Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery

Coronary Artery Disease Clinical Trial

— RAPPER-MAN  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04870073
• Other study ID #: RAPPER-MAN_2021
• Status: Withdrawn
• Phase: Phase 3
• Start date: September 21, 2022
• Est. completion date: September 21, 2022

Study information

• Verified date: February 2023
• Source: Hamilton Health Sciences Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 21, 2022
• Est. primary completion date: September 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. =18 years of age.

2. 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:

1. Left ventricle ejection fraction <25%

2. Emergency surgery

3. History of bleeding disorder

4. Inherited thromboembolic or infective endocarditis (active)

5. Previous cardiac surgery

6. Severe renal impairment (serum creatinine >250 µmol/L)

7. Hemoglobin <80 g/L

8. Thrombocytopenia (<50,000 platelets per µL)

9. Expected circulatory arrest

10. Body weight =50 kg

11. Allergy to mannitol

12. Pregnancy or breast feeding

Related Conditions & MeSH terms

• Coronary Artery Disease
• Fluid Overload
• Hemodilution

Intervention

Procedure:
• Retrograde autologous priming
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.

Drug:
• Mannitol
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:
• Conventional Priming
The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (4)

Hensley NB, Gyi R, Zorrilla-Vaca A, Choi CW, Lawton JS, Brown CH 4th, Frank SM, Grant MC, Cho BC. Retrograde Autologous Priming in Cardiac Surgery: Results From a Systematic Review and Meta-analysis. Anesth Analg. 2021 Jan;132(1):100-107. doi: 10.1213/ANE.0000000000005151. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood transfusion	Proportion of patients experiencing red blood cell transfusion	Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
Other	Change in oxygen consumption during cardiopulmonary bypass	Change in oxygen consumption during cardiopulmonary bypass	Start to end of cardiopulmonary bypass
Other	Autologous prime volume	Total prime volume removed from the extracorporeal circuit during the retrograde autologous priming procedure	Within 10 minutes before cardiopulmonary bypass
Other	Hyponatremia	Sodium concentration of less than 135 mmol/L (135 mEq/L)	Before and 24 hours after surgery
Other	Diuresis	Total volume of urine within 24 hours of surgery	Within 24 hours of surgery
Other	Hemofiltration use	Proportion of patients undergoing hemofiltration	During cardiopulmonary bypass
Other	Fluid balance	Net fluid balance (intake minus output) calculated using a cumulative fluid chart	Daily in ICU from admission to hospital discharge or 5 days maximum (whichever occurs first)
Other	Acute kidney injury	Acute kidney injury as measured by peak postoperative creatinine and KDIGO	Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
Other	Length of hospital stay	Length of hospital stay (days)	Time from admission to hospital discharge or 5 days maximum (whichever occurs first)
Other	Major adverse cardiovascular events	Composite outcome of cardiovascular death, non-fatal myocardial infarction or stroke	Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
Primary	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
Primary	Change in hemoglobin concentration during cardiopulmonary bypass	Change in arterial hemoglobin concentration during cardiopulmonary bypass	Start to end of cardiopulmonary bypass
Secondary	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)