Much attention has been given in the past to the study of changes in the blood produced by hemorrhage. Considerably less study has been devoted to changes in body fluid resulting from ether anesthesia, though such findings as elevation of blood sugar, increase in hydrogen ion concentration of the blood, and reduction in plasma bicarbonate, have been well established. The present work presents measurements of changes in quantity, as well as concentration, of certain components of body fluid as found in 16 patients subjected to the traumatizing factors of major surgical operations and to ether anesthesia. The time chosen for obtaining data to compare with the preoperative normal values was just at the end of operation, while the patient was still anesthetized. None of the patients studied showed evidence of more than mild shock or anoxemia during the study period. METHODSOn the morning of operation, before administration of preanesthetic drugs, the fasting patient was weighed. Determinations were then made of plasma volume, body fluid "available for solution of thiocyanate" (1), hematocrit, plasma protein, serum protein and serum albumin. In addition, serum nonprotein nitrogen and serum sodium, potassium, chloride, and bicarbonate were measured. These determinations were repeated at the end of operation while the patient was still anesthetized and before parenteral fluid had been given. In most instances blood loss during operation was measured, using the method of Gatch and Little (2).Plasma volume was determined by the technic devel-

Much consideration has been given to the changes which result in man and in experimental animals from administering by vein various quantities of fluids of different composition (1, 2, 3). Thus, the dislocation of body fluid and the urinary changes which follow rapid infusion of massive quantities of fluid in animals have been described (4,5,6). Shifts of water and salts between muscle and blood after infusion of isotonic fluids of varying pH have been studied in dogs by means of muscle biopsy and analysis (7). The circulatory effects of administering fluid by vein in various clinical conditions have been investigated, having in mind the primary importance of circulatory dynamics in determining response to intravenous fluid therapy (1,8). Such studies have served to emphasize the fundamental conclusions of Gamble (9, 10, 11), Peters (12, 13), and others.In the work on which the present report is based it seemed desirable to determine the results of large amounts of isotonic glucose and NaCl solutions administered by constant intravenous drip over a period of several days. The physiological responses to sustained submaximal infusions were under inquiry rather than the reaction to a large or small intravenous injection of brief duration, for it seemed possible that compensatory mechanisms of a different nature might be brought into play as the infusions were continued. MATERIAL AND METHODSPatients undergoing mild or moderately severe operations under ether anesthesia were studied just before operation, just after operation, at the end of the infusion period, and several days afterwards when the effects of the infusion had subsided. Determinations were made on a fasting basis, and the patients took water as desired during the infusion period but were allowed only small amounts of fruit juices in addition. The patients 'Aided by grants from the William F. Milton Fund, Harvard University, and the Josiah Macy, Jr. Foundation.were well-nourished women without cardiovascular or renal disease. During the study they were under constant observation by trained attendants and, if a patient objected, the infusion was discontinued. Urine was collected quantitatively by an indwelling catheter. Arm or leg veins were used for the infusion, the extremity being splinted, and except for slight redness about the needle in two or three instances no local reaction was noted. The patients were entirely afebrile, or nearly so, during the study. Intake of fluid by oral and intravenous routes and output of urine were totaled at 12-hour intervals. Four patients received 5 per cent glucose solution and six 0.9 per cent NaCl solution.

Observations on the relationship of administered dosage per unit of body surface area and blood concentration achieved when different amounts of sulfadiazine and acetylsalicylic acid were given patients varying widely in size indicate that a direct proportionality exists for these two drugs regardless of patient size. On the basis of this finding body surface area was used as the common denominator in the calculation of dosages of a large variety of drugs for a period of more than one year on a service dealing with patients ranging from small prematures to young adults. The clinical results suggest that this method of dosage calculation offers the advantages of simplification and greater accuracy over calculations based on a unit of body mass or on the patient's age.

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