HEMODILUTION WITH RHEOMACRODEX DURING TOTAL BODY PERFUSION

HEMODILUTION WITH RHEOMACRODEX DURING TOTAL BODY PERFUSION G. Hellstrom, M.D., and V. 0. Bjork, M.D., Uppsala, Sweden

T

HE indications for hemodilution during extracorporeal circulation have been twofold: (1) to improve capillary flow, especially in cyanotic patients with a very high hematocrit, and (2) to diminish the priming volume of fresh, heparinized blood in the machine, thereby saving blood. Gollan (1954) used saline for hemodilution, Zuhdi (1961) 5 per cent dextrose in water, and Long and Lillehei (1961 and 1962) Bheomacrodex. All these hemodilution perfusions have been performed with a bubble oxygenator with a relatively low priming volume, hypothermia, and reduced flows. The aim of this paper is to present the effect of hemodilution by 500 ml. of Rheomacrodex in total body perfusion at a temperature of 30° to 33° C, when a spinning disc oxygenator is used at high flow rates. METHOD

The spinning disc oxygenator and a roller pump has been used for extracorporeal circulation at a temperature of 30° to 33° C ; 3 mg. heparin per kilogram of body weight was given before cannulation and 3 mg. protamine afterward. The machine for adults was primed with 7 units of fresh blood, each unit of 450 ml. containing 20 mg. heparin in 30 ml. 5.5 per cent glucose solution. For children 5 units were used. Blood loss during operation was replenished with ordinary ACD blood. Five hundred milliliters of low molecular dextran, Rheomacrodex,* 10 per cent with dextrose, was used instead of one unit of blood in one group of cases. The postoperative bleeding from the drainage tubes was measured from the end of operation until 8 A.M. the following day and then every 24 hours. The thrombocytes were counted according to Kristensson—30 minutes before, 30 minutes after the beginning, and then at the end of perfusion. Coagulation time was determined 10 to 20 minutes after the injection of protamine sulfate. Hemolysis was measured according to Crosby, fibrinolysis according to Schneider, hematocrit according to Guest, and potassium and sodium according to Eppendorf. From the Department of Thoracic Surgery (Head: V. O. BjSrk, M.D.), University Hospital, Uppsala, Sweden. Received for publication May 14, 1962. 'Rheomacrodex. The average molecular weight is about 40,000 and the intrinsic viscosity about 0.19. More than 90 per cent of the dextran molecules are within the molecular weight range 10,000 to 80,000. The dextran solutions were obtained from AB Pharmacia, Uppsala, Sweden. 395

396

H E L L 8 T E 0 M AND B J 6 R K 1500'

Normothermia w i t h

750-

500-

0J

Rheo-macrodex

Normothermia without Rheo-macrodex

1250-

ipoo-

J . Thoracic and Cardiovas. Surg.

ll First 24 hr.

Second 24 hr.

Third 24 hr.

Total during first 72 hr.

Fig. 1.—The postoperative bleeding in the group having received Rheomacrodex in comparison with the group without this addition. t/50 1500 ■

1250

Perfusion-time ZOi = - 9 0 min. H 60-90 min. WOL 30-60 min. I I < 30 min.

1000

Hi

am

First 24 he

1 ID Second 24 hr.

0fsE3 □ Third 24 hr.

Fig. 2.—The correlation between the postoperative bleeding and the duration of the perfusion.

MATERIAL,

During this study, 48 of a series of 72 patients operated upon under extracorporeal circulation at 30° to 33° C. received Eheomacrodex. Age and weight distribution was similar in the two groups. The perfusion time was on an average the same in the two groups (Table I ) . The severity of the heart lesion was on the whole the same in the two groups although most patients with a combination of aortic insufficiency and stenosis received Rheomacrodex (Table II). RESULT

1. The postoperative bleeding was on an average 550 ml., or 13.6 ml. per kilogram of body weight, in patients without Rheomacrodex as compared to 950 ml. total, or 19.2 ml. per kilogram of body weight, in patients receiving Rhe-

397

HEMODILUTION WITH RHEOMACRODEX

Vol. 45, No. 3 March, 1963 TABLE I.

T H E MATERIAL:

AGE, WEIGHT, AND PERFUSION

TIME

WITHOUT RHEOMACRODEX

WITH RHEOMACRODEX

No. of cases

24

48

Age (years) Average Range

26 3-53

26 4-56

Weight (Kg.) Average Range

52.5 9-80

51.3 13-86

60 38-88

66 17-143

Perfusion time Average Range

TABLE I I .

T H E MATERIAL:

CLINICAL DIAGNOSES WITH WITHOUT RHEOMACRODEX RHEOMACRODEX

Atrial septal defect with or without abnormal venous return Atrial septal defect, mitral stenosis Ventricular septal defect Atrioventricular canal Aorticopulmonary window Pulmonary stenosis, infundibular stenosis Tetralogy of Fallot Left ventricular aneurysm Aortic valvular stenosis Aortic valvular insufficiency Mitral valvular insufficiency Mitral valvular insufficiency, aortic valvular insufficiency Totals

1 1 4' 1 0 1 5 0 1 2 8 0 24

4 0 1 1 1 3 14 1 4 14 4 1 48

omacrodex (Pig. 1 and Table I I I ) . This difference is statistically significant. The bleeding was more pronounced only in those perfusions of more than 90 minutes as compared to shorter procedures (Pig. 2). If all cases (11) of more than 90 minutes of perfusion are excluded, the postoperative bleeding in cases in which Rheomaerodex was used is somewhat smaller for the first day, 830 ml. or 18.7 ml. per kilogram of body weight. TABLE I I I .

POSTOPERATIVE BLEEDING ( ML./KG.) LONG ET AL. 1 9 6 1 CHEST DRAINAGE NO. OP FIRST 1 2 HR. CASES

Without Rheomaerodex With Rheomaerodex

45 41

21.2 + 2.0 23.2 ± 2.0

THIS MATERIAL NO. OF CHEST DRAINAGE CASES FIRST 18 HR.

20 43

13.6 ± 2.1 19.2 ± 2.0

2. A significant decrease of thromboeytes is encountered in all perfusions and is more pronounced in those instances of longer perfusion (Pig. 3). The addition of Rheomaerodex has statistically and significantly diminished this fall in thrombocyte count (Pig. 4 and Table I V ) . The reduction in the thrombocyte count following the addition of Rheomaerodex is statistically significant.

H E L L S T R 6 M AND BJORK

398

J . Thoracic and Cardiovas. Surg.

Platelets in thousands per mm?

250 Platelet* in thousands per mm.

3

250-

//

200

200

150-

150

100

100-

>90min. — 60-90min. X-60min. <30min.

i #1 * Post perfusion

■ Normothermia with Rheom. • Normolhermia without Rheom.

50>

I

ill*** I

t period

Post Perfusion Period

Pig. 3.

Fig. 4.

Fig. 3.—Correlation between the duration of the perfusion and the decrease in thrombocyte count. Fig. 4.—The correlation between the thrombocyte count and the addition of Rheomacrodex. The drop in the thrombocyte count is less pronounced if Rheomacrodex was added in the heart-lung machine during the perfusion.

TABLE

IV.

THROMBOCYTE DECREASE DURING PERFUSION

( I N THOUSANDS) T H I S MATERIAL

LONG ET AL. 1 9 6 1

Without Rheomacrodex With Rheomacrodex

NO. OF CASES

VARIATION AFTER PERFUSION

NO. OF CASES

VARIATION AFTER PERFUSION

26 23

-111 + 17.2 -65 ± 8.3

21 40

-101 + 12.5 -76 ± 10.8

3. Coagulation time has been within normal limits after the perfusion in all eases. 4. Hemolysis was below 50 mg. per cent plasma hemoglobin, irrespective of Rheomacrodex addition, even in those perfusions lasting more than 90 minutes (Pigs. 5 and 6). 5. Fibrogen was not significantly diminished in either group, with or without Rheomacrodex. 6. Fibrinolysis was encountered in 2 patients; one having received Rheomacrodex. 7. The addition of 500 ml. of Rheomacrodex lowered the hematocrit from 43.5 to 40 per cent in the machine. This dilution effect is visible during the perfusion and results in a hemoconeentration on the first postoperative day

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HEMODILUTION WITH RHEOMACRODEX

Vol. 45, No. 3 March, 1963

plasma hemoglobin mg%

mg.% plasma hemoglobin - Normothermwith Rheom. —Normoth.without Rheom.

Post perfusion period

Ftost perf.ptriod

Fig. 6. Fig. 5.—The correlation between hemolysis and the addition of Rheomacrodex. No significant change was encountered. Fig. 6.—The correlation between the duration of the perfusion and the hemolysis encountered. F i g . 6.

% Hematocrit

>90min.

50% Hematocrit

60-90 min. 30-60 min.

Normothermia with Rheom.

<30 min.

Normotherm.without Rheom.

45-

45-

40

40

3b>

(A

t S m 0

,L , - (M

Post perfusion period Fig. 7.

35

I

.£ e

!J!i*l t 9 f> —

I

Post perfusion period Fig. 8.

Fig. 7.—The correlation between the hematocrit and the addition of 500 ml. Rheomacrodex to the heart-lung machine. Fig. 8.—Correlation between the duration of the perfusion and the hematocrit. No significant difference was found.

J. Thoracic and Cardiovas. Surg.

HELLSTEOM AND BJoEK

400

(Pig. 7). Perfusions of more than 90 minutes did not show a more pronounced fall of the hematocrit than the shorter procedure (Fig. 8). 8. Potassium, sodium, and serum protein did not show any difference during the perfusion, irrespective of the addition of Rheomacrodex (Table V ) . TABLE V.

POTASSIUM, SODIUM, AND SERUM PROTEIN DEFICIT AFTER PERFUSION

Total no. of cases Potassium < 3 , 6 mEq. No. of cases Average deficit Eange Sodium <135 mEq. No. of cases Average deficit Bange Serum protein < 6 mg. % No. of cases Average deficit Eange

WITHOUT RHEOMACRODEX

WITH RHEOMACRODEX

23

42

3 0.3 0.1-0.6

11 0.2 0.1-0.4

9 5.5 1-12

19 3.0 1-9

3 0.2 0.1-0.3

4 0.4 0.1-0.4

DISCUSSION

Gelin and co-workers have described improved capillary circulation from Rheomacrodex. Long and Lillehei, therefore, added Rheomacrodex to the circulation during total body perfusion. Then DeWall and Lillehei carried out open-heart procedures without blood for priming, utilizing either 10 per cent or 15 per cent Rheomacrodex or 5 per cent dextrose in distilled water as advocated by Zuhdi and his associates. Lillehei used the bubble oxygenator which has a lower priming volume than the spinning disc oxygenator. We have used Rheomacrodex in the spinning disc oxygenator with investigation of the bleeding tendency and blood changes after a standard dose of 500 ml. Rheomacrodex is a temporary plasma volume expander decreasing the hematocrit (Gelin). This hemodilution will explain the increased postoperative bleeding tendency. This increased bleeding, although statistically significant, is still within acceptable limits. At any rate no more blood is lost postoperatively than is gained in priming the machine. After perfusion of more than 90 minutes, the bleeding also is increased. Longer perfusions are more traumatic to the blood and cause increased hemolysis and a decreased thrombocyte count. As did Long, we found a statistically significant reduction of the decrease of thrombocytes when Rheomacrodex was given. This is the most important evidence of the usefulness of Rheomacrodex in reducing the intravascular aggregation of the corpuscular elements of the blood during total body perfusion. The coagulation time was not influenced by the addition of Rheomacrodex. Long found a decrease in hemolysis from 123 to 106 mg. per cent by the

Vol. 45, No. 3

March, 1963

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401

addition of Rheomacrodex. We found a slight increase from 31 to 45 mg. per cent, a difference which is not statistically significant. The degree of hemolysis in our material is very low, especially when compared with results when the bubble oxygenator is used. Serum protein and plasma electrolytes are not influenced by the addition of Rheomacrodex, either in our material or in that described by Long. CONCLUSION

The use of 500 ml. of Rheomacrodex during total body perfusion utilizing the spinning disc oxygenator has resulted in: (1) a slight but statistically significant increase in the postoperative bleeding, (2) a statistically significant diminished reduction of the thrombocytes, and (3) no changes in the serum protein and electrolytes. As the advantages of using Rheomacrodex seem greater than the disadvantages, we have continued to add 500 ml. Rheomacrodex in the heart-lung machine in more than 100 consecutive cases. REFERENCES DeWall, R. A., and Lillehei, C. W . : Simplified Total Body Perfusion, J . A. M. A. 179: 430, 1962. Engell, H. C , Rygg, I., Arnfred, E., Frederiksen, Th., and Poulsen, T.: Clinical Comparison Between a Stationary-Screen Oxygenator and a Bubble Oxygenator in Total Body Perfusion, Acta chir. scandinav. 122: 243, 1961. Gelin, L. E., and Ingelman, B . : Rheomaerodex—A New Dextran Solution for Rheological Treatment of Impaired Capillary Flow, Acta chir. scandinav. 122: 294, 1961. Gelin, L. E., Solvell, L., and Zederfelt, B . : The Plasma Volume Expanding Effect of Low Viscous Dextran and Macrodex, Acta chir. scandinav. 122: 309, 1961. Gollan, F., Hoffman, J . E., and Jones, R. M.: Maintenance of Life of Dogs Below 10° C. W i t h o u t Hemoglobin, Am. J . Physiol. 179: 640, 1954. Long, D. M., Sanchez, L., Varco, R. L., and Lillehei, C. W . : The Use of Low Molecular Weight Dextran and Serum Albumin as Plasma Expanders in Extracorporeal Circulation, Surgery 50: 12, 1961. Zuhdi, N/., and others: Hypothermia Perfusion for Open H e a r t Surgical Procedures, J . Internat. Coll. Surgeons 35: 319, 1961.