Cardiac surgery poses specific challenges in fluid management. The role of albumin administration during cardiac surgery has long been controversial. Although it has theoretical advantages, it is expensive and there is limited evidence that it improves clinical outcomes in cardiac surgery patients. However, over the past five years, evidence has emerged that albumin may be beneficial as a targeted therapy in selected patients.

The physiological rationale for albumin infusion is closely related to the pathophysiology of cardiopulmonary bypass (CPB). CPB can induce a systemic inflammatory response, disrupt cellular endothelial function, increase capillary permeability, and result in hypoalubinemia due to hemodilution and the adsorption of plasma proteins such as albumin by the CPB circuit. These changes lower plasma oncotic pressure which causes fluid to leak from the intravascular space, resulting in tissue edema. Albumin is the main determinant of plasma oncotic pressure, and physically retains approximately 18 mL of water per gram in the intravascular space. In addition, it binds drugs, hormones, and toxins, neutralizes reactive oxygen species, and may limit glycocalyx degradation. These beneficial properties of albumin provide a physiological rationale for considering its perioperative use in cardiac surgery.

However, recent clinical evidence does not support routine albumin use in adult cardiac surgery with CPB. The Albumin in Cardiac Surgery (ALBICS) trial, a double-blinded randomized controlled trial (RCT) in 1386 on-pump cardiac surgery patients, showed that 4% albumin versus Ringer’s lactate for CPB priming and perioperative fluid, did not reduce major adverse clinical events at 90 days, but was associated with increased perioperative bleeding, higher transfusion requirements, and the need for more reoperations [1, 2]. A recent network meta-analysis confirmed the increased need for perioperative Red Blood Cells (RBC) transfusion with albumin priming compared to using crystalloid solutions [3]. There have also been concerns regarding decreased renal function following the routine use of albumin during cardiac surgery. The Albumin Infusion and Acute Kidney Injury following Cardiac Surgery (ALBICS-AKI) trial involving high-risk cardiac surgery patients, 50% of whom had a baseline estimated glomerular filtration rate (eGFR) $<$60 mL/min/1.73 m², the use of postoperative 20% albumin resulted in an increased incidence of cardiac surgery-associated acute kidney injury (CSA-AKI) (48.9% vs 43.4%; adjusted Relative Risk (RR) 1.12, 95% CI 1.04–1.21) and an increased need for blood transfusions [4]. A large retrospective analysis also found that intraoperative 20% albumin increased the risk of CSA-AKI, particularly in patients with normal or elevated preoperative albumin levels [5]. Based on these findings, multiple contemporary guidelines recommend against routine albumin use for CPB priming or perioperative volume replacement in adult cardiac surgery [6, 7, 8]. These trials primarily evaluated short- to medium-term outcomes (up to 90 days) following albumin infusions. More studies with longer follow-up which assess recovery of organ function, hospital re-admissions, and patient-reported quality of life, are still needed to fully determine the clinical value of albumin therapy during cardiac surgery.

Albumin still remains the most physiological colloid and the preferred fluid when a colloid is required, given the well-documented risks of synthetic colloids, which include anaphylaxis, coagulopathy, and AKI [9, 10, 11, 12, 13]. In the era of precision medicine, its role should be considered within a more refined fluid management approach, both in its clinical application and in research, with attention not only to whether albumin should be administered, but also to the appropriate timing, dosing, and concentration. The following sections discuss three patient groups in whom targeted albumin administration could be of potential benefit and may warrant further investigation.