Albumin Use in Cardiac Surgery

Albumin has been used in clinical medicine for more than seven decades. At the time of circulation and deairing of asanguineous primes during CPB, many programs will first remove the prebypass filter before adding albumin to the circulating fluid due to concerns of prebypass filter blockage and over pressurization. However, it should be noted that during the manufacturing process of isolating albumin from human plasma, the extracted albumin is first filtered through a 0.5 micron filter before entering into the ultrafiltration and pasteurization process. Therefore, personal experience and the latter explanation of albumin preparation demonstrate that circulating albumin primes through prebypass filters is not hazardous or contraindicated.

In a healthy individual, the albumin protein accounts for about 67-75% of their normal colloid osmotic pressure and has a reference range of 3.4 to 5.4 g/dl. Albumin is synthesized in the liver at a rate of about 150-250 mg/Kg/day, and only about 40% of the body’s total stores are found in the intravascular compartment at one time. Commercial serum albumin is a blood derived plasma volume expander that has an intravascular expansion ratio of 1:1 for the infused volume when using 5% Albumin (iso-osmotic) and a ratio of 1:3.5 when infusing 20-25% Albumin (hyperosmotic). It has an initial plasma half-life of around 16 hours, with an aver- age molecular weight (Mw) of 66,500 daltons. Albumin is extracted from large donor pools of plasma and prepared by the Cohn cold alcohol fractionation process. In fact, >33 million liters of plasma are fractionated every year in about 78 privately owned and government regulated companies throughout the world. The Asian-Pacific market for plasma is extremely under-capacity with around 35 fractionating facilities (45% of total) producing only 20% of the global needs in an area that has 60% of the world’s population. The latter is reflected in the world price of human albumin. As previously stated, after filtration and ultrafiltration, albumin is heated to 600± 0.5C for a period of 10 hours to destroy all viruses; it is then filtered again to remove any remaining bacteria. The final product contains 96% albumin, 4% globulins and some other proteins. The entire sterilization process eliminates the need for cross matching during clinical use. However, most institutions require the use of cross checking or cross matching for administrative purposes only. Saltzman and co-workers discovered that platelets did not adhere to in vitro surfaces that were precoated with albumin. As a result of this and other observations at the time and in an attempt to preserve platelets during CPB, the practice of adding albumin to the perfusate developed over 40 years ago.

The addition of albumin to the priming solution provides excellent effects on COP, plasma volume expansion capabilities and is a factor in the reduction of post bypass lung water. But due to its increasing costs, occasional supply shortages and concerns about the rare possibility of prion transmission (which may or may not be removed during processing), albumin was gradually replaced by other commercially available volume expanders (hetastarches) in many parts of the world. One of the main advantages albumin has in extracorporeal circulation is its protein surface coating capabilities when used as a priming fluid in circuits with PVC and silicone surfaces. Due to the fact that PVC surfaces carry a negative charge, positively charged albumin proteins tend to bind to their surface if left to recirculate in the extra- corporeal circuit for approximately 30 minutes. The effect this protein layer creates is a delay in fibrinogen adsorption and platelet activation by passivating the extracorporeal circuit at the start of cardiopulmonary bypass. How long the latter applies to in vivo situations may still be a matter of debate but it is suggested that this passivating period may extend three times longer than non-treated surfaces.

As with all volume expanders, albumin has a hemodilutional effect on all blood components, but appears to have no adverse effects on postoperative coagulation profiles. There are no maximum dosages for the administration of albumin, except for the reported delete- rious effects on renal function when the clinician attempts the use of large amount of albumin to restore high COP values during CPB. The frequency of anaphylactoid reactions during the use of commercially available albumin ranges from 0.011 % up to 0.015 %.

The use of albumin preparations in CPB perfusates appears to be a safe and reliable source of increasing colloid osmotic pressure during bypass. The advantages of coating the bypass components with plasma proteins are unique to albumin and cannot be duplicated with the use of dextran, gelatin or hydroxyethyl starch. It is recommended to use albumin in all CPB primes when using uncoated oxygenators to passivate platelets and avoid the sudden and dramatic oxygenator failures called high pressure excursions (HPE).When albumin is not available for use with uncoated oxygenators, the best alternative to avoid HPE seems to be oxygenators that are coated with the biopassive material phosphorylcholine. However, in those situations where albumin is not available and the use of synthetic or heparin coated devices is also not an option, Myers et al found that withdrawal of 40 mls of the patients own ‘heparinized blood’ and circulated into the crystalloid prime prior to going on bypass, provided similar effects on platelet protection, total proteins and COP when compared to albumin primes. However, the occurrence of HPE was found to be 1.11%, or 1 in every 90 bypass cases.

How much albumin is required to prevent platelet aggregation? Many years ago Palanzo and coworkers investigated this question and determined that only very small amounts of albumin are actually required in the perfusate to protect platelets. In fact, they found that as little as 0.0375 grams of albumin per 100 mls of prime (3 mls of 25% human albumin in a 2000 ml prime) will achieve the platelet protection necessary. However, once a bottle of albumin is opened, it should be used within 4 hours or discarded to avoid contamination. This may help to explain why centers using 12.5 grams of albumin in their primes have had no reported occurrence of problems resembling HPE. There has never been any reported incidence linking human serum albumin and Creutzfeldt-Jakob disease, but due to the uncertainty of removing all prions during processing and the costs associated with albumin, many programs have elected to remove it from their perioperative care.