The purpose of this paper is to examine the validity of the single injection thiosulfate method, proposed by Cardozo and Edelman (1) for the measurement of the extracellular fluid volume. The conclusion is that the method does not give a valid estimate of the extracellular fluid volume and probably does not even measure the volume of distribution potentially available to thiosulfate.Cardozo and Edelman gave an accurately known amount of sodium thiosulfate (about 10 gm. of Na2S2O3 5 H20 in 10 per cent solution) by intravenous injection over a period that varied from 7 to 16 minutes. They then collected venous blood samples at intervals and plotted the logarithms of the serum thiosulfate concentrations against time. The points usually fell on a straight line; this was extrapolated back to zero time, which arbitrarily was set as the moment the infusion had been started. If the points did not fall on a straight line, the test was discarded because of the variable clearance rate of the thiosulfate. The extrapolated value for serum concentration of thiosulfate (P.) is presumed to be what the concentration would be if the thiosulfate were instantaneously injected and evenly distributed in its final volume of dilution. This extrapolated P0 is then divided into the total amount of thiosulfate injected to calculate the volume of distribution.Aside from the fact that virtually none of the thiosulfate has been injected at this zero time, the method is based upon rather questionable assumptions, which will be discussed later.In some of the evaluations of the single injection method that follow, comparisons were made between the volumes of distribution of thiosulfate and sucrose as calculated by different methods. The other procedures used were the infusion/ slope method devised by Schwartz (2) and the calibrated infusion (IV minus UV) method of Deane, Schreiner, and Robertson (3).
MATERIAL AND METHODSAll experiments were done with hospitalized women. While they were not "normal," they were selected.Patients with any discernible cause for disturbance in hydration, such as fever, renal disease or heart disease, were excluded. All In the calibrated infusion method this solution was given intravenously at the rate of 1.05 to 1.10 ml. per minute. Half-hourly collections of venous blood and of urine were begun 2 hours after the start of the infusion. After the collection of 3 or 4 blood and urine samples the thiosulfate was given for the single injection procedure.In measuring the volume of sucrose distribution by the 327