Battle Casualties in Korea, Studies of the Surgical Research Team, Volume I
A Study of Plasma Amylase Activity in the Combat Casualty*
Captain John M. Howard, MC, USAR
First Lieutenant John P. Frawley, MSC, USAR
and
Lieutenant Colonel Curtis P. Artz, MC, USA
with the technical assistance of Corporal William Bohley and
Private First Class Edmund Hess
Amylase is secreted by the pancreas and by the salivary glands. Following injury to the pancreas and to a lesser extent following injury to the salivary glands, there is a sharp rise in the plasma amylase concentration. This rise characteristically lasts from 1 to 3 days. The rise following pancreatic injury has been so characteristic that an increased plasma amylase concentration in the presence of abdominal symptoms has become accepted by clinicians as a rather reliable diagnostic indication of pancreatic injury.
Total pancreatectomy in the dog,8, 9 and cat14 usually results in a fall in the concentration of plasma amylase concentration, but amylase does not disappear from the blood and after a variable number of days the concentration returns to normal. Observations following total pancreatectomy in the human have been too limited to describe accurately the trend in plasma amylase concentration. Disease of the liver has usually been found to be accompanied by a normal or low amylase,11, 15, 16 although high amylase values have been reported in several patients with hepatitis.7 Anesthesia may produce a fall in the serum amylase concentration; Gray11 postulated that this fall was due to hepatic damage.
Cope and his co-workers4-6 found that a bilateral adrenalectomy in dogs was followed by a rise of the serum amylase before any other sign of adrenal insufficiency. The serum amylase was subsequently depressed following the administration of adrenocortical extract or desoxycorticosterone acetate. Furthermore, they demonstrated that hypophysectomy resulted in an increased serum amylase.
*Previously published in Annals of Surgery 141: 337, 1955.
247
If the posterior pituitary alone was removed, a normal amylase was maintained. Injection of anterior pituitary extract in the normal dog resulted in a decrease in serum amylase activity. They found that thyroidectomy or thyroid extract produced no constant change in serum amylase in the animals studied. Adrenalin did not affect the serum amylase concentration in the dog althoughCohen,3 on the basis of two observations, had reported that a decrease in serum amylase concentration followed the administration of adrenalin in dogs.
Purpose of Study
The systemic response to major trauma appears to be a response of every organ and of every system of the body.17 This study was designed to measure the changes in plasma amylase which occur following injury and resuscitation, and to determine the magnitude and duration of these changes. In addition, it was hoped to ascertain whether traumatic pancreatitis resulted from indirect injuries to the pancreas (such as the transmission of force as a missile passed near the pancreas without directly involving the organ)or from surgical trauma or bacterial invasion.
Methods
Serial plasma samples were collected and immediately frozen. Analysis was performed by the Somogyi method (normal range of plasma amylase activity-80 to 150 units).15
A series of 19 soldiers was used as control. The amylase activity in this group ranged from 45 to 117 Somogyi units with an average of 67 units. Storage in the frozen state for 14 days did not interfere with the analysis in these control studies. The in vitro presence of dextran had no detectable effect on the amylase activity of the plasma.
Creatinine and creatine determinations were carried out according to technics described by Bonsnes and Taussky.2
Results
Serial plasma amylase and blood glucose determinations on 14 patients are outlined in Table 1.
248
Table 1. Serial Plasma Amylase and Blood Glucose Determinations
Patient | Wound | Hours Postwound | Glucose | Plasma Amylase (Somogyi Units) |
|
No. 1 |
Abdominal |
8 |
228 |
420 |
|
No. 2 |
Abdominal-Extremity |
4 |
180 |
20 |
|
No. 3 |
Abdominal-Extremity |
20 |
127 |
288 |
|
No. 4 |
Abdominal |
24 |
130 |
58 |
|
No. 5 |
Thoraco-Abdominal |
10 |
138 |
52 |
|
No. 6 |
Abdominal-Extremity |
2 |
133 |
40 |
|
No. 7 |
Thoraco-abdominal |
20 |
173 |
35 |
|
No. 8 |
Abdominal |
16 |
142 |
108 |
249
Table 1. Serial Plasma Amylase and Blood Glucose Determinations-Continued
Patient | Wound | Hours Postwound | Glucose (mg./100 cc.) | Plasma Amylase (Somogyi Units) |
|
No. 9 |
Abdominal-Extremity |
7 |
185 |
33 |
|
No. 10 |
Abdominal-Extremity |
4 |
128 |
37 |
|
No. 11 |
Chest-Extremity |
13 |
102 |
7 |
|
No. 12 |
Extremity |
3 |
175 |
40 |
|
No. 13 |
Extremity |
8 |
125 |
53 |
|
No. 14 |
Extremity |
5 |
170 |
43 |
250
FIGURE1.
Graphic illustration of serial plasma amylase concentrations in
Patient No. 1. The shaded area represents the normal range of plasma amylase.
Case Studies
Patient No. 1. This 21-year-old American soldier was wounded at 2015 hours, 12 May 1953, by small arms fire. The injury included perforation of the spleen, pancreas and kidney. He was given dextran,500 cc., at the battalion aid station. His blood pressure on admission to the hospital at 2230 hours was 120/60, pulse rate 80, hematocrit 39.5 per cent.
Operation, 5 hours after injury, was performed under pentothal, nitrous oxide, oxygen, and ether. Splenectomy and nephrectomy were performed. A drain was placed near a small tear in the tail of the pancreas. A total of 7,000 cc. of blood was used because of persistent hypotension (65 to80 mm. of mercury systolic, pulse rate 120). The hypotension never responded until noradrenalin was added to the infusion.
His postoperative course, which was marked by a moderate hypertension, was fairly smooth until the fifth day when he developed a secondary paralytic ileus, convulsion and hypotension. He died on the sixth day after injury.
Autopsy revealed a moderate inflammatory reaction around the tail of his pancreas but the cause of death was not satisfactorily explained.
Figure 1 demonstrates the high plasma amylase concentration, postoperatively, which subsided during the first few days.
This patient displayed a traumatic pancreatitis due to direct injury to the pancreas.
Patient No. 2. This 26-year-old Korean soldier was wounded at 1400 hours 10 April 1953 by multiple shell fragments. His wounds included multiple soft tissue wounds, fracture of the femur, patella, phalanges of the hand, and a perforation of the transverse colon. The fragments did not penetrate the pancreas.
One hour after wounding his blood pressure was 120/80,pulse 119. He was given 500 cc. of blood at the collecting station.
251
FIGURE2.
Graphic illustration of serial plasma amylase
concentrations in Patient No. 2.
On arrival at the hospital, 3.5 hours after injury, a plasma sample was drawn for amylase determination before further therapy was instituted (Table 1).
Débridement of wounds and colostomy were performed under pentothal, nitrous oxide, and oxygen anesthesia. The operation which began 6 hours after injury required 5 hours. His operative and postoperative courses were smooth. There was no direct operative manipulation of the pancreas. He received 1,000 cc. of dextran postoperatively.
Serial amylase studies revealed a low concentration on admission that remained low immediately after operation. The concentration rose to an abnormally high level 16 hours after injury and fell to normal the next day (Fig. 2). This may well represent a traumatic pancreatitis without penetration of the pancreas.
Patient No. 3. This 22-year-old Korean soldier was wounded by mortar fragments at 1320 hours on 26 July 1953. He suffered fragment wounds of the pelvis with rectal involvement, wounds of the back at the level of the pancreas, and soft tissue wounds of the left forearm, right arm and left shoulder. He was evacuated by ambulance, arriving at the hospital at 1655 hours. Blood was exuding from the rectum on admission. He received 500 cc. of blood preoperatively. His abdomen was explored and a moderate amount of blood was found in the abdominal cavity. There was a wound of the anterior wall of the rectosigmoid and four perforations of the ileum. There was a hematoma posterior to the rectum in the retroperitoneal area. On further exploration of the abdomen, no additional injury was found. The perforations of the intestinal tract were sutured and a diverting colostomy was performed. This patient had an uneventful postoperative course and was evacuated on the fifth postoperative day.
Figure 3 illustrates the changes that occurred in plasma amylase activity. His plasma amylase 20 hours after injury was quite high,288 units, but 24 hours later the level had fallen to normal.
The wound of the back is believed to have produced a traumatic pancreatitis;
252
FIGURE 3.
Graphic illustration of serial plasma
amylase concentrations in Patient No. 3.
but it was impossible to determine whether this was direct injury or indirect transmission of force to the pancreas.
Patient No. 4. This 22-year-old American soldier was wounded by small arms fire at 0800 hours on 24 July 1953. He was evacuated by helicopter and arrived at the hospital at 1015 hours. He received 1,000cc. of blood and 500 cc. of dextran preoperatively.
This patient had abdominal injuries without evidence of trauma in other areas. He experienced penetrating wounds of the abdomen with involvement of the descending colon, ileum, and liver. Prior to operation, he exhibited a hypertensive response to his injury. There were four lacerations of the lower portion of the ileum and one laceration in another area. Twenty-four inches of ileum were resected. The descending colon showed a large, avulsive wound which was exteriorized. There was a moderate amount of bleeding in the left retroperitoneal area. A biopsy of the liver was taken for study.
On the fourth postoperative day the patient developed an infection in the abdominal wall near the lower portion of the exploratory wound. This was drained and he was evacuated on 2 August 1953 in good condition.
This patient had a normal plasma amylase which fell slightly below normal at 48 hours and then gradually rose until on the sixth day the amylase was 219 units (Table 1). The cause for this elevation is not clear. It is probably related to the abdominal wound or infection.
Patient No. 5. This 21-year-old American soldier was wounded by shell fragments at 2320 hours, 26 July 1953. Fragments entered the right shoulder and the back, injuring the right lung and liver. He arrived at the hospital at 0120 hours on 27 July 1953. He received 500 cc. of blood preoperatively and 1,000 cc. during surgery. There was a hemopneumothorax which was treated by repeated aspiration. On exploration of the abdomen, no blood was found. There was a very small penetrating wound of the dome of the right lobe of the liver. No wound of exit from the liver was seen. The perforation of the diaphragm was so small that it could not be determined by palpation. No other injury of intra-abdominal organs was found. Four drains were inserted around the liver. The patient had an uneventful postoperative course and was evacuated on 4 August 1953.
253
This patient`s plasma amylase remained at low normal levels during the first 2 days and then gradually rose to a high normal level(Table 1). This represents a casualty with an injury to the liver whose amylase rose to high normal or slightly abnormal levels, the maximum being177 units at 106 hours after injury.
Patient No. 6. This 19-year-old American soldier was wounded at 1245 hours, 15 April 1953, by mortar fragments. The wounds included a perforation of the ascending colon, traumatic amputation of five fingers and soft tissue wounds of the arm. He was given 500 cc. of dextran at the clearing station. He arrived at the hospital at 1415 hours with a blood pressure of 180/90, pulse 84, hematocrit 45. The blood pressure rapidly fell to normal. The first plasma amylase sample was drawn 2 hours after injury before further restorative therapy. Operation under pentothal, nitrous oxide, ether anesthesia was performed at 1600 hours. The soft tissue wounds were débrided, the fingers reamputated, and the cecum was exteriorized. Five hundred cc. of blood was given during the operative procedure. His subsequent course was uneventful.
The plasma amylase concentration remained quite low throughout the period of study (Table 1).
Patient No. 7. This 18-year-old American soldier was wounded on 8 July 1953 at 2100 hours, by small arms fire. At the battalion aid station his blood pressure was 120/80 and upon arrival at the hospital it was 118/78. He had a penetrating wound of the chest and abdomen. There were two lacerations of the stomach, a small laceration of the left diaphragm, and perforation of the liver. Operation was performed at 1600 hours on9 July, during which time the lacerations of the diaphragm and stomach were sutured. The bullet was removed from the right lateral abdominal wall and drains were inserted about the liver, which had been perforated. He received 1,000 cc. of blood during the operation.
This patient`s plasma amylase remained low throughout the period of study (Table 1).
Patient No. 8. This 18-year-old American soldier was wounded by mortar fragments at 1630 hours on 22 July 1953. He was evacuated by helicopter to the hospital at 1745 hours. He was given 1,000 cc. of blood preoperatively and 500 cc. during operation. He experienced a laceration of the liver and penetrating wounds of the back. At exploratory laparotomy it was found that the laceration of the liver was not bleeding. Drains were placed around the injured area and the abdomen closed. His postoperative course was uneventful and he was evacuated on the third postoperative day. The only intra-abdominal injury was the small laceration of the liver.
This patient`s serum amylase remained normal throughout the period of study (Table 1).
Patient No. 9. This 21-year-old American soldier was wounded at 0100 hours, 15 April 1943, by a burp gun. The injury included perforation of the spleen, kidney, thigh, and a penetrating wound of the back with paralysis of the spinal cord at the level of the first lumbar vertebra.
He received 100 cc. of albumin and 250 cc. of dextran at the battalion aid station and 500 cc. of blood at the collecting station. He arrived at the hospital at 0415 hours in good condition. The first amylase specimen was drawn at 0740 hours after another 200 cc. of blood. Nephrectomy, splenectomy and laminectomy were carried out at 0940 hours under pentothal, nitrous oxide and ether anesthesia. He received an additional 300 cc. of blood and 500 cc. of dextran. His operative course was smooth. There was no period of hypotension. His postoperative course was marked by persistent paralytic ileus, a marked hypertension to 200 mm. of mercury systolic and azotemia without oliguria.
254
FIGURE4.
Graphic illustration of serial plasma amylase concentrations in
Patient No. 9. The shaded area represents the normal range of plasma amylase.
The serum amylase remained low throughout the stormy postoperative course and returned to normal only after his clinical course had shown a marked improvement (Fig. 4).
Patient No. 10. This 25-year-old Korean soldier was wounded by mortar fragments at 1445 hours on 9 July 1953. He received 500 cc. of blood at the battalion aid station and was admitted in fair condition to the hospital with a blood pressure of 124/60. He experienced a wound of the pelvis and wounds of the ear, arm, scalp and legs. There was a perforating wound of the rectum. The abdomen was opened at exploratory laparotomy and 500 cc. of cloudy fluid was found in the pelvis. There was no blood. The mesentery of the sigmoid colon contained air bubbles. No intraperitoneal bowel perforation could be demonstrated. There was induration beneath the pelvic reflection of the peritoneum. A diverting sigmoid colostomy was carried out and a drain inserted in the retrorectal space. This patient experienced no intra-abdominal injury except the minimal trauma that occurred at the time of surgery.
The plasma amylase remained normal throughout the period of study (Table 1).
Patient No. 11. This 22-year-old American soldier was wounded at 2400 hours, 14 April 1953, by mortar fragments. There was a penetrating wound of the chest and soft tissue wounds of the buttocks. He received 500 cc. of dextran and 500 cc. of blood before arriving at the hospital 4 hours after injury. His blood pressure was 120/80, pulse92. He was given 1,000 cc. of blood and 500 cc. of dextran and a thoracentesis was performed, after which the lung re-expanded.
The first amylase specimen was drawn 13 hours after injury, but prior to anesthesia. Five hundred cc. of dextran was given during the1-hour operative procedure. His postoperative course was smooth.
The first amylase specimen 13 hours after injury showed that almost all the plasma amylase had disappeared from the plasma, asindicated by a level of 7
255
FIGURE5.
Graphic illustration of serial plasma
amylase concentrations in Patient No. 12.
units. Thereafter the plasma amylase level remained subnormal throughout the period of study (Table 1).
Patient No. 12. This 21-year-old American soldier was wounded at 1000 hours on 10 April 1953, by mortar shell fragments. The wounds included fractures of the left mandible and bilateral fractures of the radius and ulna. There were multiple soft tissue injuries including a very severe wound of the tongue.
At the battalion aid station, the patient received 300cc. of albumin. He arrived at the hospital at 1345 hours, with a systolic blood pressure of 90 mm. of mercury. Bleeding from the tongue was profuse. Operation at 1850 hours consisted of a tracheotomy, ligation of the lingual artery and vein, and débridement of the soft tissue wounds. He was given 9,500 cc. of blood and 1,000 cc. of dextran. His postoperative course was uneventful.
The patient`s plasma amylase remained near normal levels throughout the period of study (Fig. 5).
Patient No. 13. This 23-year-old American soldier was wounded at 1545 hours on 14 April 1953, by mortar shell fragments. His wounds included multiple penetrating wounds of both thighs, left arm, forearm, shoulder and sacrum. There were compound fractures of the left humerus, radius and ulna. He was given 500 cc. of dextran and 1,000 cc. of blood at the clearing station. He arrived at the hospital at 2220 hours with a blood pressure of 140/70, pulse 120. After an additional 1,000 cc. of blood, he was taken to the operating room, where all wounds were débrided and casts were applied. Another 1,500 cc. of blood was given at operation. His postoperative course was uneventful.
This patient`s amylase remained at low normal to subnormal levels throughout the short period of study. The lowest level occurred at about the twenty-seventh hour post-injury (Table 1).
Patient No. 14. This 28-year-old Korean soldier stepped on a land mine at 0345 hours, 13 April 1953. His injuries included traumatic amputation of the right foot, multiple wounds of the leg and thigh and multiple fractures of the bones of the hand. He was given 500cc. of blood at the clearing station. On
256
FIGURE6.
Graphic illustration of serial plasma
amylase concentrations in Patient No. 14.
arrival at the hospital at 0850 hours, the first amylase specimen was drawn before additional therapy. He then received 1,000 cc. of dextran and 125 cc. of blood. Re-amputation and débridement were performed at 1240 hours. His postoperative course was uneventful.
This patient had a subnormal amylase level throughout the period of study (Fig. 6). On the first day the plasma amylase activity had practically disappeared as indicated by a level of 3 units.
Plasma Amylase Activity and Urinary Creatinine Excretion
In three patients (Nos. 6, 9 and 12) the urinary creatinine and creatine were determined along with the plasma amylase activity. The findings in these patients are shown in Figures 7, 8 and 9. In patient No. 6 (Fig.7), the plasma amylase activity remained low throughout the period of study and there was increasing excretion of creatinine in the urine during the first 3 days post-injury. In patient No. 9 (Fig. 8), the plasma amylase activity remained low throughout the first 5 days after injury and rose to normal levels. During this period, the urinary creatinine excretion slowly fell, then rose again on the fifth day.
In patient No. 12 (Fig. 9), the amylase activity was low during the first 2 days, then rose to normal levels. The creatinine excretion slowly increased daily during the first 4 days.
There was a similar negative correlation of urinary creatine and plasma amylase activity.
257
FIGURE7.
Graph of plasma amylase concentration and bar graph of simultaneous
urinary creatinine and creatine excretion in Patient No. 6. The amylase remains
at low normal levels and the creatinine increases.
Discussion
Four casualties developed a distinct elevation in serum amylase concentration in the early post-injury period. All four of these casualties experienced abdominal trauma. In three of these patients, the elevation is interpreted to be due to a release of the enzyme from the pancreas following injury to the pancreas from direct or indirect trauma from the missile. In the other instance, injury to the pancreas was probably due to trauma during the operative procedure or later bacterial injury.
One patient who showed no evidence of injury to the pancreas showed a high normal serum amylase on the fifth day after injury.
Nine casualties had a normal or low amylase concentration. The trend was definitely toward the development of subnormal plasma amylase activity when the injury was not in the vicinity of the pancreas. At times the anylase activity was almost imperceptible.
It might be postulated that the low plasma amylase activity was due to vasoconstriction and pancreatic ischemia leading to a func-
258
FIGURE 8.
Graph of plasma amylase concentration and bar graph
of simultaneous urinary creatinine and creatine excretion in Patient No. 9.
tional pancreatectomy, but there are no data to suggest such a relationship. Neither starvation nor hyperglycemia have been found to affect the amylaseconcentration.10, 13 Plasma dilution with amylase-free dextran or banked blood was not responsible for the decrease in amylase concentration, because the fall was often a progressive one.
Standard hepatic function studies in the battle casualty indicate a decreased or altered hepatic function.1, 17 It may be that the low amylase activity is a reflection of abnormal hepatic function, but no confirming correlation can be made.
Hardy12 has pointed out that the increase in creatinine excretion following trauma may be due to increased adrenocortical activity. Cope6has demonstrated in the dog that low plasma amylase activity could be correlated with an increased adrenocortical response. However, in the three patients on whom creatinine excretion and plasma amylase activity were determined, there was no constant relationship between an increasing creatinine and a low plasma amylase activity, as might be expected if both increased creatinine and depressed amylase activity were due to increased adrenocortical function following injury. Depressed plasma amylase activity in nonspecific wounds deserves further study and correlation with the adrenocortical response.
259
FIGURE9.
Graph of plasma amylase concentration and bar graph of simultaneous urinary creatinine and
creatine excretion in Patient No. 12. The amylase was low during the first 2 post-injury days,
then rose to normal levels. The creatinine and creatine excretion increased steadily during the same period.
Summary
Following injuries distant to the pancreas, the plasma amylase activity falls below normal levels. This subnormal level may be maintained as long as 3 to 5 days after the injury.
Abdominal wounds produced by shell fragments or small arms fire frequently may be associated with a traumatic pancreatitis as indicated by a rise in plasma amylase activity. This injury may result from direct injury to the organ or to indirect injuries, such as the transmission of force froma missile passing near the pancreas, injury at the time of surgery, or later bacterial injury.
260
References
1. Board for the Study of the Severely Wounded: The Physiologic Effects of Wounds, p. 88. Government Printing Office, Washington, D. C.,1952.
2. Bonsnes, R. W., and Taussky, H. H.: The Colorimetric Determination of Creatinine by the Jaffe Reaction. J. Biol. Chem. 158:581, 1945.
3. Cohen, C.: Studies on Blood Diastase. Am. J. Physiol.69:215, 1924.
4. Cope, O., Hagstromer, A. and Blatt, H.: The Activity of the Blood Serum Amylase in the Hypophysectomized Dog. Am. J. Physiol.122:428, 1938.
5. Cope, O., Kapnick, I., Lamber, A., Pratt, T. D. and Verlot, M. G.: Endocrine Function and Amylase Activity. Endocrinology 25:236, 1939.
6. Ibid.: Endocrine Function and Amylase Activity. Endocrinology 25: 248, 1939.
7. Cummins, A. J., and Bockus, H. L.: Abnormal Serum Pancreatic Enzyme Values in Liver Disease. Gastroenterology 18: 518, 1951.
8. Dozzi, D. L.: Origin of Blood Amylase and Blood Lipase in the Dog. Arch. Int. Med. 68: 232, 1941.
9. Ibid.: Urinary Amylase: Its Estimation and Significance. Am. J. Digest. Dis. 7: 123, 1940.
10. Elman, R., and McCanghan, J. M.: The Quantitative Determination of Blood Amylase with the Viscosimeter. Arch. Int. Med. 40:58, 1927.
11. Gray, J. H., Probstein, J. G. and Heifetz, C. J.: Clinical Studies on Blood Diastase. Arch. Int. Med. 67: 805, 1941.
12. Hardy, J. D.: Some Physiologic Aspects of Surgical Trauma, Final Report, Army Project DA-49-007-MD-84, Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, 30 Sept.1951.
13. Milne, L. S., and Peters, H.: Observations of the Glycolytic Power of the Blood and Tissues in Normal and Diabetic Conditions. J. Med. Res. 26: 416, 1912.
14. Roe, J. H., and Goldstein, J. P.: Studies of Pancreatic Function. J. Lab. and Clin. Med. 28: 1334-1344, 1943.
15. Somogyi, M.: Blood Diastase as an Indicator of Liver Function. Proc. Soc. Exper. Biol. & Med. 32: 538, 1934.
16. Sorkin, S. Z.: Blood Amylase Activity in Disease of Carbohydrate Metabolism and in Non-diabetic Pancreatic Disease. J. Clin. Investigation 22: 329, 1943.
17. Surgical Research Team In Korea: Unpublished data.
