AlbuRx® 25, Albumin (Human) 25% solution is a sterile aqueous solution for intravenous administration containing the albumin component of human blood. This product is prepared from the plasma of US donors. The product has been produced by alcohol fractionation and has been heated for 10 hours at 60°C for inactivation of infectious agents. The results of virus validation studies have shown that the manufacturing process, particularly alcohol fractionation, eliminates enveloped and non-enveloped viruses. Additionally, heat treatment at 60°C for a period of 10 hours efficiently inactivates viruses. The solution contains 130-160 milliequivalents of sodium per liter (mEq/L) and the potassium content is not over 2 mEq/L. The aluminum content does not exceed 200 µg/L. The solution is stabilized with 0.08 millimole of sodium acetyltryptophanate plus 0.08 millimole of sodium caprylate per gram of albumin. The solution contains no preservative.
3.1 General Principles17
3.1.1 Volume Deficit
Since the oncotic pressure of AlbuRx® 25, Albumin (Human) 25% solution is about four times higher than that of normal human serum, it will expand the plasma volume if interstitial water is available for an inflow through the capillary walls. However, many patients suffering from an acute volume deficit also have some degree of interstitial dehydration. In the absence of hyperhydration, the treatment of an acute volume deficit with AlbuRx® 25 should therefore include isotonic electrolyte solutions with an albumin:electrolyte ratio of 1:3 or 1:4. By contrast, chronic volume deficits have usually been at least partially compensated for by the renal retention of sodium and water with some degree of tissue edema, and in these circumstances a trial with AlbuRx® 25 only is indicated. In any case, an anemia of clinically relevant magnitude requires specific treatment, and the metabolic needs of the patient with respect to fluid and electrolytes must be cared for.
3.1.2 Oncotic Deficit
The common causes of hypoproteinemia are protein-calorie malnutrition, defective absorption in gastro-intestinal disorders, faulty albumin synthesis in chronic hepatic failure, increased protein catabolism postoperatively or with sepsis, and abnormal renal losses of albumin with chronic kidney disease. In all these settings, the circulating albumin mass is initially maintained by a gradual transfer of extravascular albumin to the circulation, and hypoproteinemia ensues only when this compensatory potential has been exhausted. This implies that manifest hypoproteinemia is usually accompanied by a hidden extravascular albumin deficit of equal magnitude as the measurable intravascular deficit, which must be allowed for if AlbuRx® 25, Albumin (Human) 25% solution is infused because of the capillary permeability of that protein.
The primary sequel of the oncotic deficit resulting from hypoproteinemia is a loss of plasma and a gain of interstitial volume with increased lymphatic flow. As a secondary response, the kidney retains sodium and water which distribute themselves on both sides of the capillary walls and the plasma volume may be returned almost to normal when the interstitial hydrostatic pressure increases sufficiently to compensate for the decrease of the serum oncotic pressure. This chain of events is accelerated by the infusion of crystalloid fluids. The plasma volume is maintained at the price of interstitial edema.2
There is some evidence that a serum oncotic pressure near 20 mmHg – equaling a total serum protein (TSP) concentration of 5.2 g/100 mL – represents a threshold, below which the risk of complications increases.17 The target organs of hypoproteinemia include the skin, the lungs, and the intestine.10 Cutaneous edema lowers the oxygen tension of wounds and may thus impair the healing process.5 An oncotic deficit favors the development of interstitial pulmonary edema4 and the intestinal accumulation of fluids, which may progress to a paralytic ileus.9
Relief of the basic pathology is the definitive mode of therapy for the restoration of the plasma protein content, but this process takes time to become effective, and the rapid correction of a critical oncotic deficit by the administration of AlbuRx® 25, Albumin (Human) 25% solution – possibly in conjunction with a diuretic – may therefore be indicated, particularly in high-risk patients who have undergone abdominal, cardio-vascular, thoracic, or urologic surgery or who have acute bacteremia. In notably catabolic patients, attempts to raise the TSP level above 6 g/100 mL usually prove futile, even with massive doses of Albumin (Human).17
It is emphasized that whereas AlbuRx® 25, Albumin (Human) 25% solution may be necessary to prevent or treat the aforementioned acute complications of hypoproteinemia, it is not indicated for treatment of the chronic condition itself.
3.2 Specific Indications17
3.2.1 Acute circumstances in which AlbuRx® 25, Albumin (Human) 25% solution use is usually appropriate
Though electrolyte solutions such as Ringer's lactate and colloid-containing plasma substitutes may be used as an emergency treatment of shock, AlbuRx® 25, Albumin (Human) 25% solution used according to the aforementioned principles has a much longer intravascular half-life and may therefore be preferable. In addition, anemia of clinically relevant magnitude requires specific therapy with red cells.
Immediate therapy during the first 24 hours is directed at the administration of large volumes of crystalloid solutions and lesser amounts of AlbuRx® 25, Albumin (Human) 25% solution to maintain an adequate plasma volume and protein (colloid) content. For continuation of therapy beyond 24 hours, larger amounts of AlbuRx® 25 and lesser amounts of crystalloid are generally used.17 An optimum regimen for the use of Albumin (Human), electrolytes, and fluid in the early treatment of burns has, however, not yet been established.
With restoration of normal capillary function, a close relationship exists once again between infused Albumin (Human) and resultant increase in plasma oncotic pressure. A goal should be sought of maintaining a plasma albumin concentration of about 2.5 ±0.5 g/100 mL or a plasma oncotic pressure of 20 mmHg (equivalent to a TSP concentration of 5.2 g/100 mL).17 In the presence of extensive granulating wounds, a daily loss of up to 30 g of albumin may continue into the late post-burn period.1 Protein-rich oral feedings, or adequate parenteral nutrition should be included in the overall regimen to the fullest possible extent, though such treatment does not permit the rapid correction of an oncotic deficit.
3.2.2 Acute circumstances in which AlbuRx® 25, Albumin (Human) 25% solution use may be appropriate
Adult Respiratory Distress Syndrome
Several factors are usually involved in the development of the state now commonly called the adult respiratory distress syndrome, one of these being a hypoproteinemic fluid overload. If present, this may be corrected by the use of AlbuRx® 25, Albumin (Human) 25% solution and a diuretic.14,17
An adequate blood volume during cardiopulmonary bypass can be maintained with crystalloids as the only pump priming fluid, but only at the price of interstitial edema. A commonly employed program is an AlbuRx® 25, Albumin (Human) 25% solution and crystalloid pump prime adjusted so as to achieve a hematocrit of 20% and a plasma albumin level of 2.5 g/100 mL in the patient, but the level to which either may be lowered safely has not yet been defined.17
Pre- and postoperative Hypoproteinemia
Patients undergoing major surgery may lose more than half of their circulating albumin mass6,9,15, and complications attributable to an oncotic deficit may occur in such cases, as well as in septic and intensive care patients. Oncotic therapy with AlbuRx® 25, Albumin (Human) 25% solution may therefore be indicated in such patients, according to the principles outlined in 3.1.2. Temporary redistribution of protein is usually not an indication for Albumin (Human).
Third Space Problems of Infectious Origin
The sequestration of protein-rich fluid during acute peritonitis, pancreatitis, mediastinitis or extensive cellulitis may be of sufficient magnitude to require the treatment of a volume or an oncotic deficit with AlbuRx® 25, Albumin (Human) 25% solution3, although this occurrence is relatively rare.
Acute Liver Failure
In acute liver failure, AlbuRx® 25, Albumin (Human) 25% solution may serve the triple purpose of stabilizing the circulation, correcting an oncotic deficit and binding excessive serum bilirubin. The therapeutic approach is guided by the individual circumstances.17
Patients with acute nephrosis may prove refractory to cyclophosphamide or steroid therapy and their edema may even be aggravated initially by steroids. In such cases, a response may be elicited by combining 100 mL of 20–25% Albumin (Human) solution with an appropriate diuretic. This combination should be repeated daily for about one week, after which the patient may react satisfactorily to drug therapy.17
The use of AlbuRx® 25, Albumin (Human) 25% solution for blood volume support may be indicated if circulatory instability follows the withdrawal of ascitic fluid.
Red Cell Resuspension Media
As a rule, the use of Albumin (Human) for resuspending red cells can be dispensed with. However, in exceptional circumstances such as certain types of exchange transfusions and the use of very large volumes of erythrocyte concentrates and frozen or washed red cells, the addition of AlbuRx® 25, Albumin (Human) 25% solution to the resuspension medium may be indicated in order to provide sufficient volume and/or avoid excessive hypoproteinemia during the subsequent transfusion. If necessary, 20–25 g or more of Albumin (Human) per liter of red cell suspension should be added as a concentrated solution to the isotonic, electrolyte suspension of erythrocytes immediately before transfusion, the individual dosage depending on the TSP level of the recipient.
Patients undergoing long-term hemodialysis may need AlbuRx® 25, Albumin (Human) 25% solution for the treatment of a volume or an oncotic deficit. As a rule, the initial dose should not exceed 100 mL of a 20–25% solution, and the patients should be carefully observed for signs of a circulatory overload, to which they are particularly sensitive.
Hemolytic Disease of the Newborn
AlbuRx® 25, Albumin (Human) 25% solution may be indicated in order to bind and thus detoxify free serum bilirubin in severely hemolytic infants pending an exchange transfusion.
3.2.3 Circumstances in which AlbuRx® 25, Albumin (Human) 25% solution use is not justified
For the reasons set forth in sections 2. and 3.1, there is no valid reason for the use of AlbuRx® 25, Albumin (Human) 25% solution as an intravenous nutrient or for treating the stabilized hypoproteinemia accompanying chronic cirrhosis, chronic nephrosis, protein-losing enteropathy, malabsorption and pancreatic insufficiency.
If, however, a patient in this category has to cope with a superimposed acute stress, e.g. anesthesia, surgery or major infections, the patient's hemodynamic state, oncotic deficit and fluid balance should be carefully assessed and the appropriate steps taken as indicated by the individual circumstances.