Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery (RAPPER-MAN)

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

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.

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.

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.

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.

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.

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.

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.

The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.

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%.

Total prime volume removed from the extracorporeal circuit during the retrograde autologous priming procedure

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

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Ljunggren M, Skold A, Dardashti A, Hyllen S. The use of mannitol in cardiopulmonary bypass prime solution-Prospective randomized double-blind clinical trial. Acta Anaesthesiol Scand. 2019 Nov;63(10):1298-1305. doi: 10.1111/aas.13445. Epub 2019 Jul 29.

Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Cardiothoracic Anaesthesiology (EACTA); Boer C, Meesters MI, Milojevic M, Benedetto U, Bolliger D, von Heymann C, Jeppsson A, Koster A, Osnabrugge RL, Ranucci M, Ravn HB, Vonk ABA, Wahba A, Pagano D. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. J Cardiothorac Vasc Anesth. 2018 Feb;32(1):88-120. doi: 10.1053/j.jvca.2017.06.026. Epub 2017 Sep 30. No abstract available.

Trapp C, Schiller W, Mellert F, Halbe M, Lorenzen H, Welz A, Probst C. Retrograde Autologous Priming as a Safe and Easy Method to Reduce Hemodilution and Transfusion Requirements during Cardiac Surgery. Thorac Cardiovasc Surg. 2015 Oct;63(7):628-34. doi: 10.1055/s-0035-1548731. Epub 2015 Mar 24.