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Massive Transfusions, Blood Derivatives and Plasma Expanders

Medical Science Publication No. 4, Volume 1

MASSIVE TRANSFUSIONS, BLOOD DERIVATIVES AND PLASMA EXPANDERS*

MAJOR CURTIS P. ARTZ, MC

Experiences of World War II pointed out the value of whole blood in the management of severely wounded. As the Korean conflict progressed, it became apparent that large quantities of blood should be administered to the battle casualty. In a survey of 995 consecutive casualties admitted between February and August 1953 to the general surgical service of the 46th Surgical Hospital in Korea, 138 (or 14 percent) required replacement of 5 or more pints of blood. During the first 24 hours, 27 (or 3 percent) of these 995 casualties required over 15 pints of blood and plasma expander. Admissions totaled 684 American casualties and 311 Korean casualties. Mortality rate for the American patients was 2.2 percent, and for all general surgical casualties, the overall mortality rate was 3.2 percent.

Casualties Who Received 5 or More Pints of Blood

The mortality rate in relation to blood requirement in the group of 138 patients is outlined in table 1. As the blood requirement increased, the mortality rate increased. Twenty casualties died and, of this number, 16 died within the first 48 hours. Of the 122 patients who survived for 48 hours, 6 developed a marked degree of renal insufficiency and 4 of these died.

Table 1. Mortality Related to Blood Requirement (February to August 1953)

Amount of blood given

Number of patients

Deaths

Mortality (percent)

5-10 pints

61

1

1. 6

10-15 pints

50

8

16. 0

15-20 pints

12

3

25. 0

20-56 pints

*15

8

53. 3

Total series

†138

20

14. 5

*Only 10 lived more than 48 hours.
†Only 122 lived more than 48 hours.


*Presented 20 April 1954, to the Course on Recent Advances in Medicine and Surgery, Army Medical Service Graduate School, Walter Reed Army Medical Center, Washington, D. C.


203

Mortality and Type of Injury. The mortality rate in relation to the type of injury is outlined in table. 2. Casualties whose injuries were primarily in the abdomen had a mortality rate of 16 percent. In the group whose injuries were primarily in the extremities, the mortality rate was 10 percent. Casualties sustaining thoraco-abdominal wounds had a higher mortality rate (26.6 percent); while for those who had chest wounds it was 9 percent.

Table 2. Mortality Related to Type of Injury

Type of injury

Number of patients

Deaths

Mortality (percent)

Abdomen

60

10

16. 0

Extremity

52

5

10. 0

Thoraco-abdominal

15

4

26. 6

Chest

11

1

9. 0

Total

    138

20

14. 5

Resuscitative Fluids during Various Phases of Care. The amount of blood or colloid solution given prior to admission to the hospital is summarized in table 3. Eighty-one of the 138 patients received resuscitative fluids, predominantly dextran; but some received modified fluid gelatin, albumin and blood. Patient in the 5- to 10-pint group received about 1 pint of blood or plasma expander, while the patients in the 10- to 56-pint group received about 3 pints of fluid prior to admission.

Table 3. Pre-admission Blood and Plasma Expander


Category

Total number
patients in
category

Number receiving
therapy
pre-admission

Average amount
received
pre-admission* (cc.)

5-10 pint group

61

38

685

10-56 pint group

77

43

1,440


Entire series


138


81


1,090

*Mostly dextran.

The average amount of blood replacement during various phases of resuscitation is shown in table 4. Patients in the 5- to 10-pint group were given an average of 3,440 cc. of fluid therapy during the first 24 hours after injury. Those requiring 10 to 35 pints averaged more than twice as much as those in the first group, namely, 7,300 cc. In


204

each group the amount of blood given preoperatively was essentially the same as the amount given during the operation. Of the 73 casualties in the 10- to 35-pint group, 38 received an average of 1,130 cc. of resuscitative fluids postoperatively; and of the 61 casualties in the 5- to 10-pint group, 18 received 720 cc. of fluids.

Table 4. Blood Replacement During Phases of Resuscitation

  Category

Number receiving therapy

Amount prior to operation (cc.)

Amount during operation (cc.)

Amount postoperative (cc.)

5-10 pint group

Total patients-61

59

1,770

-----

-----

Average total blood in first 24 hours-3,440 cc

55
18

-----
-----

1,500
-----

-----
720

10-35 pint group*

Total patients-73

67

3,400

-----

-----

Average total blood in first 24 hours-7,300 cc

66
38

-----
-----

3,200
-----

-----
1,130

*For more accurate sampling 4 patients who received 40, 46, 52, and 56 pints of blood were excluded.

Fifty percent of the patients in the abdominal group and 48 percent of the patients in the extremity group were given approximately 1 liter of plasma expander in addition to blood. Most of this plasma expander was administered before these patients arrived at the hospital.

Control of Hemorrhage. Hemorrhage was controlled preoperatively in all 61 casualties in the 5- to 10-pint group. Of the 77 casualties in the 56-pint group, hemorrhage was not controlled prior to operation in 13; and control of hemorrhage preoperatively was questionable in 8. Of these 21 patients, hemorrhage was brought under control at operation in all but 4. Two of these four patients died on the operating table (one had a large laceration of the common iliac artery and the other had a high bilateral amputation of the thigh). One patient with a massive liver wound died during the first postoperative day because of uncontrolled bleeding. The fourth patient had a massive liver and retroperitoneal muscle wound. He continued to bleed after operation, requiring 875 cc. of blood per hour to replace the blood lost. His wound was re-explored 4 hours after the first operation. There were multiple bleeding sites in the retro-


205

peritoneal area; and this area was packed with two 5-yard-roll gauze packs. The oozing did not stop, however, until after 6 pints of fresh blood was administered. The patient subsequently recovered. During the first 24-hour period, this patient was given 46 pints of blood. In three other casualties with uncontrolled hemorrhage preoperatively, the major points of hemorrhage were controlled at operation. Oozing continued from all surfaces and these three casualties died after several hours, having received 35, 52, and 56 pints of blood respectively.

Patients Admitted in Shock. In the group of 138 most severely wounded casualties, 33 were admitted in severe shock; and of this number 7 died (table 5). Severe shock was a clinical diagnosis. Each of the 33 casualties had a systolic blood pressure of 80 mm. of mercury or less. The type of wound varied; but no particular type of injury predominated. The average time of evacuation was 2 hours and 20 minutes. The total amount of blood given in the first 24 hours ranged from 2,500 cc. to 28,000 cc. The average amount of blood administered preoperatively was 4,300 cc., averaging 7,600 cc. for the first 24 hours.

Ten casualties in this group were admitted with a blood pressure that was too low to be obtained by the usual cuff method. Three of these died; two died from uncontrolled hemorrhage, and the cause of death of the other was unknown. The seven casualties who lived required from 11 to 26 pints of blood in the first 24 hours.

The causes of three of the other four deaths in this severely shocked group were cardiac arrest, refractory postoperative shock and uncontrollable oozing, and in one instance the cause of death could not be determined. In the 33 most severely wounded casualties who were admitted in severe shock and required an average of 15 pints of blood, the mortality rate was 21 percent.

Deaths. There were 20 deaths in the group of the 138 most severely wounded casualties (table 6). Most of this group were held at the hospital for a period of from 5 to 8 days; and they were evacuated only after their condition became stable. Soon after injury, a few were evacuated to the Renal Insufficiency Center at the 11th Evacuation Hospital because of post-traumatic renal insufficiency. Deaths listed included those that occurred at the 46th Surgical Hospital and at the Renal Insufficiency Center. Renal failure was not listed as a cause of death in these patients because it was considered a contributing factor rather than a primary cause of death.

Causes of death were determined by clinical review of the case histories and autopsy findings.


206-207

Table 5. Very Severely Wounded-Admitted in Severe Shock, 33 Patients-7 Deaths-Mortality 21 Percent

No.

Patient

Type wound

Evac. Time minutes

Admission blood pressure

Preoperative blood in cc.

Blood total first 24 hours in cc.

Remarks

1

S. D. K.

Ext

110

70/30

2,000

2,5000

Recovered.

2

L. J. B.

Ext

105

80/40

2,000

3,000

Recovered.

3

J. C. D.

Abd

180

70/40

2,500

3,000

Recovered.

4

P. Y.

Ext

120

40/0

-----

3,500

Recovered.

5

L. N. W.

Abd

60

66/0

2,000

3,500

Recovered.

6

C. J. S.

Ext

270

80/40

2,000

4,000

Recovered

7

H. C.

Abd

185

60/30

2,500

4,000

Recovered.

8

N. E.

Ext

270

70/40

3,750

4,750

Recovered.

9

L. S. C.

Chest

-----

60/0

2,500

3,500

Recovered.

10

A #1

Abd

-----

40/0

3,000

5,000

Recovered.

11

J. A.

Thor-Abd

150

80/40

3,000

5,000

Recovered.

12

C. S. W.

Abd

-----

70/40

4,000

5,500

Recovered.

13

A. B. S.

Ext

120

70/40

3,500

6,000

Recovered.

14

C. F.

Ext

195

80/0

5,500

6,500

Recovered.

15

W. D.

Ext

45

70/30

3,000

7,000

Recovered.

16

G. H.

Ext

170

70/40

2,500

7,000

Recovered.

17

Y. M. S.

Abd

130

70/0

4,000

9,000

Recovered.

18

J. K.

Abd

90

70/40

5,000

10,000

Recovered.

19

K. Y. S.

Abd

90

74/52

3,500

11,500

Recovered.

20

K. J. B.

Ext

103

0/0

5,500

5,500

Recovered.

21

F. M.

Abd

180

0/0

4,000

6,000

Recovered.

22

T. R.

Ext

120

0/0

6,000

6,000

Recovered.

23

H. B. S.

Chest

190

0/0

4,000

7,000

Recovered.

24

W. W. S.

Abd

180

0/0

6,500

8,500

Recovered.

25

P. K. C.

Abd

-----

0/0

2,500

11,000

Recovered.

26

D. J. P.

Chest

70

0/0

5,500

13,000

Recovered.

27

C. C. S.

Thor-Abd

205

0/0

4,000

8,000

Expired, unknown.

28

M. H.

Abd

105

0/0

5,500

9,000

Expired, uncontrolled hemorrhage.

29

J. M. J.

Ext

125

0/0

12,000

16,000

Expired, uncontrolled hemorrhage.

30

G. G. C.

Ext

330

80/60

2,500

6,000

Expired, cardiac arrest.

31

T. K.

Ext

90

80/60

5,500

9,500

Expired, postoperative shock.

32

J. J.

Ext.

85

40/0

5,500

11,500

Expired, undetermined.

33

P. T.

Abd.

180

50/30

12,000

28,000

Expired, uncontrolled oozing.

Averages

140

-----

4,300

    7,600


208

Table 6. Cause of Death

Causes*

Number of death

Uncontrolled oozing postoperatively

4

Postoperative shock

3

Uncontrolled hemorrhage

3

Peritonitis

2

Cardiac arrest

2

Massive lung damage

1

Pancreatitis

1

Septicemia

1

Aspiration pneumonia

1

Undetermined

1

Unknown

1


Total


20

*Post-traumatic renal insufficiency was a complication in four patients of this series.

Casualties Who Received 15 or More Pints of Blood or Plasma Expander

During 1952 and the first half of 1953, a study was made of 89 battle casualties during the first 24 hours after injury. Each of the casualties required a minimum of 15 pints of blood or plasma expander, or one and one-half times the normal blood volume. Included in this group of 89 casualties were those from the previous group of 138 casualties who required 15 or more pints of blood or plasma expander.

Some patients received 30, 40, and even 50 pints of resuscitative fluids within the first 24 hours. Of the patients who received more than 15 pints of blood or plasma expander, the mortality rate was 44 percent (table 7).

Table 7. Mortality-Casualties Who Required 15 or More Pints of Blood and Plasma Expander

Injury

Number

Number died

Mortality (percent)

Number dying of continued hemorrhage

Mortality excluding continued hemorrhage (percent)

Abdomen

24

19

79

11

61. 5

Abdomen and extremities


29


12


41


3


35

Extremities

29

5

17

1

14

Chest

7

3

43

1

33


Total


89


39


44


16


31. 5


209

Massive Transfusions

The successful use of massive transfusions re-emphasizes certain lessons learned in World War II, namely, that the treatment of wound shock is primarily the control of hemorrhage and the administration of adequate quantities of blood. One of the primary differences in resuscitation during the Korean conflict and during World War II was the difference in the amount of blood administered. Massive transfusions were used frequently and only rarely was there evidence of overtransfusion. From the data on blood volume determinations after massive transfusions collected by Captain Theodore Prentice, it appears that large quantities of blood were lost from the effective circulation. In most instances, recovery from the initial hypotension followed the administration of large quantities of blood. An occasional patient who reached the hospital alive, but who had vital organ damage, succumbed even though there was only a minimal blood loss. This was most frequently observed in casualties who had injuries of the brain. In general, the severity of the injury was in direct proportion to the amount of blood lost. Both the injury and blood loss continued to exert a deleterious effect.

Blood Derivatives

Lyophilized pooled plasma and serum albumin were used as emergency shock solutions during the early phases of the Korean conflict. Plasma had two undesirable aspects, namely, a high percentage of the bottles contained the virus of serum hepatitis, and a large number of bottles were broken during cold weather. Approximately 20 percent of the patients in Korea who received pooled plasma subsequently developed homologous serum hepatitis. Many of the battalion surgeons complained that the water used for reconstitution of the plasma froze during the cold weather and bottles were broken. Serum albumin was used: 100 cc. of 25 percent solution. Its particular advantage was its availability in small containers which were easily carried by the aidman. Comparatively little dependable information is available on the efficacy of albumin. The battalion surgeons, however, generally believed albumin to be a satisfactory resuscitative agent for emergency treatment.

Plasma Volume Expanders

Dextran replaced plasma and serum albumin in many division areas toward the end of the Korean conflict. Two thousand units of dextran were administered to approximately 1,000 casualties. No toxic reactions were observed. Part of the material was used at the


210

division level-prior to admission to a forward hospital-as an emergency plasma volume expander. An equal amount was utilized at forward hospitals in patients who had wounds of minimal severity; and these patients were resuscitated entirely with dextran. Some dextran was utilized with blood as a resuscitative agent in patients having more severe wounds.

The Surgical Research Team in Korea studied 19 battle casualties in order to determine the fate of infused dextran. Severely injured patients were given 1,000 cc. of dextran in the immediate postoperative period. This infusion required from 2 to 4 hours. Immediately after infusion, approximately 40 percent of the dextran was present in the plasma. Three hours after infusion, approximately 28 percent of the dextran remained in the circulation. Six hours after infusion, 22 percent of the dextran remained in the plasma; and 12 hours after infusion, 16 percent remained. Only from 2 to 3 percent was still present in the plasma at the end of 72 hours. It must be pointed out that the dextran used in this study was of lower molecular weight than is presently acceptable, having an average molecular weight of 43,000.

The loss of dextran from the circulation appears to be directly related to urinary excretion. After 3 hours, approximately 37 percent of the infused material was found in the urine; after 6 hours, 42 percent; and after 24 hours, 54 percent. Thereafter, dextran was excreted in small amounts. Approximately 30 percent of the dextran administered could not be accounted for in the plasma or urine. This unaccounted-for fraction was presumably lost into the wound, the extravascular compartment, or possibly metabolized.

In a similar study, 200 units of modified fluid gelatin were administered to battle casualties. The average molecular weight of this material was 34,000. The quantity of gelatin administered was 1,000 to 1,500 cc. A few patients received as much as 2,500 cc.; and one patient received 3,000 cc. No evidence of toxicity was seen. The gelatin solution flowed freely and, over a period of 8 months in storage, it did not change color. No data are available on the flow of gelatin during extremely cold weather. However, there was no record of difficulty with the administration of gelatin given at the battalion aid stations during the winter months.

The fate of gelatin was studied in 10 patients immediately after operation. Over a 4-hour period, 1,000 cc. was given. At the termination of infusion, approximately 50 percent of the material remained in the plasma, 30 percent having been excreted in the urine. At 72 hours after administration, only from 2 to 3 percent of the gelatin remained in the plasma, approximately 80 percent having been excreted in the urine.


211

In comparing the fate of dextran and gelatin in two similar patients, it was found that the amounts of each remaining in the plasma-at similar intervals after infusion-were essentially the same. The amount of gelatin excreted in the urine immediately after infusion was slightly higher than the amount of dextran excreted in the urine during a similar period.

Ratio of Dextran to Blood. Dextran was used in conjunction with whole blood on several occasions during the preoperative, operative and postoperative periods of resuscitation. A study was made of 35 patients who received 1,000 cc., or more of dextran, in addition to blood, in an attempt to find a safe and practical ratio of this plasma expander to blood. From these studies, certain trends were observed that would justify a conservative rule as to the ratio of dextran to blood (table 8). If a patient has a blood volume deficiency of from 1,000 to 1,500 cc., he can be entirely resuscitated with dextran. If the deficiency is between 1,500 and 4,000 cc., then a safe ratio is 1 unit of dextran to 1 unit of blood. If the patient requires from 4,000 to 7,000 cc. of fluid for resuscitation, the ratio suggested is 1 unit of dextran to 2 units of blood. In patients who are severely wounded and require over 7,000 cc. of resuscitative fluids during their first 24 hours, a maximum of 2,500 cc. of dextran should be used; while the remainder of supportive fluids given should be whole blood.

Table 8. Acceptable Ratio, Dextran to Blood

Blood volume deficiency

Ratio

1,000-1,500 cc.

Dextran alone.

1,500-4,000 cc.

1 dextran: 1 blood.

4,000-7,000 cc.

1 dextran: 2 blood.

Over 7,000 cc.

Maximum dextran-2,500 cc. Remainder blood.

Although 2,000 cc. or more of dextran caused a rather distinct hemodilution, with a rapid fall in the hematocrit, patients tolerated a limited red-cell mass as long as the plasma volume was adequately expanded. Some patients exhibited a rapid pulse for varying periods of time; however, when additional whole blood was given, the pulse rate returned to normal. This concept of a conservative ratio of dextran to blood has wide implications in time of catastrophe when adequate amounts of whole blood are not available. A patient who has a minor blood volume deficiency can be supported adequately by the use of dextran. Likewise, blood may be conserved in more severely injured patients by administration of dextran in an appropriate ratio.


212

Use of Plasma Expanders at the Division Level. As experiences in Korea accumulated, it became evident that early resuscitation was of considerable value. It was observed that casualties who were prepared for transportation at the battalion level withstood the further injury of evacuation better than casualties who were sent back to a surgical hospital without restoration. Preparation included the administration of a plasma volume expander. After loss of considerable quantities of blood, a battle casualty withstands the trauma of transportation better if his plasma volume is expanded.

Soon it became apparent that the earlier after injury a plasma volume expander could be administered, the better the casualty withstood transportation to an aid station. In several instances, the littercarry was quite long from point of injury at the forward outpost or from some point on a patrol mission. During this period, the casualty's condition might deteriorate considerably. It was learned that some type of plasma volume expander was quite useful during transport to an aid station. Early in the Korean conflict, serum albumin was utilized for this purpose because it was packaged in a small bottle enabling the company aidman to carry several of these units in his pocket. As dextran was used more extensively, it was found quite useful in the division area when packaged in plastic bags. Dextran-thus packaged, in a small, convenient bag-was carried by company aidmen on patrol so that infusion could be started immediately after a soldier was injured. The use of dextran in plastic bags permitted the early institution of restorative measures and proved to be an important advance in the initial care of severely wounded men.

Summary

Experiments in the Korean conflict pointed out the value of massive transfusions in the management of the severely wounded. The average amount of blood administered to the group of patients who received from 5 to 10 pints was 3,440 cc. The average amount of blood given in 10- to 35-pint group was 7,300 cc. In both groups the amount of blood given prior to operation was approximately equal to the amount of blood given during operation.

The mortality rate in 33 casualties who were admitted in severe shock and who received an average of 7,600 cc. of blood in the first 24 hours after injury was 21 percent.

Lyophilized pooled plasma and serum albumin were used as emergency shock solutions in the early part of the war. Plasma had two undesirable aspects, namely, a high percentage of the bottles contained the virus of serum hepatitis and a large number of the bottles broke during cold weather. Dextran replaced plasma and albumin as an


emergency shock solution toward the end of the hostilities. It was found to be a safe, effective plasma volume expander.

Acknowledgement

The tables and data in this report are from:

    Artz, C. P., Howard, J. M., Sako, Y., Bronwell, A., and Prentice, T.: Clinical Experiences in the Management of the Most Severely Injured Battle Casualties. (To be published.)