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Summary Solutions of crystalloids cannot be considered as substitutes for mammalian blood since they quickly leave the blood stream and are unable to maintain blood volume and pressure. This is true even of hypertonic solutions. The only effective blood substitutes are those which contain sufficient colloidal material to give a colloidal osmotic pressure approximating that of normal blood. Blood plasma, blood serum, Ringer‐Locke solutions containing dissolved hemoglobin, and gum‐saline are the only substitutes of practical importance. Gelatine‐saline has also been used, but it is not now recommended. Blood plasma is an effective substitute for much of the blood if the red cells in the mixture in the body are not too much reduced. Investigators are not agreed as to which organic constituent of blood plasma is most important. One group of workers supports the thesis that the plasma proteins are of major importance, another that it is the plasma lipoids which are most significant. Nearly all are agreed in the recognition of some organic colloidal factor. Blood plasma is to be preferred to serum because of the formation, in the latter, of vaso‐dilator or constrictor substances, produced in the act of clotting. The vaso‐motor effects are partly chemical, partly mechanical in origin. Carefully prepared serum may, however, be used. The oxygen capacity of the blood substitute is of vital importance. There is no substitute for hemoglobin. It must be present within the blood in a concentration of 3 per cent, or more, either within red cells, or dissolved in solution. The final mixture within the body cannot drop below this value. When carefully prepared, properly balanced as to ion content, and well buffered, gum‐saline solutions furnish an effective blood substitute, particularly when washed red cells of the same species are suspended in the solutions. With solutions of the latter type it is possible to remove all of the normal blood and reduce the concentration of the normal plasma colloids to the vanishing point. In such total plasmapheresis there should be at least 30 per cent, of red cells added to the gum‐saline. Difficulties arise in the use of gum‐saline for the following reasons: The sedimentation rate of the red cells is greatly increased. Gum appears to coat the red cells and considerably reduces their ability to combine with oxygen. Gum leaves the blood stream with fair ease and cannot maintain the colloidal osmotic pressure of the blood for much more than 48 hours. Gum is fixed in some of the tissues, particularly in the liver, and may be held in the body for as long as three years. In association with its retention in the liver it is said considerably to diminish the concentration of the plasma proteins, possibly by blocking the liver. It is chemically related to the antigenic polysaccharides produced by pneumococcus and other bacteria. Occasional instances of an antigenic action are on record, but these cases appear to be very rare. In spite of these difficulties gum‐saline has had an increasing us...

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