Battle Casualties in Korea: Studies of the Surgical Research Team, Volume II
Equilibration Time of Water (Deuterium Oxide)Following Intravenous Injection in the Battle Casualty*
Captain John M. Howard, MC, USAR
and
First Lieutenant Russell Scott, Jr., MC, USAR
in collaboration with
The Division of Atomic and Radiation Physics
National Bureau of Standards
Washington, D. C.
This study of the equilibration time of water (deuterium oxide) following intravenous injection was part of a broad survey of the systemic response to injury carried out by the Surgical Research Team on the Eastern Front in Korea during 1952-53. The reaction to severe injury appears to involve a response of every organ, every system, and presumably every cell in the body. This response to injury is not a response of a few hours but is of days or weeks in duration.
Following its intravenous injection in the normal subject, deuterium oxide diffuses very rapidly throughout the total body water. Equilibration was found by Schloerb andassociates2 to be complete within 2 hours.
This rate of diffusion may well be a measure of the efficiency of the "total circulation" of the body. It measures the over-all efficiency of the mixing within the blood stream, delivery to various parts of the body, diffusion into extracellular and intracellular fluid, secretion into the gastrointestinal tract and finally equilibration. By measurement of the efficiency of the over-all circulation in this broader sense the status of the circulation may be assayed as to its efficiency in taking substances from one fluid compartment or from one cell to another across several membranes and across several fluid compartments. For example, the circulation must move oxygen from the pulmonary alveoli to the muscles of the leg and metabolites from the cells of the leg to the cells of the liver, kidneys or lungs across several fluid compartments. This activity cannot be evaluated by measure-
*Previously published in Surgery, Gynecology and Obstetrics, 99: 703, 1954.
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ments of blood pressure, blood volume, cardiac output, or peripheral resistance, but the equilibration rate of intravenously injected deuterium oxide offers a means of testing it.
Material and Methods
The study was done in a Forward Surgical Hospital in Korea. Deuterium oxide (99.8 percent pure) was prepared as an isotonic solution of sodium chloride. The injection was made by syringe and required approximately 1 minute.
Venous samples were then taken at intervals from the opposite arm. The plasma was separated, placed in a sealed glass test tube and shipped via air to the Bureau of Standards for analysis of deuterium content by a method which has been previouslydescribed.1
Five battle casualties and two normal subjects were studied.
Observations
Normal Subjects. Two normal male subjects were studied, one 32 years of age (Fig. 1), the other 20 years of age (Fig. 2). Each was given 50 grams of deuterium oxide in the antecubital vein.
FIGURE 1. Equilibration was very rapid and was complete within 60 minutes.
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FIGURE 2. Equilibration probably occurred within 45 minutes.
Patient No. 1. This 22-year-old soldier was injured 6 hours prior to admission to the forward hospital. His injury, inflicted by small arms fire consisted of a penetrating wound of the arm. Arterial bleeding was controlled by ligation of a small vessel. The radial pulse was palpable. His blood pressure was 60/20, pulse 120 per minute. After a transfusion of 500 ml. of blood, his blood pressure was 80/50. He was then given a rapid injection of deuterium oxide (50 grams) intravenously. Sixty minutes later transfusion was again started as a slow drip. His subsequent course was smooth. His plasma volume (T-1824 method) indicated a deficiency of 23 per cent of the normal volume calculated as 45 ml. per kilogram of body weight. All studies of deuterium concentration were made from venous plasma from the arm opposite the one used for the infusion of deuterium oxide and blood.
The results of the study are shown in Figure 3.
Patient No. 2. This 31-year-old American soldier was admitted to the forward hospital 5 hours after injury. The wound was produced by artillery shell fragments penetrating the chest, diaphragm and liver. Laparotomy under pentothal, nitrous oxide and ether anes-
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thesia permitted drainage of the small hepatic wound. His subsequent course was very smooth.
On the first day after injury, his plasma volume measurement demonstrated a deficit of 12 per cent but he appeared in excellent condition. His vital signs were normal. At this time he was given 50 grams of deuterium oxide intravenously (Fig. 4). His course remained uneventful.
Patient No. 3. This 20-year-old Korean soldier was injured by mortar shell fragments. The wounds included a perforation of the transverse colon and a penetration of the face. He was slightly hypotensive (blood pressure 100/70) on admission to the hospital. After a transfusion of 1,000 ml. of blood, colostomy was performed under pentothal, nitrous oxide and ether anesthesia. His subsequent course was smooth.
On the second day after injury, his plasma volume deficit was 10 per cent. He was, at this time, given 50 grams of deuterium oxide intravenously (Fig. 5). His blood pressure was 110/75, pulse rate 80, pulse volume full.
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Patients No. 4 and 5. These patients, who were identical twins, were injured on 2 March 1952, by fragments of the same exploding shell. They were admitted to the Forward Surgical Hospital 6 hours after injury.
Patient No. 4 was admitted in a state of incipient shock. His injuries included soft tissue wounds of three extremities. The left femoral artery and vein had been severed and were ligated. The foot became cold and pale and was without a detectable pulse. The capillary circulation was decreased as indicated by a delayed return of color following release of pressure on the skin. Edema was marked. Only after a lapse of several days was the survival of the leg assured.
His postoperative plasma volume determination indicated a deficiency of 24 per cent.
Patient No. 5 had three small wounds of the face and extremities. D?bridement was a minor surgical procedure. He was ambulatory immediately after operation. His plasma volume determination indicated a normal volume.
Each patient was given 100 grams of deuterium oxide on the fifth day after injury (Figs. 6, 7).
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Discussion
Following the intravenous injection of 50 grams of deuterium oxide into two normal subjects, a similar equilibration pattern evolved. The venous concentration of deuterium rose sharply but fell immediately so that 15 minutes after the injection the plasma concentration had fallen to a level approximating the concentration of equilibration (Figs. 1 and 2). In both subjects, this initial period of elevation was 15 minutes or less in duration. After minor changes in concentration, equilibration was complete within 60 minutes.
Patient No. 1, who was in a state of moderate hypotension due to blood volume deficiency, demonstrated a sharp rise in deuterium concentration which slowly subsided over a period of 80 minutes. Equilibration was apparently reached after 150 minutes (Fig.3). This prolonged period of equilibration may well have been the result of blood volume deficiency and vasoconstriction. A reduction in the active capillary bed would decrease the rate of diffusion from the blood
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to the extravascular fluid compartments. Arteriovenous shunts could also result in such a prolonged equilibration time.
Patient No. 3 required 120 minutes to equilibrate on the second day after perforation of the colon. This deficiency may represent, in part, the effect of the initial injury and, in part, the effect of the continuing nature of the injury in the form of peritonitis.
Patients No. 4. and 5, being identical twins, differed only in the magnitude and nature of their wounds. Patient No. 4 was severely injured and had one extremity with a very limited circulation. His equilibration curve was very similar to that of Patient No. 1 who was hypotensive from blood loss. In contradistinction, Patient No. 5 had an elevated deuterium concentration for only 15 minutes although he did not equilibrate within the first hour. Thus anesthesia and minor injuries affected his circulatory efficiency to a minor degree for a period of at least 5 days.
Summary
1. The equilibration time and pattern of intravenously injected deuterium oxide offers a test of function of the circulation following injury.
2. Equilibration in two normal subjects was almost complete within 15 minutes and was apparently complete within 60 minutes.
3. The hypotensive state following hemorrhage was associated in one patient with a prolonged equilibration time.
4. Severe injury followed by anesthesia was associated with a prolonged deficiency in the circulation as indicated by a prolonged equilibration time of deuterium oxide.
Conclusions
Following severe injuries, the deficiency in the "total body circulation" is quite marked. This deficiency may persist for several days in spite of an apparently smooth convalescence. This defect is presumably due to oligemia and vasoconstriction but this has not been proved.
The response of the circulatory system to severe trauma, like the response of every other system in the body, appears to be of considerable magnitude and to extend over a long period of time.
References
1. Howard, J. M.: Studies of the Absorption and Equilibration of Water(Deuterium Oxide) From the Gastrointestial Tract Following Injury. Surg., Gynec. Obst. 100:69, 1955 (Chapter 2, this volume.)
2. Schloerb, P. R., Friis-Hansen, B. J., Edelman, I. S., Solomon, A. K., and Moore, F. D.: The Measurement of Total Body Water in the Human Subject by Deuterium Oxide Dilution. J. Clin. Invest. 29: 1296, 1950.
