Battle Casualties in Korea: Studies of the Surgical Research Team, Volume II
Studies of the Absorption and Equilibration of Water(Deuterium Oxide) from the Gastrointestinal Tract Following Injury*
A Study of Battle Casualties in Korea
Captain John M. Howard, MC, USAR
in collaboration with
The Division of Atomic and Radiation Physics
National Bureau of Standards
Washington, D. C.
This study of the absorption of deuterium oxide from the gastrointestinal tract and its equilibration has as its primary purpose the investigation of the limitations of oral fluid administration to mass casualties. The administration of fluids to mass casualties poses problems which have not been previously explored.
The secondary purpose of this study was to gain factual observations upon which to base routine postoperative care in the field of fluid administration.
Finally, the authors hoped to gain additional information on the nature and scope of the systemic response to injury. Studies by the Surgical Research Team in Korea demonstrated that every organ and system which could be studied responds to severe trauma. In general, this response is not of a few moments` or hours` duration but is a response which lasts for days or weeks. This study was, therefore, designed to extend these observations to the response of the gastrointestinal tract to injury.
Schloerb and his co-workers9 described an equilibration curve in venous blood following the oral ingestion of deuterium oxide in a human subject. They found an equilibration time of approximately 3 hours. This study was designed to extend this observation in the normal and to study the equilibration time after injury.
Material and Methods
The study was carried out at a Forward Surgical Hospital on the Eastern Front in Korea during 1952 to 1953. During this time the
*Previously published in Surgery, Gynecology and Obstetrics 100: 69, 1955.
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average time between wounding and reaching the forward hospital was 3.5hours. Healthy young soldiers in noncombat areas volunteered as controls. The wounded subjects were young battle casualties in the 18 to 34 age range. Those casualties who were studied immediately after arrival at the hospital were selected on the basis that they had fasted for 5 to 12 hours prior to injury and gastric suction had confirmed the presence of an empty stomach. Each casualty was given 50 to 100 grams of deuterium oxide (heavy water)as isotonic saline. The deuterium oxide was 99.8 per cent pure.
Gastrointestinal Deuterium Oxide Absorption
Venous samples were obtained prior to ingestion of D2O and at frequent periods thereafter. Several were studied at 5, 10, 15, 20, 30, 45, 60, 90, 180 and 240minutes after ingestion. In addition, when feasible, subsequent samples were obtained after a prolonged period of time. Other casualties were, of necessity, studied less intensively but enough points on the equilibration curve were obtained to describe its pattern. The venous blood was centrifuged, the plasma withdrawn, placed in a paraffin-sealed test tube, and shipped via air to Washington, D. C., for analysis. Deuterium analyses were performed at the National Bureau of Standards. The deuterium content of the samples was determined by converting the "free water" to hydrogen over hot magnesium. Mass-spectrometric analyses of the isotopic hydrogens were made with a Consolidated 21-103 mass spectrometer using established technics including operational procedures suggested by Honig.4 The hydrogen samples were cooled to 190? C to prevent possible introduction of water vapor. At least three determinations were made of each duplicate sample. Analyses of samples containing less than 0.5 atom per cent D were generally repeated if the duplicates disagreed by more than 0.01 atom per cent. The reproducibility of a single determination was usually of the order of 0.003 atom per cent D.
Experiments with nearly pure D2O indicate the technics used in the conversion process result in memory effects of considerably less than 1 per cent. Analyses of test mixtures of hydrogens indicated the mass spectrometer uncertainty to be of the order of 1 per cent for samples containing about 0.3 atom per cent D. However, the necessary delay in receiving, converting and analyzing the samples undoubtedly contributes to the experimental error. Furthermore, although all samples were intended to be hermetically sealed, a number showed definite evidence of evaporation in transit. Those showing marked evaporation were not analyzed.
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Gastrointestinal Absorption in the Uninjured Soldier
Six healthy soldiers volunteered as controls. All six had been fasting for 14 hours and continued to fast throughout the period of study. Each was given 100 grams of deuterium oxide orally.
The results are depicted in Figures 1 to 6. Equilibration of the concentration of deuterium in the venous plasma was complete in 120 minutes. In several instances equilibration appeared to be complete within 90 minutes. Furthermore, without exception, the venous concentration at 30 minutes demonstrated evidence of absorption of an appreciable amount of deuterium.
Absorption of water obviously occurred in the normal and in many of the wounded men. This was demonstrated by control of thirst, maintenance of urinary output, and the solid consistency of the stools. That the curve of absorption is directly related to the curve of equilibration of deuterium oxide has not been absolutely proved. Evidence is presented which suggests that the two are directly related but the term absorption isused with this reservation throughout the paper.
FIGURE 1. Demonstrating the very rapid equilibration in the control subject.
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FIGURE 2. Demonstrating a similar equilibration curve in a second subject.
FIGURE 3. Demonstrating equilibration within 90 minutes.
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FIGURE 5. Equilibration time 120 minutes.
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Gastrointestinal Absorption Following Injuries of the Chest and Extremities
Three casualties were selected for study because their wounds did not include abdominal injuries. These three men had wounds which were representative of three types of injuries seen, namely, perforation of the chest, traumatic amputation of the foot, and a moderately severe flash burn. Emphasis was placed upon studying these men shortly after injury in order to determine their gastrointestinal function in this early period.
Patient No. 1. This 21-year-old Korean soldier suffered severe second and third degree flash burns of the scalp, face, neck, hands and wrists on 22January 1952. He was admitted to the Forward Surgical Hospital 1 hour after injury. His vital signs were normal except for a tachycardia. His hematocrit was 50 per cent. He had received no therapy at this time.
Three hours after injury and 8 hours after ingestion of food or water, he was given orally 100 grams of deuterium oxide. The venous equilibration curve is demonstrated in Figure 7.
Patient No. 2. This 20-year-old South American soldier was wounded on 17 January 1952 by machine-gun fire. The bullet penetrated his left lung, producing a large hematoma of the lung but no pneumothorax. He arrived at the Forward Surgical Hospital 3 hours after injury and appeared to be in a state of incipient shock. D?bridement of the superficial tissues was performed 6 hours after injury under ether-nitrous oxide anesthesia. His subsequent course was uneventful.
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After having fasted for 24 hours after injury, he was given 100 grams of deuterium oxide orally. The only medication except antibiotics which he had received subsequent to d?bridement was codeine, 65 mg., 7 hours prior to the study.
The equilibration curve of the deuterium is shown in Figure 8.
At the conclusion of the deuterium study, the casualty was given 100 grams of glucose orally. This glucose tolerance study (Table 1) demonstrated the rapid absorption of glucose.5 The rising limb of the glucose tolerance curve is very similar to the corresponding phase of the deuterium curve. This suggests that the deuterium was absorbed from the bowel by an active process rather than simply bydiffusion.2, 3
Table 1. Blood Glucose Concentration Following Oral Administration of 100 Grams of Glucose
(Patient No. 2)
|
Minutes After Ingestion |
Blood Glucose* mg./100 ml. |
Minutes After Ingestion |
Blood Glucose* mg./100 ml. |
|
0 |
95 |
90 |
165 |
|
30 |
177 |
120 |
123 |
|
45 |
217 |
180 |
105 |
|
60 |
237 |
240 |
71 |
*Analysis by the Folin-Wu Method.
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Patient No. 3. This 34-year-old Korean Service Corpsman was injured on 17 May 1952 when he stepped on a land mine. The injury included a traumatic amputation of the right foot above the ankle. In addition, there were penetrating wounds of the left leg and right hand. Hemorrhage from the amputation stump was controlled by a tourniquet.
Two hours after injury he was admitted via helicopter to the Forward Surgical Hospital. His blood pressure was 160/90, pulse 112, hematocrit 40 per cent. He appeared to be severely injured and in a state of incipient shock. Within the first hour after admission, he received 500 ml. of blood. At this time, 3 hours after injury and prior to operation, a Levin tube was inserted into the stomach and the stomach emptied of a small amount of clear gastric juice. Deuterium oxide, 100 grams, was then instilled through the tube.
Re-amputation and d?bridement were subsequently performed under pentothal-nitrous oxide anesthesia.
By the third postoperative day, his course was smooth. Peristalsis was active and he had one bowel movement since operation. At this time, after fasting for 12hours, the patient was again given deuterium oxide, 100 grams, orally. The results of the two studies are demonstrated in Figure 9.
These three soldiers were all severely injured men. They fell into a similar functional pattern. All three were treated with oral fluids only. Thirst was controlled and urinary output was maintained by oral therapy. Equilibration was slower than normal in all three casualties but was fairly rapid in the first two. The third soldier
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had an equilibration rate which was definitely slower than normal, but which increased during the 3 days following injury.
A fourth casualty with gasoline burns of the face, neck, scalp, hands and wrists was given glucose (100 grams) orally, immediately after injury and again the following day. On the day of injury, the blood glucose rose from 163 mg. per 100 ml.(fasting) to 314 mg. after 90 minutes. On the following day, the blood glucose rose from120 mg. per 100 ml. (fasting) to 240 mg. after 90 minutes. This observation was repeatedly noted in a study of the metabolic response of the battle casualties and demonstrated the residual absorptive function of the gastrointestinal tract after peripheral injuries.5
Gastrointestinal Absorption Following Intraperitoneal Injuries
Six casualties with intraperitoneal injuries and one with retroperitoneal injuries were studied. Two patients were studied immediately after injury and prior to surgery. The others were studied during the postoperative period.
Patient No. 4. This young Turkish soldier was wounded at noon on29 February 1952 by artillery shell fragments. The fragments penetrated the right side of the chest, the right lung and the right side of the liver. He arrived at the forward hospital 3.5 hours later by helicopter. His blood pressure at this time was 46/20 and he was in a state of severe shock. After 1,500 ml. of blood his pressure had risen to 70/40and his blood volume measurement (T-1825 dye method) demonstrated a residual deficit of 19per cent. At this time, prior to operation and prior to any medication, he was given 100grams of deuterium oxide orally (Fig. 10). He remained hypotensive throughout the ensuing30 minutes of the study.
Subsequently, he underwent a right exploratory thoracotomy under nitrous oxide and ether. The diaphragm was opened and the liver was drained subdiaphragmatically. The pleural cavity was drained to an underwater seal.
His subsequent course was smooth. The deuterium study was repeated on the fifth day after injury.
Patient No. 5. This 24-year-old American soldier was wounded at 1635 hours 10 May 1952 by mortar shell fragments. The wound included a massive wound of the ascending colon necessitating a right colostomy. On admission to the forward hospital, 3 hours after injury, he was in excellent condition. His blood pressure was 120/60, pulse 92 per minute. His plasma volume measurement (T-1824 dye method) demonstrated a deficit of 14 per cent.* His hematocrit was 54 per cent.
At this time, prior to operation, he was given 100 grams of deuterium oxide by mouth (Fig. 11).
After the conclusion of the study, his stomach was emptied and found to contain 32 ml. of fluid containing only 0.3 per cent of the ingested deuterium.
Patient No. 6. This 22-year-old American soldier had a perforation of the bowel 6 or 8 hours prior to laparotomy. Operation was performed under nitrous oxide-ether anesthesia. He was found to have an advanced peritonitis.
*Normal plasma volume calculated on basis of 45 ml. per kilogram of body weight.
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FIGURE 9 (Patient No. 3). This corpsman had severe wounds of the extremities and was in a state of incipient shock when studied prior to therapy. Equilibration proceeded fairly rapidly although slower than it did 3 days later. On the third day post-injury, equilibration, although faster, was still slower than normal. A state of equilibrium was not reached within 4 hours. Throughout the postoperative period oral intake of water permitted adequate hydration as indicated by lack of thirst and by urinary output.
Note. The concentration of deuterium for the second study has been corrected for the residual plasma deuterium concentration from the previous study.
On the first postoperative day, his condition was good. At this time, his blood volume deficiency was measured at 2 per cent. His hematocrit was 49 per cent. He was then given deuterium oxide, 100 grams, orally. The study was terminated after 120minutes when the patient vomited.
The study was repeated on the fourth postoperative day (Fig. 12). By this time, peristaltic activity seemed normal by auscultation.
Patient No. 7. This 21-year-old American soldier was shot through the stomach, jejunum and colon by a .45 caliber pistol at 1500 hours on 24 January1952. He arrived at the forward hospital 2 hours later. He was given 500 ml. of blood prior to operative repair which was done under pentothal, nitrous oxide and ether. At the beginning of operation, his systolic blood pressure dropped to 90 mm. Hg., so he was given a second 500 ml. of blood.
On the day following injury, his stomach being empty, he was given 100grams of deuterium oxide through the Levin tube (Fig. 13). At the conclusion of the study, one-third of the deuterium was recovered from the stomach. On the following day the patient developed evidence of a spinal cord paralysis which was apparently due to indirect trauma from the missile. He became severely hypotensive and died a few hours later.
Autopsy revealed a generalized peritonitis.
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Patient No. 8. This 25-year-old American soldier was admitted to a forward hospital a few hours following a perforation of the bowel. Laparotomy was performed about 12 hours after injury under spinal anesthesia and the perforation was closed. A widespread peritonitis had developed.
On the first postoperative day his temperature was 99.8?, orally, pulse 100, respiration 20 per minute. No peristalsis could be heard. His stomach having been emptied via a Levin tube, he was given 100 grams of deuterium oxide through the tube.
His plasma deuterium curve is demonstrated in Figure 14.
Patient No. 9. This 21-year-old American soldier was wounded at0230 hours 21 February 1952 when shot through the abdomen with a carbine. The missile perforated the jejunum and the colon. On admission to the Forward Surgical Hospital by ambulance at 0800 hours, his blood pressure was 70/60, pulse 124 per minute. The perforation of the small bowel was closed and a colostomy was performed.
Peristalsis became audible on the fourth day after injury and by the sixth day after injury his bowels were moving normally. His oral temperature still rose to102? daily for several days thereafter.
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By the tenth day after injury he was afebrile and his bowels had been moving normally each day for the preceding 7 days. At this time he was given 100 grams of deuterium oxide by mouth. The resultant curve of plasma deuterium concentration is demonstrated in Figure 15.
Patient No. 10. This 41-year-old Korean Service Corpsman was wounded in the back by mortar shell fragments at 1300 hours on 15 January 1952. On admission to the forward hospital his blood pressure was 64/40, pulse 100, respirations 18per minute. The wounds were explored a few hours after injury under pentothal, nitrous oxide, and ether. Each kidney had been penetrated by the missiles but the abdomen had not been injured.
His vital signs stabilized and his subsequent course was smooth. Bowel sounds were absent for a few hours but returned by the second day after operation. At this time he was given, orally, 100 grams of deuterium oxide mixed with 100grams of glucose (Fig. 16). After 4 hours, the concentration of deuterium in the gastric fluid had decreased to 3 per cent. His blood sugar rose from 127 mg. per 100 ml. (fasting)to 352 mg. after 45 minutes. After 4 hours only 5 per cent of the glucose could be recovered from the stomach.
Discussion
The studies of the six normal subjects (Figs. 1-6) demonstrate the rapid equilibration of water (deuterium) following its ingestion. Equilibration appears to occur in the normal man within 2 or 3 hours after the ingestion of 100 grams of deuterium oxide, an observation
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FIGURE12 (Patient No. 6). This casualty had a severe peritonitis. Equilibration after 2 hours had not been approached on the first day after injury. By the fourth day, there had been a marked clinical improvement as well as an improvement in deuterium absorption. Note, however, that compared with the concentration after 24 hours, equilibration had not been reached after the first 4 hours. Again, a prolonged period is observed during which the deuterium is entering the plasma faster than it is leaving.
Note. In the graph, the deuterium concentration for the second study has been corrected for the residual deuterium from the earlier study.
which confirms this finding in the subject reported by Schloerb and associates.9The equilibration curve reflects the effects of peristaltic activity, gastrointestinal absorption, intravascular circulation and diffusion throughout the extracellular and intracellular fluids. The summation of these dynamic processes normally permits equilibration to occur very rapidly.
The study of the first three battle casualties demonstrates, as a preliminary observation, that following rather severe injuries to the chest or extremities, or burns of moderate extent, equilibration is delayed. The delayed rise in venous deuterium concentration in these patients represents a decreased rate of absorption, for when deuterium oxide is given intravenously to the injured man, it leaves the circulation more slowly than in the normal man.6
Patient No. 3 (Fig. 9) demonstrates that, 3 hours after injury, the absorption of water was slower than normal. Three days later, the rate of absorption had increased but still was slower than normal. This impairment in absorption is quite definite and unexpectedly prolonged.
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When the study was repeated on the third day, the patient had peristalsis which was normal by auscultation. He had also had a normal bowel movement.
The rapid rise in blood glucose concentration following the ingestion of glucose strongly suggests an active absorption process rather than a process of passive diffusion, for numerous studies have shown that such an active process is normally responsible for the transfer of glucose across the bowel membrane.2, 3 This observation appears valid in spite of the fact that under these circumstances glycogen deposition is known to be retarded.1
Although in these first three casualties the absorption of water did not appear to be normal, the deficiency was not great. All three patients were maintained on oral fluids only and this therapy controlled their thirst and maintained an adequate urinary output. Further study is necessary but these observations, backed by clinical experiences, suggest that most such patients can be treated effectively by the oral administration of water. Certainly, in the treatment of
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mass casualties, water must be given orally to such patients unless anesthesia is impending.
Following injury to the abdominal viscera, the delay in absorption and equilibration was often quite marked. When superimposed on injury, hypotension also was associated with a profound deficiency in absorption (Fig. 10). The deficiency in absorption was present immediately after injury and persisted through the first few days thereafter. Like the function of the kidney,8 liver10 and other organs the function of the gastrointestinal tract was slow to return to normal. As with the other organs, the function had not returned to a normal state even when function appeared normal by clinical observations. Thus Patient No. 9 demonstrated a residual deficiency in the absorption of water as late as 7 days after the resumption of daily bowel movements. Absorption was definitely occurring as his stools were formed instead of liquid. The equilibration curve, however, demonstrated a delay.
During the early period after abdominal injuries, peristalsis was usually inaudible. Nevertheless, the occasional peaking in the curve
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of plasma deuterium concentration (Fig. 10) suggests the activity of intermittent peristalsis and raises the question as to whether the basic defect underlying the slow equilibration is primarily in motility rather than the absorptive process per se. Clinical experience with advanced paralytic ileus, however, has demonstrated numerous instances in which the entire bowel was filled with fluid and a defect in the absorptive process was obvious.
Whatever the underlying mechanism, the soldiers with abdominal injuries absorbed water quite slowly following its oral administration. They often vomited if given water orally in appreciable quantities. Anesthesia and laparotomy had to be performed at the earliest possible time. Motility was reduced and the bowel was often found to be distended with unabsorbed fluids. Thus even under the compromises necessary in the treatment of mass casualties, the oral administration of fluids has no place in the early treatment of patients with major intra-abdominal injuries.
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Summary
1. As measured by deuterium equilibration curves, water rapidly enters the blood from the gastrointestinal tract of the normal man. Equilibration of deuterium throughout the body appears to occur in the normal man within 2 or 3 hours after the ingestion of 100grams of deuterium oxide.
2. Preliminary studies indicate that, following burns of moderate extent or severe wounds of the chest and extremities, deuterium absorption is impaired but remains much more rapid than after an abdominal injury
3. Following intra-abdominal injuries, deuterium absorption from the gastrointestinal tract is markedly delayed. This function may still be impaired as late as 10 days after injury and as late as 7 days after the resumption of "clinically normal" gastrointestinal function.
Peripheral vascular collapse due to an intra-abdominal injury is associated with only a negligible absorption of deuterium.
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4. The rapid fall in concentration and total amount of deuterium and glucose in the upper gastrointestinal tract following their oral administration and the concurrent rise in blood glucose concentration, as well as in plasma deuterium concentration, suggests that an active absorptive process is functioning rather than a process of simple diffusion. The control of thirst, the solid nature of the stools, and the maintenance of urinary output proves that water is being absorbed in all patients except those with acute abdominal injuries.
Conclusions
The healthy, unwounded soldier absorbs water (deuterium oxide) rapidly from the gastrointestinal tract. Gastrointestinal absorption of deuterium oxide is slightly retarded after injury to the chest or extremities, or after burns. Following intra-abdominal injuries, absorption of deuterium oxide from the gastrointestinal tract is markedly retarded for several days. These studies suggest that in the compromises which may be necessary in the treatment of mass casualties, water may be given orally at anytime following injury, if there is no intra-abdominal injury, if anesthesia is not anticipated for the immediate future, and if the casualty is not comatose. Even under conditions in which mass casualties must be treated, oral fluid therapy for the casualties with major abdominal injuries should be avoided during the first few days following injury.
The response of the gastrointestinal tract to severe trauma, like the response of every other system and organ in the body, is a response of tremendous magnitude extending over a long period of time.
References
1. Chute, A. L.: Changes in Liver Function during Shock. Proceedings of the Symposium on Shock. Army Medical Service Graduate School, Washington, D. C., 7 May1951.
2. Cori, C. F.: The Fate of Sugar in the Animal Body. J. Biol. Chem. 66:691, 1925.
3. Hewitt, J. D.: The Metabolism of Carbohydrates. Biochem. J. 18:161, 1925.
4. Honig, R. E.: The Comparison of the Ionization Cross Section of H2and D2. J. Chem. Phys. 16: 837, 1948.
5. Howard, J. M.: Studies of the Absorption and Metabolism of Glucose Following Injury. Ann. Surg. 141: 321, 1955 (Chapter 14 of Volume I in this series).
6. Howard, J. M., and Scott, R.: Equilibration Time of Water (Deuterium Oxide) Following Intravenous Injection in the Battle Casualty. Surg., Gynec. & Obst. 99:542, 1954 (Chapter 4, this volume).
7. Knowlton, J. W., and Rossini, F. C.: Methods and Apparatus for the Rapid Conversion of Deuterium Oxide into Deuterium. J. Research Natl. Bur. Standards. 19:605, 1937.
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8. Ladd, M.: Renal Sequelae of War Wounds in Man. Chapter 11 of Volume IV in this series.
9. 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.
10. Scott, R., Olney, J. M., and Howard, J. M.: Hepatic Function of the Battle Casualty. Chapter 8 of Volume I in this series.
