Optimization of Prime Fluid Strategy to Preserve Microcirculatory Perfusion During Cardiac Surgery With Cardiopulmonary Bypass, Part II

NCT ID: NCT05647200

Last Updated: 2023-04-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-15
• Study Completion Date: 2025-01-15

Brief Summary

Acute microcirculatory perfusion disturbances is common in critical illness and associated with increased morbidity and mortality. Recent findings by our 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 forty two percent, 42%) 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. For part I see trial registration: PRIME, part I.

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.

Conditions

Endothelial Dysfunction; Hemolysis; Fluid Overload

Study Design

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

Study Groups

T (Treatment)

The most optimal prime fluid from part I (based on the effect on perfused vessel density) + additional albumin during cardiopulmonary bypass.

Group Type: ACTIVE_COMPARATOR

Treatment: additional albumin during cardiopulmonary bypass

Intervention Type: DRUG

Treatment group (T): administration of 100 mL Human Albumin (20%), first dose directly after aortic cross clamping and blood cardioplegia administration, second dose after the third blood cardioplegia administration (± 30 min after the first dose).

C (control)

The most optimal prime fluid from part I (based on the effect on perfused vessel density) + additional ringers during cardiopulmonary bypass.

Group Type: SHAM_COMPARATOR

control: additional ringers during cardiopulmonary bypass

Intervention Type: DRUG

Control group (C): administration of 100 mL of Ringer's solution, first dose directly after aortic cross clamping and blood cardioplegia administration, second dose after the third blood cardioplegia administration (± 30 min after the first dose).

Interventions

Treatment: additional albumin during cardiopulmonary bypass

Treatment group (T): administration of 100 mL Human Albumin (20%), first dose directly after aortic cross clamping and blood cardioplegia administration, second dose after the third blood cardioplegia administration (± 30 min after the first dose).

Intervention Type: DRUG

control: additional ringers during cardiopulmonary bypass

Control group (C): administration of 100 mL of Ringer's solution, first dose directly after aortic cross clamping and blood cardioplegia administration, second dose after the third blood cardioplegia administration (± 30 min after the first dose).

Intervention Type: DRUG

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
• 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

Central Contacts

A.M. Beukers, MD

Role: CONTACT

a.beukers@amsterdamumc.nl

020-4444444

A.B.A. Vonk, MD PhD

Role: CONTACT

020-4444444

Other Identifiers

NL82500.029.22, part II

Identifier Type: -

Identifier Source: org_study_id