In surgical patients, fluid overload, as often caused by crystalloids, has been demonstrated to be an independent risk factor for morbidity and mortality and the benefits of the use of human albumin in cardiac surgery are discussed here
During cardiac surgery, large fluid transfers, priming of the cardiopulmonary bypass (CPB) circuit and blood and blood product transfusions, as well as long surgery durations, almost always lead to fluid overload. Despite the large amount of fluids administered, patients who have had CPB often have blood volume deficit because of fluid shift from the intra- to extravascular space due to systemic inflammatory response and damage of the endothelial glycocalix.1 The fluid ‘leakage’ after cardiac surgery lasts for between several hours and several days.2 Conversely, haemodynamics are often affected after cardiac surgery. The phenomenon of myocardial stunning is described widely and, in the early postoperative period, a significant number of patients need inotropic support and/or vasopressors because of the reversible acute heart failure. Additionally, the majority of postoperative patients need more intravascular volume for cardiac output optimisation.
CPB impairs blood coagulation and, in some cases, renal function. There are several mechanisms of coagulation disturbance during CPB. The contact pathway is triggered when Factor XII, prekallikrein and high-molecular weight kininogen interface with the non-biological surfaces of the CPB circuit.3 The extrinsic coagulation pathway is triggered when Factor VIIa complexes with tissue factor being expressed on leucocytes, platelets or exposed subendothelium within the vessel wall. Therefore, thrombin generation increases strongly.4 By contrast, CPB initiation leads to the decrease of coagulation factors (partially, due to haemodilution) and increases the fibrinolytic activity.5 The incidence of severe bleeding in cardiac surgery exceeds 10%, and approximately 5–7% of these patients experience blood loss in excess of 2l within the initial 24h following surgery.6
After CPB, patients are predisposed to different complications, and finding optimal recovery conditions is challenging. The optimal volume resuscitation after CPB should be performed using small amounts of fluid, which remain for at least several hours intravascularly without undesirable side effects.
Benefits of albumin during cardiac surgery
Different solutions, both crystalloids and colloids, have been used for volume replacement after cardiac surgery. A Cochrane systematic review did not find any difference in major outcomes when colloids were compared with crystalloids.7 Crystalloids do not have significant side-effects, apart from haemodilution, but their volume effect is low (about 20%) and they remain in the intravascular space for a very short time, before shifting to the extravascular space.8 This leads to the repetitive administration of crystalloids, which causes fluid overload and oedema. In surgical patients, fluid overload has been demonstrated to be an independent risk factor for morbidity and mortality, and the restriction of intra- and postoperative fluids lead to dramatic outcome improvements.9
Colloids stay longer (for up to six hours) in the intravascular space, and their volume effect is higher than those of crystalloids (80–300%). However, the majority of colloid solutions with non-biological origin have been shown to have undesirable side effects. They could impair blood coagulation and renal function, which are already compromised after cardiac surgery.
Albumin is a colloid solution which does not have any clinically significant effect on blood coagulation apart from haemodilution. The volume effect of albumin solution is 80–100% (in the case of 4% or 5% solution), but for hyperoncotic solutions it rises to up to 300%. Therefore, using these solutions, it is possible to increase intravascular volume with small amounts (100–200ml) of fluid. In critically ill patients, significantly less volume of 20% albumin was effective for haemodynamics compared with 4%–5% solution;9 additionally, patients who received 20% albumin had less Na and Cl overload. The volume effect of albumin lasts for up to four hours, which is also desirable during and after cardiac surgery.
There are no large randomised controlled trials in cardiac surgery patients comparing albumin with any other fluid. The results from the ALBICS study in which 1250 patients will be randomised, are anticipated in 2020.11 Engelman et al reported that pre-operative hypoalbuminaemia (<25g/l) is an independent risk factor for multiple poor outcomes after cardiac surgery.12 However, Fritz et al demonstrated that hypoalbuminemia predicts mortality after cardiac surgery even better than EUROscore.13 In this study, cut-off for hypoalbuminaemia was 18g/l. Several studies have investigated the use of albumin for CPB priming.
In a retrospective cohort of 19,578 patients undergoing CABG procedure, Sedrakyan et al demonstrated that albumin use was associated with reduced mortality (OR=0.8, CI 0.67–0.96) compared with older generation colloids with non-biological origin.14 Compared with crystalloids, less volume of priming is required in groups receiving albumin. Additionally, the use of albumin solution as prime fluid decreased the amount of postoperative bleeding. Onorati et al retrospectively compared low dose albumin to pure crystalloid priming in 377 patients.15 Patients receiving albumin needed smaller amounts of blood transfusions and had lower blood loss postoperatively. Additionally, the rate of resternotomies was significantly less in the albumin group.
In the postoperative setting, albumin has been compared with different solutions in numerous small prospective studies. In 2006, Niemi et al demonstrated that the use of both starch and gelatin solutions correlates with the amount of postoperative bleeding after cardiac surgery, but the use of 4% albumin solution does not.16 Schramko et al compared the postoperative infusion in the dose of 15ml/kg of two starch solutions (HES200/0.5 and HES130/0.4) to 4% albumin: albumin did not cause any changes in maximum clot firmness, but both starch solutions decreased this parameter of thromboelastometry slightly, but significantly.17 After administration of all colloids, cardiac index increased significantly compared to preoperative level; however, HES solutions increased cardiac index more than albumin. Skhirtladze demonstrated that perioperative fluid balance in cardiac surgical patients was similar in albumin and HES groups, but significantly lower compared with Ringer’s solution.18
Navickis et al have published meta-analysis compared use of HES solutions to albumin: haemodynamics was similar in both groups, but the use of albumin decreased blood loss, the amount of blood product transfusions required and the need for reoperation postoperatively.19 However, this meta-analysis has insufficient data about the use of tetrastarch HES130/0.4. Some investigators reported a very interesting fact: when the use of albumin solution was compared with other colloids with non-biological origin or with crystalloids, the platelet count in the albumin group was significantly higher postoperatively then in the other fluid groups.15 This ‘platelet preservation’ effect of albumin has been discussed in several forums; however, the mechanisms of this effect are still unclear. Some studies reported slight hypocoagulation after albumin use, but these changes are caused more by a haemodilution effect. Based on these findings, the use of albumin solution after cardiac surgery is also in those patients who already have increased blood loss. The meta-analysis of controlled studies published in 2004 included 1346 patients and compared the use of albumin with crystalloid solution for CPB priming. Albumin priming preserved platelet counts better than crystalloid, and favourably influenced colloid oncotic pressure and positive fluid balance after cardiac surgery.20
Because of its biological origin, albumin has multiple functions. It is possible that albumin coats the insides of the tubes and the reservoir of the CPB circuit and therefore reduces contact activation of leucocytes and platelets, which occurs during CPB. Albumin also has a protective effect on the endothelial glycocalix, which is damaged during CPB.8,21
At this time, debates about volume replacement therapy still continue. Some countries stopped the use of synthetic colloids because of the results of several studies in critically ill patients, which demonstrated that HES solutions probably impair renal function and even outcome.22 Despite the fact that the conclusions of these studies are questionable and their results are impossible to extrapolate to the surgical patients, nowadays more and more hospitals have abandoned the use of synthetic colloids. Another point for this is that the use of HES solutions did not improve outcome compared to crystalloids.
The use of only crystalloids, even for volume replacement, leads to the increased amount of fluids given. Because the degree of systemic inflammatory response reaction and damage of endothelial glycocalix after cardiac surgery is high, and patients often have a lot of co-morbidities, the use of pure crystalloid volume replacement is possibly not justified. Use of albumin solution should be considered for volume replacement during or after cardiac surgery, at least in those patients at risk of bleeding or renal dysfunction.
Albumin solution provides a good haemodynamic effect, which lasts several hours without any clinically significant side-effects. In those special cases when patients are already fluid overloaded (for example, emergency surgery or cardiac transplantation patients), the use of small amounts of hyperoncotic albumin solution should be considered.
In the field of cardiac surgery, only data from small prospective randomised studies compared albumin with crystalloids or other colloids. We await results of large RCTs of high quality.
- Chappell D et al. A rational approach to perioperative fluid management. Anesthesiology 2008;109(4):723–40.
- Rehm M et al. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation 2007;116(17):1896–906.
- Boisclair MD et al. Mechanisms of thrombin generation during surgery and cardiopulmonary bypass. Blood 1993;82(11):3350–7.
- Edmunds LHJr, Colman RW. Thrombin during cardiopulmonary bypass. Ann Thorac Surg 2006;82(6):2315–22.
- Linden MD. The hemostatic defect of cardiopulmonary bypass. J Thromb Thrombolysis 2003;16(3):129–47.
- Despotis GJ, Avidan MS, Hogue CW. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thorac Surg 2001; 72(5):S1821–31.
- Lewis SR et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev 2018;3:000567.
- Jacob M et al. Albumin augmentation improves condition of guinea pig hearts after 4 hr of cold ischemia. Transplantation 2009;87(7):956–65.
- Brandstrup B et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 2003;238(5): 641–8.
- Mårtensson J et al. Small volume resuscitation with 20% albumin in intensive care: physiological effects: The SWIPE randomissed clinical trial. Intensice Care Med 2018;44:1797–1806.
- Clinicaltrials.gov. Albumin in cardiac surgery (ALBICS). https://clinicaltrials.gov/ct2/show/NCT02560519 (accessed June 2019).
- Engelman DT et al. Impact of body mass index and albumin on morbidity and mortality after cardiac surgery. J Thorac Cardiovasc Surg 1999;118:866–73.
- Fritz HG et al. Post-operative hypoalbuminaemia and procalcitonin elevation for prediction of outcome in cardiopulmonary bypass surgery. Acta Anaesthesiol Scand 2003;47(10):1276–83.
- Sedrakyan A et al. Volume expansion with albumin decreases mortality after coronary artery bypass graft surgery. Chest 2003;123:1853–7.
- Onorati F et al. Does priming implementation with low-dose albumin reduce postoperative bleeding following cardiopulmonary bypass? Int J Artif Organs 2003;26(3):211–6.
- Niemi TT et al. Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery. Anesth Analg 2006;102(4):998–1006.
- Schramko AA et al. Rapidly degradable hydroxyethyl starch solutions impair blood coagulation after cardiac surgery: a prospective randomized trial. Anesth Analg 2009;108(1):30–6.
- Skhirtladze K et al. Comparison of the effects of albumin 5%, Hydroxyethyl starch 130/0.4 6%, and Ringer’s lactate on blood loss and coagulation after cardiac surgery. Br J Anaesth 2014;112:255-64.
- Navickis RJ, Haynes GR, Wilkes MM. Effect of hydroxyethyl starch on bleeding after cardiopulmonary bypass: a meta-analysis of randomized trials. J Thorac Cardiovasc Surg 2012;144(1):223–30.
- Russell JA, Navickis RJ, Wilkes MM. Albumin versus crystalloid for pump priming in cardiac surgery: meta-analysis of controlled trials. J Cardiothorac Vasc Anesth 2004;18(4):429–37.
- Torres LN et al. Low-volume resuscitation with normal saline is associated with microvascular endothelial dysfunction after hemorrhage in rats, compared to colloids and balanced crystalloids. Crit Care 2017;21:160.
- Myburgh JA et al. The CHEST Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012;367(20):1901–11.