Effects of pulsatile cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery with median sternotomy Surgery
Conditions
Interventions
Group allocation - institution-stratified permuted block randomization:
Patients will be randomly allocated in a 1:1 ratio in blocks of 6 patients within each institution (i.e., stratified by institut
for that purpose the cardiac index of 2.0-2.4 L/min/m2 will be maintained for all patients in a balanced manner with the vasoactive agents (first-line noradrenaline, first-line vasodilator glyceryl tr
Sponsors
Slovenian Research and Innovation Agency
Croatian Science Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) 2. Expected aortic cross-clamp (ACC) time of >45 minutes 3. Full or partial median sternotomy with central cannulation (mini-CPB should not be used) 4. surgery starting in the morning: 4.1. Cardiac valve surgery 4.2. Isolated coronary artery bypass grafting (CABG) 4.3. Combination of valvular and CABG surgery 4.4. Any of the above combined with ascending aorta surgery (NO concomitant radio-frequency ablations, NO concomitant carotid artery surgery)
Exclusion criteria
Exclusion criteria: Exclusion criteria: 1. Refusal to participate in the study 2. Pregnant women 3. Patients with previous cardiac surgery (i.e., redo surgery) 4. Patients with left ventricular ejection fraction 35 kg·m-2 or 2.20 m2 (as it would be impossible to achieve pulsatile pump flow equivalent to a cardiac index of 2.0-2.4, without exceeding maximum safe line pressure in the extracorporeal circuit) 8. Patients with any autoimmune diseases, immunocompromised patients (e.g., with AIDS) or with leucopoenia (34.2µmol·L-1) 12. Patients with renal failure (serum creatinine >176 µmol·L-1) 13. Patients with malignant diseases within the last 5 years (i.e., remission or cure 5 years or longer) 14. Patients with ischemic stroke or myocardial infarction (STEMI) within the last 3 months 15. Patients with known epilepsy 16. Patients with known allergy to any drugs used in the study protocol Exclusion criteria - after enrolment: Two analyses will be performed, one based on the treatment received and the second one with the additional exclusion criteria which could have an additional effect on the measured outcomes of endothelial dysfunction, inflammation, and/or oxidative stress; for example, patients who received systemic glucocorticoid medication before the last blood sampling.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Endothelial dysfunction: peak plasma syndecan-1 level measured with ELISA at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB. 2. Inflammation: peak plasma IL-6/IL-10 ratio measured with ELISA at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB. 3. Oxidative stress: peak plasma malondialdehyde (MDA) measured with ELISA at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB. 4. Microcirculation: perfused vessel density (variable of diffusive capacity) measured with GlycoCheck at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB. 5. Clinical outcomes: peak lactate levels measured at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Other markers of endothelial dysfunction, all measured with ELISA at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB: 1.1. Heparan sulphate 1.2. Angiopoetin Ang-1 and angiopoetin Ang-2 and Ang-2/Ang-1 ratio 1.3. Endokan 1.4. Syndecan-4 1.5. Glypican-1 1.6. Hyaluronic acid 1.7. Orosomucoid 1.8. Fractalkine 1.9. Von Willebrand factor 1.10. Vascular endothelial growth factor (VEGF) 2. Other markers of inflammation, all measured with ELISA at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB: 2.1. IL-6/IL-10 patterns 2.2. IL-10 2.3. IL-6 2.4. IL-5 2.5. IL-16 2.6. IL-8 2.7. MMP-9 2.8. MMP-13 2.9. IL-1ß 2.10. IL-7 2.11. IL-17 2.12. IL-18 2.13. IL-18BP 3. Other markers of oxidative stress, all measured with ELISA at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB: 3.1. Reactive oxygen species 3.2. Reactive nitrogen species 4. Other microcirculatory parameters, all measured with GlycoCheck at baseline, 45 minutes after aortic cross-clamp, 2 hours after CPB, 6 hours after CPB, 18 hours after CPB (i.e., the next morning following surgery), 42 hours after CPB and 66 hours after CPB: 4.1. Convective blood flow: proportion of perfused vessels (proportion of perfused vessels = perfused vessel density/total vessel density) 4.2. Variables of diffusive capacity: Total vessel density and De Backer score 4.3. Variable of heterogeneity: Heterogeneity index 4.4. Variable of glycocalyx: Perfused boundary region 5. Clinical outcomes: Vascular (extracted from patients’ medical records for all): 1. Total dose of NA administered intraoperatively and in ICU until | — |
Countries
Croatia, Slovenia
Contacts
Public ContactMarko Zdravkovic
Outcome results
None listed