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Surgical correction of congenital heart defects in children requires the utilization of cardiopulmonary bypass, a technique that temporarily substitutes heart and lung functions during surgery. During this process the patient´s circulation is controlled by a bypass machine which provides several functions:
Remote ischaemic preconditioning (RIPC) describes a procedure that could potentially reduce the injury to heart muscle during cardiac surgery. The procedure consists of the inflation of a blood pressure cuff on the child's leg for three 5 minute cycles. This process acts by briefly reducing blood flow to the leg muscle, which will then activate the body´s own protective mechanisms and thereby reduce heart injury.
Several animal studies have been used to help the understanding of the mechanisms behind this process, and trials in human adults have showed optimistic results; however evidence regarding the paediatric population is limited and necessary since children present different basal profiles, risks and requirements.
The investigators propose a randomized clinical trial assessing the efficacy of RIPC to provide protection against injury to the heart and other organs in children going through cardiac surgery using CPB at the Royal Hospital for Sick Children. The research project will have a translational approach, integrating basic molecular mechanisms to clinical outcome. The investigators hope it will allow the understanding and utilisation of the patient´s own protective mechanisms, reducing CPB-related injury and ultimately improving patient outcome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RIPC group | Experimental | Patients assigned to this arm will go through a remote ischaemic preconditioning (RIPC)protocol |
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| Control | Placebo Comparator | Patients assigned to this arm will not receive the intervention, however the protocol will be applied to a wooden block in order to maintain blinding to relatives and investigators. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Remote ischaemic preconditioning (RIPC) | Procedure | RIPC will be performed by 3 cycles of 5 minute leg ischaemia induced by inflation of a blood pressure cuff to 40 mmHg above the patient's systolic pressure. This protocol will be performed at two phases: 24 hours before surgery and during anaesthesia immediately prior to surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Measurement of the final cardiac injury after cardiopulmonary bypass assessed by markers of cardiac injury and echocardiography. | Echocardiography assessment will take place before surgery, 24 and 48 hours after surgery. Blood markers of cardiac injury: B-type natriuretic peptide and Troponin will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points. | Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery) |
| Measure | Description | Time Frame |
|---|---|---|
| Protein and mRNA expression in the cardiac tissue related to the preconditioning process. | Cardiac tissue will be obtained only from patients who require tissue excision as part of the surgical procedure. Protein and mRNA expression will be assessed after extraction. | Expression assessed at the time of tissue extraction |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Hospital for Sick Children - Yorkhill | Glasgow | G3 8SJ | United Kingdom |
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| Placebo | Procedure |
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| End organ damage assessment by measurement of markers relevant to lung and kidney function and evaluate a possible benefit from preconditioning. |
Blood markers (creatinin, cystatin C, Neutrophil gelatinase associated lipocalin,cGMP and Phosphodiesterase 5)will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points. |
| Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery) |
| Systemic immune response assessment by measurement of inflammatory mediators such as cytokines and nitric oxide metabolites. | Inflammatory blood markers (MDA, isoprostanes, NO metabolites, Cytokines, adhesion molecules, among others)will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points | Pre and postoperatively (immediately before and after surgery, 24 and 48 hours after surgery) |