Measures to Lower the Stress Response in Pediatric Cardiac Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00848393
Recruitment Status : Completed
First Posted : February 20, 2009
Last Update Posted : June 29, 2015
Information provided by (Responsible Party):
Aymen N Naguib, Nationwide Children's Hospital

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.

Condition or disease Intervention/treatment Phase
Tetralogy of Fallot Ventricular Septal Defects Atrioventricular Septal Defects Drug: Fentanyl Drug: Dexmedetomidine and Fentanyl Not Applicable

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 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, one will receive low dose fentanyl with dexmedetomidine, and one will receive high dose fentanyl. 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, ACTH, Interleukin 8, TNF-alpha, 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 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 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Stress Response in Children Undergoing Cardiac Surgery: a Prospective Randomized Comparison Between Low Dose Fentanyl, Low Dose Fentanyl Plus Dexmedetomidine and High Dose Fentanyl.
Study Start Date : November 2008
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Arm Intervention/treatment
Active Comparator: High Dose Fentanyl
patients in this arm will receive a total of 25 mcg/kg of fentanyl in two divided doses. first half will be given at induction and the second half will be given before incision.
Drug: Fentanyl
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.

Active Comparator: Low Dose Fentanyl
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
Drug: Fentanyl
patients will receive a total of 10mcg/kg of fentanyl. half the dose will be given at induction and the second half before incision.

Active Comparator: Low dose fentanyl plus Dexmedetomidine
patients in this group will receive a total of 10mcg/kg of fentanyl 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.
Drug: Dexmedetomidine and Fentanyl
Dexmedetomidine at 1mcg/kg loading dose over 10 minutes, followed by an infusion at a rate of 0.5mcg/kg/ addition this group will receive a total of 10 mcg/kg fentanyl. Half the dose will be given at induction and the second half before incision.
Other Name: Precedex for dexmedetomidine

Primary Outcome Measures :
  1. The use of Dexmedetomidine in addition to low dose narcotic will lower the stress response as effective as the high dose narcotic. [ Time Frame: stress hormones and cytokines levels will be measured at the following points; after induction, after sternotomy, after starting cardiopulmonary bypass, at the end of the procedure and 24 hours after the procedure ]
  2. Overall IQ score [ Time Frame: 1-4 yrs. post-surgery ]
    Overall IQ score from the assessment of cognitive ability, to determine if different anesthetic techniques during surgery for children with congenital heart disease result in differences in children's intellectual functioning.

Secondary Outcome Measures :
  1. The use of dexmedetomidine in addition to low dose narcotic will allow early extubation after pediatric cardiac surgery. [ Time Frame: two years ]
  2. Cognitive factor scores [ Time Frame: 1-4 yrs post-surgery ]
  3. Overall measure of developmental status [ Time Frame: 1-4 yrs post-surgery ]
  4. A "total problems" score for emotional and behavioral adjustment. [ Time Frame: 1-4 yrs post-surgery ]

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Ages Eligible for Study:   1 Month to 3 Years   (Child)
Sexes Eligible for Study:   All
Accepts 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:

  • Patient who are having reoperation.
  • Patients with comorbidities, such as heart failure.
  • Patients receiving digoxin preoperatively.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00848393

United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Nationwide Children's Hospital
Principal Investigator: Aymen N Naguib, MD Nationwide Children's Hospital

Responsible Party: Aymen N Naguib, Director of Pediatric Cardiothoracic Anesthesia, Nationwide Children's Hospital Identifier: NCT00848393     History of Changes
Other Study ID Numbers: IRB08-00029
101911 ( Other Identifier: FDA )
First Posted: February 20, 2009    Key Record Dates
Last Update Posted: June 29, 2015
Last Verified: June 2015

Keywords provided by Aymen N Naguib, Nationwide Children's Hospital:
pediatric cardiac surgery
stress response
early extubation

Additional relevant MeSH terms:
Heart Septal Defects
Tetralogy of Fallot
Heart Septal Defects, Ventricular
Endocardial Cushion Defects
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General