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Measures to Lower the Stress Response in Pediatric Cardiac Surgery

Primary Purpose

Tetralogy of Fallot (TOF), Ventricular Septal Defects (VSD), Atrioventricular Septal Defects (AVSD)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fentanyl (High Dose)
Fentanyl (Low Dose)
Fentanyl (Low Dose) + Dexmedetomidine
Sponsored by
Nationwide Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tetralogy of Fallot (TOF) focused on measuring pediatric cardiac surgery, stress response, early extubation, Dexmedetomidine, TOF, VSD, AVSD

Eligibility Criteria

1 Month - 3 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Nationwide Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Fentanyl (High Dose)

Fentanyl (Low Dose)

Fentanyl (Low Dose) + Dexmedetomidine

Arm Description

This arm will receive a total of 25 mcg/kg of Fentanyl (High Dose) in two divided doses. First half-dose given at induction and second half-dose given before incision.

This arm will receive a total of 10 mcg/kg of Fentanyl (Low Dose). First half-dose will be given at induction and second half -dose given before incision.

This arm will receive10 mcg/kg of Fentanyl (Low Dose) -2 divided doses. Dexmedetomidine (Dex) loading dose-1 mcg/kg over 10 min, then Dex infusion at 0.5mcg/kg/hr.

Outcomes

Primary Outcome Measures

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.
Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Length of CTICU Stay.
Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator.
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).
Stress Hormone Levels
Cortisol, epinephrine, and norepinephrine assayed by enzyme-linked immunosorbent assay (ELISA).

Secondary Outcome Measures

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.
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.

Full Information

First Posted
February 19, 2009
Last Updated
July 2, 2018
Sponsor
Nationwide Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00848393
Brief Title
Measures to Lower the Stress Response in Pediatric Cardiac Surgery
Official Title
Stress Response in Children Undergoing Cardiac Surgery: a Prospective Randomized Comparison Between Low Dose Fentanyl (LDF), Low Dose Fentanyl Plus Dexmedetomidine (LDF + Dex) and High Dose Fentanyl (HDF).
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nationwide Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tetralogy of Fallot (TOF), Ventricular Septal Defects (VSD), Atrioventricular Septal Defects (AVSD)
Keywords
pediatric cardiac surgery, stress response, early extubation, Dexmedetomidine, TOF, VSD, AVSD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fentanyl (High Dose)
Arm Type
Active Comparator
Arm Description
This arm will receive a total of 25 mcg/kg of Fentanyl (High Dose) in two divided doses. First half-dose given at induction and second half-dose given before incision.
Arm Title
Fentanyl (Low Dose)
Arm Type
Active Comparator
Arm Description
This arm will receive a total of 10 mcg/kg of Fentanyl (Low Dose). First half-dose will be given at induction and second half -dose given before incision.
Arm Title
Fentanyl (Low Dose) + Dexmedetomidine
Arm Type
Active Comparator
Arm Description
This arm will receive10 mcg/kg of Fentanyl (Low Dose) -2 divided doses. Dexmedetomidine (Dex) loading dose-1 mcg/kg over 10 min, then Dex infusion at 0.5mcg/kg/hr.
Intervention Type
Drug
Intervention Name(s)
Fentanyl (High Dose)
Other Intervention Name(s)
Fentanyl citrate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fentanyl (Low Dose)
Other Intervention Name(s)
Fentanyl citrate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fentanyl (Low Dose) + Dexmedetomidine
Other Intervention Name(s)
Fentanyl citrate + Precedex for dexmedetomidine
Intervention Description
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.
Primary Outcome Measure Information:
Title
ACTH and Cytokine Levels
Description
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.
Title
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)
Title
Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator.
Time Frame
Time of intubation to extubation (variable)
Title
Stanford-Binet Intelligence Scales
Description
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
Title
Stress Hormone Levels
Description
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.
Secondary Outcome Measure Information:
Title
Stanford-Binet Cognitive Ability
Description
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
Title
ABAS-II
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aymen N Naguib, MD
Organizational Affiliation
Nationwide Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16790625
Citation
Mukhtar AM, Obayah EM, Hassona AM. The use of dexmedetomidine in pediatric cardiac surgery. Anesth Analg. 2006 Jul;103(1):52-6, table of contents. doi: 10.1213/01.ane.0000217204.92904.76.
Results Reference
background
PubMed Identifier
17312200
Citation
Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children. Anesth Analg. 2007 Mar;104(3):509-20. doi: 10.1213/01.ane.0000255729.96438.b0.
Results Reference
background
PubMed Identifier
1530752
Citation
Anand KJ, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med. 1992 Jan 2;326(1):1-9. doi: 10.1056/NEJM199201023260101.
Results Reference
background
PubMed Identifier
2221435
Citation
Anand KJ, Hansen DD, Hickey PR. Hormonal-metabolic stress responses in neonates undergoing cardiac surgery. Anesthesiology. 1990 Oct;73(4):661-70. doi: 10.1097/00000542-199010000-00012.
Results Reference
background
PubMed Identifier
17827544
Citation
Kapoor MC, Ramachandran TR. Inflammatory response to cardiac surgery and strategies to overcome it. Ann Card Anaesth. 2004 Jul;7(2):113-28.
Results Reference
background
PubMed Identifier
11273919
Citation
Gruber EM, Laussen PC, Casta A, Zimmerman AA, Zurakowski D, Reid R, Odegard KC, Chakravorti S, Davis PJ, McGowan FX Jr, Hickey PR, Hansen DD. Stress response in infants undergoing cardiac surgery: a randomized study of fentanyl bolus, fentanyl infusion, and fentanyl-midazolam infusion. Anesth Analg. 2001 Apr;92(4):882-90. doi: 10.1097/00000539-200104000-00016.
Results Reference
background

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Measures to Lower the Stress Response in Pediatric Cardiac Surgery

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