The Role of Dexmedetomidine as Myocardial Protector in Pediatric Cardiac Surgery Total Correction of Tetralogy of Fallot
Condition: Congenital Heart Disease in Children; Cardiopulmonary Bypass; Tetralogy of Fallot
MeSH terms: Heart Diseases; Heart Defects, Congenital; Tetralogy of Fallot
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Congenital heart disease (CHD) is the most common congenital abnormality found in newborns
      with Tetralogy of Fallot (TOF) being the most common cyanotic CHD. Total correction of TOF
      was performed using a cardiopulmonary bypass (CPB) machine. However, the use of CPB has a
      negative effect that causes inflammation and myocardial injury. Myocardial protection in
      patients undergoing total correction of TOF surgery is more difficult than other cyanotic CHD
      due to a hypertrophic right ventricular condition. Dexmedetomidine (DEX) is a selective α-2
      adrenergic, which has major effects including hypnosis, sedation, and analgesia as well as
      cardiovascular effects. The sedation is induced by stimulating the α-2 adrenergic receptor in
      the locus coeruleus (LC) in the pons cerebri. DEX also increases the level of GABA and
      Galanin and reduces endogenous norepinephrine. The lower level of endogenous norepinephrine
      decreases the afterload of the ventricles, increases cardiac output, and reduces myocardial
      injury as a result. Furthermore, the peripheral effects of DEX can reduce myocardial
      ischemia-reperfusion (MIR) by inhibiting NF-кB pathway activation and reducing the number of
      pro-inflammatory cytokines released. Thus, the administration of DEX can prevent myocardial
      necrosis and apoptosis, also reducing reperfusion injury when using CPB machines. Research
      related to the effectiveness of administering DEX as a myocardial protector in classic TOF
      patients undergoing elective total correction cardiac surgery in Indonesia is less reported.
      The aim of this study is to determine the effectiveness of DEX as myocardial protector in
      classic TOF patients undergoing elective total correction cardiac surgery.
    

Detailed description: 
      This study is a double blind randomized controlled trial to determine the effectiveness of
      DEX during CPB as myocardial protection between DEX group and control group. The study
      population is classic TOF patients who underwent elective total correction cardiac surgery.
      This study was approved by the research ethical committee (Institutional Review Board) of the
      National Cardiovascular Center Harapan Kita Jakarta (NCCHK). Before randomization,
      participants who are eligible based on inclusion and exclusion criterias will be given
      informed consent. If the guardians of the participants agree, the participants will be
      included in this research. Sixty-six pediatric participants with classic TOF undergoing
      elective total correction will be randomly divided into two groups, DEX group and control
      group. Dexmedetomidine HCl is provided in the form of a liquid injection (Precedex/Kabimidine
      200 mcg/2 ml). For the DEX group, DEX was calculated with a priming dose of 0.5 mcg/kg in a 5
      ml syringe mixed in priming fluid and 0.25 mcg/kg/hour DEX infusion diluted in 0.9% NaCl 20
      ml in a 20 ml syringe administered to the CPB reservoir with an infusion rate of 10 ml/hour.
      For the control group, the volume of administration of 0.9% NaCl as priming and 0.9% NaCl
      infusion was given to the CPB machine with adjusted amount and rate same as the DEX group.

      We will measure myocardial injury biomarker plasma levels (Troponin I) and cytokines
      proinflammatory biomarkers plasma level (IL-6) as the primary outcome of myocardial
      protection. Serum plasma levels of troponin I and IL-6 will be taken 4 times (T1, 5 minutes
      after induction as baseline level; T2,1 hour after CPB; T3, 6 hours after CPB, and T4, 24
      hours after CPB). Secondary outcomes including hemodynamic profile (cardiac output, cardiac
      index, and systemic vascular resistance, at 5 minute before induction as baseline level, 6
      hours, 24 hours, and 48 hours after CPB), serum lactate levels at 5 minutes after induction
      as baseline level, 1 hour, 6 hours, and 24 hours after CPB, morbidity outcomes (vasoinotropic
      score at 1 hour, 6 hours, and 24 hours after CPB, length of ventilator use, and length of
      stay in intensive care).
    

Intervention name(s): Dexmedetomidine Hcl 100 Mcg/mL Inj; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Priming dose of 0.5 mcg/kg in a 5 ml syringe mixed in priming fluid and 0.25 mcg/kg/hour DEX infusion diluted in 0.9% NaCl 20 ml in a 20 ml syringe administered to the CPB reservoir with an infusion rate of 10 ml/hour; Priming dose of NaCl 0.9% in a 5 ml syringe mixed in priming fluid and NaCl 0.9% 20 ml in a 20 ml syringe administered to the CPB reservoir with an infusion rate of 10 ml/hour
Other intervention name(s): Precedex; Kabimidine; NaCl 0.9%
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Dexmedetomidine; Myocardial Protection; Tetralogy of Fallot; Total Correction; Double Blind Randomized Controlled Trial; Cardiopulmonary Bypass