Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery

Study Overview
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Brief Summary
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Hemodilution reduces concentrations of blood constituents: concentration of hemoglobin, red blood cells (hematocrit), physiological ions and coagulation factors that can contribute to impaired hemostasis and increasing the risk of perioperative blood transfusions. This pilot study will assess the feasibility of a large RCT to evaluate 2 techniques for reducing hemodilution during cardiac surgery: 1) retrograde autologous priming and 2) intraoperative mannitol. The aim of this pilot trial is to demonstrate feasibility of a larger trial to evaluate whether retrograde autologous priming and/or mannitol are superior to conventional priming alone.

Detailed Description
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The use of large volumes of artificial priming fluids is still very high in cardiac surgery for routine CABG surgery with cardiopulmonary bypass. The resulting hemodilution is deleterious for patients and often requires counter measures to maintain fluid balance during and after surgery. Retrograde autologous priming and mannitol are simple low-cost solutions to the problem of hemodilution but their effectiveness, either alone or in combination, is unclear due to a lack of high-quality evidence. RAPPER-MAN is a single-centre 2x2 factorial cluster randomized trial. Participants will be randomly assigned (1:1:1:1 ratio) to the intervention groups: 1) Retrograde autologous priming (≥600 mL) + mannitol (0.3 g/kg bolus), 2) Retrograde autologous priming (≥600 mL) alone, 3) Conventional priming + mannitol (0.3 g/kg bolus), and 4) Conventional priming alone. The primary outcome is the change in hemoglobin concentration during cardiopulmonary bypass. Retrograde autologous priming will be performed within 10 minutes before, and mannitol will be added to the venous reservoir of the CPB machine within 5 minutes before, the start of cardiopulmonary bypass. The results of the larger trial are expected to have broad implications for fluid management in cardiac surgery in Canada.

Official Title
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Retrograde Autologous Priming for Preserving Hemoglobin Peri-operatively With or Without Mannitol: A Pilot Study

Conditions
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Hemodilution, Coronary Artery Disease, Fluid Overload

Intervention / Treatment
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* Procedure: Retrograde autologous priming
* Drug: Mannitol
* Procedure: Conventional Priming


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age. Undergoing a first-time cardiac surgical procedure (i.e. isolated CABG, isolated single cardiac valve surgery or a combination of both or isolated ascending aorta replacement) with the use of cardiopulmonary bypass (CPB) and median sternotomy. Exclusion Criteria: Left ventricle ejection fraction <25% Emergency surgery History of bleeding disorder Inherited thromboembolic or infective endocarditis (active) Previous cardiac surgery Severe renal impairment (serum creatinine >250 μmol/L) Hemoglobin <80 g/L Thrombocytopenia (<50,000 platelets per μL) Expected circulatory arrest Body weight ≤50 kg Allergy to mannitol Pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: single-centre, single blinded, 2x2 factorial, cluster randomized trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Retrograde autologous priming + mannitol<br>Priming solution (≥600 mL) will be removed from the extracorporeal circuit within 10 minutes before the initiation of cardiopulmonary bypass. Priming solution may be removed from 3 locations within the extracorporeal circuit (i.e. arterial, venous and cardioplegia lines) as determined by the perfusionist team. In addition, mannitol will be added as a bolus (0.3 g/kg) to the venous reservoir of the cardiopulmonary bypass machine within 5 min before the start of cardiopulmonary bypass. | Procedure: Retrograde autologous priming<br>* Priming solution (≥600 mL) will be removed from the extracorporeal circuit within 10 minutes before the initiation of cardiopulmonary bypass. Priming solution may be removed from 3 locations within the extracorporeal circuit (i.e. arterial, venous and cardioplegia lines) as determined by the perfusionist team.<br>* Other names: RAP;Drug: Mannitol<br>* Mannitol will be added as a bolus (0.3 g/kg) to the venous reservoir of the cardiopulmonary bypass machine within 5 min before the start of cardiopulmonary bypass.<br>|
| Experimental: Retrograde autologous priming alone<br>Priming solution (≥600 mL) will be removed from the extracorporeal circuit within 10 minutes before the initiation of cardiopulmonary bypass. Priming solution may be removed from 3 locations within the extracorporeal circuit (i.e. arterial, venous and cardioplegia lines) as determined by the perfusionist team. | Procedure: Retrograde autologous priming<br>* Priming solution (≥600 mL) will be removed from the extracorporeal circuit within 10 minutes before the initiation of cardiopulmonary bypass. Priming solution may be removed from 3 locations within the extracorporeal circuit (i.e. arterial, venous and cardioplegia lines) as determined by the perfusionist team.<br>* Other names: RAP;|
| Experimental: Conventional priming + mannitol<br>Participants will receive conventional priming. In addition, mannitol will be added as a bolus (0.3 g/kg) to the venous reservoir of the cardiopulmonary bypass machine within 5 min before the start of cardiopulmonary bypass. | Drug: Mannitol<br>* Mannitol will be added as a bolus (0.3 g/kg) to the venous reservoir of the cardiopulmonary bypass machine within 5 min before the start of cardiopulmonary bypass.<br>Procedure: Conventional Priming<br>* The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.<br>|
| Active Comparator: Conventional priming alone<br>Participants will receive conventional priming alone. | Procedure: Conventional Priming<br>* The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility Outcomes | Feasibility will be established in the pilot phase if all the following criteria are met: Average recruitment rate of 7 patients per week. Complete Hb data before and after cardiopulmonary bypass in 90% of patients. Compliance of the research team members, OR staff and ward medical staff with the protocol of 90%. | Start to end of study recruitment, which is anticipated to take 20 weeks | 
| Change in hemoglobin concentration during cardiopulmonary bypass | Change in arterial hemoglobin concentration during cardiopulmonary bypass | Start to end of cardiopulmonary bypass | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin concentration after cardiopulmonary bypass | Change in arterial hemoglobin concentration from baseline to discharge | Start of cardiopulmonary bypass to hospital discharge or 5 days maximum (whichever occurs first) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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retrograde autologous priming, mannitol, cardiopulmonary bypass, cardiac surgery, hemodilution