Cardioprotective Effect of Ketamine-dexmeditomidine Versus Fentanyl-midazolam in Open Heart Surgery in Pediatrics
Condition: Anesthesia
Study type: Interventional
Phase: Phase 1

Summary: 
      congenital hearts are very sensitive and irritable to deal with, especially during repair
      defects, the child's heart is exposed to impaired myocardial function during the entire
      procedure. Moreover, reperfusion of the heart during open-heart surgery when the myocardium
      is exposed to a global ischaemic cardioplegic arrest can induce myocardial injury. Myocardial
      reperfusion injury activates neutrophils, which trigger an inflammatory response resulting in
      the generation of reactive oxygen species (ROS), cytokine release, and complement activation,
      which further induce more cardiac injury. In addition to the inflammatory response generated
      as a result of tissue reperfusion injury, there is a significant systemic inflammatory
      response that is triggered by cardiopulmonary bypass (CPB) during open-heart surgery
    

Detailed description: 
      Myocardial protection is an important issue. This is reflected in the clinical prognosis of
      patients undergoing cardiac surgery and this can be measured by the most popular Cardiac
      biomarkers ( cardiac troponin I (cTnI)). (2)

      A large number of anesthetic agents have been implicated in protecting the heart against
      ischemia and reperfusion injury. Ketamine has an anti-inflammatory effect and has been shown
      to reduce ROS generation by neutrophils and to decrease endotoxin stimulated IL6 production
      in human whole blood although it does not impair neutrophil function. (3)

      Dexmedetomidine is a highly selective, short-acting, central α2-adrenergic agonist with
      intense sympatholytic qualities. Dexmedetomidine has been increasingly used as a component of
      general anesthesia, including cardiac surgical applications due to its sedative/hypnotic and
      analgesic effects which are enhanced by its cardioprotective properties. (4) Riha et.al
      showed that ketamine - Dexmedetomidine combination had superior cardioprotective effects as
      measured by cardiac markers as compared to sevoflurane- sufentanil anesthesia after cardiac
      surgery. (5) Midazolam is known to have potential anti-inflammatory effects and antioxidant
      activity. They have been proven to provide protective effects for patients who underwent
      cardiac surgery. (6) Fentanyl is one opioid that has been closely linked to inflammatory
      mediators and myocardial protection. It reduces the CPB-induced inflammatory response and
      ischaemic reperfusion injury during cardiac surgery. These effects are related to improvement
      in intracellular Ca2+ mobilization and do not seem to be related to the adhesion of
      neutrophils in the coronary system. (7) To the best of our knowledge, this is the first study
      comparing the combined effect of Ketamine- Dexmedetomidine versus fentanyl- midazolam against
      ischemia and reperfusion injury in pediatric congenital heart surgery repair.
    

Intervention name(s): Ketamine- dexmedetomidine; Fentanyl- midazolam; Isoflurane
Intervention type(s): Drug; Drug; Drug
Intervention description(s): ketamine - Dexmedetomidine combination had superior cardioprotective effects as measured by cardiac markers as compared to sevoflurane- sufentanil anesthesia after cardiac surgery; Midazolam is known to have potential anti-inflammatory effects and antioxidant activity. They have been proven to provide protective effects for patients who underwent cardiac surgery.Fentanyl is one opioid that has been closely linked to inflammatory mediators and myocardial protection. It reduces the CPB-induced inflammatory response and ischaemic reperfusion injury during cardiac surgery; Anesthetic inhalational gas
Intervention MeSH terms: Midazolam; Fentanyl; Dexmedetomidine; Ketamine; Isoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: patients will be allocated to three groups
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Supportive Care