The Role of Dexmedetomidine As Myocardial Protection In Pediatric Cyanotic Congenital Heart Disease Undergoing Open Cardiac Surgery Using Cardiopulmonary Bypass Machine: A Preliminary Study
Condition: Congenital Heart Disease in Children; Cardiopulmonary Bypass
MeSH terms: Heart Diseases; Heart Defects, Congenital
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Congenital Heart Diseases (CHD) are one of the most common congenital anomalies. Worldwide, 8
      to 9 out of 1000 of children are born with a CHD, of which 25 percent of are cyanotic CHD. In
      Indonesia, the prevalence is 43.200 out of 4.8 million births annually. The morbidity and
      mortality of cyanotic CHDs in the National Cardiovascular Center Harapan Kita (NCCHK) are
      higher than acyanotic CHDs. Open-heart surgery using a cardiopulmonary bypass (CPB) machine
      temporarily takes over the function of the heart and lung during surgery. However, the use of
      CPB has several negative effects such myocardial injury, systemic inflammation, and
      reperfusion injury. Preoperative hypoxia in cyanotic CHD tends to be associated with a higher
      risk of myocardial injury. Myocardial protection has an important role in attenuating those
      effects. Generally, we use a cardioplegia solution as myocardial protection, but there are
      several non-cardioplegia techniques that can be used to enhance myocardial protection during
      cardiac bypass, such as adding an anesthetic agent. Dexmedetomidine (DEX) is the active
      dextroisomer of medetomidine, 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 proinflammatory cytokines released. Research related to
      the priming and infusion of DEX during CPB in patients with cyanotic CHDs who are undergoing
      open-heart surgery is less reported. The aims of this study are to determine the
      effectiveness of the priming and infusion of DEX during CPB as myocardial protection by using
      two different doses compared to the control group. The population included in this study is
      pediatric patients with cyanotic CHD who are undergoing open-heart surgery using CPB and who
      classified as 6 to 9 in the Aristotle Score.
    

Detailed description: 
      The investigators will conduct a double-blind randomized controlled trial preliminary study
      to determine the effectiveness of the priming and infusion of DEX during CPB as myocardial
      protection by using two different doses compared to the control group. The population
      included in this study will be pediatric patients with cyanotic CHD who are undergoing
      open-heart surgery using CPB and who classified as 6 to 9 in the Aristotle Score. 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 patients agree, the patient will be included in this research. Fifteen
      pediatric patients with cyanotic CHD will be randomly divided into three groups A, B, and C.
      Group A is the control group and will be given 50 ml Ringer acetate solution in a 50 ml
      syringe that will be added to the priming solution in CPB, followed by 50 ml of Ringer
      acetate solution administered in a syringe pump infusion running at 25 ml/hour and which will
      be ended by the end of CPB. Group B will received DEX 1 mcg/kg diluted in 50 ml of Ringer
      acetate solution in a 50 ml syringe added in the priming solution in CPB, followed by 50 ml
      of Ringer acetate solution administered in a syringe pump infusion running at 25 ml/hour and
      which will be ended by the end of CPB. Group C will be administered 0.5 mcg/kg DEX, diluted
      in 50 ml of Ringer acetate solution in a 50 ml syringe added in the priming solution in CPB,
      followed by 0.25 mcg/kg/hour DEX diluted in 50 ml of Ringer acetate solution administered in
      a syringe pump infusion running at 25 ml/hour infusion which will be ended by the end of CPB.

      Age, gender, body weight, body length, body surface area, Aristotle scores, aortic
      cross-clamp time, CPB time, and operation time are included as demographics and
      characteristics data. The investigators will measure myocardial injury biomarker serum levels
      (Troponin I) and cytokines proinflammatory biomarker serum levels (IL-6) as the primary
      outcome of myocardial protection. Serum 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 include hemodynamic profile (Cardiac
      output, cardiac index, and systemic vascular resistance, at 6 hours, 24 hours, and 48 hours
      after CPB plus serum lactate levels at 5 minutes after induction as baseline level, 1 hour, 6
      hours, and 24 hours after CPB), morbidity outcomes (the highest Vasoinotropic Score at the
      first 24 hours after CPB, length of mechanical ventilation, and length of intensive care
      stay), and adverse event occurrences such as hypotension and bradycardia (at 5 minutes after
      induction as baseline level, 1 hour, 6 hours, and 24 hours after CPB).
    

Intervention name(s): Placebo; Dexmedetomidine Hcl 100 Mcg/mL Inj; Dexmedetomidine Hcl 100 Mcg/mL Inj
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 50 ml of Ringer acetate will be added to the priming solution and followed by a continuous 50 ml infusion of Ringer acetate running at 25 ml/hour.; 1 mcg/kg diluted DEX will be added to the priming solution and followed by a continuous infusion of 50 ml Ringer acetate running at 25 ml/hour.; 0.5 mcg/kg DEX will be added to the priming solution and followed by a continuous infusion of 0.25 mcg/kg/hour DEX diluted in 50 ml of ringer acetate running at 25 ml/hour.
Other intervention name(s): Ringer Acetate; Kabimidine; Kabimidine
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; Pediatric Cyanotic Congenital Heart Disease; Cardiopulmonary Bypass; Aristotle Score