CPB Prime Fluid Strategies to Preserve Mcirocirculatory Perfusion

NCT ID: NCT05647057

Last Updated: 2025-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-10
• Study Completion Date: 2024-08-08

Brief Summary

Acute microcirculatory perfusion disturbances is common in critical illness and associated with higher morbidity and mortality. Recent findings by the investigators' group showed that microcirculatory perfusion is disturbed during cardiac surgery with cardiopulmonary bypass (CPB) and remain disturbed up to 72 (seventy two) hours after surgery. A cardiopulmonary bypass is a machine which takes over heart and lung function, during the procedure. The disturbed microcirculation is associated with organ dysfunction induced by cardiac surgery using CPB, which is frequently seen (up to 42%, forty two percent) and results in a six-fold increase in mortality rate. The underlying cause of disturbed microcirculation is a higher endothelial permeability and vascular leakage and are a consequence of systemic inflammation, hemodilution (dilution of blood), hypothermia and hemolysis (breakdown of red blood cells). To gain the knowledge regarding disturbed microcirculation the investigators previously showed that hemodilution attributes to this disturbed perfusion. Hemodilution lowers colloid oncotic pressure (COP). Also, COP is affected by free hemoglobin, which increases with hemolysis and attributes to a disturbed microcirculation following CPB. This is interesting, as to the best of our knowledge, the effect of minimizing hemodilution and hemolysis during cardiac surgery on the microcirculatory perfusion has never been investigated, but could be the key factor in reducing organ dysfunction.

Detailed Description

In this project the investigators focus on reducing microcirculatory perfusion disturbances by exploring therapeutic approaches with different prime fluid strategies, by acting on COP (part I) and free hemoglobin scavenging with human albumin (part II).

In part I, patients undergoing elective coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass will be randomized in three groups receiving different prime fluid strategies. The study endpoint is the reduction in functional capillary density during the perioperative period. Sublingual microcirculatory measurements and blood sampling will take place after induction of anesthesia, during and after surgery to determine microcirculatory perfusion and parameters for hemodilution, hemolysis, COP, markers for endothelial damage and glycocalyx shedding. Measurements start on the day of surgery and end one day after surgery.

In part II, participants will be randomized in two groups receiving the first dose directly after aortic cross clamping and blood cardioplegia administration, and the second dose after the third blood cardioplegia administration (± 30 min after the first dose).The most optimal prime fluid in order to preserve microcirculatory perfusion from study one, will be used as prime fluid in the second study. Microcirculatory perfusion parameters will be measured at time points comparable with study one. Blood samples are taken to determine markers for hemodilution, hemolysis, COP and endothelial damage and glycocalyx shedding. For part II see trial registration: PRIME, part II.

Conditions

Endothelial Dysfunction; Hemolysis; Fluid Overload

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

A: gelofusine + ringers

Prime fluid strategy containing gelofusine and ringers

Group Type: ACTIVE_COMPARATOR

A: gelofusine + ringers

Intervention Type: COMBINATION_PRODUCT

750 milliliter (mL) modified fluid gelatin (Braun Melsungen, Germany), 650 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands)

B: albumin + ringers

Prime fluid strategy containing albumin and ringers

Group Type: ACTIVE_COMPARATOR

B: albumine + ringers

Intervention Type: COMBINATION_PRODUCT

200 mL human albumin (20%, Sanquin, Amsterdam, Netherlands), 1200 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands)

C: ringers + retrograde autologous priming

Prime fluid strategy containing ringers combined with retrograde autologous priming

Group Type: ACTIVE_COMPARATOR

C: ringers + retrograde autologous priming

Intervention Type: COMBINATION_PRODUCT

1400 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands) with retrograde autologous priming.

Retrograde autologous priming (RAP) is applied using clinical parameters such as Central Venous Pressure, Mean Arterial Pressure (MAP), and intra cardiac filling pressure based on Trans Esophageal Echo as guidance to the amount of fluid displaced. RAP is applied to a maximum volume of 475 mL provided that systolic blood pressure will remain >90 millimeter of mercury (mmHg). Phenylephrine can be administered up to 200 mcg to keep the system hemodynamics stable during RAP. In case of a body surface area <1.7m2, a maximum volume of 375 mL is desired. Once the desired amount of prime is displaced, the transfusion bag is clamped and CPB is started. If additional fluids are needed during CPB to maintain optimal perfusion, the displaced prime is used prior to the vasoplegia protocol.

Interventions

A: gelofusine + ringers

750 milliliter (mL) modified fluid gelatin (Braun Melsungen, Germany), 650 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands)

Intervention Type: COMBINATION_PRODUCT

B: albumine + ringers

200 mL human albumin (20%, Sanquin, Amsterdam, Netherlands), 1200 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands)

Intervention Type: COMBINATION_PRODUCT

C: ringers + retrograde autologous priming

1400 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands) with retrograde autologous priming.

Retrograde autologous priming (RAP) is applied using clinical parameters such as Central Venous Pressure, Mean Arterial Pressure (MAP), and intra cardiac filling pressure based on Trans Esophageal Echo as guidance to the amount of fluid displaced. RAP is applied to a maximum volume of 475 mL provided that systolic blood pressure will remain >90 millimeter of mercury (mmHg). Phenylephrine can be administered up to 200 mcg to keep the system hemodynamics stable during RAP. In case of a body surface area <1.7m2, a maximum volume of 375 mL is desired. Once the desired amount of prime is displaced, the transfusion bag is clamped and CPB is started. If additional fluids are needed during CPB to maintain optimal perfusion, the displaced prime is used prior to the vasoplegia protocol.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• Adult subjects
• Informed consent
• Elective coronary artery bypass surgery with cardiopulmonary bypass

Exclusion Criteria

• Emergency operations
• Re-operation
• Elective thoracic aortic surgery
• Elective valve surgery
• The use of crystalloid cardioplegia
• Combined procedure CABG and valve surgery
• Known allergy for human albumin or gelofusine

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

Alexander B.A. Vonk

Cardiothoracic surgeon, Principle Investigator, doctor.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

A.B.A. Vonk, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cardiothoracic surgeon

Locations

Amsterdam UMC, AMC location

Amsterdam, North Holland, Netherlands

Countries

Netherlands

References

Beukers AM, Bulte CSE, Bosch RJ, Eberl S, van den Brom CE, Loer SA, Vonk ABA. Optimization of cardiopulmonary bypass prime fluid to preserve microcirculatory perfusion during on-pump coronary artery bypass graft surgery: PRIME study protocol for a double-blind randomized trial. Trials. 2024 Mar 26;25(1):219. doi: 10.1186/s13063-024-08053-5.

Reference Type: DERIVED

PMID: 38532434 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Explanation of Randomization process

View Document

Other Identifiers

NL82500.029.22, part I

Identifier Type: -

Identifier Source: org_study_id