[The use of plasma substitutes and albumin in blood component therapy].
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Biomedical subjects
Publications and source records attributed to P Lundsgaard-Hansen.
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It was previously shown, in theory and in practice, that a blood component program utilizing 80--85% of all donations as red cell concentrates with a hematocrit of 70% contributes substantially to the coverage of national albumin demands without increasing the need for that protein. The current trend towards the production of red cell concentrates with hematocrits around 85% by the removal of more plasma prompted a computer simulation study of the effects of this modification on the protein and monetary economy of a component program. The results suggest that a hematocrit around 70% constitutes an optimum in these respects. In a general way, they point to the desirability of examining the repercussions of isolated modifications of the processing of blood donations on the system as a whole prior to their large-scale application.
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This review deals with the rationale for the use of hemodilution in patients not subjected to open heart surgery. The claim for an optimum of circulatory oxygen transport at 30% hematocrit has been disproved; hemodilution thus simply means acute normovolemic anemia. Accordingly, it generates a cardiovascular strain and particularly jeopardizes cerebral and myocardial oxygen supply. Potentially serious clinical side effects have been reported. Hemodilution should therefore not be carried beyong the lower normal range for the hemoglobin or hematocrit level, i.e. 12--12.5 g% or 35--36%.
On the basis of recent pathophysiological data and clinical observations in three patients, this paper draws attention to the commonly neglected importance of postoperative hypoproteinemia as the cause of an edema of the intestinal wall with a consequent "interstitial" paralytic ileus. The characteristic features of this syndrome are its onset between the third and the eighth postoperative day; the absence of other known causes of intestinal hypomotility; the benign, but protracted course without treatment; and the therapeutic success achieved by the correction of a hypoproteinemic fluid overload with concentrated albumin and a diuretic. In addition, parenteral hyperalimentation and Rheomacrodex-Sorbit may be indicated, but the hypoproteinemia should at any rate be corrected.
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The use of a gelatin plasma substitute as an integral part of a unified national program for the procurement of blood components and derivatives paves the way for the extensive use of red cell concentrates in the treatment of hemorrhage, the plasma from the original donations being partly diverted to the fractionation program of a national transfusion service. We estimated the potential of such a system paced by the demand for red cells and predicted that the use of 20% of fresh whole blood and 80% concentrates would not increase the demand for albumin, the yield of which would suffice to cover three-quarters of current needs in our country. The actual performance of a program using 85% of red cell concentrates in a university hospital with an exceptionally high incidence of major hemorrhage was analyzed in detail. The use of albumin per unit of transfused red cells rose by 9%. With a nationwide increase of this magnitude, 67% of the demand in our country could still be met and the estimated true need for albumin of 200 kg per million inhabitants and year would be fully covered. The yield of factor VIII is 200--300% of the demand. The determinants of the effects of such a system vary from country to country, but its fundamental potential is obviously considerable.
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The published specifications of the acceptable limits of the maximum plasma volume to be "harvested" by plasmapheresis from one individual per year vary from 10-15 liters in Europe to 50-60 liters in the United States. To answer the question which of these widely diverging precepts is appropriate, the effects of plasmapheresis on serum protein levels and their relationship to albumin metabolism, the accepted safeguards for the donation of whole blood, and the disease known as the nephrotic syndrome are considered. A living person who cosents to his bodily integrity being violated for the benefit of others must be protected not only against the generation of manifest illness by such violation, but also against any prolonged deviation from the normal state of his body. It is concluded that plasmapheresis donors should not deliver more than 10 to 15 liters of plasma per year, as now recommended by European authorities. Not more than 500 ml of plasma should be withdrawn per session, and the interval between two such sessions should not be less than 2 weeks.
Recent studies suggest that the analogy between intensive plasmapheresis and the nephrotic syndrome with respect to plasma protein loss includes events which are generally recognized as risk factors for the development of arteriosclerotic cardiovascular disease. Experimental nephrosis and plasmapheresis alike increase the synthesis of very low density and low density lipoproteins in response to the hypoproteinemic stimulation of plasma protein synthesis. During electrophoresis, these lipoproteins move with the alpha2- and beta-globulins, and the serum levels of these fractions are often elevated in humans subjected to intensive plasmapheresis. Hyperlipoproteinemias of the alpha2- and beta-types are recognized risk factors in the genesis of arteriosclerosis. Another such factor appears to be an increased synthesis of fibrinogen. This protein enhances plasma viscosity and red cell aggregation and may play a role in myocardial infarction. Intensive plasmapheresis thus not only creates an unphysiological and partly depletional state; it is also, like the nephrotic syndrome, capable of producing surplus abnormalities of plasma constituents with a potential for delayed, insidious injury.
We simulated the use of massive volumes of crystalloid fluids as a treatment of acute plasma loss in a standardized experimental model and studied the factors determining the retention or excretion of the resulting acute hypoproteinemic fluid overload, its distribution within the body, and its treatment with concentrated albumin and diuretics. In accordance with the classic Starling concept, the serum protein level, i.e. the serum colloid osmotic pressure, determined the excretion/retention ratio of a given water and sodium load. Of the total fluid retention, fat and muscle each accommodated 25%, whereas the skin, which contributes only 7% to the total body weight, accounted for 37% and increased its volume by roughly one third. Concentrated albumin promoted fluid excretion in direct proportion to the achieved increment of the serum protein level and abolished the edema of fat, muscle and skin. Furosemide was virtually ineffective. The implications of these results for the 'adult respiratory distress syndrome' and disturbed wound healing are discussed and related to the concept of a critical threshold of the serum protein level.
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