CPB Prime Fluid Strategies to Preserve Mcirocirculatory Perfusion

NCT05647057 | Completed DMC

• 1 other identifier: NL82500.029.22, part I
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Endothelial Dysfunction; Hemolysis; Fluid Overload

Keywords

Microcirculation; Cardiopulmonary bypass; Colloid oncotic pressure; Hemodilution; Hemolysis

Outcome Measures

Primary Outcomes (5)

• Perfused vessel density (PVD, mm mm-²)

  reflecting microcirculatory diffusion capacity

  T1: within 5-10 minutes after induction of anesthesia

• Perfused vessel density (PVD, mm mm-²)

  reflecting microcirculatory diffusion capacity

  T2 within 5-10 minutes after aortic cross clamping

• Perfused vessel density (PVD, mm mm-²)

  reflecting microcirculatory diffusion capacity

  T3 within 5-10 minutes after weaning from cardiopulmonary bypass

• Perfused vessel density (PVD, mm mm-²)

  reflecting microcirculatory diffusion capacity

  T4 within 15-30 min after arrival on the intensive care unit

• Perfused vessel density (PVD, mm mm-²)

  reflecting microcirculatory diffusion capacity

  T5 twenty four (24) hours after arrival on the intensive care unit

Secondary Outcomes (24)

• Colloid oncotic pressure (COP, mmHg)

  T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.

• albumin (g L-¹)

  T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.

• hemolysis index (H-index)

  T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.

• haptoglobin (g L-¹)

  T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.

• syndecan-1 (ng/ml)

  T1, 5-10 min after induction of anesthesia; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.

Other Outcomes (43)

• Age

  Preoperative

• Gender

  Preoperative

• Body Surface Area (BSA)

  Preoperative

Study Arms (3)

A: gelofusine + ringers

ACTIVE COMPARATOR

Prime fluid strategy containing gelofusine and ringers

Combination Product: A: gelofusine + ringers

B: albumin + ringers

ACTIVE COMPARATOR

Prime fluid strategy containing albumin and ringers

Combination Product: B: albumine + ringers

C: ringers + retrograde autologous priming

ACTIVE COMPARATOR

Prime fluid strategy containing ringers combined with retrograde autologous priming

Combination Product: C: ringers + retrograde autologous priming

Interventions

A: gelofusine + ringers 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)

A: gelofusine + ringers

B: albumine + ringers 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)

B: albumin + ringers

C: ringers + retrograde autologous priming 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.

C: ringers + retrograde autologous priming

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Amsterdam UMC, AMC location

Amsterdam, North Holland, 1105AZ, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 38532434 DERIVED

MeSH Terms

Conditions

Hemolysis; Edema

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• A.B.A. Vonk, MD, PhD

  Cardiothoracic surgeon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiothoracic surgeon, Principle Investigator, doctor.

Model Details: In two consecutive randomized controlled trials, the investigators study the effect of prime fluid strategies on perfused vessel density (part I) and the effect of additional albumin during cardiopulmonary bypass compared with ringers on perfused vessel density (part II). In this study part (I), the effect of prime fluid strategies on perfused vessel density. A single centre, double-blind randomized trial

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: December 12, 2022
• Study Start: July 10, 2023
• Primary Completion: July 8, 2024
• Study Completion: August 8, 2024
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Time Frame: Upon request

Locations

NL (1)