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Chapter 13

Chapter 13

The Fate of Dextran and Modified Fluid Gelatin in Casualties with Renal Insufficiency*

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

Previous studies have demonstrated that much of the dextran or modified fluid gelatin, when infused into the normal subject or the injured soldier,3 is rapidly excreted in the urine. Cumulative measurement of the urinary excretion, and serial measurements of plasma concentration and volume in the severely injured soldier fail to account for approximately 30 per cent of the infused dextran and 20 per cent of the modified gelatin 24 hours after infusion.3 (Evidence has been presented that at least part of the dextran is metabolized.)4, 5, 8

The treatment of casualties with acute renal insufficiency offered an opportunity to study the fate of these expanders under conditions where urinary excretion would be minimized.

The study was carried out on the Eastern Front in Korea in 1953. Studies were begun at the forward Surgical Hospital and continued following evacuation to the Renal Insufficiency Center, 100 miles to the rear.

Materials and Methods

The dextran used in this study and in the study of the nonoliguric casualties was lot number 250R2, Commercial Solvents Co. Its average molecular weight was 42,000.3 Dextran analysis was by the method of Bloom and Wilcox.2

The modified fluid gelatin used in this study and the study of the nonoliguric casualties was lot MFG # 9 of Knox Gelatine Company. Its average molecular weight was 34,000.3

Gelatin analysis was by the method of Neuman and Logan (hydroxyproline).7, 3

Plasma volume determinations were made by the T-1824 dilution procedure6 using three interval samples to assure complete mixing. 


*Previously published in Surgery, Gynecology and Obstetrics 100: 207, 1955.


177

Observations

Dextran

Dextran was administered to two casualties with renal insufficiency.

Patient No. 12. This Korean soldier, blood type A, was admitted with a perforating wound of the intestine and several penetrating wounds of the extremities. During operation he received 500 ml. of type B blood. A hemolytic reaction with hemoglobinemia and hemoglobinuria resulted. He was immediately given 2,000 ml. of dextran (120 gm.) in an effort to produce a diuresis but his urinary output during the ensuing 24 hours was only 700 ml. This represented a relative oliguria after such an infusion of dextran. The second day his urinary output was 950 ml. and thereafter was 1,600 ml., 2,100 ml., and 3,000 ml. on succeeding days. His blood nonprotein nitrogen concentration rose to 100 mg. per 100 ml. but the patient was never critically ill. He represented a patient with a mild form of renal insufficiency.

Patient No. 17. This American soldier was admitted with severe compound, comminuted fractures of both upper femurs, which resulted from a jeep accident. His blood pressure was imperceptible and rose very slowly during transfusion. After the administration of 10,000 ml. of blood, his pressure was 120 mm. systolic. Operation was not performed. There was no external blood loss. One thousand ml. of dextran was then given intravenously during a 3-hour period. His urinary output averaged approximately 200 ml. per day for 2 weeks after which he diuresed. During the course of the oliguria his blood nonprotein nitrogen rose to 250 mg. per 100 ml. and his rising serum potassium concentration was controlled only by three periods of dialysis on the artificial kidney. This patient had a very severe degree of renal failure.

The retention of dextran in the two patients with renal insufficiency is demonstrated in Figure 1. Sixteen casualties without renal insufficiency, previously given dextran of the same molecular weight, excreted 54 per cent of the administered drug within the first 24 hours. By comparison, Patient No.12 with a mild renal insufficiency excreted 28 per cent during the first 24 hours and Patient No. 17 with severe renal insufficiency excreted only 6.5 per cent. The excretion during the ensuing 2 or 3 days was minimal. The curve of renal excretion after the first 24 hours paralleled the curve of excretion in the other casualties (Fig. 1).

Thus after 3 days, Patient No. 17 retained almost 90 per cent of the administered dextran and Patient No. 12 approximately 70 per cent. Nevertheless, the dextran disappeared from the plasma as rapidly as in those patients who had the better renal function (Fig. 2). Thus the fraction unaccounted for in plasma and urine of the non-


178

FIGURE 1. Dextran Excreted in the Urine.
Only 11 per cent of the dextran was excreted in the urine by Patient No. 17.

azotemic patient ranged around 35 per cent of the administered dose, while the unaccounted-for fraction was 60 to 80 per cent in the two azotemic patients (Fig. 3).

Since the wounds were not detectably larger in the azotemic patients, it would seem unlikely that wound exudation accounted for this tremendous loss. The progressive "metabolic loss" after the first 24 hours is essentially the same in the two groups, that is, 1 to 3 per cent per day.

Even after diuresis occurred, dextran did not appear in increasing amounts (Patient No. 12). Equilibration of the dextran between the plasma and extravascular fluid could not be the explanation, as indicated by the following calculations.

If the total body water is assumed to represent approximately 60 per cent of the body weight, the patient's total body water is 40,800 ml. Similarly the extracellular fluid, calculated as 15 per cent of the body weight, is 10,200 ml.

Thus, at 121 hours if the dextran is in equilibrium throughout the total body water, the dextran in this water would be 15.9 grams, leaving an additional 67.7 grams (54.7 per cent of total dose) of dextran metabolized or stored. Similarly, at 121 hours, if the dextran is in equilibrium throughout the extracellular fluid, there would be a


179

FIGURE 2. Loss of Dextran from Plasma.
Although most of the dextran was retained by the oliguric patients, their plasma concentration was equivalent to that of the nonoliguric patients.

calculated 4 grams in the extracellular fluid, leaving 77.6 grams of the unaccounted-for fraction which had to be metabolized or stored. Equilibration of this fraction with the dextran of the plasma at 121 hours would require the absurd volume of 209,231 ml. (Table 1).

Table 1. Patient No. 12
Weight-68 Kilograms
Dextran Administered-120 Grams
 

Hours after Infusion

Dextran Unaccounted for in Urine and Plasma

Plasma Dextran Concentration mg./ml.

Calculated Equilibration Volume* ml.

% of Administered Dose

gm.

0

60

72.0

11.75

6,127

13

63

75.6

5.12

14,766

49

66

79.2

2.40

33,000

97

68

81.6

0.86

94,888

121

68

81.6

0.39

209,231

*A volume of fluid necessary to contain the "unaccounted-for" dextran if the latter fraction is in equilibrium with the dextran of the plasma.


180

FIGURE 3. Dextran Deficit.
(Plasma dextran plus urine dextran expressed in terms of dose administered).
Eighty-seven per cent of the dextran could not be accounted for in urine and plasma of Patient No. 17.

An even higher percentage of dextran was unaccounted for in Patient No. 17 (Fig. 3).

These studies extend the observations of Bloom1 who demonstrated a similar degree of disappearance of dextran from the plasma of rats which had undergone bilateral nephrectomy.

Modified Fluid Gelatin

Two patients with post-traumatic renal insufficiency were studied following the intravenous administration of 3 per cent modified gelatin.

Patient No. 3. This 22-year-old American soldier was wounded on patrol by small arms fire. The injury included perforations of the liver, kidney and colon. He was admitted to the forward Surgical Hospital 4 hours later. Following operation he remained hypotensive although he had received 9,500 ml. of blood. He was then given 2,500 ml. (75 gm.) of modified gelatin. His blood pressure gradually returned to normal. His urinary output during the first 24 hours was 365 ml. but during the second 24 hours fell to 100 ml. His blood nonprotein nitrogen concentration rose to 300 mg. per 100 ml. and his plasma potassium concentration to 7.6 mEq. per liter. He diuresed


181

on the fifth day post-injury but subsequently died of renal abscesses.

Patient No. 4. This 21-year-old Korean soldier was injured by small arms fire. The injuries included perforations of the small intestine and spleen. He was given 2,500 ml. of blood during splenectomy and repair of the bowel. Postoperatively, he was found to have a plasma volume of only 1,590 ml. and to be oliguric. He was then given an infusion of 1,000 ml. (60 gm.) of modified gelatin within a 4-hour period. The anticipated diuresis did not result but he remained relatively oliguric for 12 hours after which he diuresed. This patient, therefore, represented a very mild form of renal insufficiency which may have been on a functional basis only.

These two patients who were treated with gelatin had degrees of renal insufficiency comparable to the two who were given dextran. The disappearance of the gelatin (Figs. 4 and 5) was also comparable to that of the dextran.

Patient No. 3 excreted only 32 per cent, of the administered dose in 24 hours and Patient No. 4 only 35 per cent. In contradistinction

FIGURE 4. Gelatin Excreted in the Urine.
The oliguric patients excreted only half as much gelatin as did the nonoliguric patients.


182

the nonoliguric casualties excreted during this period an average of 70 per cent. Again, in spite of the marked retention of gelatin by the oliguric patients the total amount of gelatin in the plasma was comparable to that of the nonoliguric patients (Fig. 5). Thus the gelatin fraction unaccounted for in plasma and urine after 24 hours was 20 per cent of the administered dose in the nonoliguric group and approximately 60 per cent in the oliguric patients (Fig. 6).

FIGURE 5. Loss of Gelatin from Plasma.
In spite of renal insufficiency, gelatin left the plasma very rapidly.

As with the dextran, the disappearance of gelatin cannot be explained on the basis of equilibration (Table 2).

Table 2. Patient No. 3
Weight-80 Kilograms
Gelatin Administered-75 Grams
 

Hours after Infusion

Gelatin Unaccounted for in Urine and Plasma

Plasma Gelatin Concentration mg./ml.

Calculated Equilibration Volume ml.

% of Administered Dose

gm.

3

59

44.3

3.6

12,250

38

61

45.8

1.4

32,714

124

61

45.8

0.2

229,000


183

FIGURE 6. Plasma Gelatin plus Urine Gelatin.
Expressed in Terms of Dose Administered.
Sixty per cent of the gelatin could not be measured in urine and plasma of the oliguric patients.

Calculations as above would indicate that if equilibration was assumed throughout the estimated total body water, 39.8 grams (53.1 per cent of the administered gelatin) was stored or metabolized. If equilibration was assumed throughout the extracellular water, 43.4 grams (57 per cent) was stored or metabolized. Again the theoretical equilibration volumes demonstrated in Table 2 become absurd at 124 hours.

Modified gelatin, therefore, must also be stored or metabolized in large quantities in this type of patient.

Conclusions

1. The disappearance rate of dextran and modified gelatin from the plasma is not entirely dependent upon the rate of urinary excretion.

2. In the patients with acute renal insufficiency of the types observed dextran and modified gelatine appear to be stored or metabolized in large quantities.


184

References

1. Bloom, W. L.: National Research Council Report, 1951.

2. Bloom, W. L., and Wilcox, M. L.: Determination of Dextran in Blood and Urine. Proc. Soc. Exper. Biol. & Med. 76: 3, 1951.

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. Gray, I.: Metabolism of Plasma Expanders Studied with Carbon-14-labeled Dextran. Am. J. Physiol. 174: 462, 1953.

5. Gray, I., Siiteri, P. K., and Pulaski, E. J.: Metabolism of Plasma Substitutes, 1-dextran. Proc. Soc. Exper. Biol. & Med. 77: 626, 1951.

Gregersen, M. I.: A Practical Method for the Determination of Blood Volume with the Dye T-1824. J. Lab. and Clin. Med. 29: 1266, 1944.

7. Neuman, R. E., and Logan, M. A.: The Determination of Hydroxyproline. J. Biol. Chem. 184: 299, 1950.

8. Terry, R., Yuile, C. L., Golodetz, A., Phillips, C. E., and White, R. R.: Metabolism of Dextran-a Plasma Volume Expander. J. Lab. and Clin. Med. 42: 6, 1953.

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