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Chapter 14

Chapter 14

Clinical Observations on the use of Dextran and Modified Fluid Gelatin in Combat Casualties*

Lieutenant Colonel Curtis P. Artz, MC, USA
Captain John M. Howard, MC, USAR
First Lieutenant John P. Frawley, MSC, USAR

Immediately after World War II, the search was intensified for some type of macromolecular substance that could be given to maintain plasma volume expansion until whole blood was available. A complete review of the history and status of these plasma volume expanders was reported by Gropper, Raisz and Amspacher1 in 1952. It appeared that dextran and modified fluid gelatin were safe compounds and effective plasma volume expanders.

In the summer of 1952, Amspacher and Curreri2 conducted an initial study on the use of dextran in combat casualties in Korea. After using approximately 200 bottles in the treatment of 60 casualties, it was their impression that, although dextran was not a substitute for whole blood, it was a good plasma volume expander for use until blood was available. They found no toxic reactions.

Further study appeared warranted for three basic reasons: (1) blood was seldom available at the most forward medical installations, (2) the incidence of hepatitis following the use of pooled plasma in Korea was almost prohibitive, and (3) experience was needed as a background for the use of blood substitutes in any possible atomic conflict or accident in the future.

With this background, a broad metabolic and clinical investigation was undertaken during 1952-53. During the last 6 months of the study, two infantry divisions used the plasma expanders almost exclusively. Additional experience was gained at the Mobile Army Surgical Hospital supporting these divisions.

As a result of these studies, and based on recommendations of the National Research Council's Subcommittees on Shock and on Sterilization of Whole Blood, pooled plasma was withdrawn from the medical installations in Korea and dextran and human serum albumin were used instead. As a result, during the last 3 months of the study, dextran and albumin were used almost exclusively for resuscitation forward of blood-bank facilities. 


*Previously published in Surgery 37: 612, 1955.


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Studies of plasma volume expansion and the plasma retention and urinary excretion of dextran and modified fluid gelatin in the Korean casualties have previously been recorded.3, 4, 5 It is the purpose of this report to summarize the clinical experiences in the use of 4,000 units (500 cc.) of dextran and 200 units (500 cc.) of gelatin in the anticipation that the experience may prove of value in the management of mass casualties in any possible future disaster.

Dextran

Approximately 4,000 units of dextran were administered to 2,000 casualties. Careful observations were made for the presence of allergic reactions. There was no evidence of urticaria, bronchospasm, or vasomotor instability. Three patients had a pulse rate of 160 per minute and a blood pressure of 160/100 after the infusion of two units of dextran. These reactions seemed out of proportion to the anemia. They were transient and without apparent sequelae. Their etiology was uncertain. Therefore, it must be stated that no toxic reactions, definitely attributable to dextran, were encountered. An increased bleeding tendency or oozing after the administration of dextran was not clinically appreciated although it was not specifically investigated. Many patients with extensive wounds lost blood by oozing into the dressing, but if this was excessive following the administration of dextran, it was overlooked.

Preparation, Shipping and Storage of Dextran*

The dextran was bottled in units of 500 cc. It withstood shipping well and no breakage was reported. Part of the study was carried out during the winter months. Neither freezing nor gelling was a problem as almost all the dextran was administered within a heated bunker or within the hospital. Freezing occurred during transportation without obvious evidence of damage. The dextran flowed freely and battalion surgeons gave as much as 1,500 cc. within 15 or 20 minutes.

A total of 250 units of dextran in plastic bags was administered. The shipping weight per unit of dextran was 1.5 pounds in the bag and 2.5 pounds in the bottle. Only one bag was defective. It appeared that the plastic bag was ideal for use under conditions where dextran was generally used, namely, at the division level. Manual pressure permitted rapid administration. The bag was universally 


*Prepared by the Commercial Solvents Company, Terra Haute, Indiana. The average molecular weight of most of the dextran used in the clinical studies was 42,000 and 48,000, which is less than the average molecular weight of 75,000 prescribed by the National Research Council.


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accepted by medical officers in the more forward areas. It could be carried by the company aid man on patrol in pockets of fatigue clothes, thereby permitting plasma volume expansion almost immediately after a soldier was injured.

Effectiveness of Dextran as a Resuscitative Agent at the Division Level

Approximately 3,000 units of dextran were administered to 1,500 casualties at the division level. In most areas it was used routinely when support of the blood volume was required. Many of the patients to whom the dextran was administered were severely hypotensive. Throughout the period of study, the average time of evacuation from injury to arrival at the hospital, at least on the Eastern Front, was 3.5 hours. Cooperating battalion surgeons found dextran to be nontoxic, easily administered, undamaged by freezing, and effective in producing prompt increase in blood pressure and urine flow. At the time of admission to the hospital the condition of patients to whom dextran had been given appeared comparable to the condition of those given like amounts of plasma or albumin.

Clinical Observations on Patients Who Received Dextran at the Hospital

Hemorrhage is obviously accompanied by loss of erythrocytes and the oxygen-carrying capacity of the circulation cannot be replaced by dextran. For this basic reason, the quantitative use of plasma volume expanders was limited. It was found, as demonstrated below, that the healthy young adult could usually withstand the loss of approximately 50 per cent of his erythrocytes without serious complications. A comparable loss of total circulating fluid, however, may be fatal unless it is corrected. Dextran proved to be effective in restoring blood volume, in restoring blood pressure and supporting circulation if the loss of erythrocytes had not produced too serious a state of anemia. Many observations on the response of 150 carefully studied battle casualties have supported these facts. During resuscitation, each unit of dextran caused a fall of approximately 5 volumes per cent in the hematocrit. This resulted in part from bleeding and in part from hemodilution by the infused dextran. In general, it was found that a casualty with moderately severe injuries could tolerate 2,000 cc. of dextran prior to blood replacement without immediate serious danger from anemia.

Two thousand cubic centimeters was not an absolute limit in the face of continued hypotension, but beyond this limit the surgeon had to


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weigh carefully the hazards of acute anemia. A few patients who received more than 2,000 cc. of dextran were maintained without blood for several days after the use of dextran as the sole supportive agent. The hematocrit of these patients fell to 20 to 30 per cent. Very severely injured casualties (those sustaining excessive red cell loss) could not be maintained for more than a few hours without whole blood replacement.

These observations were documented by experience of which the following cases were typical. Knowing from civilian experience that patients could withstand profound but gradually developing anemia, these observations were made in an effort to delineate the limits of dextran therapy against the possible day of atomic disaster when compromises in therapy, if previously considered, might be more judiciously planned.

Patient No. 1. This 22-year-old American soldier, height 61 inches, weight 173 pounds, had been in combat for the previous 8 days. He was wounded at 1130 hours, 12 August 1952, by mortar shell fragments. His wounds included partial amputation of the left foot and approximately 50 small penetrating wounds of both lower extremities. After receiving 100 cc. of albumin, he was evacuated to the forward hospital via helicopter. At the time of arrival at the hospital, 1 hour after injury, his blood pressure was 120/78. He was warm, pale, dry, with fair capillary refilling.

The foot was amputated and many of the wounds were débrided under spinal anesthesia. There was a drop in pressure with the onset of anesthesia. This was controlled by an intravenous drip of neosynephrine and by the rapid administration of dextran. Blood loss from the many sites of débridement was extensive.

By the end of operation 3,400 cc. of dextran had been administered (Fig. 1). His hematocrit had fallen to 12 per cent and he was in respiratory distress for a few minutes. He was immediately given 3,000 cc. of fresh, group-specific blood. His further course was marked by fever (101°-102°) and necrosis of the edges of the amputation stump. Secondary débridement was carried out on the fifth postoperative day under spinal anesthesia. Multiple transfusions of fresh, group-specific blood were given, but in spite of a rising hematocrit and blood volume, his pallor remained quite marked.

This study clearly demonstrated to the observers that if many casualties with injuries of this magnitude were resuscitated with dextran only, serious complications might be encountered. Although this patient's subsequent course was reasonably smooth, and his hepatic, renal and adrenal responses were not unusual,6, 7 dextran therapy of this magnitude and at this rate is unsafe. Delayed dé-


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FIGURE 1. Following the administration of 3,400 cc. of dextran, the patient revealed signs of anoxia. Tachycardia was marked; the blood pressure essentially normal. The last fall in blood pressure probably reflected the rapid excretion of dextran. Although the dextran supported the total blood volume, the rapidly falling hematocrit (12 per cent) probably reflected the limiting factor, the total mass of circulating erythrocytes.

bridement would probably prove safer than the use of dextran in this quantity, for this patient demonstrated acute symptoms of anoxia.

Patient No. 2. This 22-year old American soldier, weight 192 pounds, was wounded at 2200 hours, 3 November 1952. He arrived at the hospital via ambulance at 0715 hours the following morning. His injury, from mortar and grenade fragments, included approximately 50 small penetrating wounds of all extremities in addition to fractures of the mandible and one metatarsal.

At the time of admission, his blood pressure was 110/80, pulse rate 100 per minute. He was pale, cool, had slow capillary refilling and a pulse volume of low magnitude. His plasma volume was 3,470 cc. (Evans Blue Dye method), blood volume 6,800 cc. This represented an estimated deficit of 14 per cent in the plasma volume. After 1,000


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cc. of dextran, operation was begun (1200 hours) under pentothal, nitrous oxide, oxygen, and ether anesthesia.

Débridement of 30 of the larger wounds required 2 hours and was associated with an uneventful course. A total of 2,000 cc. of dextran had been administered by 2000 hours. At this time his plasma volume was measured as 4,160 cc., blood volume 5,940 cc. Thus his operative blood loss had been replaced by dextran and his plasma volume deficit had been corrected.

The following day his pulse rate rose to 160 per minute, his blood pressure fell to 105/70. A fifth pint of dextran resulted in a fall of his pulse to 130 per minute, his pressure rising to 120/80. Gradually thereafter, the tachycardia decreased although it remained 80 to 110 per minute for 10 days.

Fifteen wounds were closed under local anesthesia on the sixth day and 15 on the tenth day. Healing was progressing satisfactorily at the time of evacuation on his twelfth postoperative day.

This patient tolerated well 2,000 cc. of dextran during surgery. The dextran was given more slowly than to the preceding patient and his hematocrit did not fall below 30 per cent during the period of operation and anesthesia. The following day, however, as the dextran was excreted, a marked tachycardia and slight hypotension developed. This was improved by increasing his blood volume by the administration of the fifth pint of dextran (Fig. 2). His subsequent course, including wound healing, was uneventful. Such a patient with extremity wounds, resuscitated with blood, characteristically demonstrated a progressive fall in hematocrit over the ensuing week. The peaks in the hematocrit on 5 November and 7 November represented the result of the rapid excretion of dextran. Thereafter, continued hemodilution was noted.

Under conditions where compromise in therapy becomes essential, such a patient as this may reasonably be resuscitated with dextran only, but this represents the maximal safe limit of such therapy. Blood is unquestionably to be preferred.

Patient No. 3. This 20-year-old American soldier, weight 178 pounds, 5 feet 9 inches tall, was wounded at 0815 hours, 15 August 1952. The injury, inflicted by a land mine, consisted of a traumatic amputation of the right foot and multiple soft tissue wounds of the left thigh and leg. A tourniquet was immediately applied and he was given 15 mg. of morphine.

On arrival at the hospital at 0955 hours, his blood pressure was 120/76, pulse rate 76, hematocrit 41 per cent. His skin was cool and pale; capillary refilling was good.

After 1,000 cc. of dextran his blood pressure was 148/82, pulse 84.


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FIGURE 2. In contradistinction to patient No. 1 (Fig. 1), the hematocrit in this patient did not fall below 30 per cent during the period of the additional insult of anesthesia and débridement.

Operation was then begun (1115 hours) under pentothal, nitrous oxide, oxygen, and ether. With induction, his pressure immediately dropped to 104/38, pulse 104 per minute. Bleeding was rather rapid during the amputation and his pressure dropped momentarily to 65/35, pulse rate 132 per minute. The hypotension was partially controlled by neosynephrine. At this time (1225 hours) he had received 2,500 cc. of dextran and his hematocrit was 20 per cent. As further hemodilution was considered unwise, he was then given 1,000 cc. of fresh blood. At the end of operation (1300 hours) his blood pressure was 96/48, pulse 132, hematocrit 21 per cent. Another 500 cc. of blood was given. His subsequent course was smooth until a transfusion on the fourth day postoperative resulted in a hemolytic reaction.

This man tolerated 2,500 cc. of dextran fairly well. However, it was difficult to maintain his pressure under the combined effects of spinal anesthesia, operative bleeding, and anemia. His subsequent course, as related to the dextran, seemed uneventful. His hepatic, renal and adrenal responses were essentially those seen in patients resuscitated with fresh whole blood.6, 7 The transfusion reaction on the fourth


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postoperative day was probably unrelated to the dextran therapy. The tachycardia slowly subsided as repeated transfusions resulted in an increase in the circulating red cell mass (Fig. 3).

FIGURE 3. Each 500 cc. unit of dextran resulted in a fall in the hematocrit of five volumes per cent.

Had blood not been immediately available, interruption of the operation might have been necessary.

Patient No. 4. The following report is a typical example of a casualty who was resuscitated with dextran only.

A 21-year-old American private was injured on 7 April 1953, at 2100 hours, when a 50-caliber machine gun missile perforated his left thigh, causing an open comminuted fracture of the left femur. Three hours later, he arrived at the surgical hospital with a blood pressure of 138/80, pulse 90, and a good dorsalis pedis pulse. His hematocrit was 44 per cent. He was given 500 cc. of dextran prior to operation. He


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lost approximately 2,000 cc. of blood during the operative procedure. A tremendous amount of tissue had been destroyed. It was necessary to explore the popliteal area and to do an extensive débridement with wide excisions on both sides of the lower extremity. He was given three additional units of dextran during the operative procedure. At one time, his blood pressure fell to 80/60 and his pulse rate rose to 120. However, after the administration of the fourth unit of dextran, his blood pressure returned to normal. A few hours after operation, his hematocrit was 27.5 per cent, his urine output 60 cc. per hour. Twelve hours after operation his hematocrit was 28 per cent; on the second postoperative day it was 25 per cent. He appeared to be well except that he was pale and listless. His urinary output remained excellent. He received 1,000 cc. of blood on the third and again on the fourth postoperative day. His hematocrit rose to 39 per cent and he was in good condition at the time of evacuation.

This patient demonstrates that a large amount of tissue destruction together with the loss of approximately 2 liters of blood may be tolerated by a young man when supported with dextran. Although his hematocrit fell to a rather low level, he experienced no serious deleterious effects.

Comment

Except in a few instances, whole blood was preferred in the management of most patients at the hospital level. Dextran was preferred as the colloid in the treatment of burns. Most patients with partial-thickness burns received chiefly dextran and very little blood. In the more extensive deep burns, the colloid requirements were usually fulfilled with a ratio of 1 unit of dextran to 1 unit of blood.

Many patients who had abdominal wounds and required prolonged intra-abdominal operative procedures showed a rising hematocrit. The exact cause of this hemoconcentration is unknown, but it is believed to be a loss of fluid into lumen and wall of the gastrointestinal tract and into the peritoneal cavity. During operative procedures on massive wounds of the abdomen, it was the experience of forward surgeons that this hemoconcentration could be corrected by using from 1 to 3 units of dextran in addition to blood.

Ratio of Dextran to Blood

During the last few months of the Korean conflict, 35 casualties were studied who received 1,000 cc. or more of dextran in addition to blood. This was part of a clinical investigation in which dextran and


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blood were given in varying proportions in order to find a safe and practical ratio in the event that unlimited quantities of whole blood were not available. These casualties had wounds of various types, abdominal, abdominal-extremity, thoraco-abdominal, chest and extremity. All the patients did well. In a few instances it was necessary to give blood on the day following operation either because of a low hematocrit or because of a rapid pulse rate.

Table 1 outlines the maximum amount of dextran given to the patients in each category. Several patients were observed who had a blood volume deficiency of 1,000 to 1,500 cc.; these patients were completely resuscitated using only dextran.

Table 1. Maximum Dextran Given in Various Categories
 

Ratio of Dextran to Blood

Total Colloid First 24 Hours

Total Dextran

1:1

4,500 cc.

2,500 cc.

1:2

6,500 cc.

2,500 cc.

1:3

11,000 cc.

3,000 cc.

1:4

14,000 cc.

3,000 cc.

From observations on these patients, it has been possible to outline a ratio of plasma expander to blood that may be given without causing dangerous anemia (Table 2). This may be used as a compromise when the supply of blood is limited. The patient's postoperative hematocrit and pulse rate serve as indicators for the need of additional blood.

Table 2. Acceptable Ratio of Dextran to Blood
 

Resuscitative Fluids Required

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


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Modified Fluid Gelatin

Two hundred units (500 cc.) of modified fluid gelatin* were given to casualties. About one-half of this amount was given in the division area and the remainder in the surgical hospital. There was no evidence of toxicity and the gelatin flowed freely. Observations by medical officers in the division area revealed that gelatin was a clinically effective solution for supportive therapy until the patient reached an installation where blood was available. The usual quantity of gelatin administered was 1,000 or 1,500 cc.; however, some patients received 3,000 cc. On storage, the gelatin did not change color over a period of 8 months. No data were available to determine whether or not freezing had any effect on the gelatin solution. It appeared that, under the conditions in which gelatin was used, it was an effective plasma volume expander; however, it must be pointed out that the average period of evacuation was 3.5 hours. Gelatin in a small series of patients seemed to support the circulation well for this period of time.

Discussion

These experiences extend those of Amspacher and Curreri,2 who pointed out that battle casualties having mild to moderate blood loss can be treated satisfactorily using only dextran, while those having more severe blood loss require whole blood. By administering dextran, many of the severely wounded casualties can be maintained during first aid and transportation to the hospital. Haynes and DeBakey8 demonstrated that patients who had lost about 20 per cent of their blood volume could be treated successfully with saline and dextran.

Effective early resuscitation was achieved by dextran alone in patients with moderate shock or with blood volume deficiencies ranging from 20 to 30 per cent, whereas dextran and blood were required in patients who lost more than 35 per cent of their blood volume. We are in general agreement with their conclusion, namely, that a hematocrit depressed by 25 per cent through administration of dextran probably represents the approximate lower limits of a safe level of diminished circulating red cell mass compatible with effective resuscitation. 


*Modified fluid gelatin in this study was 3 per cent in 0.7 per cent sodium chloride, Lot No. MFG-9, manufactured by the Research Department of the Charles D. Knox Gelatine Company, Inc., Camden, New Jersey, average molecular weight, 34,000.


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Summary

Observations were made on the administration of 4,000 bottles of dextran to 2,000 casualties during the latter part of the Korean conflict. No toxic reactions were seen. A bleeding tendency following the administration of dextran, although not investigated, was not noted. This plasma volume expander proved to be most satisfactory. Many forward surgeons felt that it was superior as an emergency solution to plasma or albumin.

Patients who required 1,500 cc. or less of resuscitative fluids could be satisfactorily restored with dextran alone. An acceptable ratio of dextran to blood was established for use when unlimited quantities of blood were not available.

Observations were made on the administration of 200 units of modified fluid gelatin. The solution was nontoxic and did not gel. Although the molecular weight was low (average 34,000), the period of evacuation was only 3.5 hours and the circulation was supported for the required period.

References

1. Gropper, A. L., Raisz, L. G., and Amspacher, W. H.: Plasma Expanders. Surg. Gynec. & Obst. 95: 521, 1952.

2. Amspacher, W. H., and Curreri, A. R.: Use of Dextran in Control of Shock Resulting from War Wounds. Arch. Surg. 66: 730-740, 1953.

3. Frawley, J. P. Artz, C. P., and Howard, J. M.: Plasma Retention and Urinary Excretion of Dextran and Modified Fluid Gelatin in Combat Casualties. Surgery 37: 384, 1955. (Chapter 12, this volume.)

4. Frawley, J. P., Artz, C. P., and Howard, J. M.: The Use of Dextran and Gelatin as Plasma Volume Expanders in Combat Casualties. Final Report to the Army Medical Service Graduate School, July 1954.

5. Howard, J. M., Frawley, J. P., Artz, C. P., and Sako, Y.: The Fate of Dextran and Modified Fluid Gelatin in Casualties with Renal Insufficiency. Surg., Gynec. & Obst. 100: 207, 1955. (Chapter 13, this volume.)

6. Scott, Russell, Jr., and Howard, J. M.: Hepatic Function Following Wounding and Resuscitation with Plasma Expanders. Ann. Surg. 141: 357, 1955. (Chapter 9 in Volume 1 of this series.)

7. Howard, J. M., Olney, J. M., Frawley, J. P., Peterson, R. E., Guerra, S., and Dibrell, W. H.: Studies of Adrenal Function in Combat and Wounded Soldiers. (Chapter 4 in Volume 1 of this series.)

8. Haynes, B. W., Jr., and DeBakey, M. E.: Evaluation of Plasma Substitutes in Clinical Shock: Dextran. In Surgical Forum, American College of Surgeons, 1951. W. B. Saunders Company, Philadelphia, 1952.

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