Colloid solutions are widely used for volume replacement therapy because of their high oncotic pressure, which could reduce interstitial fluid shifting. Human albumin is the only colloid solution of biologic origin with a molecular weight of 60 kDa. As the most abundant plasma protein, it has physiological importance in the well-being of the endothelial glycocalyx. Older studies in septic patients, however, did not show any benefit of albumin over saline solution. Crystalloid solutions, such as Ringer's acetate, do not impair neither renal function nor coagulation, but their volume expanding effect is questionable.

For several reasons (use of heart-lung machine, systemic inflammation, coagulation disturbances), patients undergoing cardiac surgery need especially large amounts of fluids. However, there are no large trials comparing albumin solutions to crystalloid solutions cardiac surgery.

This double-blinded trial will randomize according to a power analysis 1250 cardiac surgery patients (=625+625) at Meilahti hospital to use either 4% Albumin or Ringer's acetate solutions for both priming of the heart-lung machine and perioperative volume replacement therapy. The primary efficacy and safety endpoint of this study is the incidence of major adverse events (MAE), defined as a composite endpoint of all-cause mortality, acute myocardial infarction, acute heart failure or low output syndrome, resternotomy, stroke, certain arrhythmias, major bleeding, infections compromising post-procedural rehabilitation, acute kidney injury within 90 days postoperatively. The secondary outcomes are total number of MAEs, major adverse cardiac events (MACE), perioperative fluid balance, blood product transfusions, blood loss, acute kidney injury, days alive without mechanical ventilation/outside ICU/at home in 90 days as well as 90-day mortality. Blood samples for biochemical analyses will be collected at four perioperative time points.

This trial will provide data about efficacy and safety of 4% albumin in cardiac surgery patients. The biochemical mechanisms of albumin will be assessed.

The use of cardiopulmonary bypass (CPB) between two study solutions: albumin solution with the final concentration of 4% and Ringer's acetate solution. The trial consists of two phases as follows. For each patient, one and the same study solution will used in both phases of the trial according to randomization.

In the first phase of the trial, the study solution will be used for priming of the CPB tubing. The CPB priming volume comprises only of the study solution. See the Blinding section below for more details.

• Albumin group (trial group): A mixture of 20% (200 mg/mL) albumin solution (Albuman® 200 g/L, Sanquin, the Netherlands) with Ringer's acetate solution (see below) in the final albumin concentration of 4%.
• Ringer group (conventional group): Ringer's acetate solution (Ringer-acetate®, Baxter; pH 6.0, contents Na+ 131 mmol/L, Cl- 112 mmol/L, acetate 30 mmol/L) alone.

In the second phase of the trial, during surgery and the first 24 hours of ICU treatment, study solution will be used up to 3200 mL for volume replacement therapy. Ringer's acetate solution is used thereafter, i.e. if more than 3200 mL are needed for volume replacement therapy during the second study phase. The volume replacement therapy is not protocolled but will be based on the clinical decision.

Albumin group (trial group):4% (40 mg/mL) albumin(Albuman®, Sanquin, the Netherlands)

•Ringer group (conventional group): Ringer's acetate solution (Ringer-acetate®, Baxter; pH 6.0, contents Na+ 131 mmol/L, Cl- 112 mmol/L, acetate 30 mmol/L) The trial will end after the first 24 hours of ICU treatment or when the patient leaves the ICU if the latter occurs within the first postoperative 24 hours. After the study period, fluids are administered according to the local clinical practice.

The use of blood products, excluding albumin, is not protocolled, but will be based on the clinical decision.

For physiological basic need of fluid, Ringer's acetate solution will be given throughout the study period, i.e. during surgery and postoperatively, as a background infusion of 0.5 ml/kg/h, rounded to the nearest multible of 10 ml.

Inclusion Criteria:

• following primary or repeat open heart surgery procedures, either independently or in combinations:CABG,aortic valve replacement/repair, mitral valve replacement/repair,tricuspid valve replacement/repair,the MAZE procedure or its modifications,surgery on the aortic root or ascending aorta not requiring hypothermic circulatory arrest;
• scheduled for elective surgery or operated during the index admission

Exclusion Criteria:

• immediate emergency surgery (i.e. no time for recruitment)
• end-stage kidney disease (estimated GFR<20 mL/min - based on serum/ plasma creatinine)
• hemophilia A, hemophilia B
• patient denial of the use of blood products and derivatives of blood products
• ticagrelor, prasugrel, clopidogrel,apixaban or rivaroxaban treatment within 2 days preoperatively or that of dabigatran within 3 days
• correction of a congenital heart defect
• preoperative infection compromising post-procedural rehabilitation
• preoperative heart failure / low output syndrome (preoperative inotropic support, intra-aortic balloon pump, preoperative EF(ejection fraction) < 20 %)
• preoperative dependency of mechanical ventilation, preoperative ECMO(extra-corporeal membrane oxygenation),left ventrical mechanical assistance.