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

• ClinicalTrials.gov Identifier: NCT05314569
• Recruitment Status: Recruiting
• First Posted: April 6, 2022
• Last Update Posted: April 6, 2022
• Sponsor: Cairo University
• Information provided by (Responsible Party): Amany Hassan Saleh, Cairo University

Tracking Information

• First Submitted Date: March 27, 2022
• First Posted Date: April 6, 2022
• Last Update Posted Date: April 6, 2022
• Estimated Study Start Date: April 15, 2022
• Estimated Primary Completion Date: September 20, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2022)

troponin level [ Time Frame: 6 hours ]

mean troponin level post arotic declamping.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 5, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

patients will be allocated to three groups

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

patients will be allocated to the study using a computer-generated random list and the group assignments will be sealed in opaque envelopes that will be opened after induction. The drugs will be prepared by an anesthetist who is blind to the study groups.

Primary Purpose: Supportive Care

• Condition: Anesthesia

Intervention

• Drug: Ketamine- dexmedetomidine
  ketamine - Dexmedetomidine combination had superior cardioprotective effects as measured by cardiac markers as compared to sevoflurane- sufentanil anesthesia after cardiac surgery
• 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
• Drug: Isoflurane
  Anesthetic inhalational gas

Study Arms

• Placebo Comparator: Control group(C)
  anesthesia will be maintained using Isoflurane 1.2MAC keeping the bispectral index( BIS) between 40-60%.
  Intervention: Drug: Isoflurane
• 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),
  Intervention: Drug: Ketamine- dexmedetomidine
• 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 ).
  Intervention: Drug: Fentanyl- midazolam

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 5, 2022): 81
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 25, 2022
• Estimated Primary Completion Date: September 20, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 24 Months (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amany H Saleh, MD; +201224259808; dr_amanyhassan@hotmail.com

Contact: passaint f hassan, MD; 01000990952; passaintf@yahoo.com

• Listed Location Countries: Egypt

Administrative Information

• NCT Number: NCT05314569
• Other Study ID Numbers: N-11-2022
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amany Hassan Saleh, Cairo University
• Original Responsible Party: Same as current
• Current Study Sponsor: Cairo University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Amany H Saleh, MD; Cairo University

• PRS Account: Cairo University
• Verification Date: April 2022