Cardioprotective Effect of Ketamine-dexmeditomidine Versus Fentanyl-midazolam in Open Heart Surgery in Pediatrics

Cardioprotective Effect of Ketamine-dexmeditomidine Versus Fentanyl-midazolam in Open-heart Surgery in Pediatrics: A Randomized Controlled Double-blinded Study

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

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Isoflurane; Drug: Ketamine- dexmedetomidine; Drug: Fentanyl- midazolam

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Giza, Egypt, 02
    • Amany Hassan Saleh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group(C); anesthesia will be maintained using Isoflurane 1.2MAC keeping the bispectral index( BIS) between 40-60%.	Drug: Isoflurane; Anesthetic inhalational gas
Active Comparator: Ketamine-dexmedetomidine group( KD); After induction of anesthesia , dexmedetomidine will be given(1 ug /kg ) over 10 min, then ketamine(2 m/kg) . maintenance throughout the procedure, with the bispectral index between 40 and 60%. by infusing Dexmedetomidine( 0.5 μg/.kg /.h r)) ketamine,( 1 m/kg/hr),	Drug: Ketamine- dexmedetomidine; ketamine - Dexmedetomidine combination had superior cardioprotective effects as measured by cardiac markers as compared to sevoflurane- sufentanil anesthesia after cardiac surgery
Active Comparator: . Fentanyl- midazolam group (FM); After induction of anesthesia fentanyl( 3 μg/kg), midazolam( 100 ug /kg over 2 to 3 minutes) maintenance throughout the procedure, with the bispectral index between 40 and 60%. by infusing midazolam (1 ug /kg /min)-fentanyl( 2 μg/kg/h ).	Drug: Fentanyl- midazolam; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
troponin level	mean troponin level post arotic declamping.	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
heart rates	records of reading till the end of the surgery	every 15 minutes
aortic cross clamping	duration of clamping	2 hours
inotropic support	number of patients	6 hours
blood pressure	records of reading till the end of the surgery	every 15 minutes
need of nitroglycerin infusion	number of patients	6 hours

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: Amany H Saleh, MD, Cairo university

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2022
• Primary Completion (Actual): September 20, 2022
• Study Completion (Actual): September 25, 2022

Study Registration Dates

• First Submitted: March 27, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 6, 2022

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anesthetics, Inhalation; Ketamine; Fentanyl; Midazolam; Dexmedetomidine; Isoflurane
• Other Study ID Numbers: N-11-2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No