Clinical trial NCT05647200: Optimization of Prime Fluid Strategy to Preserve Microcirculatory Perfusion During Cardiac Surgery With Cardiopulmonary Bypass, Part II
Official title: Optimization of Prime Fluid Strategy to Preserve Microcirculatory Perfusion During Cardiac Surgery With Cardiopulmonary Bypass
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Endothelial Dysfunction
Hemolysis
Fluid Overload
Keywords: Microcirculation
Cardiopulmonary bypass
Colloid oncotic pressure
Hemodilution
Hemolysis
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2022-12-12
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In two consecutive randomized controlled trials, we 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 (II), the effect of additional albumin during cardiopulmonary bypass compared with ringers on perfused vessel density.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Perfused vessel density (PVD, mm mm-²)
timeFrame: Timepoint 1: 5-10 min after induction of anesthesia
measure: Perfused vessel density (PVD, mm mm-²)
timeFrame: Timepoint 2: 5-10 min after aortic cross clamping
measure: Perfused vessel density (PVD, mm mm-²)
timeFrame: Timepoint 3: 5-10 min after weaning from cardiopulmonary bypass
measure: Perfused vessel density (PVD, mm mm-²)
timeFrame: Timepoint 4: 15-30 min after arrival on the intensive care unit
measure: Perfused vessel density (PVD, mm mm-²)
timeFrame: Timepoint 5: twenty four (24) hours after arrival on the intensive care unit
Secondary outcomes:
measure: Colloid oncotic pressure (COP, mmHg)
timeFrame: 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.
measure: albumin (g L-¹)
timeFrame: 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.
measure: hemolysis index (H-index)
timeFrame: 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.
measure: haptoglobin (g L-¹)
timeFrame: 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.
measure: NO consumption (μmol L-¹)
timeFrame: 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.
measure: syndecan-1 (ng/ml)
timeFrame: 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.
measure: heparan sulphate (ng/ml)
timeFrame: 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.
measure: hemoglobin (Hb, mmol L-¹)
timeFrame: 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.
measure: hematocrit (Ht, L L-¹)
timeFrame: 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.
measure: perioperative use of packed red blood cells (PRBCs, mL)
timeFrame: intraoperative and postoperative up to 24 hours postoperative
measure: fluid balance (mL)
timeFrame: intraoperative and postoperative up to 24 hours postoperative
measure: fluid requirements (mL)
timeFrame: intraoperative and postoperative up to 24 hours postoperative
measure: Total vessel density (TVD, mm mm-²)
timeFrame: 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.
measure: Proportion of perfused vessels (PPV, %)
timeFrame: 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.
measure: Heterogeneity index
timeFrame: 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.
Other outcomes:
measure: Age
timeFrame: Preoperative
measure: Gender
timeFrame: Preoperative
measure: Body Surface area (BSA)
timeFrame: Preoperative
measure: Smoking
timeFrame: Preoperative
measure: Diabetes on medication
timeFrame: Preoperative
measure: Comorbidities
timeFrame: Preoperative
measure: EuroSCORE II
timeFrame: preoperative
measure: CPB time (min)
timeFrame: Intraoperative
measure: Aortic cross clamping time (AoX time, min)
timeFrame: Intraoperative
measure: heparin (IU)
timeFrame: Intraoperative
measure: protamin (mg)
timeFrame: Intraoperative
measure: Activated clotting time (ACT, min)
timeFrame: Intraoperative
measure: Temperature (celsius)
timeFrame: 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.
measure: Oxygen saturation (Sat, %)
timeFrame: 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.
measure: Urine production (ml)
timeFrame: 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.
measure: Blood pressure (mmHg)
timeFrame: 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.
measure: Noradrenaline
timeFrame: 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.
measure: Phenylephrine
timeFrame: 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.
measure: Vasopressin (IU/min)
timeFrame: 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.
measure: Methylene Blue
timeFrame: 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.
measure: Lactate (mmol/L)
timeFrame: T1, 5-10 min after induction of anesthesia; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
measure: Creatinin levels (umol/L)
timeFrame: T1, 5-10 min after induction of anesthesia; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
measure: estimated glomerular filtration rate (eGFR)(ml/min/1,73 m2)
timeFrame: T1, 5-10 min after induction of anesthesia; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
measure: Blood product use
timeFrame: Intraoperative and postoperative up to 24 hours postoperative
measure: Blood loss (ml)
timeFrame: Intraoperative and postoperative up to 24 hours postoperative
measure: Duration of mechanical ventilation (hours)
timeFrame: Postoperative until 30 days postoperative
measure: ICU stay (hours)
timeFrame: Postoperative until 30 days postoperative
measure: Hospital stay (days)
timeFrame: Postoperative until 30 days postoperative
measure: Acute kidney injury (AKI)
timeFrame: Postoperative until 30 days postoperative
measure: Respiratory failure
timeFrame: Postoperative until 30 days postoperative
measure: Pneumonia
timeFrame: Postoperative until 30 days postoperative
measure: non-preexisting atrial fibrillation
timeFrame: Postoperative until 30 days postoperative
measure: re-do surgery
timeFrame: Postoperative until 30 days postoperative
measure: Extra corporeal membrane oxygenation (ECMO)
timeFrame: Postoperative until 30 days postoperative
measure: Mortality
timeFrame: Postoperative until 30 days postoperative
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, AMC location
state: Noord Holland
Study officials:
affiliation: Cardiothoracic surgeon
name: A.B.A. Vonk, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: