Clinical trial NCT05314569: Cardioprotective Effect of Ketamine-dexmeditomidine Versus Fentanyl-midazolam in Open Heart Surgery in Pediatrics
Official title: Cardioprotective Effect of Ketamine-dexmeditomidine Versus Fentanyl-midazolam in Open-heart Surgery in Pediatrics: A Randomized Controlled Double-blinded Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anesthesia
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2022-04-06
Enrollment: 81
Sex: ALL
Minimum age (years): 6
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: patients will be allocated to three groups
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Eligibility criteria: Inclusion Criteria:

* the American Society of Anesthesiologists II and III
* elective open Congenital cardiac surgery(VSD, AV canal, and partial anomaly) using cardiopulmonary bypass

Exclusion Criteria:

* less than 6 months or more than 24 months.
* weight \< 5 kg.
* cyanotic heart disease
* patients with heart failure, an implantable pacemaker, pulmonary hypertension, preoperative administration of inotropic agents, serum creatinine higher than1.5 mg/dL, chronic liver disease, patients receiving sulfonylurea, theophylline, or allopurinol

Primary outcomes:
measure: troponin level
timeFrame: 6 hours
Secondary outcomes:
measure: heart rates
timeFrame: every 15 minutes
measure: aortic cross clamping
timeFrame: 2 hours
measure: inotropic support
timeFrame: 6 hours
measure: blood pressure
timeFrame: every 15 minutes
measure: need of nitroglycerin infusion
timeFrame: 6 hours
Other outcomes:
Locations:
city: Giza
country: Egypt
facility: Amany Hassan Saleh
Study officials:
affiliation: Cairo University
name: Amany H Saleh, MD
role: PRINCIPAL_INVESTIGATOR
References: