Clinical trial NCT00848393: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tetralogy of Fallot (TOF)
Ventricular Septal Defects (VSD)
Atrioventricular Septal Defects (AVSD)
Keywords: pediatric cardiac surgery
stress response
early extubation
Dexmedetomidine
TOF
VSD
AVSD
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
First posted: 2009-02-20
Enrollment: 52
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: ACTH and Cytokine Levels
timeFrame: 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.
measure: Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Length of CTICU Stay.
timeFrame: Hospital admission to discharge from CTICU (average of 2-4 days)
measure: Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator.
timeFrame: Time of intubation to extubation (variable)
measure: Stanford-Binet Intelligence Scales
timeFrame: 1-4 yrs. post-surgery
measure: Stress Hormone Levels
timeFrame: 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 outcomes:
measure: Stanford-Binet Cognitive Ability
timeFrame: 1-4 yrs post-surgery
measure: ABAS-II
timeFrame: 1-4 yrs post-surgery
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Nationwide Children's Hospital
name: Aymen N Naguib, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
citation: Kapoor MC, Ramachandran TR. Inflammatory response to cardiac surgery and strategies to overcome it. Ann Card Anaesth. 2004 Jul;7(2):113-28.
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.