Medical Science Publication No. 4, Volume 1

MASSIVE TRANSFUSIONS, BLOOD DERIVATIVES ANDPLASMA EXPANDERS*

MAJOR CURTIS P. ARTZ,MC

Experiences of World War II pointed out the value of whole blood inthe management of severely wounded. As the Korean conflict progressed,it became apparent that large quantities of blood should be administeredto the battle casualty. In a survey of 995 consecutive casualties admittedbetween February and August 1953 to the general surgical service of the46th Surgical Hospital in Korea, 138 (or 14 percent) required replacementof 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. Mortalityrate for the American patients was 2.2 percent, and for all general surgicalcasualties, 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 of138 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 for48 hours, 6 developed a marked degree of renal insufficiency and 4 of thesedied.

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

*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.

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Mortality and Type of Injury. The mortality rate in relationto the type of injury is outlined in table. 2. Casualties whose injurieswere primarily in the abdomen had a mortality rate of 16 percent. In thegroup whose injuries were primarily in the extremities, the mortality ratewas 10 percent. Casualties sustaining thoraco-abdominal wounds had a highermortality rate (26.6 percent); while for those who had chest wounds itwas 9 percent.

Table 2. Mortality Related to Type of Injury

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

Table 3. Pre-admission Blood and Plasma Expander

*Mostly dextran.

The average amount of blood replacement during various phases of resuscitationis shown in table 4. Patients in the 5- to 10-pint group were given anaverage 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 thosein the first group, namely, 7,300 cc. In

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each group the amount of blood given preoperatively was essentiallythe same as the amount given during the operation. Of the 73 casualtiesin the 10- to 35-pint group, 38 received an average of 1,130 cc. of resuscitativefluids 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 ofResuscitation

*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 percentof the patients in the extremity group were given approximately 1 literof plasma expander in addition to blood. Most of this plasma expander wasadministered before these patients arrived at the hospital.

Control of Hemorrhage. Hemorrhage was controlled preoperativelyin all 61 casualties in the 5- to 10-pint group. Of the 77 casualties inthe 56-pint group, hemorrhage was not controlled prior to operation in13; and control of hemorrhage preoperatively was questionable in 8. Ofthese 21 patients, hemorrhage was brought under control at operation inall but 4. Two of these four patients died on the operating table (onehad a large laceration of the common iliac artery and the other had a highbilateral amputation of the thigh). One patient with a massive liver wounddied 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 hourto replace the blood lost. His wound was re-explored 4 hours after thefirst operation. There were multiple bleeding sites in the retro-

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peritoneal area; and this area was packed with two 5-yard-roll gauzepacks. The oozing did not stop, however, until after 6 pints of fresh bloodwas administered. The patient subsequently recovered. During the first24-hour period, this patient was given 46 pints of blood. In three othercasualties with uncontrolled hemorrhage preoperatively, the major pointsof hemorrhage were controlled at operation. Oozing continued from all surfacesand 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 severelywounded casualties, 33 were admitted in severe shock; and of this number7 died (table 5). Severe shock was a clinical diagnosis. Each of the 33casualties 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 amountof 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 thatwas 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 otherwas unknown. The seven casualties who lived required from 11 to 26 pintsof blood in the first 24 hours.

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

Deaths. There were 20 deaths in the group of the 138 most severelywounded casualties (table 6). Most of this group were held at the hospitalfor a period of from 5 to 8 days; and they were evacuated only after theircondition became stable. Soon after injury, a few were evacuated to theRenal Insufficiency Center at the 11th Evacuation Hospital because of post-traumaticrenal insufficiency. Deaths listed included those that occurred at the46th Surgical Hospital and at the Renal Insufficiency Center. Renal failurewas not listed as a cause of death in these patients because it was considereda contributing factor rather than a primary cause of death.

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

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

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Table 6. Cause of Death

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

Casualties Who Received 15 or More Pints of Blood or PlasmaExpander

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

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

Table 7. Mortality-Casualties Who Required15 or More Pints of Blood and Plasma Expander

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Massive Transfusions

The successful use of massive transfusions re-emphasizes certain lessonslearned in World War II, namely, that the treatment of wound shock is primarilythe control of hemorrhage and the administration of adequate quantitiesof blood. One of the primary differences in resuscitation during the Koreanconflict and during World War II was the difference in the amount of bloodadministered. Massive transfusions were used frequently and only rarelywas there evidence of overtransfusion. From the data on blood volume determinationsafter massive transfusions collected by Captain Theodore Prentice, it appearsthat large quantities of blood were lost from the effective circulation.In most instances, recovery from the initial hypotension followed the administrationof large quantities of blood. An occasional patient who reached the hospitalalive, but who had vital organ damage, succumbed even though there wasonly a minimal blood loss. This was most frequently observed in casualtieswho had injuries of the brain. In general, the severity of the injury wasin direct proportion to the amount of blood lost. Both the injury and bloodloss continued to exert a deleterious effect.

Blood Derivatives

Lyophilized pooled plasma and serum albumin were used as emergency shocksolutions during the early phases of the Korean conflict. Plasma had twoundesirable aspects, namely, a high percentage of the bottles containedthe virus of serum hepatitis, and a large number of bottles were brokenduring cold weather. Approximately 20 percent of the patients in Koreawho received pooled plasma subsequently developed homologous serum hepatitis.Many of the battalion surgeons complained that the water used for reconstitutionof the plasma froze during the cold weather and bottles were broken. Serumalbumin was used: 100 cc. of 25 percent solution. Its particular advantagewas its availability in small containers which were easily carried by theaidman. Comparatively little dependable information is available on theefficacy of albumin. The battalion surgeons, however, generally believedalbumin to be a satisfactory resuscitative agent for emergency treatment.

Plasma Volume Expanders

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

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

The Surgical Research Team in Korea studied 19 battle casualties inorder to determine the fate of infused dextran. Severely injured patientswere given 1,000 cc. of dextran in the immediate postoperative period.This infusion required from 2 to 4 hours. Immediately after infusion, approximately40 percent of the dextran was present in the plasma. Three hours afterinfusion, 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 percentwas still present in the plasma at the end of 72 hours. It must be pointedout that the dextran used in this study was of lower molecular weight thanis presently acceptable, having an average molecular weight of 43,000.

The loss of dextran from the circulation appears to be directly relatedto urinary excretion. After 3 hours, approximately 37 percent of the infusedmaterial was found in the urine; after 6 hours, 42 percent; and after 24hours, 54 percent. Thereafter, dextran was excreted in small amounts. Approximately30 percent of the dextran administered could not be accounted for in theplasma or urine. This unaccounted-for fraction was presumably lost intothe wound, the extravascular compartment, or possibly metabolized.

In a similar study, 200 units of modified fluid gelatin were administeredto battle casualties. The average molecular weight of this material was34,000. The quantity of gelatin administered was 1,000 to 1,500 cc. A fewpatients received as much as 2,500 cc.; and one patient received 3,000cc. No evidence of toxicity was seen. The gelatin solution flowed freelyand, over a period of 8 months in storage, it did not change color. Nodata are available on the flow of gelatin during extremely cold weather.However, there was no record of difficulty with the administration of gelatingiven 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 percenthaving been excreted in the urine. At 72 hours after administration, onlyfrom 2 to 3 percent of the gelatin remained in the plasma, approximately80 percent having been excreted in the urine.

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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 similarintervals after infusion-were essentially the same. The amount of gelatinexcreted in the urine immediately after infusion was slightly higher thanthe amount of dextran excreted in the urine during a similar period.

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

Table 8. Acceptable Ratio, Dextran to 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-cellmass as long as the plasma volume was adequately expanded. Some patientsexhibited a rapid pulse for varying periods of time; however, when additionalwhole blood was given, the pulse rate returned to normal. This conceptof a conservative ratio of dextran to blood has wide implications in timeof catastrophe when adequate amounts of whole blood are not available.A patient who has a minor blood volume deficiency can be supported adequatelyby the use of dextran. Likewise, blood may be conserved in more severelyinjured patients by administration of dextran in an appropriate ratio.

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Use of Plasma Expanders at the Division Level. As experiencesin Korea accumulated, it became evident that early resuscitation was ofconsiderable value. It was observed that casualties who were prepared fortransportation at the battalion level withstood the further injury of evacuationbetter than casualties who were sent back to a surgical hospital withoutrestoration. Preparation included the administration of a plasma volumeexpander. After loss of considerable quantities of blood, a battle casualtywithstands the trauma of transportation better if his plasma volume isexpanded.

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

Summary

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

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

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

emergency shock solution toward the end of the hostilities. It was foundto 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., andPrentice, T.: Clinical Experiences in the Management of the Most SeverelyInjured Battle Casualties. (To be published.)