Dexmedetomidine Effect on Mitochondrial Function
The Protective Effect of the α2-agonist Dexmedetomidine on Mitochondrial Structure and Function for Children With Non-cyanotic Congenital Heart Defects Having Cardiac Surgery: A Randomized Controlled Trial.
調査の概要
詳細な説明
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:
- After isolating lymphocytes, we will use high content imaging (HCI) to assess mitochondrial function and morphology. The lymphocytes will be stained with tetramethylrhodamine methyl ester (TMRM), which stains mitochondria in proportion to mitochondrial membrane potential, giving a metric for mitochondrial function. In addition, the cells will be stained with MitoTracker Green®, which can be used to assess mitochondrial morphology. Mitochondrial morphology will be quantified in a non-biased fashion using a mathematical image analysis algorithm.
- After extraction of genomic DNA, total cellular mitochondrial biomass and mitochondrial DNA damage will be measured using traditional and long-patch quantitative polymerase chain reaction (PCR).
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.
研究の種類
入学 (予想される)
段階
- フェーズ 4
連絡先と場所
研究場所
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Ontario
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Toronto、Ontario、カナダ、M5G1X8
- 募集
- Hospital for Sick Children
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主任研究者：
- James D O'Leary, MBBCh
-
副調査官：
- John Coles, MD
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副調査官：
- Jason T Maynes, MD PhD
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副調査官：
- Daniel Stocki
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- aged between 3 - 36 months
- having primary corrective heart surgery
Exclusion Criteria:
- recent surgery (< 3 months)
- previous chemotherapy
- previous transfusion of blood products
- neurodevelopmental disorders (including Trisomy 21)
- supplemental oxygen requirement (< 3 months)
- asthma requiring regular therapy
- obstructive sleep apnea
- the presence of concurrent infection or inflammation
- a known allergy to dexmedetomidine hydrochloride
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：Placebo (0.9% Saline)
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.
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他の名前：
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実験的：Dexmedetomidine
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.
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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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Mitochondrial function (use high content imaging (HCI)
時間枠：Intraoperative
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The primary outcomes for mitochondria will be grouped into mitochondrial function, morphology, content and mtDNA damage.
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Intraoperative
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Creatinine level (Marker of acute renal injury)
時間枠：Postoperative day 1
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Marker of acute renal injury
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Postoperative day 1
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Cardiac function (Left ventricular ejection fraction measured by trans-thoracic echocardiography)
時間枠：Postoperative day 1
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Left ventricular ejection fraction measured by trans-thoracic echocardiography
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Postoperative day 1
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Inotropes and vasopressors (Duration and dose of inotropes and vasopressors after surgery)
時間枠：Postoperative day 1
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Duration and dose of inotropes and vasopressors after surgery
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Postoperative day 1
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Analgesic effects (Morphine equivalent dose of narcotics consumed)
時間枠：Perioperative (from induction of anesthesia for 24 hours)
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Morphine equivalent dose of narcotics consumed
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Perioperative (from induction of anesthesia for 24 hours)
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Sedative effects (Duration of intubation)
時間枠：Perioperative (from induction of anesthesia for 24 hours)
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Duration of intubation.
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Perioperative (from induction of anesthesia for 24 hours)
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協力者と研究者
捜査官
- 主任研究者：James D O'Leary, MBBCh、The Hospital for Sick Children
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 1000044746
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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