard Deviation 164.9006 |
| Fentanyl (Low Dose) | Stress Hormone Levels | Post-Bypass Cortisol | 395.1298 ng/mL | Standard Deviation 173.3926 |
| Fentanyl (Low Dose) | Stress Hormone Levels | 24 hour Post-Surgery Cortisol | 266.8754 ng/mL | Standard Deviation 239.2913 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Post-Bypass Cortisol | 354.8089 ng/mL | Standard Deviation 210.7565 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | 24 hour Post-Surgery Epinephrine | 4.418208 ng/mL | Standard Deviation 6.764226 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | End-of-Surgery Norepinephrine | 7.727055 ng/mL | Standard Deviation 13.04373 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | End-of-Surgery Cortisol | 387.3673 ng/mL | Standard Deviation 191.7376 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Baseline Cortisol | 352.4913 ng/mL | Standard Deviation 265.2216 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Post-Bypass Norepinephrine | 19.73612 ng/mL | Standard Deviation 17.07041 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Baseline Norepinephrine | 19.45968 ng/mL | Standard Deviation 13.08422 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Post-Sternotomy Cortisol | 361.0074 ng/mL | Standard Deviation 223.3172 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Post-Sternotomy Epinephrine | 10.89824 ng/mL | Standard Deviation 16.85818 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Baseline ephinephrine | 5.876335 ng/mL | Standard Deviation 9.551871 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Post-Sternotomy Norepinephrine | 12.74458 ng/mL | Standard Deviation 11.4669 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | Post-Bypass Epinephrine | 20.5294 ng/mL | Standard Deviation 17.2838 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | 24 hour Post-Surgery Norepinephrine | 26.67379 ng/mL | Standard Deviation 26.06332 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | 24 hour Post-Surgery Cortisol | 265.7373 ng/mL | Standard Deviation 291.3256 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stress Hormone Levels | End-of-Surgery Epinephrine | 8.083004 ng/mL | Standard Deviation 8.808354 |
Secondary
ABAS-II
The ABAS-II is designed to evaluate whether an individual displays various functional skills necessary for daily living without the assistance of others. Thus, this instrument focuses on independent behaviors and measures what an individual actually does, in addition to measuring what he or she may be able to do. In addition, the ABAS-II focuses on behaviors an individual displays on his or her own, without assistance from others. The Parent/Primary Caregiver Form is a comprehensive, diagnostic measure of the adaptive skills that have primary relevance for the functioning of infants, toddlers, and preschoolers in the home and other settings, and can be completed by parents or other primary care providers. Each composite or domain score is determined by summing the appropriate scaled scores and then determining its equivalent composite or domain score by looking it up in a table located in the manual.The range for all scores is 50-150, with a higher score equaling a better outcome.
Time frame: 1-4 yrs post-surgery
Population: Six patients underwent their surgical repair after 1 y of age and were excluded from the follow-up neurodevelopmental testing post-surgery. 2 patients were deceased, 11 families refused to participate, 8 patients could not be reached due to relocation to other states or outside the country leaving a total of 21 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (High Dose) | ABAS-II | ABAS-II Practical Adaptive Domain Score | 93 units on a scale | Standard Deviation 15 |
| Fentanyl (High Dose) | ABAS-II | ABAS-II Social Adaptive Domain Score | 102 units on a scale | Standard Deviation 24 |
| Fentanyl (High Dose) | ABAS-II | ABAS-II Conceptual Adaptive Domain Score | 99 units on a scale | Standard Deviation 21 |
| Fentanyl (High Dose) | ABAS-II | ABAS-II General Adaptive Composite Score | 96 units on a scale | Standard Deviation 21 |
| Fentanyl (Low Dose) | ABAS-II | ABAS-II Social Adaptive Domain Score | 106 units on a scale | Standard Deviation 8 |
| Fentanyl (Low Dose) | ABAS-II | ABAS-II Conceptual Adaptive Domain Score | 106 units on a scale | Standard Deviation 16 |
| Fentanyl (Low Dose) | ABAS-II | ABAS-II General Adaptive Composite Score | 102 units on a scale | Standard Deviation 13 |
| Fentanyl (Low Dose) | ABAS-II | ABAS-II Practical Adaptive Domain Score | 96 units on a scale | Standard Deviation 14 |
| Fentanyl (Low Dose) + Dexmedetomidine | ABAS-II | ABAS-II Conceptual Adaptive Domain Score | 99 units on a scale | Standard Deviation 13 |
| Fentanyl (Low Dose) + Dexmedetomidine | ABAS-II | ABAS-II General Adaptive Composite Score | 100 units on a scale | Standard Deviation 13 |
| Fentanyl (Low Dose) + Dexmedetomidine | ABAS-II | ABAS-II Practical Adaptive Domain Score | 95 units on a scale | Standard Deviation 11 |
| Fentanyl (Low Dose) + Dexmedetomidine | ABAS-II | ABAS-II Social Adaptive Domain Score | 105 units on a scale | Standard Deviation 13 |
Secondary
Stanford-Binet Cognitive Ability
The Stanford-Binet Intelligence Scale is now in its fifth edition (SB5) and was released in 2003. It is a cognitive ability and intelligence test that is used to diagnose developmental or intellectual deficiencies in young children. The test measures five weighted factors and consists of both verbal and nonverbal subtests. The five factors being tested are knowledge, quantitative reasoning, visual-spatial processing, working memory, and fluid reasoning. Raw scores for each subtest within the overall test are converted to scaled scores using a table within each test manual to look up equivalents. Scaled scores are then converted to standard scores (range=50-150). Higher scores suggest a higher level of functioning related to each category.
Time frame: 1-4 yrs post-surgery
Population: Six patients underwent their surgical repair after 1 y of age and were excluded from the follow-up neurodevelopmental testing post-surgery. 2 patients were deceased, 11 families refused to participate, 8 patients could not be reached due to relocation to other states or outside the country leaving a total of 21 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (High Dose) | Stanford-Binet Cognitive Ability | Fluid Reasoning Score | 86 units on a scale | Standard Deviation 20 |
| Fentanyl (High Dose) | Stanford-Binet Cognitive Ability | Working Memory Score | 94 units on a scale | Standard Deviation 17 |
| Fentanyl (High Dose) | Stanford-Binet Cognitive Ability | Quantative Reasoning Score | 106 units on a scale | Standard Deviation 22 |
| Fentanyl (High Dose) | Stanford-Binet Cognitive Ability | Visual Spatial Processing Score | 91 units on a scale | Standard Deviation 17 |
| Fentanyl (High Dose) | Stanford-Binet Cognitive Ability | Knowledge Score | 91 units on a scale | Standard Deviation 27 |
| Fentanyl (Low Dose) | Stanford-Binet Cognitive Ability | Quantative Reasoning Score | 96 units on a scale | Standard Deviation 18 |
| Fentanyl (Low Dose) | Stanford-Binet Cognitive Ability | Working Memory Score | 92 units on a scale | Standard Deviation 10 |
| Fentanyl (Low Dose) | Stanford-Binet Cognitive Ability | Fluid Reasoning Score | 93 units on a scale | Standard Deviation 19 |
| Fentanyl (Low Dose) | Stanford-Binet Cognitive Ability | Knowledge Score | 97 units on a scale | Standard Deviation 10 |
| Fentanyl (Low Dose) | Stanford-Binet Cognitive Ability | Visual Spatial Processing Score | 97 units on a scale | Standard Deviation 16 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stanford-Binet Cognitive Ability | Working Memory Score | 84 units on a scale | Standard Deviation 13 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stanford-Binet Cognitive Ability | Visual Spatial Processing Score | 92 units on a scale | Standard Deviation 7 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stanford-Binet Cognitive Ability | Knowledge Score | 95 units on a scale | Standard Deviation 12 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stanford-Binet Cognitive Ability | Fluid Reasoning Score | 75 units on a scale | Standard Deviation 10 |
| Fentanyl (Low Dose) + Dexmedetomidine | Stanford-Binet Cognitive Ability | Quantative Reasoning Score | 82 units on a scale | Standard Deviation 15 |