HEMODILUTION STUDIES IN EXTRACORPOREAL CIRCULATION WITH THE USE OF A ROTATING-DISC OXYGENATOR

H E M O D I L U T I O N STUDIES I N EXTRACORPOREAL CIRCULATION W I T H THE USE OF A ROTATING-DISC O X Y G E N A T O R Donald R. Kahn, M.D.* (by invitation),

(by invitation),

Georgine M. Steude, M.D.

Judith A. Ericsson, M.D. (by invitation), (by invitation),

Hugo F. Hidalgo, (by

M.D.

invitation),

Robert W. S. Lee, B.S.

and Herbert Sloan, M.D., Ann Arbor,

Mich.

O

NE of the technical problems in open-heart surgery with extracorporeal cir­ culation is how to prime the oxygenator so as to achieve optimum perfusion without added risk for the patient. Eecent reports have emphasized the harmful results of using large amounts of homologous blood for this procedure. Intravascular aggregation and capillary thrombosis may be induced, with eventual micro-infarction. 1 Prolonged oxygenation of blood in a disc, bubble, or screen oxygenator may so denaturize plasma proteins as to result in blood sludging and fat embolism.2 Gadboys and associates3 believe that the sequestration of both red cells and plasma in areas separate from the circulating blood volume is a result of homologous blood. Some of these difficulties may be obviated by adding low molecular weight dextran or 5 per cent glucose-in-water to the blood used for priming.4"6 The question of whether such hemodilution techniques could be applied to the use of the rotating-disc oxygenator gave rise to the laboratory studies reported here. In addition to the considerations of adequate perfusion and effect on the animal, the effects of hemodilution were studied in relation to total blood volume, red cell volume, plasma volume, the phenomenon of unaccountable blood loss, plasma hemoglobin levels, platelet counts, pH, pC0 2 , p0 2 , and oxygen saturation values. METHODS

For our experiments, total open cardiopulmonary bypass was instituted in dogs for one hour at 32° C , with the use of a De Bakey roller pump and a rotating-disc oxygenator with a priming volume of 2,000 ml. No extra blood was given during or after the perfusion, and the volume in the extracorporeal circuit was not changed. To evaluate the effects of hemodilution, the following conFrom the Departments of Surgery and Anesthesiology, University of Michigan Medical Center, Ann Arbor, Mich. Sponsored by University of Michigan Office of Research Administration 05196 and the Michigan Heart Association. Read at the Forty-third Annual Meeting of The American Association for Thoracic Sur­ gery a t Houston, Texas, April 8-10, 1963. •Fellow, American Thoracic Society. 765

K A H N E T AL.

766

J. Thoracic and Cardiovas. Surg.

centrations were used in priming the oxygenator: (1) undiluted homologous blood; (2) 75 per cent blood and 25 per cent dextran* (31 ml./Kg. body weight); (3) 75 per cent blood and 25 per cent of 5 per cent glucose in water (31 ml./Kg. body weight); (4) 50 per cent blood and 50 per cent dextran (62 ml./Kg. body weight); (5) 50 per cent blood and 50 per cent glucose-in-water (62 ml./Kg. body weight); (6) 25 per cent blood and 75 per cent dextran (94 ml./Kg. body weight); (7) 25 per cent blood and 75 per cent glucose-in-water (94 ml./Kg. body weight); (8) 100 per cent dextran (125 ml./Kg. body weight) ; and (9) 100 per cent glucose-in-water (125 ml./Kg. body weight). A total of twenty-two

5

89

75-

65-

» 3 u.

5

55-

ALL BLOOD

45Jr —I— -I ALL 29 SO 75 IOO BLOOD PRIMING SOLUTION Cft)

Fig. 1.—Plow rates during perfusion.

experiments were performed with 2 or 3 animals in each group. Red cell vol­ umes as determined by Cr 51 and plasma cell volumes as determined by radio­ active iodinated serum albumin were recorded before the perfusion and one hour afterward. These determinations were repeated after one week in selected animals. Values for platelets, plasma hemoglobin,7 pH, pC0 2 , p0 2 , and oxygen saturation were determined before the perfusion, a half hour after the start of perfusion, and one hour after perfusion was completed. Approximate values for oxygen saturations were determined according to the nomogram of Severinghaus, 8 and acid-base values were determined with the IL-113 meter, t The amounts of blood loss during and after the perfusion were accurately measured. RESULTS

The flow rates during perfusion, as determined by the amount of venous return, were considerably higher with all dilutions than with undiluted blood (Pig. 1), but appeared to be highest when dextran was used. There was no significant difference in blood loss among the various groups of animals, and •Six per cent dextran in isotonic sodium chloride (molecular weight of 75,000), Baxter Laboratories, Inc., Morton Grove, 111. ■(•Instrumentation Laboratory, Inc., 11 Galen S t , Boston 72, Mass.

Vol. 46, No. 6 December, 1963

HEMODILTJTION

767

STUDIES

postoperative hemorrhage was not a problem. Oxygenation was adequate during perfusion in all groups, as indicated by normal arterial and venous oxygen saturations; an hour after perfusion the values remained normal in all groups except that involving 100 per cent hemodilution, in which the venous oxygen saturation had fallen to 20 per cent. Plasma hemoglobin levels were consistently highest when 5 per cent glucose-in-water was used (Fig. 2 ) ; dextran was found to produce the least change in the plasma hemoglobin level one hour after per­ fusion. There was no significant difference in the values for pH and p C 0 2 among the various groups. Before perfusion was started all the animals showed respira­ tory alkalosis secondary to overventilation; during perfusion they became acidotic, but practically normal balance was restored within an hour after perfusion was completed. With the dilution factor taken into account, there appeared to be less destruction of platelets during perfusion with diluted blood than with undiluted blood (Fig. 3). In both groups, the decrease in total platelets was greater in 400'

5%G/W

300CD

3 o

o

200 ALL BLOOD

100

DEXTRAN 3 0 MINUTES ON PERFUSION

BEFORE PERFUSION

I HOUR AFTER PERFUSION

Fig:. 2 . — P l a s m a h e m o g l o b i n levels.

%

-70-,

BEFORE TO 1 HOUR AFTER PERFUSION

BEFORE TO 1/2 HOUR ON PERFUSION

-60ALL BLOOD

-50-40-30-20-

V\DEXTRAN

\ 5 % 6/W

-100-

\ \

\ _AJ_L._BL0_0D

V\oEXTRAN 1 1 ALL 25 BLOOD

\ 50

^ F^"!

75 100

5% 6 / w \ ALL 25 BLOOD

50 75 100

PRIMING SOLUTION (%) F i g . 3. - P e r c e n t d e c r e a s e in t o t a l p l a t e l e t s ( c o u n t s m i n u s dilution f a c t o r ) .

KAHN ET AL.

768

J. Thoracic and Cardiovas. Surg.

the sample taken during perfusion than in the sample taken an hour after the perfusion was completed, indicating that platelets may be released after per­ fusion. With regard to total blood volume, there was an unaccountable loss in all groups (Fig. 4), the amount being least in the dextran group and greatest in the glucose-in-water group. The greater part of the unmeasurable loss in total blood volume involved the red cell mass (Fig. 5). Even when the dilution factor was considered, the loss in red cells after hemodilution was as great as that occurring with undiluted blood. With regard to plasma volume (Fig. 6), the unaccountable loss in the un­ diluted blood group was determined to be 10 per cent. With dextran hemodilu­ tion there was an actual gain in plasma volume, so that this group showed the least change in total blood volume. With 5 per cent glucose-in-water hemodilu-

% -50 -40 5 % 6/W

-30-

ALL BLOOD

-20-

DEXTRAN

-10

o-

75 100 ALL 25 50 BLOOD PRIMING SOLUTION (%)

Fig. 4.—Per cent change in total blood volume before and one hour after perfusion.

%

-701

-60 -50-40

5% G/W ■^-ALL BLOOD DEXTRAN

-30 -20 -10 0 ALL BLOOD

BEFORE a AFTER PERFUSION. BEFORE 8. AFTER PERFUSION MINUS DILUTION FACTOR.

25

50

75

100

PRIMING SOLUTION (%) Pig. 5.—Per cent change in red cell volume.

Vol. 46, No. 6 December, 1963

HEMODILTJTION S T U D I E S

769

tion, however, there was a greater loss in plasma volume than with undiluted blood, except when all 5 per cent glucose-in-water was used. This did not appear to be secondary to evaporation, since the red cell loss also was greatest in this group. In the groups representing no hemodilution, 25 per cent dilution, and 50 per cent dilution, the total volumes of blood, plasma, and red cells rose only

DEXTRAN

ALL 25 50 75 100 BLOOD PRIMING SOLUTION (%)

Fig. 6.—-Per cent change in plasma volume before and one hour after perfusion.

-TOTAL BLOOD VOLUMES -PLASMA CELL VOLUMES -RED CELL VOLUMES 100% G/W

32002800-

„.» 100% G/W 75 % DEXTRAN

2400 -l a

2000-

75%

G/W

ui 2

1600

7 5 % DEXTRAN

O

1200

z

>

75% G/W

800-

\.:v —

100 % G/W s ^ "

-

75 % DEXTRAN

400 BEFORE PERFUSION

I HOUR AFTER PERFUSION

Fig. 7.

I WEEK AFTER PERFUSION

KAHN ET

770

AL.

J. Thoracic and Cardiovas. Surg.

slightly after one ween, as compared to the determinations made one hour after perfusion. In the 75 and 100 per cent hemodilution groups, however, the total volumes returned close to the pre-perfusion values within the week, the increase in red cells being less pronounced than the increase in total volume of blood and plasma (Pig. 7). From the clinical standpoint, it appeared that 100 per cent hemodilution carried the greatest risk, since half the animals in this group died soon after the operation and the others remained lethargic and weak for some time. In all other groups the animals were considered to be in good condition after the perfusion, although those in the 75 per cent hemodilution group were less active than the others. DISCUSSION

Our results indicate that the blood used to prime a rotating-disc oxygenator in cardiopulmonary bypass can be diluted without risking the animal's survival or the success of the perfusion. Dextran appears to be superior to 5 per cent glucose-in-water as a hemodilution agent, since it induces less change in total volume of blood, red cells, and plasma cells. In addition, 5 per cent glucose-inwater produces higher levels of plasma hemoglobin. With regard to unmeasurable loss in red-cell volume, it is difficult to im­ plicate homologous blood alone as responsible for this phenomenon, since in our studies the loss was as great with 100 per cent hemodilution as with undiluted blood. This was true even when the dilution factor was taken into account. I t is difficult to ascertain the clinical significance of the demonstrable ad­ vantages of dextran hemodilution in connection with extracorporeal circulatory systems. At the University of Michigan Medical Center we have used undiluted blood and a rotating-disc oxygenator in more than 800 clinical cases. Our mor­ tality rate associated with extracorporeal circulation alone is less than 1 per cent, as determined by the uncomplicated cases of ventricular septal defect, atrial septal defect, or pulmonic stenosis. I t is likely that any advantages asso­ ciated with hemodilution would have more clinical significance in cases that require more prolonged perfusion. The greatest advantage may well lie in the possibility that hemodilution can prevent intravascular aggregation of red cells. SUMMARY

Results of experimental cardiopulmonary bypass procedures in dogs indi­ cate that the relatively large volumes of blood required for priming a rotatingdisc oxygenator can be diluted without harm to the animal. In these studies, arterial and venous oxygen saturations during perfusion remained normal in all groups of animals. Only in those subjected to 100 per cent hemodilution did the venous oxygen saturation show a decrease, an hour after perfusion. Flow rates during perfusion were highest with dextran as the hemodilution agent, and lowest with undiluted blood. No bleeding problems were encountered. Plasma hemoglobin levels were highest with 5 per cent glucose-in-water as the dilution agent, and lowest with dextran. Actual platelet destruction was de-

Vol. 46, No. 6 December, 1963

HEMODILUTION STUDIES

771

creased by the hemodilution techniques. Unaccountable blood loss was least with dextran and greatest with 5 per cent glucose-in-water; in all experimental groups, this unmeasurable loss affected the red cell mass chiefly, and 100 per cent hemodilution did not prevent such loss. The authors are indebted to Mr. John H. Dufek for his technical assistance and to the University of Michigan Research Coagulation Laboratory (sponsored by the Michigan Heart Association) for making the platelet counts required by this study.

REFERENCES 1. Long, D. M., Jr., Sanchez, L., Varco, R. L., and Lillehei, C. W . : The Use of Low Molecular Weight Dextran and Serum Albumin as Plasma Expanders in Extracorporeal Cir­ culation, Surgery 50: 12-28, 1961. 2. Lee, W. H., Jr., Krumhaar, D., Fonkalsrud, E. W., Sehjeide, O. A., and Maloney, J . V., J r . : Denaturation of Plasma Proteins as a Cause of Morbidity and Death After Intracardiac Operations, Surgery 50: 29-30, 1961. 3. Gadboys, H. L., Slonim, E., and Litwak, R. S.: Homologous Blood Syndrome, Ann. Surg. 156: 793-804, 1962. 4. Zuhdi, N., MeCollough, B., Carey, J., Krieger, C , and Greer, A.: Hypothermic Perfusion for Open-Heart Surgical Procedures. Report on the Use of a Heart-Lung Machine Primed With 5% Dextrose-in-Water, Inducing Hemodilution, J . Internat. Coll. Sur­ geons 3 5 : 319-326, 1961. 5. DeWall, E. A., Lillehei, E. C , and Sellers, E. D . : Hemodilution Perfusions for Open-Heart 6. Eaison, J . C. A.: A Clinical Report of the Use of Low Molecular Weight Dextran in a Rotating Oxygenator, Thorax 17: 338-341, 1962. Surgery, New England J . Med. 266: 1078-1084, 1962. 7. Hauk, P., Oser, B., and Summerson, W . : Practical Physiological Chemistry, ed. 13, New York, 1954, McGraw-Hill Publishing Company. 8. Severinghaus, J . W . : Handbook of Respiration. National Academy of Sciences and Na­ tional Eesearch Bureau, Philadelphia, 1958, W. B. Saunders Company, pp. 72-73. (For Dismission,

see page

780)