Endothelial Dysfunction Clinical Trial
— PRIME part IIOfficial title:
Optimization of Prime Fluid Strategy to Preserve Microcirculatory Perfusion During Cardiac Surgery With Cardiopulmonary Bypass
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.
Status | Not yet recruiting |
Enrollment | 64 |
Est. completion date | January 15, 2025 |
Est. primary completion date | July 15, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Netherlands | Amsterdam UMC, AMC location | Amsterdam | Noord Holland |
Lead Sponsor | Collaborator |
---|---|
Amsterdam UMC, location VUmc |
Netherlands,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Age | Age in years | Preoperative | |
Other | Gender | Gender (male/female) | Preoperative | |
Other | Body Surface area (BSA) | BSA in m2 | Preoperative | |
Other | Smoking | Medical history of smoking (yes/no) | Preoperative | |
Other | Diabetes on medication | Medical history of diabetes on medication (yes/no) | Preoperative | |
Other | Comorbidities | Other comorbidities in medical history (yes/no) | Preoperative | |
Other | EuroSCORE II | The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II predicts risk of in-hospital mortality after cardiac surgery. | preoperative | |
Other | CPB time (min) | Cardiopulmonary bypass time in minutes | Intraoperative | |
Other | Aortic cross clamping time (AoX time, min) | Aortic cross clamping time in minutes | Intraoperative | |
Other | heparin (IU) | Dosing of heparin in international units | Intraoperative | |
Other | protamin (mg) | Dosing of protamin | Intraoperative | |
Other | Activated clotting time (ACT, min) | Activated clotting time in minutes | Intraoperative | |
Other | Temperature (celsius) | Temperature in Celsius | 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 | Oxygen saturation (Sat, %) | Oxygen saturation in % | 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 | Urine production (ml) | Urine production | 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 | Blood pressure (mmHg) | Blood pressure (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. | |
Other | Noradrenaline | Noradrenaline (mcg/kg/min) | 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 | Phenylephrine | Phenylephrine (mcg) | 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 | Vasopressin (IU/min) | Vasopressin (IU/min) | 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 | Methylene Blue | Methylene Blue (mg) | 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 | Lactate (mmol/L) | Serum lactate | 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. | |
Other | Creatinin levels (umol/L) | serum creatinin level | 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. | |
Other | estimated glomerular filtration rate (eGFR)(ml/min/1,73 m2) | estimated glomerular filtration rate | 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. | |
Other | Blood product use | Blood product use (ml) | Intraoperative and postoperative up to 24 hours postoperative | |
Other | Blood loss (ml) | Blood loss | Intraoperative and postoperative up to 24 hours postoperative | |
Other | Duration of mechanical ventilation (hours) | Duration of mechanical ventilation (hours) | Postoperative until 30 days postoperative | |
Other | ICU stay (hours) | ICU stay (hours) | Postoperative until 30 days postoperative | |
Other | Hospital stay (days) | Days until hospital discharge (days) | Postoperative until 30 days postoperative | |
Other | Acute kidney injury (AKI) | Acute kidney injury (yes/no) | Postoperative until 30 days postoperative | |
Other | Respiratory failure | Respiratory failure (yes/no) | Postoperative until 30 days postoperative | |
Other | Pneumonia | pneumonia (yes/no) | Postoperative until 30 days postoperative | |
Other | non-preexisting atrial fibrillation | non-preexisting atrial fibrillation (yes/no) | Postoperative until 30 days postoperative | |
Other | re-do surgery | re-do surgery (yes/no) | Postoperative until 30 days postoperative | |
Other | Extra corporeal membrane oxygenation (ECMO) | Extra corporeal membrane oxygenation (yes/no) | Postoperative until 30 days postoperative | |
Other | Mortality | in-hospital mortality (yes/no) | Postoperative until 30 days postoperative | |
Primary | Perfused vessel density (PVD, mm mm-²) | reflecting microcirculatory diffusion capacity | Timepoint 1: 5-10 min after induction of anesthesia | |
Primary | Perfused vessel density (PVD, mm mm-²) | reflecting microcirculatory diffusion capacity | Timepoint 2: 5-10 min after aortic cross clamping | |
Primary | Perfused vessel density (PVD, mm mm-²) | reflecting microcirculatory diffusion capacity | Timepoint 3: 5-10 min after weaning from cardiopulmonary bypass | |
Primary | Perfused vessel density (PVD, mm mm-²) | reflecting microcirculatory diffusion capacity | Timepoint 4: 15-30 min after arrival on the intensive care unit | |
Primary | Perfused vessel density (PVD, mm mm-²) | reflecting microcirculatory diffusion capacity | Timepoint 5: twenty four (24) hours after arrival on the intensive care unit | |
Secondary | Colloid oncotic pressure (COP, mmHg) | colloid oncotic pressure in plasma | 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. | |
Secondary | albumin (g L-¹) | concentration of albumin in plasma | 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. | |
Secondary | hemolysis index (H-index) | the grade of hemolysis in plasma | 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. | |
Secondary | haptoglobin (g L-¹) | concentration of haptoglobin in plasma | 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. | |
Secondary | NO consumption (µmol L-¹) | consumption of nitric oxide in plasma | 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. | |
Secondary | syndecan-1 (ng/ml) | Concentration of syndecan-1 in plasma | 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. | |
Secondary | heparan sulphate (ng/ml) | concentration of heparan sulphate in plasma | 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. | |
Secondary | hemoglobin (Hb, mmol L-¹) | concentration of hemoglobin in serum | 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. | |
Secondary | hematocrit (Ht, L L-¹) | hematocrit in serum | 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. | |
Secondary | perioperative use of packed red blood cells (PRBCs, mL) | amount of packed red blood cells | intraoperative and postoperative up to 24 hours postoperative | |
Secondary | fluid balance (mL) | fluid balance | intraoperative and postoperative up to 24 hours postoperative | |
Secondary | fluid requirements (mL) | Amount of fluids required | intraoperative and postoperative up to 24 hours postoperative | |
Secondary | Total vessel density (TVD, mm mm-²) | density of capillaries reflecting the functional state of the microcirculatory diffusion capacity | 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. | |
Secondary | Proportion of perfused vessels (PPV, %) | reflecting the aspect of heterogeneity of microcirculatory perfusion | 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. | |
Secondary | Heterogeneity index | reflecting the aspect of heterogeneity of microcirculatory perfusion | 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. |
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