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The investigators hypothesize that in addition to a known sympatholytic effect, intraoperative dexmedetomidine reduces adverse changes in mitochondrial function and structure attenuating ischaemia-reperfusion and end-organ injury for children with non cyanotic congenital heart defects having corrective heart surgery.
PICO: For children with non cyanotic congenital heart defects having corrective heart surgery (P) does intraoperative dexmedetomidine (I) reduce real-time changes in mitochondrial function and content (O) compared with children not receiving dexmedetomidine (C).
The study drug (dexmedetomidine or placebo) will be mixed in a standardized syringe of 4mcg/mL for active syringes or 50mL 0.9% sodium chloride for placebo. Blinded syringes will be prepared by the Research Support Pharmacy.
Administration is via the existing central venous line. A bolus dose of 0.125mL/kg (0.5 mcg/kg dexmedetomidine) infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery. The dexmedetomidine/placebo continuous infusion (CI) dose will run at 0.15mL/kg/hr (0.6 mcg/kg/hr dexmedetomidine).
Blood samples will be obtained from each child at three points in the operating room: 1) after the induction of anesthesia, 2) at the first separation from CPB (prior to administration of blood products), and 3) at the end of the surgery.
Samples obtained will be analyzed for mitochondrial function and morphology, total cellular mitochondrial biomass, and mitochondrial deoxyribonucleic acid (mtDNA) damage:
Myocardial tissue will be also collected prior to closure of the atriotomy. Samples will be placed into 3% buffered glutaraldehyde at the time of biopsy, and imaging of mitochondrial structure using electron microscopy will be performed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo (0.9% Saline) | Placebo Comparator | 0.9% Saline: bolus dose of 0.125mL/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.15mL/kg/hr for the duration of surgery. |
|
| Dexmedetomidine | Experimental | Dexmedetomidine: bolus dose of 0.5 mcg/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.6 mcg/kg/hr for the duration of surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine | Drug | A bolus dose of 0.5 mcg/kg infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery at 0.6 mcg/kg/hr. |
| Measure | Description | Time Frame |
|---|---|---|
| Mitochondrial function (use high content imaging (HCI) | The primary outcomes for mitochondria will be grouped into mitochondrial function, morphology, content and mtDNA damage. | Intraoperative |
| Measure | Description | Time Frame |
|---|---|---|
| Creatinine level (Marker of acute renal injury) | Marker of acute renal injury | Postoperative day 1 |
| Cardiac function (Left ventricular ejection fraction measured by trans-thoracic echocardiography) |
| Measure | Description | Time Frame |
|---|---|---|
| Analgesic effects (Morphine equivalent dose of narcotics consumed) | Morphine equivalent dose of narcotics consumed | Perioperative (from induction of anesthesia for 24 hours) |
| Sedative effects (Duration of intubation) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| James D O'Leary, MBBCh | Contact | (416) 813-1500 | 228845 | james.oleary@sickkids.ca |
| Name | Affiliation | Role |
|---|---|---|
| James D O'Leary, MBBCh | The Hospital for Sick Children | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital for Sick Children | Recruiting | Toronto | Ontario | M5G1X8 | Canada |
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| ID | Term |
|---|---|
| D015427 | Reperfusion Injury |
| D006330 | Heart Defects, Congenital |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| 0.9% NaCl | Drug |
|
|
Left ventricular ejection fraction measured by trans-thoracic echocardiography
| Postoperative day 1 |
| Inotropes and vasopressors (Duration and dose of inotropes and vasopressors after surgery) | Duration and dose of inotropes and vasopressors after surgery | Postoperative day 1 |
Duration of intubation.
| Perioperative (from induction of anesthesia for 24 hours) |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018376 | Cardiovascular Abnormalities |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000077324 |
| Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |