Measures to Lower the Stress Response in Pediatric Cardiac Surgery

NCT00848393 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB08-00029101911
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

• 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)

• Comparisons Between Groups for Narcotic and/or Dexmedetomidine Intervention Influence on Time on Ventilator.

  Time of intubation to extubation (variable)

• 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).

  1-4 yrs. post-surgery

• Stress Hormone Levels

  Cortisol, epinephrine, and norepinephrine assayed by enzyme-linked immunosorbent assay (ELISA).

  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 (2)

• Stanford-Binet Cognitive Ability

  1-4 yrs post-surgery

• ABAS-II

  1-4 yrs post-surgery

Study Arms (3)

Fentanyl (High Dose)

ACTIVE COMPARATOR

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.

Drug: Fentanyl (High Dose)

Fentanyl (Low Dose)

ACTIVE COMPARATOR

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.

Drug: Fentanyl (Low Dose)

Fentanyl (Low Dose) + Dexmedetomidine

ACTIVE COMPARATOR

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.

Drug: Fentanyl (Low Dose) + Dexmedetomidine

Interventions

Fentanyl (High Dose) DRUG

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.

Also known as: Fentanyl citrate

Fentanyl (High Dose)

Fentanyl (Low Dose) DRUG

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.

Also known as: Fentanyl citrate

Fentanyl (Low Dose)

Fentanyl (Low Dose) + Dexmedetomidine DRUG

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.

Also known as: Fentanyl citrate + Precedex for dexmedetomidine

Fentanyl (Low Dose) + Dexmedetomidine

Eligibility Criteria

• Age: 1 Month - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Childrens with the diagnosis of tetralogy of fallot, ventricular septal defect and atrioventricular septal defect who are under one year of age.

You may not qualify if:

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

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (6)

• 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.

  PMID: 16790625 BACKGROUND

• 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.

  PMID: 17312200 BACKGROUND

• 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.

  PMID: 1530752 BACKGROUND

• 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.

  PMID: 2221435 BACKGROUND

• Kapoor MC, Ramachandran TR. Inflammatory response to cardiac surgery and strategies to overcome it. Ann Card Anaesth. 2004 Jul;7(2):113-28.

  PMID: 17827544 BACKGROUND

• 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.

  PMID: 11273919 BACKGROUND

MeSH Terms

Conditions

Tetralogy of Fallot; Heart Septal Defects, Ventricular; Endocardial Cushion Defects; Fractures, Stress; Atrioventricular Septal Defect

Interventions

Fentanyl; Dexmedetomidine

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Septal Defects; Fractures, Bone; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazoles; Azoles

Limitations and Caveats

Small sample size related to: study components conceived after completion of initial stress response study, declined participation, and loss to follow-up. Inability to obtain pre-surgical baseline neurodevelopmental evaluations.

Results Point of Contact

• Title: Aymen Naguib, MD
• Organization: Nationwide Children's Hospital

Aymen.Naguib@nationwidechildrens.org

6147220596

Study Officials

• Aymen N Naguib, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Pediatric Cardiothoracic Anesthesia

Study Record Dates

• First Submitted: February 19, 2009
• First Posted: February 20, 2009
• Study Start: November 1, 2008
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: July 27, 2018
• Results First Posted: July 27, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)