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Chapter 5

Battle Casualties in Korea: Studies of the Surgical Research Team, Volume II

Equilibration Time of Deuterium Oxide Following Subcutaneous or Intramuscular Injection*

(A Study of Korean Battle Casualties)

Captain John M. Howard, MC, USAR
in collaboration with

The Division of Atomic and Radiation Physics
National Bureau of Standards
Washington, D. C.

Since a previous report1 demonstrated the limitations of gastrointestinal absorption of water following injury, this study had as its objective to measure the time required for equilibration of deuterium oxide (heavy water) throughout the body following subcutaneous and intramuscular injection and to compare the equilibration time in the normal subject with that in the battle casualty. Such observations might prove of value in planning methods of administration of fluids to mass casualties.

Materials and Methods

The study was carried out in a Forward Surgical Hospital on the Eastern Front in Korea in 1952-1953.

Deuterium oxide (99.8 per cent pure) was given over a period of approximately 1 minute by injection. Venous blood samples were drawn at frequent intervals, the plasma separated and placed in sealed test tubes.

The plasma was then shipped via air to the National Bureau of Standards where analysis was performed as previously described.1

Results

Equilibration Time Following Subcutaneous Injection

Normal Subject. The equilibration curve of deuterium oxide following the subcutaneous injection of 50 grams into the lateral thigh of a normal subject is shown in Figure 1. The subject was lying quietly throughout this period. The curve flattens out after 120 


*Previously published in Surgery 36: 1119, 1954.


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FIGURE 1. The equilibration curve in the normal. Equilibration appears to be complete within 120 minutes.

minutes and equilibration throughout the water of the entire body has probably occurred. This evidently represented, in part, a transfer of water (D2O) from the thigh into the circulation and thence throughout the body. The belief that this represented an actual transfer of water rather than an exchange of water by diffusion is based on the disappearance of the mass and the resultant disappearance of the discomfort in the thigh. Furthermore, clinical experience has amply demonstrated that fluid, subcutaneously administered, will prevent thirst and maintain urinary output.

The equilibration curve depicted in Figure 1 is similar to the curve reported by Schloerb and his associates2 although the latter described a more prolonged equilibration time following the administration of deuterium oxide over a longer period of time.

Battle Casualties. The equilibration time following subcutaneous injection was studied in four battle casualties. Three were selected on the basis that they could not, at this early time, take fluids orally due to the nature of their injuries (bowel, brain and cervical spinal cord). The fourth patient had received an injury to the extremity and could have tolerated fluids orally.

Patient No. 1. This Korean soldier was injured by shell fragments at 1800 hours on 22 March 1952. The fragments penetrated the right side of the neck and the spinal cord in the cervical region. On admission to the hospital, by ambulance, 24 hours later, his blood


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FIGURE 2 (Patient No. 1). This patient had an incomplete severance of the cervical spinal cord. The venous concentration rose very rapidly, presumably as a result of redistribution of blood flow following spinal cord destruction.

pressure was unobtainable. His pulse was barely palpable. He had not lost a significant amount of blood. His blood pressure did not respond to the intravenous administration of neosynephrine. After a transfusion of 1,000 ml. of blood, he was given subcutaneously 100 gm. of deuterium oxide into the lateral tissues of the thigh. His equilibration curve is demonstrated in Figure 2.

He died 8 hours later. Autopsy revealed an incomplete severance of the cervical spinal cord.

Patient No. 2. This 20-year-old South Korean soldier was wounded by mortar shell fragments on 28 January 1952. He was slightly hypotensive when admitted to the forward hospital. His blood pressure was 100/70 but responded to a transfusion of 500 ml. of blood. He was then given a subcutaneous injection of 50 gm. of deuterium oxide into the lateral aspect of the thigh. His equilibration curve is demonstrated in Figure 3.

Subsequently, the patient was found to have a perforation of the transverse colon which was exteriorized. His postoperative course was smooth.

Patient No. 3. This 20-year-old American soldier was wounded at an unknown hour on 21 February 1952 by artillery shell fragments. The fragments perforated the skull in four or five places and produced an extrusion of the cerebral cortex. He was admitted to the forward hospital by Marine helicopter on the same day. His blood pressure was 140/90, pulse 64, respiration 24. He was unconscious and his pupils were dilated and fixed. He was considered inoperable. Three hours after admission he was given an injection of 100 gm. of deu-


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FIGURE 3 (Patient No. 2). The plasma concentration of deuterium after 24 hours was high, indicating that equilibration was incomplete at the end of 2 hours.

terium oxide into the lateral subcutaneous tissues of the thigh. During the subsequent period of observation, his pressure gradually fell to 60/50. He died shortly thereafter.

The equilibration curve of deuterium in the venous plasma is demonstrated in Figure 4.

Patient No. 4. This 22-year-old American soldier received a perforating wound of the knee at 1900 hours, 28 January 1952. His blood pressure 1 hour later, on admission to the forward hospital, was 80/40. Following a single 500 ml. transfusion, his pressure rose to 110 mm. systolic. He was then given a subcutaneous injection of 50 gm. of deuterium oxide into the lateral aspect of his unwounded thigh. The equilibration curve is depicted in Figure 5.

His wound was subsequently débrided. At the time of evacuation, he appeared in excellent condition.

Equilibration Time Following Intramuscular Injection

Normal Subjects. Two normal subjects were each given 100 gm. of deuterium oxide intramuscularly into the lateral thigh. This was given by injection within a period of 1 minute. During a subsequent period 1 to 2 months later, the study was repeated but to the deuterium


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FIGURE 4 (Patient No. 3). This casualty, with a fatal brain wound and resultant neurogenic hypotension, had a rapid equilibration time similar to Patient No. 1 with the spinal cord injury. A postmortem plasma sample taken at the time of death, 3 hours after the above study, demonstrated a deuterium concentration of 0.110 atom per cent.

oxide was added 150 turbidity units of hyaluronidase. The equilibration curves with the comparative studies are demonstrated in Figures 6 and 7.

Patient No. 5. This 22-year-old Turkish soldier was wounded at 1645 hours 15 May 1952 when he stepped on a land mine. His injuries included a traumatic amputation of the right leg at the calf and multiple penetrating wounds of the left thigh. On arrival at the hospital by helicopter 2 hours later, his blood pressure was 90/50. He was given 500 ml. of blood and his pressure rose to 130/90.

He was then given 100 gm. of deuterium oxide by intramuscular injection into the right thigh. The equilibration curve is demonstrated in Figure 8.

The right leg was subsequently amputated at the calf. His further course was smooth.

Patient No. 6. This 23-year-old American soldier was wounded at 1645 hours, 16 May 1952, by mortar shell fragments. He suffered a traumatic amputation of the right lower leg, along with penetrating wounds of the right thigh. He arrived via helicopter at the forward


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FIGURE 5 (Patient No. 4). Equilibration has not been reached after 3 hours in this soldier with a rather severe wound of the opposite leg.

FIGURE 6. Equilibration has been achieved within 180 minutes in both studies. There is suggestive evidence of an effect of hyaluronidase but this is indefinite. Note that in the graph a correction has been made for the residual deuterium from the first study.


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FIGURE 7. Subsequent specimens indicated equilibration after 4 hours. Hyaluronidase did not affect the equilibration time. As in Figure 6, a correction has been made for the residual deuterium concentration in the second study.

FIGURE 8 (Patient No. 5). Equilibration was very slow and may reflect, in part, a decrease in circulation in the thigh following injuries distal to the area of study.


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FIGURE 9 (Patient No. 6). The highest plasma deuterium concentration was reached within 4 hours. This patient had wounds similar to those of the previous patient except that in this patient there was no injury to the extremity in which the deuterium was injected.

hospital 2 hours later. His blood pressure was 130/80, pulse 120. He appeared hard hit and was immediately given 1,500 ml. of blood.

Ninety grams of deuterium oxide was injected intramuscularly into the left thigh (Fig. 9). His subsequent course was smooth.

Discussion

Equilibration following subcutaneous injection in a normal subject occurred within 2 hours.

Patient No. 1 and Patient No. 3 had severe injuries to the central nervous system. The venous deuterium concentration rose very rapidly following subcutaneous injection and equilibration was apparently reached rapidly. This was probably the result of injury to the central nervous system with a resultant increase in blood flow to the skin and subcutaneous tissues.

Patient No. 2 and Patient No. 4, with wounds of the colon and leg respectively, were slow to equilibrate.

Patients with cerebral injuries often cannot take fluids orally because they may be comatose and may aspirate water or vomitus. They do not usually require intensive fluid therapy; yet, under conditions of mass casualties, they may have to wait hours for operation and then for adequate postoperative care.


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When compromises in fluid therapy have to be made, this group probably offers the best opportunity for the subcutaneous administration of fluid. Such a method is less time consuming and requires less skill on the part of the attendant. Within the limits of this study, it appears most promising in this group of casualties.

Conversely, the previous study1 has shown that casualties such as Patient No. 4 with injuries of the extremity can tolerate and absorb water from the gastrointestinal tract.

Patients with abdominal injuries do not tolerate nor absorb well the fluids taken orally. Similarly, equilibration time following subcutaneous injection was prolonged in Patient No. 2 and this route of administration has many disadvantages in the management of casualties with gastrointestinal injuries.

Equilibration following intramuscular injection occurred in 3 to 4 hours. This did not appear appreciably influenced by the addition of hyaluronidase. Perhaps, however, the force of the injection acted as a spreading factor, accounting for the fact that hyaluronidase had no further benefit.

In six other studies, a bottle of saline (1,000 ml.) was placed at a height of 3 feet above the patient. The time required for intramuscular infusion (three subjects) and subcutaneous infusion (three subjects) into the thigh averaged 3 hours and was quite painful. The study was then repeated in the opposite thigh but hyaluronidase (150 turbidity units) was added to each bottle. The average time of infusion was 45 minutes and the discomfort was minimal. Under similar circumstances, hyaluronidase would doubtless speed up the equilibration of deuterium.

Patients No. 5 and 6 who had wounds of the extremities demonstrated a slight to marked slowing of equilibration.

The studies on Patient No. 5 suggested the possibility of a reduced blood flow in the muscles of the thigh proximal to a severe injury of the leg. This remains in doubt; knowledge is needed concerning the changes in the circulation in and around major wounds.

Summary

1. In this preliminary study, the equilibration time following the subcutaneous injection into the thigh of 50 gm. of deuterium oxide was 120 minutes.

2. Following injury to the central nervous system, equilibration time following subcutaneous injection into the thigh was shortened. Two other patients with injuries of the abdomen and leg respectively demonstrated a prolonged equilibration time.


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3. The equilibration time following the intramuscular injection into the thigh of 100 gm. of deuterium oxide was 3 to 4 hours. This time was not appreciably changed by the addition of hyaluronidase.

4. Following injury, two patients demonstrated a moderate delay in equilibration following intramuscular injection of deuterium oxide.

5. In the treatment of mass casualties, subcutaneous fluid administration would probably prove useful as an adjunct to therapy of the neurosurgical patients. Hyaluronidase speeds the infusion and lessens the discomfort. Although it did not appear to hasten equilibration under the conditions of this study, it may well prove effective when added to a gravity infusion.

References

1. Howard, J. M.: Studies on the Absorption and Equilibration of Deuterium Oxide from the Gastrointestinal Tract. A study of battle casualties in Korea. 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.